J Mater Sci

Review
REVIEW

Surfactant-assisted synthesis of hydroxyapatite

particles: a comprehensive review
P. Siva Prasad1, Bharat C. G. Marupalli1, Siddhartha Das1, and Karabi Das1,*

1
Department of Metallurgical and Materials Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India

Received: 30 November 2022 ABSTRACT

Accepted: 2 March 2023 Calcium phosphates are extensively used biomaterials for repairing bone tissue
due to their osteoconduction and osteoinduction properties. Hydroxyapatite
Ó The Author(s), under (HAp) is a type of calcium phosphate that has gained the attention of
exclusive licence to Springer researchers because of its high crystallinity, superior corrosion resistance, and
Science+Business Media, LLC, good mechanical and biological properties. This makes it ideal for use in dental
part of Springer Nature 2023 and orthopaedic applications. Natural HAp particles present in physiological
tissues have plate-like or rod-like morphology in the nanometre range, while
synthetic HAp particles exhibit an irregular morphology and are in the micron
range. The usage of surfactants as templates during the synthesis has become a
successful strategy to regulate the morphology and size of the HAp particles to
closely resemble the natural HAp. In this article, the authors have reviewed the
effects of various chemical surfactants (such as cationic, anionic, zwitterionic,
and non-ionic), biosurfactants (or biomolecules extracted from different parts of
plants such as roots and leaves), and bio-wastes on the structural (morphology,
size, and shape) and biological (bioactivity and biocompatibility) properties of
the HAp particles synthesized through various methods. The nucleation and
growth mechanisms of HAp particles in the presence of various surfactants
through different methods are discussed. Even though there has been significant
research on surfactant-assisted HAp particles, the detailed mechanisms behind
the changes in the biological properties with the addition of surfactant are
poorly understood. This review paper also highlights the current progress in the
synthesis and characterization of surfactant-assisted HAp and provides guid-
ance for future research on this topic.

Handling Editor: Annela M. Seddon.

Address correspondence to E-mail: karabi@[Link]

[Link]
 J Mater Sci

GRAPHICAL ABSTRACT

Introduction embedded in a triple helix structure of collagen [27].

HAp has a stable hexagonal structure where Ca2?
and PO43- ions are settled around the column of
Calcium phosphates (CaPs) are widely investigated monovalent OH- [28]. It is the most thermodynami-
for their mechanical and biological properties that cally stable Ca-P phase up to a temperature of
make them ideal for use in various biomedical 1300 °C and in the pH range between 4 and 12 [29].
applications, such as scaffolds for bone tissue engi- The composition, crystallinity, Ca/P ratio, morphol-
neering, bone fillers, and bioactive composites [1–5]. ogy, size, surface roughness, porosity, and texture are
Additionally, CaPs are suitable for potential appli- the critical specifications of HAp that influence the
cations such as drug/protein/gene delivery [6–10], mechanical and biological properties of the implant
fluorescence labelling, cell targeting [11], and diag- [30, 31]. Morphology and crystal size play an essen-
nostic and imaging materials [12–16]. CaPs also have tial role in enhancing biological properties. The bio-
practical applications in various other technical logical HAp particles found in physiological hard
fields, such as catalysts and catalyst carriers for tissues have a thickness of several nanometres and a
chemical reactions and in environmental sciences length of tens of nanometres, and they have a rod-like
[17–19], ion conductors [20, 21], sensors [22], and also or plate-like morphology. Hence, synthetic HAp
as adsorbents in the removal of metallic pollutants particles with morphology, size, and composition
[23, 24]. closely resemble natural HAp particles inside the
Apatite, which belongs to the CaPs family, is the human bone without showing any toxic behaviour
primary inorganic constituent of dentin, enamel, and are of great interest. The HAp particles in nanosized
vertebrate bone. The CaP compounds include form have high surface activity similar to bone min-
hydroxyapatite (HAp), a- and b-tricalcium phos- erals. Researchers have found that nanosized HAp
phates (TCP), octacalcium phosphate (OCP), brushite particles promote osteointegration more rapidly than
or dibasic calcium phosphate dihydrate (DCPD), micron-sized HAp particles. Bone replacement or
monobasic calcium phosphate monohydrate regeneration is practically feasible when the mor-
(MCPM), monetite or dibasic calcium phosphate phology of synthetic HAp is identical to natural bone
anhydrous (DCPA), and amorphous calcium phos- minerals. Synthetic HAp particles with unique crystal
phate (ACP) [25, 26]. structures have a great advantage in various appli-
The human bone is naturally consisting of HAp (in cations such as bone repairing and augmentation,
nanocrystalline form) with a Ca/P ratio of 1.67, hard tissue engineering, and drug/gene delivery.
J Mater Sci

Several synthesis routes are available to obtain surfactants as templates during the synthesis process.
HAp particles depending on the desired applications. Numerous reports have suggested that the closest
The most common synthesis methods for HAp are possible morphology of HAp particles present in the
hydrothermal, hydrolysis, solid-state, combustion, human body can be achieved by adding surfactants
chemical precipitation, emulsion, liquid–solid-solu- during synthesis [65–68].
tion phase transfer, soft template method, sol–gel, Surfactants are organic and inorganic compounds
and biomimetic deposition. These synthesis methods that can reduce the surface tension of a liquid or
are reviewed in Table 1. interfacial tension between two liquids. They contain
The synthetic HAp particles produced through both hydrophilic and hydrophobic parts, and the size
regular methods are typically spherical in shape and and shape of the hydrophilic and hydrophobic parts
range in size in the micrometre length scale. In order determine their properties [69–71]. The surfactant
to obtain optimal biological properties, it is important molecules can form different structures depending
to control the size and shape of the HAp particles. on their arrangement, as represented in Fig. 1a [72].
Many efforts have been made to regulate the mor- Chemical surfactants are classified into four cate-
phology and size of the HAp particles using novel gories based on the charge of the hydrophilic head
and modified techniques [63, 64]. One successful (cationic, anionic, amphoteric/zwitterionic, and non-
strategy that has been employed is the use of ionic), as shown in Fig. 1b. The type of chemical

Table 1 Advantages and limitations of various techniques to synthesize HAp particles

Technique Advantages Limitations

Hydrothermal Easy and simple method to prepare nanocrystals; highly Less capability in regulating the morphology and size
[32–36] crystalline and stoichiometric phases can be obtained distribution of HAp nanoparticles
Chemical Low processing temperature; simple and low-cost Poor HAp crystallinity; formation of non-stoichiometric
Precipitation process; relatively inexpensive raw materials phases
[37–39]
Hydrolysis [40–42] Simple and low-cost technique; nanoparticles can be Need long processing time to complete the
prepared from other CaPs transformation of HAp; poor control over the
processing parameters; could lead to the development
of a non-stoichiometric HAp
Solid state [43] Simple procedure; mass production of highly crystalline High calcination temperatures; low diffusion
HAp powders of diverse morphologies are possible; low coefficients of ions in the solid phase causes
cost heterogeneity in phase composition
Emulsion [44–46] Low synthesis temperature; more efficient in particle size Relatively high-cost process; wide size range of
reduction, controlling morphology, and limiting the particles
agglomeration of HAp particles
Sol–gel [47–54] Low processing temperatures; inexpensive; high purity Higher sintering temperatures; thermal expansion
mismatch
Combustion Inexpensive raw materials; relatively simple process; high Involves high temperatures; irregular morphology of
[55–57] purity and homogeneous HAp powders with high HAp particles
crystallinity can be obtained
Liquid–Solid- Effective in nanocrystals synthesis with controllable sizes High synthesis temperatures and prolonged reaction
Solution phase and shapes time
transfer [58, 59]
Soft template Not sensitive regarding the preparation conditions; easy to Further steps are needed to remove the template
method [60, 61] implement and operate; nanocrystals with controlled
morphology and size are possible
Biomimetic [62] Can generate bone-like apatite; low processing Time-consuming; involves a frequent change of the
temperatures; can integrate drug carriers/proteins/growth solution and requires maintaining a simulated body
factors fluid with constant pH
 J Mater Sci

Figure 1 a Different molecular structures of surfactants, b classification of chemical surfactants, and c structures of surfactant aggregates
as a function of surfactant packing parameter.

Table 2 Types of chemical surfactants along with their applications [73]

Surfactant type-charge of Examples Applications

the hydrophilic group

Cationic-positive Cetyltrimethyl ammonium bromide (CTAB); cetylpyridinium Antimicrobial and antifungal agents;
chloride (CPC); cetrimonium chloride; benzalkonium cleaning products
chloride
Anionic-negative Sodium lauryl ether sulphate; sodium dodecyl sulphate (SDS); Shampoos; cleaning products; wetting
alkylbenzene sulphonates; lignosulfonate agents; concrete plasticiser
Zwitterionic/amphoteric- Cocamidopropyl betaine Membrane solubilization; latex paints
both positive and
negative
Non-ionic-no charge Span; Triton X-100, Tween-80; Tween 20; polyethylene glycol Food additives; enzymatic saccharification;
(PEG) cleaning products; extractive fermentation

surfactants along with their applications is illustrated their critical micelle concentration, self-assemble into
in Table 2. Surfactants are of great interest to various shapes and serves as templates for the con-
researchers due to their unique properties and trolled nucleation and growth of HAp particles [74].
extensive applications in various fields, including Surfactants are crucial in producing well-controlled,
medical sciences, biotechnology, pollution control, nanosized HAp particles because they can adjust the
analytical chemistry, and physics and engineering. surface/interface tensions between solid/liquid
As a result, research on surfactants is interfaces and enhance dispersion stability. The
interdisciplinary. amphiphilic properties of surfactants play a crucial
Surfactants, after being added to a solution con- role in creating HAp nanoparticles by preventing the
taining calcium and phosphorous precursors above synthesised particles from aggregating and
J Mater Sci

increasing their stability in colloidal systems [75–77]. advances in this area and potential avenues for future
The molecular weight and the surfactant packing research are also discussed, providing valuable
parameter (SPP, which is the ratio of the hydrophobic insights for researchers in the field.
tail area to the hydrophilic head area) significantly
affect the final shape and size of the HAp particles.
The structures of surfactant aggregates as a function Synthesis of HAp using chemical
of the SPP are shown in Fig. 1c, and HAp particles and biosurfactants
with similar morphology can be obtained depending
on the structure of the surfactant aggregate. In recent years, research on HAp structures has
In contrast, HAp particles synthesized without shifted from control over stoichiometry to control
surfactants tend to form agglomerates. The addition over particle morphology, as the medical applications
of surfactants significantly reduces the aggregation of of HAp structures largely depend on the morphol-
HAp particles and enables the growth of the HAp ogy, crystallinity, and size of the HAp particles. To
nanoparticles to be controlled during the nucleation enhance the biocompatibility of HAp, researchers
process. As the hydrophobicity of the surfactant focus on controlling particle morphology using vari-
increases, the rate of surfactant migration to the ous techniques by using different surfactants (either
surface of nanoparticles increases, developing a chemical or biosurfactants) or by incorporating pro-
strong protective layer that maintains the dispersion teins or growth factors into HAp.
of the nanoparticles in solution with less agglomer-
ation [78]. These multiple functional roles of surfac- Chemical surfactants assisted HAp
tants made the researchers focus more on using synthesis
surfactants in the synthesis of HAp particles.
HAp crystals have been synthesized with unique Cationic surfactant-assisted HAp synthesis
morphologies including sphere, rod, needle, wire,
The positively charged hydrophile of cationic sur-
fibre, whiskers, sheet, disc, flake, platelet, and strip
factant provides unique properties that are essential
from nano- to macroscopic scales, which have been
in many applications. These cationic surfactant
widely reported over the past decades [79]. However,
molecules are widely used in the field of biotech-
some of these morphologies are dissimilar to physi-
nology due to their ability of self-assembling and
ological HAp particles and are, therefore, unsuit-
regulate the morphology of materials [83–85]. The
able for biological applications due to their poor
cationic charge of the hydrophilic molecules plays a
biological properties. Hence, the synthetic HAp
critical role in biotechnical applications such as drug
crystals that more closely resemble physiological
delivery systems. Among the other cationic surfac-
HAp morphology are preferred for biological prop-
tants, quaternary ammonium (QA) compounds are
erties [80]. The morphology of HAp crystals is
highly used in many biotechnical applications due to
strongly influenced by the synthesis methods and the
their disinfectant and bactericidal properties [86, 87].
parameters used. Despite many attempts to control
Some examples of cationic surfactants are benzalko-
particle size and shape, the role of surfactants in the
nium, benzethonium, methylbenzethonium,
synthesis of HAp particles of various morphologies
cetylpyridinium, alkyl-dimethyl dichlorobenzene
and sizes using different routes is not yet fully
ammonium, dequalinium and phenamylinium chlo-
understood. Although several researchers have
rides, cetrimonium, and cethexonium bromides. The
investigated the synthesis and properties of various
CTAB, benzalkonium chloride, and CPC are the most
HAp particles [33, 64, 79, 81, 82], no review has
commonly used cationic surfactants. Cationic sur-
specifically addressed surfactant-aided HAp particle
factants have recently been employed as nucleation
synthesis.
and crystal growth regulators to synthesize nano-
This review aims to provide a comprehensive
sized HAp utilizing various techniques. Besides their
understanding of the synthesis of HAp particles of
surface activity, cationic surfactants also have supe-
various morphologies and sizes using chemical and
rior antibacterial properties and can be used as
biosurfactants through various synthesis methods,
antiseptic agents in biomedical applications [88].
with a particular focus on the effects of surfactants on
the biological properties of HAp particles. The recent
 J Mater Sci

As discussed earlier in Sect. 1, the morphology of has been explained by Wang et al. and Yan et al.
HAp particles plays a critical role in several [92, 93]. The CTAB will form a cation with a tetra-
biomedical applications. However, the common hedral structure when dissolved in an aqueous sys-
synthesis routes of HAp particles have poor control tem. The phosphate anion of the precursor solution is
over the morphology of the final structures. CTAB is also a tetrahedral structure. The structure and charge
the most efficient cationic chemical surfactant com- complementarities of both of these ions will enable
monly utilized to regulate HAp particle morphology. them to be incorporated easily. The mixture of
Zhang et al. have synthesized HAp powders by CTAB–phosphate ions contains rod-like micelles with
precipitation method and analysed the effect of sur- phosphate ions on the surface. The addition of cal-
factant. With the addition of CTAB surfactant, the cium anions will result in the formation of calcium
aggregation of HAp powder particles decreases, phosphate clusters on the rod-shaped micellar sur-
resulting in a reduction in the particle size of the HAp face. These micelles act as nucleating points for the
powders. It is also reported that the crystallization transformation of calcium phosphate clusters into
process can be regulated with the addition of CTAB HAp crystals upon providing the necessary condi-
surfactant, whereas PEG surfactant addition does not tions. The generalized mechanism to synthesize HAp
affect the HAp powder morphology [89]. Gopi et al. particles with unique morphology in the presence of
have revealed that the concentration of CTAB is a CTAB is illustrated in Fig. 2. This nucleation mecha-
significant factor in depicting the HAp particle mor- nism is demonstrated based on the synthesis of HAp
phology. In this study, spherical-shaped HAp parti- particles through a hydrothermal process. However,
cles are formed with an average particle size of the nucleation mechanism of HAp particles is also
83.4 nm at a CTAB concentration of 0.0012 M, valid for other synthesis methods such as hydrolysis,
whereas HAp nanorods are formed at a higher CTAB biomimetic and chemical precipitation [42, 92–95].
concentration of 0.024 M with a mean length of The nucleation mechanism in the microemulsion
936.43 nm. HAp nanofibers were formed by increas- method is slightly different compared to other HAp
ing the CTAB concentration further to 0.24 M. These synthesis methods. In the microemulsion technique,
nanofiber structures can enhance bone formation and the surfactant is added droplet wise to the aqueous
tissue regeneration in several biomedical applications solution containing phosphate ions, which forms oil
[90]. Similar findings have been obtained by J Anita and water phases. The phosphate ions will be
Lett et al. with the addition of CTAB surfactant to enwrapped by the oil phase of the surfactant. The
pure HAp. The addition of CTAB surfactant inhibits phosphate ions reach the surface of the oil phase due
the HAp particle agglomeration by adsorbing on its to concentration difference. The HAp particles
surfaces, resulting in the formation of uniform and nucleate on this surface upon the release of Ca2? ions
long rod-like morphology with an increase in the [96].
degree of crystallinity [91]. Mujahid et al. have syn- The size and morphology of HAp crystals are
thesized the HAp powders using CTAB as a tem- directly influenced by the behaviour of micelles,
plate. The micelles of the CTAB surfactant were which, in turn, is affected by the concentration of
mixed with the phosphate precursor solution. The CTAB. Along with the CTAB surfactant concentra-
negatively charged phosphate ions are adsorbed on tion, the temperature is also a significant factor that
the surface of the positively charged micelle due to affects the final morphology of the HAp crystals
the electrostatic force of attraction between the [92, 93]. The growth rate of HAp crystals is slow at a
oppositely charged ions. The addition of calcium lower temperature, and the critical size of the nuclei
precursor solution to the micelles containing phos- is small, which leads to the formation of smaller-
phate has resulted in the formation of calcium sized products. Conversely, at higher temperatures,
phosphate. The newly formed calcium phosphate the critical size of the nuclei also increases and the
transforms to hydroxyapatite upon adjusting the pH HAp particles tend to grow at a faster rate due to the
and temperature. The morphology of resultant HAp presence of high surface energy. Considering that the
particles contains rod-shaped particles with hydrothermal process is a closed system, the pressure
200–300 nm lengths and a diameter of 50 nm [88]. inside the system increases at higher temperatures,
The mechanism behind the nucleation and growth leading to a decrease in supersaturation. These con-
of HAp particles in the presence of CTAB surfactant ditions favour the crystals to grow further, resulting
J Mater Sci

Figure 2 Schematic representation of hydroxyapatite synthesis mechanism in the presence of CTAB surfactant.

Hence, HAp particles tend to grow more on the (100)

surface [99].
The pH of the solution is one of the key parameters
during the synthesis of HAp particles. The interaction
of CTAB surfactant and phosphate ions, as well as the
conversion rate of calcium phosphate clusters into
HAp, is greatly affected by the pH of the solution.
The conversion rate increases with an increase in pH
level between 7 and 10 and decreases beyond 10. An
optimal pH of 9 is recommended during the syn-
thesis of HAp nanorods with the addition of surfac-
Figure 3 The combined effect of pH and temperature on the tants. At higher pH levels ([ 10), the presence of
morphology and growth of HAp particles. more OH- ions disturbs the interaction of CTAB with
PO43- ions by repulsing PO43- ions. It prevents the
growth of HAp particles along the c-axis and results
in the formation of bigger-sized products [97]. The in the formation of spherical structures. The low
effect of an increase in temperature on the HAp concentration of OH- ions at a pH of 9 promotes the
particle growth is depicted in Fig. 3. Nathanael et al. growth of HAp crystals along the c-axis on rod-
propose an orientation-dependant growth mecha- shaped micelles of CTAB and PO43-, which results in
nism for HAp particles. They suggest that the high needle-like structures [97]. The effect of pH level on
aspect ratio HAp particles with nanorods or needle- the morphology of HAp particles is shown in Fig. 3.
like structures are promoted by the anisotropic It is hypothesized that when the hydrothermal
charge distribution and stereochemistry of HAp temperature rises, the crystallinity of HAp particles
particles [95]. Hong et al. have also suggested that the increases. Several researchers have observed that the
orientation dependence of surface energy and charge addition of surfactant highly affects the HAp parti-
of the surface play a key role in depicting the growth cles in the post-heat treatment process. A significant
direction of the HAp particles. Since CTAB contains change in the morphology and crystallinity was
cations, it has a preference to attach to negatively observed in such HAp particles. Salarian et al. have
charged surfaces [98]. Density functional calculation synthesized HAp nanorods using a mixture of
by Rulis et al. derived that the (001) surface is more cationic CTAB surfactant and non-ionic PEG surfac-
positive, and the (100) surface is highly negative. tant by hydrothermal method and observed that the
 J Mater Sci

hydrothermal temperature improves the crystalline Gram-negative bacteria [101]. It is proven that the
nature of the HAp particles. They have concluded addition of Ti to the HAp particles prevents bacterial
that the nucleation and growth of HAp particles can infection and also ensures the in vivo viability of
be controlled with the addition of both CTAB and medical implants. However, the addition of Cu has
PEG surfactants together [67]. Similar behaviour of an adverse effect on human cells. The leaching of
increase in crystallinity with heat treatment has been Cu2? ions causes the cytotoxicity of osteoblasts, and
observed by Khalid et al. They have observed that the the addition of Cu as a metal ion doping in the syn-
powders synthesized using surfactant have needle- thesis of HAp particles is not advisable due to its
like morphology after heat treatment at 900 °C for biocompatibility issues [102].
3 h, whereas powders synthesized without surfactant
contain spherical morphology. The addition of CTAB Anionic surfactant-assisted HAp synthesis
suppresses the b-TCP phase formation and also
reduces the crystallinity of the powders. The post- Anionic surfactants are a type of surface-active
heat treatment of HAp powders with surfactant agents that form negatively charged ions when dis-
results in a huge increment of crystallinity degree solved in water-based solutions. They are extensively
from 15 to 85%. Interestingly, the addition of surfac- used in common household applications such as
tant increases the crystallinity of the HAp powders dishwashing liquids, cloth washing detergents, and
after heat treatment [96]. shampoos due to their superior cleaning and hair
conditioning properties. Anionic surfactants consti-
Influence of cationic surfactants on biological proper- tute 60% of the total worldwide surfactant produc-
ties The bone tissue in the human body consists of a tion due to their ease of manufacturing and low
HAp structure in the form of nanorods. The excellent production costs. Moreover, they are considered rel-
biocompatibility of HAp structure with human tis- atively non-toxic. The classification of anionic sur-
sues enables their usage in vast biomedical applica- factants is based on their polar groups, such as
tions. To investigate its biocompatibility, Nguyen sulphonates, sulphates, phosphate esters, carboxy-
et al. conducted in vitro tests on HAp nanorods lates, alkyl sulphates, alkyl ethoxylate sulphates, and
synthesized using CTAB as a soft template. They soaps [69, 71, 72, 103]. Sodium lauryl sulphate,
varied the aspect ratio of the nanorods from 2.6 to 7.0 sodium dodecyl sulphate (SDS), sodium bis(2-ethyl-
and embedded them in poly (D, L) lactic acid hexyl) sulfosuccinate (AOT), ethylene diamine tetra-
(PDLLA) films for the tests. They reported that the acetic acid (EDTA), and sodium tripolyphosphate
HAp nanorods with an aspect ratio ranging from (STPP) are the most common examples of anionic
5.94–7 promote the rapid formation of collagen fibres surfactants.
and cellular attachment at an early stage of culture. Sodium dodecyl sulphate (SDS) is known to be one
They have concluded that the aspect ratio and surface of the most efficient anionic surfactants for regulating
roughness of HAp/PDLLA composite films signifi- the morphology in the nanoscale, as reported by
cantly affect the adhesion and proliferation of MG 63 Kangkan et al. and Elsaeedy et al. [104, 105]. Because
human osteoblast cells [82]. Shanthi et al. conducted of their high surface energy, the HAp nanoparticles
cytotoxicity tests on a normal cell line and revealed tend to agglomerate quickly. The addition of SDS can
that the nanocrystalline HAp is relatively non-toxic in limit agglomeration by providing resistance in the
nature [94]. The in vitro cell cultural studies revealed form of electric charge at the nucleus-aqueous inter-
that the addition of CTAB enhances the preferential face in the reaction media. Tari et al. suggested a
growth of HAp nanowires, which improves the mechanism for HAp particle formation in the pres-
osteoblast cell response [95]. The L/D ratio of HAp ence of an anionic surfactant. The negative ions of
particles can be enhanced by the addition of CTAB, SDS surfactant interact with the positive Ca2? ions in
improving antibacterial activity. Metal ion doping of the aqueous solution to form zwitterions. When these
HAp nanoparticles can further enhance their Ca-rich domains come into contact with phosphate
antibacterial properties [100]. Iqbal et al. have incor- ions in an aqueous solution, the formation of HAp
porated Ag ions into the HAp particles synthesized particles accelerates. The electrostatic interaction
using CTAB as a surfactant. The resultant Ag–HAp between SDS and Ca2? ions promotes the production
particles have shown a pronounced effect against of ordered HAp crystals [106]. The generalized
J Mater Sci

Figure 4 Schematic representation of nucleation and growth mechanism of hydroxyapatite particles in the presence of SDS surfactant.

nucleation and growth mechanism of HAp particles stability of Ca–EDTA complex molecules and the pH
in the presence of SDS is represented in Fig. 4. This of the solution [108]. A similar nucleation mechanism
mechanism is valid for other synthesis methods such follows with the addition of STPP anionic surfactant,
as hydrothermal, hydrolysis, biomimetic, and chem- which controls the availability of Ca2? ions in the
ical precipitation [68, 81]. solution and regulates the morphology of HAp par-
The AOT is another anionic surfactant that has ticles to obtain a plate-like structure [109].
been widely used for the synthesis of HAp particles. Nathanael et al. have studied the influence of an
This surfactant is more suitable for HAp synthesis anionic surfactant (SDS) on the HAp nanoparticles
through the microemulsion method. The nucleation morphology synthesized through the hydrothermal
mechanism of HAp particles with the addition of growth process. The addition of SDS resulted in the
AOT surfactant is represented in Fig. 5. The AOT transformation of the HAp particle morphology from
forms stable reverse micelles in an organized manner ‘rod-like’ structures to ‘plate-like’ structures. Ab ini-
at the oil/water interface by exposing sulphur-con- tio analysis of electron charge density calculations
taining head towards the water phase and revealed that the (001) plane of HAp is positive, while
hydrophobic tail towards the oil phase in the solu- the (100) plane is negative. As an anion template, SDS
tion. The AOT micelles form a strong bond with Ca2? is attracted to the (001) surface and hinders the
ions at the water–oil interface because the sulfonate growth of HAp particles on the (001) plane, pro-
group of AOT has a strong tendency towards Ca2? moting growth in the (100) plane. Hence, plate-like
ions. The bonding between Ca2? ions and phosphate morphology has been observed in HAp particles with
ions occurs with the addition of phosphate precursor the addition of SDS surfactant. The thickness of plate-
to the solution, which results in the nucleation of like structures is determined by the concentration of
HAp particles. The crystal growth of HAp particles SDS surfactant in the solution [110]. Sarda et al.
depends on the AOT micelles structure [107]. The proposed a ‘sandwich model’ for the growth mech-
nucleation mechanism of HAp particles is slightly anism in HAp [107], which suggests that the growth
different with the addition of EDTA surfactant. When of HAp particles occurs along the c-plane due to the
EDTA is added to the solution containing Ca2? ions, presence of strongly bound AOT organic molecules
it enwraps itself around Ca2? ions. As a result of this along the a and b-planes, which inhibit growth along
complex molecule formation, the availability of those planes. This is shown in Fig. 6.
Ca2?ions decreases in the solution leading to the The anionic surfactant-based template methods are
formation of smaller HAp nuclei. The nucleation and being used to prepare the calcium phosphate and HAp
growth of HAp crystals are determined by the nanoparticles with different morphologies and
 J Mater Sci

Figure 5 HAp particle

formation mechanism in the
presence of an anionic
surfactant (AOT) through the
microemulsion method.

Figure 6 HAp particle growth

mechanism in ‘Sandwich
model’ along c-direction in the
presence of AOT molecules.

mesostructures. Nakagawa et al. used sodium dodecyl 0.039 mol/l of SDP concentration and a bilayer struc-
phosphate (SDP) anionic surfactant as a template to ture at higher concentrations (0.154 mol/l) of SDP. The
develop nanosized HAp particles with various shapes. HAp nanoparticles are nucleated over this bilayer
They observed the spindle-type morphology at structure with a rod or sheet-like morphology [111].
J Mater Sci

Antonio et al. have successfully synthesized the have revealed that the synthesized structures are
mesolamellar CaP hybrids through a precipitation biocompatible at low SDBS content [112].
method by using sodium dodecylbenzene sulfonate The HAp/PLA nanocomposites synthesized with
(SDBS) as a template. They have observed the varia- the assistance of SDS surfactant have shown excellent
tion of phase composition as the concentration of biocompatibility along with the highest thermal sta-
SDBS increases. With increasing SDBS concentra- bility and best mechanical properties [116]. In another
tions, the phase composition transitions from brush- study, Karunakaran et al. synthesized HAp
ite to a mix of brushite and apatite and finally to fully nanoparticles from bio-waste sea shells with the
nanocrystalline apatite at higher concentrations [112]. assistance of an SDS surfactant. They have observed
The polyethyleneglycol mono-p-isooctylphenyl that SDS plays a vital role in controlling the mor-
ether, also known by the trade name TX-100, is non- phology of HAp particles and successfully incorpo-
adsorbent on the HAp particle’s surface in an aque- rated Fe ions into HAp particles without modifying
ous solution. However, it shows a contrasting beha- their original structure. The doping of Fe ions resul-
viour in the presence of anionic surfactants. ted in the supermagnetic behaviour of HAp
Shimabayashi et al. have investigated the adsorption nanoparticles. The in vitro cytotoxicity studies
capability of TX-100 on the HAp surface. The TX-100 revealed that the Fe-doped HAp nanoparticles have
is claimed to be non-adsorbent in the absence of shown non-toxic nature towards the human osteo-
surfactant but highly adsorbent on the HAp surface blast cell line. The antibacterial properties are also
in the presence of SDS surfactant [113, 114]. enhanced with the addition of Fe ions in HAp par-
Mohammadi et al. have studied the influence of ticles synthesized with the assistance of SDS [117].
surfactants on the wetting behaviour of superhy- Finally, Wan et al. studied the effect of anionic
drophobic surfaces. Their investigation of the wetting surfactant (SDS) on cell cytotoxicity, transfection
behaviour of surfactants using aqueous solutions of efficiency, and DNA loading capacity. They synthe-
SA, SDS, HTAB, and MEGA 10 shows that the contact sized lamellar HAp (L-HAp) nanoplates with varying
angles and surface tension decrease with increasing concentrations of SDS surfactant to obtain optimized
surfactant concentration. However, the hydropho- biological properties. As the amount of SDS
bicity of a superhydrophobic surface is reduced by increased, the degree of ordering and size of L-HAp
the addition of a slight amount of surfactant, and the nanoplates increased. The cytotoxicity results
contact angle of solutions changes depending on the showed that all L-HAp nanoplates were biocompat-
structure and concentration of the surfactant [115]. ible. The higher DNA loading capacity and transfec-
tion efficiency were obtained in the L-HAp
Influence of anionic surfactants on biological proper- nanoplates with good lamellar structure. It was also
ties Nathanael et al. have performed the in vitro reported that L-HAp nanoplates with good lamellar
cellular analysis to examine cell proliferation and structures have the capability for gene delivery vec-
viability by seeding MG63 cell lines on the HAp tors [118].
nanoplates synthesized using SDS surfactant. The
addition of surfactant modified the HAp particle Other chemical surfactant-assisted HAp synthesis
morphology from rod to plate shape, which resulted
in a higher surface area for the HAp nanoplates. After There are other types of chemical surfactants devel-
7 days, the quantity of cells on the HAp nanoplates is oped in addition to cationic and anionic surfactants.
significantly higher. The larger surface area also These are non-ionic and zwitterionic surfactants.
enhanced the cell growth, spreading, and adhesion of Non-ionic surfactants such as alcohol, phenol, ether,
drugs and proteins. Based on these results, it is con- ester, or amide do not dissociate into ions when
cluded that this material will be effectively useful in dissolved in aqueous solutions, as their hydrophilic
drug delivery and tissue engineering fields [110]. group is non-dissociable [69]. The non-ionic surfac-
Salinas et al. have synthesized CaP hybrid materi- tant hydrophilic group is usually a polyoxyethylene
als by varying the Ca/P molar ratio and concentra- group, but other non-ionic surfactants with glyceryl
tion of SDBS anionic surfactant. The in vitro cell groups or sorbitol groups, and non-ionic surfactants
culture studies were carried out with human Saos-2 with different hydrophilic groups are also used
osteoblasts to examine biocompatibility. The results depending on the application [70]. These are the
 J Mater Sci

surfactants that are most commonly used in drug interactions may be eliminated. Iyyappan et al. [121]
delivery applications [69, 71]. Furthermore, several and Lee et al. [122] have suggested that the poly-
studies have suggested that non-ionic surfactants oxyethylene group interacts with the Ca2? ions
play a crucial role in controlling the HAp particle through the creation of ion–dipole interactions and
morphology, which can serve as filler materials in forms a hydrophobic open-ring complex. This com-
bone cement. PEG, Pluronic F127, and Triton X-100 plex can then create van der Waals interactions with
are the important non-ionic surfactants that are being the surface –OH groups of the growing HA crystals,
used in the synthesis of HAp. thereby promoting the growth of nano HAp particles
The PEG is generally used as a co-template. The in a preferential direction. The ability of Triton X-100
addition of PEG influences particle growth, coagula- to direct the alignment of small HA crystallites was
tion, and flocculation. The PEG molecule has flexible also confirmed by Zhang et al. and Bricha et al.
ether linkages that allow for sterically less hindered [68, 123]. Iyyappan et al. also suggested that the open-
addition to an aqueous medium. The PEG molecule ring complexes formed by Triton X-100 can also
can chelate and attract Ca2? ions from calcium nitrate hinder the agglomeration of HA particles. Due to the
solution to form PEG–O–Ca2?–O–PEG bonds. The formation of these complexes, the transfer rate of
nucleation of HAp crystals occurs when phosphate Ca2? from the open-ring complex to the growing HA
ions interact with this PEG–O–Ca2?–O–PEG. The crystal is reduced; therefore, the formation of nano-
nucleation and growth mechanism of HAp in the sized HA crystals takes place in a controlled manner
presence of PEG is represented in Fig. 7. Addition of [124].
PEG surfactant reduces the aggregation of nucleation, Zhao and Ma investigated the effect of Pluronic
therefore resulting in smaller particles with spherical F127 surfactant at two different concentrations (0.1 g.
structures. This mechanism suggests that the addi- ml-1 and 0.03 g. ml-1). They have obtained HA with
tion of a surfactant controls the crystallization and two different morphologies, i.e. spherical particles at
growth process of HAp particles [119]. Che et al. higher concentration (0.1 g. ml-1) and rod-like at
synthesized HAp particles of different shapes using lower concentration (0.03 g. ml-1). They have sug-
PEG as a template. Their findings showed that gested that the hydrogen bonds in the Pluronic F127
spheroid HAp particles exhibit a better binding force surfactant interact with the Ca precursor to create
than rod-shaped HAp particles. Biomineralization multiple nucleation sites for the formation of HAp
and cell proliferation studies further suggested that crystals of different morphologies [125].
spherical HAp particles promote osteogenic differ- Zwitterionic or amphoteric surfactants have catio-
entiation earlier than rod-shaped HAp particles [120]. nic and anionic centres attached to the same mole-
The molecular structure of Triton X-100 consists of cule. They can be anionic, cationic, or non-ionic in
a hydrophilic polyethylene oxide group (head) and a solution, depending on the pH and/or acidity of the
hydrophobic or lipophilic hydrocarbon (tail). Being a solution. These surfactants are not as common as
non-ionic surfactant, the possibility of electrostatic cationic, anionic, and non-ionic ones. These

Figure 7 Formation mechanism of HAp particles in the presence of PEG surfactant.

J Mater Sci

surfactants may contain two different sign-charged resulting in nanoporous HAp [146]. Govindan et al.
groups. The positively charged ion is ammonium, have synthesized supermagnetic HAp nanocompos-
and the negatively charged ion does vary (carboxy- ites with the assistance of CTAB surfactant for drug
late, sulphate, sulphonate). These are very mild and delivery in cancer therapy. The results have shown
can be useful in personal care products, shampoos, that Fe3O4/HAp nanocomposites have induced
household cleaning products, and other cosmetic apoptosis against A431 cell lines [147].
products. Alkyl betaine and lecithin are examples of Luminomagnetic nanomaterials have piqued the
zwitterionic surfactants [69, 71, 103]. interest of the research community in recent decades
Haung et al. have synthesized HAp particles using due to their potential in the field of disease diagnosis
four different types of surfactants: cationic CTAB, [148, 149]. However, the toxicity of the leaked ions,
anionic SDS, non-ionic Pluronic F127, and zwitteri- such as Cd, Pb, and Eu, of luminomagnetic nano-
onic cocamidopropyl betaine (CAPB). The rod-type materials is a critical problem [150, 151]. To address
morphology was observed in all HAp particles syn- this issue, researchers have focused on the surface
thesized using different surfactants. However, the modification of these materials with biocompatible
HAp nanorods synthesized using CTAB surfactant materials, capable of minimizing ion leakage and
demonstrated superior antibacterial properties com- enhancing biocompatibility. One approach is a
pared to HAp nanorods synthesized using other modification or doping of HAp with magnetic and
surfactants. The Pluronic F127-assisted HAp nanor- luminescent active elements [152, 153]. In this regard,
ods have shown temporary antibacterial properties few studies have reported on the co-substitution in
till 24 h and no cytotoxicity. It is concluded that HAp HAp structure to develop the magnetic and lumi-
nanorods synthesized with the assistance of CTAB nescent properties with Gd3? to bring the paramag-
surfactant are more suitable for biomedical applica- netic property and Tb3? or Eu3? to bring luminescent
tions. However, it is suggested that CTAB must be property for biomedical imaging [154, 155]. Agalya
compounded with other materials to reduce its et al. have also successfully synthesized HAp
cytotoxicity [126]. nanorods with co-substitution of Fe3? and Eu3? ions
The scientific reports related to the chemical sur- through microwave irradiation technique by using
factants that assisted HAp synthesis with various CTAB as a crystal growth modifier for the dual-
morphologies and dimensions obtained through dif- model imaging applications in biomedicine [156].
ferent techniques are summarized in Table 3, to Supermagnetic mesoporous HAp nanoparticles
enable the scientific community with an overview of were synthesized from a seashell with the assistance
HAp synthesis with different morphologies. of an SDS surfactant to introduce the magnetic
properties to HAp particles. The magnetic properties
Recent advances in chemical surfactant-assisted HAp were obtained with the incorporation of Fe ions. The
synthesis supermagnetic HAp nanoparticles have numerous
applications, such as controlled drug delivery, treat-
Mesoporous materials with small pore sizes and high ment of cancer cells, and magnetic resonance imaging
internal surface areas have gained significant atten- [117]. Tattanon et al. have synthesized HAp particles
tion from researchers due to their unique properties with the assistance of SDS as a surfactant from cut-
as absorbents, host materials, and catalysts. Based on tlebone and designed a hydrogel composite with
the mesoporous concept, researchers have started gelatine as a matrix and HAp particles as a filler
synthesizing HAp with nanoporous structures material. The synthesized hydrogel composites are
because porous HAp enhances natural bone growth cost-effective and useful in medical applications such
and also provides drug-loaded sites when used in as tissue engineering, wound healing, etc. [157].
drug delivery applications. Yanbao li et al. have Methylene blue (MB) is a commonly used dye
synthesized the nanoporous HAp using CTAB as a material in textiles, biomedicine, cosmetics, and other
template. They have reported that raising the reaction industries. However, it has been found that MB is
temperature from 40 to 160 °C during the process hazardous to the human body. Zhu et al. have initi-
increases the crystallinity and decreases the pore ated experiments to synthesize HAp particles with
diameter from 5 nm to 1.9 nm. The retained CTAB the assistance of SDS surfactant to adsorb the MB
was eliminated by calcination at 550 °C for 6 h, from wastewater. This study has reported that SDS-
 J Mater Sci

Table 3 Synthesis of HAp particles with various morphologies and dimensions through different techniques by using chemical surfactants
as templates

Technique Morphology Surfactant name Type of surfactant Dimensions of the HAp Refs.
particles

Microemulsion Spherical PVA Non-Ionic D = 16–26 nm [127]

Spherical Brij-35 (Polyoxyethylene Non-Ionic – [128]
lauryl ether)
Plate AOT Anionic L = 50–200 nm T = 10 nm [129]
Rod Triton X-100 ? CTAB Non-Ionic ? Cationic D = 8–15 nm [130]
L = 25–50 nm
Spherical Span-80 Non-Ionic 70–100 nm [131]
Hydrothermal Wires CTAB Cationic D = 30 ± 7 nm [132]
Rod CTAB Cationic D = 15–60 nm
L = 60–75 nm
Plate Ethylamine Cationic L = 50–300 nm [133]
T = 10–50 nm
Rod (\ CMC) SDS Anionic [110]
Plate (* CMC) L = 100 ± 50 nm
Disordered
([ CMC)
Rod EDTA Anionic – [134]
Plate STPP Anionic – [109]
Rod Triton X-100 Non-ionic W = 21 nm, L = 79 nm [68]
Rod Pluronic F127 Non-Ionic D = 25 nm [135]
L = 75–125 nm
Dandelion CTAB ? PEG Cationic ? Non-ionic D = 80–150 nm [136]
Rod EDTA ? CTAB Anionic ? Cationic W = 10–20 nm
L = 60–90 nm
Chemical Rod Brij 35 Non-ionic D = 30 nm [137]
precipitation L = 60–150 nm
Rod SDS: CTAB (99:1) Anionic ? Cationic – [106]
(anionic rich)
Sheet SDS: CTAB (1:99) Anionic ? Cationic –
(cationic rich)
Rod PEG Non-ionic D = 4–17 nm [138]
L = 5–39 nm
Tween 20 D = 3–9 nm
L = 9–35 nm
Trisodium Citrate D = 4–8 nm
L = 5–13 nm
Microwave Plate CTAB Cationic W = 10 nm [139]
L = 55 nm
Rod EDTA Anionic D = 25–40 nm [140]
L = 100–400 nm
Rod (pH 9) EDTA Anionic D = 40 nm [141]
L = 400 nm
Bowknot-like W = 150 nm
(pH 11) L = 1–2 lm
Flower-like (pH W = 150–200 nm
13) L = 1–2 lm
Rod Lauryl Dimethylaminoacetic Zwitterionic D = 19 nm [142]
L = 69 nm
J Mater Sci

Table 3 continued

Technique Morphology Surfactant name Type of surfactant Dimensions of the HAp Refs.
particles

Biomimetic Spherical SDS Anionic – [143]

Spherical PEG Non-ionic D = 30–50 nm [144]
Hydrolysis Needle CTAB Cationic L = 100 nm [145]
W = 45 nm
Needle CTAB Cationic L = 80 nm [146]
W = 15 nm
Where D diameter, L length, W width and T thickness

HAp is effective in removing the MB molecules due

to strong hydrogen bond interactions between the
nitrogen atom of MB and the (P-OH) group in SDS-
HAp. The addition of SDS surfactant played a vital
role in MB adsorption [158]. Additive manufacturing
is a useful technique to produce complex geometries
and morphologies in 3D shapes. It is a very useful
technique to mimic the bone structure and medical
implants. Esteves et al. produced alumina/HAp
composite structures using DLP 3D printing. Alu-
mina was added to increase bioactivity and osteoin-
tegration. High-quality pieces of human trabecular
tissue structures were fabricated. Customized
designs of medical implants can be produced using
this technique [159].
Figure 8 The number of articles published year-wise with the
Biosurfactant-assisted HAp synthesis term ‘biosurfactant’, obtained from the Thomson Reuters ISI Web
of Knowledge search platform (till 2022).
Biosurfactants (BS) or microbial surfactants are
amphiphilic molecules produced from microorgan- biosurfactants has more future scope due to their
isms, mostly microbial cells [160, 161]. Biosurfactants unique and potential applications.
can be produced from yeast, bacteria, or fungi, which Unlike chemical surfactants, which are divided
may be present in various substances such as oils, according to the charge of their polar group, biosur-
sugars, alkanes, and wastes. In general, the CMCs of factants are classified according to the origin of
biosurfactants range from 1 to 200 mg. L-1, which is microbial and chemical composition, as shown in
significantly lower than the CMC of the chemical Fig. 9. Biosurfactants differ from chemical surfactants
surfactants [162]. Compared to chemical surfactants, in that they have a variety of desirable industrial
biosurfactants have more beneficial properties, such characteristics. However, due to huge investment
as low toxicity, high efficiency, and high biodegrad- costs, they have not been commercialized [162]. Pre-
ability. These characteristics have led to biosurfac- sently, the only commercially available biosurfactants
tants being labelled as ‘green surfactants’ [163]. are rhamnolipids and surfactin due to their low cost
There is a good amount of work carried out on the of production. The major costs involved with the
topic of biosurfactants, and it is growing rapidly with production of biosurfactants are fermentation and
the discovery of new biosurfactants resulting in the recovery. Utilizing inexpensive raw materials [164],
increased number of publications on the topic of including starchy wastes, dairy and distillery wastes,
‘biosurfactants’ (Fig. 8). The research on soya molasses, animal fats, vegetable oils, and animal
 J Mater Sci

Figure 9 Classification of some commonly used biosurfactants based on their microbial origin.

fats, might help to reduce the expenses. The synthesis cause serious environmental and health problems
of rhamnolipids from olive oil mill effluent by [173]. This has led researchers to explore natural
Pseudomonas spp. has shown a great reduction in surfactants, such as biosurfactants from plants and
production costs [165]. All these improved tech- animals, due to their low environmental risk and
niques have raised productivity by 10 to 20 per cent, good biodegradable and biocompatible properties
but further improvements in this field are required. [174]. In addition, biosurfactants are very effective in
Biosurfactants have seen an increase in usage in extreme conditions of temperature, salinity, and pH
recent years due to their unique properties. The [166, 175, 176]. Table 4 represents the biosurfactants
environmental friendliness, biodegradability, and that are used for the synthesis of HAp crystals
less toxicity of biosurfactants are attracting different through different techniques by various researchers.
industries. The properties such as antifungal and Lenka Tmakova et al. have derived non-ionic bio-
corrosion resistance attract industries to use biosur- surfactants from Sapindus mukorossi, Equisetum
factants in various applications. The major applica- arvense, Verbascum densiflorum, Bellis perennis, and
tion fields of biosurfactants are microbial-enhanced Betula pendula which are plant extracts from different
oil recovery, reduction of CO2 emissions, cosmetic parts, and compared their surface-active properties
industry, food processing industry, agricultural and antioxidant activities with the chemical surfac-
industry, biomedical field, metals remediation, and tants such as sodium lauryl sulphate and TweenÒ 80.
soil washing technology [166–172]. They have observed that plant-based biosurfactants
Nowadays, plant-derived biosurfactants have have shown better properties than chemical surfac-
gained significant attention as an eco-friendly alter- tants [177]. Ovalbumin is a natural protein that can be
native to chemical surfactants, which are extensively found in egg white, forms a stable organic complex,
used in industries and household applications and and is biocompatible. Zhao et al. have synthesized
J Mater Sci

Table 4 HAp synthesis done by different techniques using various biosurfactants

Method Assisted Remarks

biosurfactant

Biomineralization Ovalbumin Large HAp spindle-like particles of 0.8 mm in length are aggregated from the needle-like
method nanocrystals [178]
Biomimetic method Bovine serum Coprecipitation of HAp and BSA with enhanced biological activity is obtained [199]
albumin (BSA)
Reverse Surfactin Brushite nanoparticles of different shapes (hexagonal, needle, and small roundish) are
microemulsion achieved [180]
technique
Hydrothermal method Saponin HAp of nanorod-shaped morphology is obtained
Increasing the content of saponin decreases the length of nanorods and crystallite size. Sap-
HAp shows better bioactivity compared to HAp without saponin [181]
L-rhamnose Biphasic calcium phosphate (mixture of b-tricalcium phosphate and hydroxyapatite) from
Monohydrate cuttlebone is synthesized successfully with uniform size distribution [200]

the spindle-like HAp nanoparticles (0.8 mm length) They have found that both HAp and Sap-HAp
using ovalbumin extracted from egg white as a nat- nanorods grow along the c-axis and are more
ural surfactant [178]. Gilman et al. have previously prominent for HAp than Sap-HAp nanorods. At 5 g
reported that with increasing the ovalbumin con- of saponin, the morphology changes totally from
centration the average HAp aggregate size decreases nanorods to an acicular structure. They have also
(still, the average diameter of the particles is in noticed that as the concentration of saponin increases,
micrometres) [179]. the crystallite size and degree of crystallinity reduce.
Maity et al. have used the reverse microemulsion After 21 days of immersion in SBF solution at 37 °C,
technique with surfactin as a biosurfactant to pro- the Sap-HAp has shown greater bioactivity in terms
duce nanocrystalline brushite particles in the size of apatite formation than the HAp without saponin.
range of 16–200 nm. The synthesized microemulsions The antibacterial activity of HAp and Sap-HAp is
consist of nanospheres and needle-like brushite par- assessed where the HAp does not show any inhibi-
ticles, and after calcination at 800 °C, the morphology tive action against all the pathogens (S. aureus, P.
of the particles transforms to nanorod calcium aeruginosa, and C. albicans), while Sap-HAp inhibits
pyrophosphate particles. The morphology of the the growth of P. aeruginosa and C. albicans, but does
particles can be altered by adjusting the ratio of the not show any inhibitive action against S. aureus [181].
calcium nitrate tetrahydrate and ammonium phos- Very recently, Ali et al. synthesized the HAp using
phate water solution to surfactin to obtain structures licorice root extract (LE) as a biotemplate through the
such as hexagonal, thin-layered, needle, and round- microwave-hydrothermal route. The licorice has
shaped crystals [180]. good anticancer, antiviral, antiallergenic, antiulcer,
Recently, Balakrishnan et al. have used saponin as anti-diabetic, antioxidant, and antithrombotic prop-
a natural surfactant to synthesize the HAp by erties. Glycyrrhizic acid (GA), an important ingredi-
hydrothermal technique. They have obtained the ent of LE, is known to be used as a green
HAp with nanorods morphology, and the length of biosurfactant due to its potential applications. The
the nanorods decreases with increasing the quantity GA is an amphipathic acid and has both non-ionic
of the saponin from 0.5 to 3 g. The exact nucleation and anionic surfactant properties. Due to the pres-
and growth mechanism of HAp particles in the ence of a large hydrophobic skeleton in its structure,
presence of saponin is still not clear and requires a GA forms rod-like micelles. LE acts as an organic
detailed investigation. It is believed that saponin template and a complexing agent with Ca2? ions, as
helps to increase the number of nucleation sites by polyphenolic compounds form complexes with Ca2?
binding/adsorbing on certain crystal faces of HAp, ions. Ali et al. proposed a mechanism (as shown in
leading to a change in its morphological features. Fig. 10) to synthesize HAp nanorods with LE. They
 J Mater Sci

Figure 10 Formation
mechanism of HAp nanorods
using LE as a template through
the microwave-hydrothermal
method.

have suggested that GA molecules form nanorod R Subramanian et al. have synthesized HAp nanor-
micelles in the initial solution mixture of LE and ods through the chemical precipitation method by
calcium precursor. The micelles are homogeneously using different concentrations (5, 10, and 20 mg) of
incorporated with polyphenolics and form polyphe- caffeine as a natural modifier to analyse its effect on
nolic-GA (pphOH-GA) micelles, which then interact morphology, size, and shape. They have observed
with polyphenolics and form HAp–polyphenolic that caffeine prevents the aggregation of HAp
complexes over the rod-shaped patterns of the nanorods and promotes the formation of smaller
micelles. Finally, these complexes are decomposed to particles by breaking the bonds between the neigh-
form the HAp nanorods by hydrothermal treatment bouring atoms. The caffeine concentration of 10 and
[182]. 20 mg is more effective in reducing the crystallite size
Gopi et al. have developed an economical and eco- and improving the crystallinity. The HAp nanorods
friendly method to synthesize HAp using natural obtained using 20 mg of caffeine are more crystalline
sucrose as a template. They extracted the sucrose than other concentrations [186].
from the three different natural sources of carrot root, Buitrago-Vásquez et al. have synthesized the HAp
pineapple, and sugarcane stem and one from a nanorods via hydrothermal reaction by using fruit
commercially available source to observe the differ- extracts of mango, tamarind, and grape as templates
ences. The results have revealed that the natural to govern the shape and size of the HAp nanoparti-
source of sucrose gives a pure HAp structure with a cles. They have noticed that the addition of the fruit
more uniform morphology as compared to commer- extracts does not affect the phase composition of the
cial sucrose. Additionally, the sucrose extracted from synthesized material, but the crystallinity, crystallite
the sugar cane stem is more effective in reducing the size, and morphology of the HAp are affected. They
particle size of HAp particles with well-defined have also stated that the grapefruit extract is more
dimensions compared to the other sources [183]. effective in reducing the length of the HAp particles
Caffeine, found in tea and coffee, is one of the most with the highest crystallinity percentage compared to
commonly consumed substances in daily life. In mango and tamarind fruit extracts [187].
addition to its use as a stimulant, it also possesses The polyphenol of grape seed is also proven to be a
bactericidal properties against pathogenic microor- good surfactant to alter the morphology of HAp
ganisms, and it is also used to treat nervous and nanoparticles but with poor crystallinity. However,
cardiovascular disorders and corrosive gastric dis- the synthesized HAp nanoparticles were crystallized
charge [184, 185]. Researchers are investigating the by heat treatment process at 500 °C for 2 h [188]. The
potential caffeine in combination with HAp. HAp powders with particle sizes of 40 – 171 nm were
J Mater Sci

synthesized using an aloe vera solution. The crys- of these biomolecules does not affect the HAp phase
tallinity of the HAp powders has been achieved formation, and in pure HAp, there is no control over
through the heat treatment process at 500 °C [189]. the size and shape of the particles, while the biomo-
Green synthesis using plant extracts is gaining lecules from the waste extracts played a critical role
attention from researchers in the nanotechnology in the size and shape control. Enoic acids in potato
field. Tannins and polyphenols are such plant peel extracts, beta carotene and other vitamins in
extracts that are being utilized as natural additives in papaya leaf extracts, limonene in orange peel
the food processing sector and for fabrication in the extracts, and carotenoids in calendula flower extracts
leather industries. The OH groups of polyphenols all play a critical role in controlling the shape and size
have the tendency to attract metal ions; thus, they of HAp particles [198].
have been widely used as chelating agents [190, 191].
Kalaiselvi et al. have green synthesized HAp nanor- Influence of biosurfactants on biological properties
ods using Moringa oleifera flower, which has good
antioxidant properties due to the presence of excess The HAp nanoparticles are gaining attention as an
polyphenols, tannins, alkaloids, vitamins, flavonoids, anti-cancerous drug to reduce growth in cancerous
carotenoids, and minerals, is used in green synthesis, cell lines. Ghate et al. synthesized HAp nanoparticles
and can act as a stabilizing agent. They have stated with the assistance of Acacia falcata leaf extract as a
that the green synthesized HAp nanorods have better surfactant. The synthesized HAp nanoparticles have
antibacterial (against Gram-positive) and antifungal shown a cytotoxic effect towards A549 lung and
activities compared to the chemically synthesized MDA-MB231 breast cancer cell lines, indicating their
HAp nanorods [192]. Sundrarajan et al. have also potential anticancer agents for cancer therapy. How-
successfully synthesized HAp nanoplates using ever, further research is required to control the drug
Moringa oleifera flower extract as a chelating agent delivery to effectively target cancerous cell lines
and 1 butyl 3methylimidazolium tetrafluoroborate [201]. Another study by Bee et al. reported on the
ionic liquid as a soft template to modulate the synthesis of HAp–Ag nanocomposites using Indian
nucleation and growth of the HAp particles [193]. curry leaves extract as a template. This study repor-
Natural gum called Gum Acacia (GA) is obtained ted that Indian curry leaf acted as an effective bio-
from the Senegal acacia tree. It is a combination of reducing and stabilizing agent. The antibacterial
calcium, magnesium, and potassium salt of a studies revealed that HAp–Ag nanocomposites
polysaccharide acid and is composed of carbohydrate showed good potency against E. coli and S. aureus
moieties with a small amount of hydroxyproline-rich bacteria. The study concluded that HAp–Ag
protein [194]. Because of the electrostatic interactions nanocomposites prepared using Indian curry leaves
between the positively charged sites on the oxide extract are promising candidates as implant material
surface and the negatively charged groups from GA, in orthopaedic applications [202].
it is an effective emulsifying, dispersing, and stabil-
ising agent [195, 196]. This is the reason Sreedhar Recent advances in biosurfactant-assisted HAp synthesis
et al. used GA as a crystal growth modifier to syn-
thesize HAp particles through the chemical precipi- Biosurfactants can be used to replace commercial
tation method. They have observed that the HAp chemical surfactants, especially when they are
particles without GA have rod, spherical, and elon- extracted through effective green methods. Elizondo-
gated structures, but the addition of GA (0.5 – 1%) Villarreal et al. developed an innovative approach to
transforms the rod-like structures into long leaf-like synthesize HAp particles using agricultural and
structures [197]. industrial wastages such as eggshells and Agave
The researchers are always looking for alternatives salmiana. They used Aloe barbadensis, a natural sur-
for artificial replacements, and in that search, they factant, to control the nucleation and growth of the
started using waste materials. Suprabha et al. have HAp particles [203]. Acid Blue 113 (AB113) is one of
used several waste materials such as orange and the most commonly used dye materials in several
potato peels, eggshell, calendula flower extract, and industrial applications. This kind of acid dye shows
papaya leaf as templates during the formation of harmful effects on the human body due to the pres-
HAp particles. They have observed that the presence ence of sulphonic groups. Vinayagam et al. have used
 J Mater Sci

an aqueous extract of copper pod trees as a template in AOT, EDTA, STPP, and PEG are also discussed.
the synthesis of HAp particles to remove AB113 dye Moreover, the review delves into the orientation
from industrial wastewater. The biosurfactant-assisted dependence of the HAp particle growth mechanism.
HAp nanoparticles they developed proved to be The ‘sandwich model’ growth mechanism of HAp
effective in removing 92.73% of the harmful dye at particles in the presence of AOT molecules is dis-
optimum conditions [204]. Similarly, Sodhani et al. cussed, as well as the effect of adding other metallic
also developed biosurfactant-assisted HAp particles to ions such as Ag, Zn, Cu, and Ti, into HAp with the
remove AB113 dye using Peltophorum pterocarpum assistance of surfactants has been discussed. The effect
pod extract as a template, reporting an even better of various surfactants on the biological properties of
removal efficiency of 94.59% under optimum condi- HAp particles is discussed, along with the recent
tions [205]. In conclusion, biosurfactant-assisted HAp advances in chemical surfactant-assisted HAp particle
particles offer an eco-friendly and economical solution synthesis. The improvement in biological properties
for removing AB113 dye from industrial wastewater. (such as biocompatibility and antibacterial properties)
is observed with the incorporation of metallic ions into
HAp with the help of various surfactants.
Summary Considering the increasing concern over environ-
mental pollution, the use of chemical surfactants is
This review provides a comprehensive summary of gradually being replaced by biosurfactants that are
the existing research in the field of surfactant-assisted derived from microbial cells such as yeast, bacteria,
HAp synthesis, encompassing both chemical and or fungi from oils, sugars, etc. Biosurfactants are
biosurfactants and different synthesis routes. The key called ‘green surfactants’ because of their low toxic-
specifications of HAp, such as composition, crys- ity, high efficiency, and high biodegradability. In
tallinity, Ca/P ratio, morphology, surface roughness, addition to the properties that can be obtained using
porosity, and texture, can significantly influence the chemical surfactants, biosurfactants have superior
mechanical, biological, and electrochemical proper- biological properties (such as antimicrobial and
ties of the implant. However, the HAp particles antifungal) and anticorrosion actions. Thus, this
produced through regular methods such as review explores the synthesis of HAp particles with
hydrothermal, hydrolysis, chemical precipitation, the help of different biosurfactants (such as ovalbu-
combustion, emulsion, and sol–gel are typically in the min, bovine serum albumin, surfactin, Gum Acacia,
micrometre-sized range with irregular or spherical and saponin) and biomolecules from different parts
shapes, unlike the rod-shaped nano HAp particles of various plants (leaves, flowers, root, seeds, etc.,)
that exist in the human bone. Several reports suggest and waste materials. The effects of these biosurfac-
that the closest possible HAp particle morphology tants/biomolecules on the morphology, size, crys-
can be obtained by using surfactants as soft tem- tallinity and biological properties of HAp crystals are
plates. Therefore, researchers are increasingly focus- discussed. Finally, the review assesses the recent
ing on using surfactants as soft templates during the advances in the usage of biosurfactants for HAp
synthesis process, which has opened up new avenues particle synthesis for various applications.
for producing surfactant-assisted HAp particles with
various surfactants.
This review discusses the effect of chemical and Future perspectives
biosurfactants on the structural and biological prop-
erties of HAp particles synthesized through various Despite the existing research on the synthesis of
techniques. In particular, it explores the effect of sur- surfactant-assisted HAp particles, there are several
factant concentration, processing temperature, and pH areas for further investigation, including:
on the morphology, size, and crystallinity of surfac-
1. Development of mesoporous HAp structures
tant-assisted HAp particles. The use of these chemical
through different routes: Mesoporous structured
surfactants can reduce the aggregation and particle
HAp has gained significant interest recently, as it
size to the nano range. The nucleation mechanisms
can be used in drug delivery applications. How-
behind the change in HAp particle morphology in the
ever, there is limited research on developing
presence of various surfactants such as CTAB, SDS,
J Mater Sci

mesoporous HAp loaded with growth factors, Author contributions

anticoagulants (such as warfarin and heparin),
proteins, and potential drug carriers. Although PSP was involved in investigation; writing original
some researchers have started working on this idea, draft and editing; and formal analysis. BCGM was
more systematic investigations are required, par- involved in investigation and writing and editing. SD
ticularly in the area of using biosurfactants in drug and KD were involved in conceptualization, formal
delivery systems. A framework needs to be devel- analysis, writing—review and editing; supervision;
oped for acquiring biosurfactants and using them and investigation.
effectively in drug delivery applications.
2. In-depth analysis of in vitro and in vivo studies:
In vitro studies (such as osteoconduction, cytotoxi-
Data and code availability
city, antimicrobial, and antifungal studies) on the Not Applicable.
surfactant (both chemical and biosurfactants)
assisted HAp have commonly reported better bio- Declarations
logical properties compared to HAp synthesized
without surfactants. However, the mechanism Conflict of interest The authors declare that they
behind the improvement of these biological proper- have no known competing financial interests or per-
ties is rarely explored. Additionally, in vivo studies sonal relationships that could have appeared to
on surfactant-assisted HAp are rarely performed, influence the work reported in this paper.
making this an interesting area to explore further.
3. Using natural biomolecules as templates during Supplementary information Not Applicable.
synthesis of HAp: The research on using biomole-
Ethical approval Not Applicable.
cules as templates for HAp synthesis is limited to
synthesis only. Very few researchers have explored
corrosion, cell proliferation, and antibacterial and References
antifungal studies, which are interesting areas for
further research using biomolecules as green [1] Vallet-Regı́ M, González-Calbet JM (2004) Calcium
templates. phosphates as substitution of bone tissues. Prog Solid State
4. Synthesis of HAp particles using various surfac- Ch 32:1–31. [Link]
tants to develop HAp-based composite biomate- 4.07.001
rials through additive manufacturing techniques: [2] Dorozhkin SV (2009) Calcium orthophosphate cements
Additive manufacturing techniques (e.g. 3D and concretes. Materials 2:221–291. [Link]
printing) is gaining attention for developing 0/ma2010221
HAp scaffolds with micro and macro porosity. [3] Xia L, Lin K, Jiang X et al (2013) Enhanced osteogenesis
To print these scaffolds, HAp powders with through nano-structured surface design of macroporous
different types of morphologies and sizes are hydroxyapatite bioceramic scaffolds via activation of ERK
needed to obtain scaffolds with enhanced and p38 MAPK signaling pathways. J Mater Chem B
mechanical and biological properties. HAp pow- 1:5403–5416. [Link]
ders synthesized using surfactants as templates [4] Bohner M, Tadier S, van Garderen N et al (2013) Synthesis
can be used in place of usual HAp powders, and of spherical calcium phosphate particles for dental and
the effect on the mechanical and biological prop- orthopedic applications. Biomatter 3:e25103. [Link]
erties of 3D printed HAp scaffolds can be studied. g/10.4161/biom.25103
[5] Dorozhkin S (2009) Nanodimensional and nanocrystalline
apatites and other calcium orthophosphates in biomedical
engineering, biology and medicine. Materials 2:1975–2045.
Acknowledgements
[Link]
P. SP and BCG. M are grateful to the Ministry of [6] Niu N, Wang D, Huang S et al (2012) Controlled synthesis
Human Resource and Development, Government of of luminescent F-substituted strontium hydroxyapatite with
India, for the Doctoral Fellowship. hierarchical structures for drug delivery. CrystEngComm
14:1744–1752. [Link]
 J Mater Sci

[7] Guo YP, Long T, Tang S et al (2014) Hydrothermal fabri- [17] Sun H, Su F-Z, Ni J et al (2009) Gold supported on
cation of magnetic mesoporous carbonated hydroxyapatite hydroxyapatite as a versatile multifunctional catalyst for the
microspheres: Biocompatibility, osteoinductivity, drug direct tandem synthesis of imines and oximes. Angew
delivery property and bactericidal property. J Mater Chem Chem Int Ed 48:4390–4393. [Link]
B 2:2899–2909. [Link] 200900802
[8] Wu L, Dou Y, Lin K et al (2011) Hierarchically structured [18] Vukomanović M, Žunič V, Otoničar M et al (2012)
nanocrystalline hydroxyapatite assembled hollow fibers as Hydroxyapatite/platinum bio-photocatalyst: a biomaterial
a promising protein delivery system. Chem Comm approach to self-cleaning. J Mater Chem 22:10571–10580.
47:11674–11676. [Link] [Link]
[9] Uskoković V, Uskoković DP (2011) Nanosized hydroxya- [19] Xu J, White T, Li P et al (2010) Hydroxyapatite foam as a
patite and other calcium phosphates: chemistry of formation catalyst for formaldehyde combustion at room temperature.
and application as drug and gene delivery agents. J Biomed J Am Chem Soc 132:13172–13173. [Link]
Mater Res B Appl Biomater 96B:152–191. [Link] 1/ja1058923
10.1002/jbm.b.31746 [20] Liu D, Savino K, Yates MZ (2009) Microstructural engi-
[10] Guo YP, Guo LH, Yao YB et al (2011) Magnetic meso- neering of hydroxyapatite membranes to enhance proton
porous carbonated hydroxyapatite microspheres with hier- conductivity. Adv Funct Mater 19:3941–3947. [Link]
archical nanostructure for drug delivery systems. Chem org/10.1002/adfm.200900318
Commun 47:12215–12217. [Link] [21] Wei X, Yates MZ (2012) Yttrium-doped hydroxyapatite
15190h membranes with high proton conductivity. Chem Mater
[11] Kozlova D, Chernousova S, Knuschke T et al (2012) Cell 24:1738–1743. [Link]
targeting by antibody-functionalized calcium phosphate [22] Zhang Y, Liu Y, Ji X et al (2011) Conversion of egg-shell to
nanoparticles. J Mater Chem 22:396–404. [Link] hydroxyapatite for highly sensitive detection of endocrine
10.1039/c1jm14683a disruptor bisphenol A. J Mater Chem 21:14428–14431. h
[12] Altinoǧlu EI, Russin TJ, Kaiser JM et al (2008) Near-in- ttps://[Link]/10.1039/c1jm12544c
frared emitting fluorophore-doped calcium phosphate [23] Lin K, Pan J, Chen Y et al (2009) Study the adsorption of
nanoparticles for in vivo imaging of human breast cancer. phenol from aqueous solution on hydroxyapatite
ACS Nano 2:2075–2084. [Link] nanopowders. J Hazard Mater 161:231–240. [Link]
nn800448r 10.1016/[Link].2008.03.076
[13] Wagner DE, Eisenmann KM, Nestor-Kalinoski AL et al [24] Oliva J, Cama J, Cortina JL et al (2012) Biogenic
(2013) A microwave-assisted solution combustion synthe- hydroxyapatite (Apatite IITM) dissolution kinetics and
sis to produce europium-doped calcium phosphate nano- metal removal from acid mine drainage. J Hazard Mater
whiskers for bioimaging applications. Acta Biomater 213–214:7–18. [Link]
9:8422–8432. [Link] 027
[14] Chen F, Huang P, Zhu YJ et al (2012) Multifunctional Eu [25] Johnsson MSA, Nancollas GH (1992) The role of brushite
3?/Gd 3? dual-doped calcium phosphate vesicle-like and octacalcium phosphate in apatite formation. Crit Rev
nanospheres for sustained drug release and imaging. Bio- Oral Biol Med 3:61–82. [Link]
materials 33:6447–6455. [Link] 10454411920030010601
ials.2012.05.059 [26] Dorozhkin SV, Epple M (2002) Biological and medical
[15] Li WM, Chen SY, Liu DM (2013) In situ doxorubicin-CaP significance of calcium phosphates. Angew Chem Int Ed
shell formation on amphiphilic gelatin-iron oxide core as a 41:3130–3146. [Link]
multifunctional drug delivery system with improved cyto- 02)41:17%3c3130::AID-ANIE3130%[Link];2-1
compatibility, pH-responsive drug release and MR imaging. [27] Rajkumar M, Sundaram NM, Rajendran V (2010) In-situ
Acta Biomater 9:5360–5368. [Link] preparation of hydroxyapatite nanorod embedded poly
io.2012.09.023 (vinyl alcohol) composite and its characterization. Int J Eng
[16] Ashokan A, Gowd GS, Somasundaram VH et al (2013) Sci Technol 2(6):2437–2444
Multifunctional calcium phosphate nano-contrast agent for [28] White AA, Best SM, Kinloch IA (2007) Hydroxyapatite
combined nuclear, magnetic and near-infrared invivo carbon nanotube composites for biomedical applications: a
imaging. Biomaterials 34:7143–7157. [Link] review. Int J Appl Ceram Technol 4:1–13. [Link]
16/[Link].2013.05.077 10.1111/j.1744-7402.2007.02113.x
J Mater Sci

[29] Rapacz-Kmita A, Paluszkiewicz C, Ślósarczyk A et al synthesized from CaHPO4
2H2O and CaCO3 by hydroly-
(2005) FTIR and XRD investigations on the thermal sta- sis method. J Cryst Growth 270:211–218. [Link]
bility of hydroxyapatite during hot pressing and pressure- 10.1016/[Link].2004.06.023
less sintering processes. J Mol Struct 744:653–656. h [42] Shih WJ, Wang MC, Hon MH (2005) Morphology and
ttps://[Link]/10.1016/[Link].2004.11.070 crystallinity of the nanosized hydroxyapatite synthesized by
[30] Sun L, Berndt CC, Gross KA et al (2001) Material fun- hydrolysis using cetyltrimethylammonium bromide
damentals and clinical performance of plasma-sprayed (CTAB) as a surfactant. J Cryst Growth 275:e2339–e2344.
hydroxyapatite coatings: a review. J Biomed Mater Res [Link]
58:570–592. [Link] [43] Pramanik S, Agarwal AK, Rai KN et al (2007) Develop-
[31] Søballe K, Overgaard S (1996) The current status of ment of high strength hydroxyapatite by solid-state-sinter-
hydroxyapatite coating of prostheses. J Bone Joint Surg Br ing process. Ceram Int 33:419–426. [Link]
78:689–691 1016/[Link].2005.10.025
[32] Zhu R, Yu R, Yao J et al (2008) Morphology control of [44] Jarudilokkul S, Tanthapanichakoon W, Boonamnuayvittaya
hydroxyapatite through hydrothermal process. J Alloys V (2007) Synthesis of hydroxyapatite nanoparticles using
Compd 457:555–559. [Link] an emulsion liquid membrane system. Colloids Surf A
COM.2007.03.081 Physicochem Eng Asp 296:149–153. [Link]
[33] Loo SCJ, Siew YE, Ho S et al (2008) Synthesis and 16/[Link].2006.09.038
hydrothermal treatment of nanostructured hydroxyapatite of [45] Lim GK, Wang J, Ng SC, Gan LM (1999) Nanosized
controllable sizes. J Mater Sci Mater Med 19:1389–1397. h hydroxyapatite powders from microemulsions and emul-
ttps://[Link]/10.1007/S10856-007-3261-9/FIGURES/12 sions stabilized by a biodegradable surfactant. J Mater
[34] Xu H, Chen Y, Zhang S-F (2011) Synthesis and charac- Chem 9:1635–1639. [Link]
terization of microporous hydroxyapatite via hydrothermal [46] Zhou WY, Wang M, Cheung WL et al (2008) Synthesis of
method. Synth React Inorg Met-Org Nano-Met Chem carbonated hydroxyapatite nanospheres through
41:31–35. [Link] nanoemulsion. J Mater Sci Mater Med 19:103–110. http
[35] Neira IS, Guitián F, Taniguchi T et al (2008) Hydrothermal s://[Link]/10.1007/S10856-007-3156-9/FIGURES/10
synthesis of hydroxyapatite whiskers with sharp faceted [47] Catauro M, Papale F, Bollino F (2015) Characterization and
hexagonal morphology. J Mater Sci 43:2171–2178. http biological properties of TiO2/PCL hybrid layers prepared
s://[Link]/10.1007/S10853-007-2032-9/FIGURES/6 via sol-gel dip coating for surface modification of titanium
[36] Zhang H, Darvell BW (2010) Synthesis and characteriza- implants. J Non Cryst Solids 415:9–15. [Link]
tion of hydroxyapatite whiskers by hydrothermal homoge- 1016/[Link].2014.12.008
neous precipitation using acetamide. Acta Biomater [48] Garcı́a C, Ceré S, Durán A (2004) Bioactive coatings
6:3216–3222. [Link] prepared by sol-gel on stainless steel 316L. J Non Cryst
011 Solids 348:218–224. [Link]
[37] Kong LB, Ma J, Boey F (2002) Nanosized hydroxyapatite 004.08.172
powders derived from coprecipitation process. J Mater Sci [49] Zhang JX, Guan RF, Zhang XP (2011) Synthesis and
37:1131–1134. [Link] characterization of sol-gel hydroxyapatite coatings depos-
[38] Kumta PN, Sfeir C, Lee DH et al (2005) Nanostructured ited on porous NiTi alloys. J Alloys Compd
calcium phosphates for biomedical applications: novel 509:4643–4648. [Link]
synthesis and characterization. Acta Biomater 1:65–83. h 196
ttps://[Link]/10.1016/[Link].2004.09.008 [50] Shen S, Cai S, Xu G et al (2015) Influence of heat treatment
[39] Wang F, Li M, sen, Lu YP, et al (2005) Synthesis of on bond strength and corrosion resistance of sol-gel derived
nanocrystalline hydroxyapatite powders in stimulated body bioglass-ceramic coatings on magnesium alloy. J Mech
fluid. J Mater Sci 40:2073–2076. [Link] Behav Biomed Mater 45:166–174. [Link]
S10853-005-1238-Y [Link].2015.02.005
[40] Durucan C, Brown PW (2000) a-tricalcium phosphate [51] Rojaee R, Fathi M, Raeissi K (2013) Controlling the
hydrolysis to hydroxyapatite at and near physiological degradation rate of AZ91 magnesium alloy via sol-gel
temperature. J Mater Sci Mater Med 11:365–371. [Link] derived nanostructured hydroxyapatite coating. Mater Sci
[Link]/10.1023/A:1008934024440 Eng C 33:3817–3825. [Link]
[41] Shih WJ, Chen YF, Wang MC et al (2004) Crystal growth 05.014
and morphology of the nano-sized hydroxyapatite powders
 J Mater Sci

[52] Ballarre J, López DA, Schreiner WH et al (2007) Protective [64] Sadat-Shojai M, Khorasani MT, Dinpanah-Khoshdargi E
hybrid sol-gel coatings containing bioactive particles on et al (2013) Synthesis methods for nanosized hydroxyap-
surgical grade stainless steel: Surface characterization. Appl atite with diverse structures. Acta Biomater 9:7591–7621. h
Surf Sci 253:7260–7264. [Link] ttps://[Link]/10.1016/[Link].2013.04.012
2007.03.007 [65] Solati-Hashjin M, Moztarzadeh F, Goudarzi A et al (2009)
[53] Ballarre J, Manjubala I, Schreiner WH et al (2010) Surfactant assisted synthesis of hydroxyapatite nano-rods
Improving the osteointegration and bone-implant interface by aqueous precipitation and hydrothermal post-treatment.
by incorporation of bioactive particles in sol-gel coatings of Mater Sci Poland 27(4):961–971
stainless steel implants. Acta Biomater 6:1601–1609. http [66] Liu Y, Hou D, Wang G (2004) A simple wet chemical
s://[Link]/10.1016/[Link].2009.10.015 synthesis and characterization of hydroxyapatite nanorods.
[54] Ballarre J, Seltzer R, Mendoza E et al (2011) Morphologic Mater Chem Phys 86:69–73. [Link]
and nanomechanical characterization of bone tissue growth tchemphys.2004.02.009
around bioactive sol-gel coatings containing wollastonite [67] Salarian M, Hashjin SM, Goudarzi A et al (2008) Effect of
particles applied on stainless steel implants. Mater Sci Eng surfactant in formation of hydroxyapatite nano-rods under
C 31:545–552. [Link] hydrothermal conditions. Int J Pharm Sci 4:157–162
[55] Ayers RA, Burkes DE, Gottoli G et al (2007) Combustion [68] Bricha M, Belmamouni Y, Essassi EM et al (2012) Sur-
synthesis of porous biomaterials. J Biomed Mater Res A factant-assisted hydrothermal synthesis of hydroxyapatite
81A:634–643. [Link] nanopowders. J Nanosci Nanotechnol 12:8042–8049. http
[56] Ghosh SK, Roy SK, Kundu B et al (2011) Synthesis of s://[Link]/10.1166/jnn.2012.6664
nano-sized hydroxyapatite powders through solution com- [69] Dave N, Joshi T (2017) A concise review on surfactants
bustion route under different reaction conditions. Mater Sci and its significance. Int J Appl Chem 13:663–672. [Link]
Eng B 176:14–21. [Link] [Link]/10.37622/IJAC/13.3.2017.663-672
8.006 [70] Nakama Y (2017) Surfactants. In: Sakamoto K, Lochhead
[57] Aizawa M, Hanazawa T, Itatani K et al (1999) Character- R, Maibach H, Yamashita Y (1st eds) Cosmetic science and
ization of hydroxyapatite powders prepared by ultrasonic technology: theoretical principles and applications. Else-
spray-pyrolysis technique. J Mater Sci 34:2865–2873. h vier, pp 231–244. [Link]
ttps://[Link]/10.1023/A:1004635418655 05-0.00015-X
[58] Hui J, Wang X (2014) Hydroxyapatite nanocrystals: col- [71] Mishra M, Muthuprasanna P, Prabha KS et al (2009) Basics
loidal chemistry, assembly and their biological applications. and potential applications of surfactants—a review. Int J
Inorg Chem Front 1:215–225. [Link] Pharmtech Res 1:1354–1365
3qi00087g [72] Farn RJ (2007) Chemistry and technology of surfactants.
[59] Wang X, Zhuang J, Peng Q et al (2006) Liquid-solid-so- Wiley & Sons, Hoboken
lution synthesis of biomedical hydroxyapatite nanorods. [73] Sánchez MS, Rocha BT, Mier AE et al (2022) Surfactants
Adv Mater 18:2031–2034. [Link] in biorefineries: Role, challenges and perspectives. Biore-
200600033 sour Technol 345:126477. [Link]
[60] Zhao J, Hu Q, Lei Y et al (2021) Facile synthesis of tech.2021.126477
ultralong hydroxyapatite nanowires using wormlike [74] Mohammad NF, Othman R, Yee-Yeoh F et al (2014)
micelles as soft templates. Cryst Eng Commun Nanoporous hydroxyapatite preparation methods for drug
23:5498–5503. [Link] delivery applications. Rev Adv Mater Sci 38:138–147
[61] Xie Y, Kocaefe D, Chen C et al (2016) Review of research [75] Khan Z, Al-Zahrani SA, AlSulami QA et al (2019) Effects
on template methods in preparation of nanomaterials. of shape-controlling cationic and anionic surfactants on the
J Nanomater. [Link] morphology and surface resonance plasmon intensity of
[62] Bigi A, Boanini E, Bracci B et al (2005) Nanocrystalline silver@copper bimetallic nanoparticles. J Mol Liq
hydroxyapatite coatings on titanium: a new fast biomimetic 275:354–363. [Link]
method. Biomaterials 26:4085–4089. [Link] 036
16/[Link].2004.10.034 [76] Yuenyongsuwan J, Nithiyakorn N, Sabkird P et al (2018)
[63] Hong Y, Fan H, Li B et al (2010) Fabrication, biological Surfactant effect on phase-controlled synthesis and photo-
effects, and medical applications of calcium phosphate catalyst property of TiO2 nanoparticles. Mater Chem Phys
nanoceramics. Mater Sci Eng R Rep 70:225–242. [Link] 214:330–336. [Link]
[Link]/10.1016/[Link].2010.06.010 2018.04.111
J Mater Sci

[77] Huang B, Huang C, Chen J et al (2017) Size-controlled Nano Met Chem 45:411–414. [Link]
synthesis and morphology evolution of Nd2O3 nano- 33174.2013.841208
powders using ionic liquid surfactant templates. J Alloys [90] Gopi D, Indira J, Nithiya S et al (2013) Influence of sur-
Compd 712:164–171. [Link] factant concentration on nanohydroxyapatite growth. Bull
COM.2017.04.009 Mater Sci 36:799–805. [Link]
[78] Shaban SM, Kang J, Kim DH (2020) Surfactants: Recent -0540-6
advances and their applications. Compo Commun [91] Lett JA (2015) Influence of surfactant on synthesis of HAp
22:100537. [Link] by hydrothermal route. J Chem Pharm Res 7:187–190
[79] Lin K, Wu C, Chang J (2014) Advances in synthesis of [92] Yan L, Li Y, Deng ZX et al (2001) Surfactant-assisted
calcium phosphate crystals with controlled size and shape. hydrothermal synthesis of hydroxyapatite nanorods. Int J
Acta Biomater 10:4071–4102. [Link] Inorg Mater 3:633–637. [Link]
tbio.2014.06.017 49(01)00164-7
[80] Dorozhkin SV (2010) Nanosized and nanocrystalline cal- [93] Wang Y, Zhang S, Wei K et al (2006) Hydrothermal syn-
cium orthophosphates. Acta Biomater 6:715–734. [Link] thesis of hydroxyapatite nanopowders using cationic sur-
[Link]/10.1016/[Link].2009.10.031 factant as a template. Mater Lett 60:1484–1487. [Link]
[81] Molino G, Palmieri MC, Montalbano G et al (2020) Bio- org/10.1016/[Link].2005.11.053
mimetic and mesoporous nano-hydroxyapatite for bone [94] Shanthi PMSL, Ashok M, Balasubramanian T et al (2009)
tissue application: a short review. Biomed Mater Synthesis and characterization of nano-hydroxyapatite at
15:022001. [Link] ambient temperature using cationic surfactant. Mater Lett
[82] Nguyen NK, Leoni M, Maniglio D et al (2013) Hydrox- 63:2123–2125. [Link]
yapatite nanorods: Soft-template synthesis, characterization .008
and preliminary in vitro tests. J Biomater Appl 28:49–61. h [95] Nathanael AJ, Hong SI, Oh TH et al (2016) Enhanced cell
ttps://[Link]/10.1177/0885328212437065 viability of hydroxyapatite nanowires by surfactant medi-
[83] Shi W, He S, Wei M et al (2010) Optical pH sensor with ated synthesis and its growth mechanism. RSC Adv
rapid response based on a fluorescein-intercalated layered 6:25070–25081. [Link]
double hydroxide. Adv Funct Mater 20:3856–3863. http [96] Lin K, Chang J, Cheng R et al (2007) Hydrothermal
s://[Link]/10.1002/adfm.201001081 microemulsion synthesis of stoichiometric single crystal
[84] Matile S, Jentzsch AV, Montenegro J et al (2011) Recent hydroxyapatite nanorods with mono-dispersion and nar-
synthetic transport systems. Chem Soc Rev 40:2453–2474. row-size distribution. Mater Lett 61:1683–1687. [Link]
[Link] org/10.1016/[Link].2006.07.099
[85] Busseron E, Ruff Y, Moulin E et al (2013) Supramolecular [97] Wang YJ, Chen JD, Wei K et al (2006) Surfactant-assisted
self-assemblies as functional nanomaterials. Nanoscale synthesis of hydroxyapatite particles. Mater Lett
5:7098–7140. [Link] 60:3227–3231. [Link]
[86] Zakharova LY, Pashirova TN, Fernandes AR, et al (2018) .077
Self-assembled quaternary ammonium surfactants for [98] Hong SI, Lee KH, Outslay ME et al (2008) Ultrastructural
pharmaceuticals and biotechnology. In: Organic Materials analyses of nanoscale apatite biomimetically grown on
as Smart Nanocarriers for Drug Delivery. William Andrew organic template. J Mater Res 23:478–485. [Link]
Publishing, pp 601–618. [Link] 10.1557/jmr.2008.0051
2-813663-8.00014-2 [99] Rulis P, Yao H, Ouyang L et al (2007) Electronic structure,
[87] Paluch E, Piecuch A, Obła˛k E et al (2018) Antifungal bonding, charge distribution, and x-ray absorption spectra
activity of newly synthesized chemodegradable dicephalic- of the (001) surfaces of fluorapatite and hydroxyapatite
type cationic surfactants. Colloids Surf B Biointerfaces from first principles. Phys Rev B Condens Matter Mater
164:34–41. [Link] Phys 76:1–15. [Link]
[88] Mujahid M, Sarfraz S, Amin S (2015) On the formation of 245410
hydroxyapatite nano crystals prepared using cationic sur- [100] Domı́nguez GG, Torre SDDL, Güitrón LC et al (2013)
factant. Mater Res 18:468–472. [Link] Effect of the structural and morphological properties of
16-1439.298014 surfactant-assisted hydroxyapatite on dermal irritation and
[89] Zhang Y, Dong Y (2015) Effect of surfactant on mor- antibacterial activity. CrystEngComm 15:7926–7935. http
phology of hydroxyapatite. Synth React Inorg, Met Org, s://[Link]/10.3390/ma14216522
 J Mater Sci

[101] Iqbal N, Kadir MRA, Malek NANN et al (2013) Charac- [112] Salinas AJ, Blanco-Bécares JM, Mersinlioglu O et al
terization and antibacterial properties of stable silver sub- (2018) Synthesis, characterization and biocompatibility of
stituted hydroxyapatite nanoparticles synthesized through mesolamellar calcium phosphate hybrids prepared by
surfactant assisted microwave process. Mater Res Bull anionic surfactant templating. ChemistrySelect
48:3172–3177. [Link] 3:6880–6891. [Link]
04.068 [113] Shimabayashi S, Satomi M, Hino T et al (2001) Adsorption
[102] Li Y, Ho J, Ooi CP (2010) Antibacterial efficacy and characteristics of non-adsorbable nonionic surfactant, TX-
cytotoxicity studies of copper (II) and titanium (IV) sub- 100 on the surface of hydroxyapatite in the presence of an
stituted hydroxyapatite nanoparticles. Mater Sci Eng C anionic surfactant. Phosphorus Res Bull 12:1–6. [Link]
30:1137–1144. [Link] org/10.3363/prb1992.12.0_1
[103] Malik MA, Hashim MA, Nabi F et al (2011) Anti-corrosion [114] Shimabayashi S, Hoshino M, Hino T (2002) Cooperative
ability of surfactants: a review. Int J Electrochem Sci adsorption of nonionic and anionic surfactants to the sur-
6:1927–1948 face of hydroxyapatite in an aqueous phase. Phosphorus
[104] Elsaeedy HI (2019) A low temperature synthesis of Ag2S Res Bull 14:39–46. [Link]
nanostructures and their structural, morphological, optical, 39
dielectric and electrical studies: an effect of SDS surfactant [115] Mohammadi R, Wassink J, Amirfazli A (2004) Effect of
concentration. Mater Sci Semicond Process 93:360–365. h surfactants on wetting of super-hydrophobic surfaces.
ttps://[Link]/10.1016/[Link].2019.01.022 Langmuir 20:9657–9662. [Link]
[105] Kangkan S, Pongprayoon T, Ummartyotin S (2020) Mor- 049268k
phologically controlled synthesis of (-tricalcium phos- [116] Wan Y, Wu C, Xiong G et al (2015) Mechanical properties
phate)-TCP particles from cuttlebone by sodium dodecyl and cytotoxicity of nanoplate-like hydroxyapatite/polylac-
sulfate (SDS) anionic surfactant: In vitro behavior of mouse tide nanocomposites prepared by intercalation technique.
osteoblast cells. J Mater Res Technol 9:3121–3127. http J Mech Behav Biomed Mater 47:29–37. [Link]
s://[Link]/10.1016/[Link].2020.01.057 1016/[Link].2015.03.009
[106] Tari NE, Motlagh MMK, Sohrabi B (2011) Synthesis of [117] Karunakaran G, Cho EB, Kumar GS et al (2019) Sodium
hydroxyapatite particles in catanionic mixed surfactants dodecyl sulfate mediated microwave synthesis of biocom-
template. Mater Chem Phys 131:132–135. [Link] patible superparamagnetic mesoporous hydroxyapatite
10.1016/[Link].2011.07.078 nanoparticles using black Chlamys varia seashell as a cal-
[107] Sarda S, Heughebaert M, Lebugle A (1999) Influence of the cium source for biomedical applications. Ceram Int
type of surfactant on the formation of calcium phosphate in 45:15143–15155. [Link]
organized molecular systems. Chem Mater 11:2722–2727. 019.04.256
[Link] [118] Wan Y, Wu C, Zuo G et al (2015) Controlled template
[108] Kalita SJ, Verma S (2010) Nanocrystalline hydroxyapatite synthesis of lamellar hydroxyapatite nanoplates as a
bioceramic using microwave radiation: synthesis and potential carrier for gene delivery. Mater Chem Phys
characterization. Mater Sci Eng C 30:295–303. [Link] 156:238–246. [Link]
org/10.1016/[Link].2009.11.007 03.011
[109] Zhang HB, Zhou KC, Li ZY et al (2009) Plate-like [119] Salarian M, Solati-Hashjin M, Shafiei SS et al (2009)
hydroxyapatite nanoparticles synthesized by the Surfactant-assisted synthesis and characterization of
hydrothermal method. J Phys Chem Solids 70:243–248. h hydroxyapatite nanorods under hydrothermal conditions.
ttps://[Link]/10.1016/[Link].2008.10.011 Mater Sci- Pol 27:961–971
[110] Nathanael AJ, Im YM, Oh TH (2020) Intrinsic effect of [120] Che Y, Min S, Wang M et al (2019) Biological activity of
anionic surfactant on the morphology of hydroxyapatite hydroxyapatite/poly(methylmethacrylate) bone cement
nanoparticles and its structural and biological properties. with different surface morphologies and modifications for
Adv Powder Technol 31:234–240. [Link] induced osteogenesis. J Appl Polym Sci 136:48188. http
[Link].2019.10.015 s://[Link]/10.1002/APP.48188
[111] Nakagawa K, Arai Y, Umezaki Y et al (2018) Template [121] Iyyappan E, Wilson P, Sheela K et al (2016) Role of triton
effect of phosphate surfactant on formation of hydroxyap- X-100 and hydrothermal treatment on the morphological
atite nanostructures with various shapes. Mater Chem Phys features of nanoporous hydroxyapatite nanorods. Mater Sci
213:183–190. [Link] Eng C 63:554–562. [Link]
04.039 02.076
J Mater Sci

[122] Lee MH, Oh SG, Suh KD et al (2002) Preparation of silver Chem Lett 30:780–781. [Link]
nanoparticles in hexagonal phase formed by nonionic Tri- 780
ton X-100 surfactant. Colloids Surf A Physicochem Eng [134] Xin R, Ren F, Leng Y (2010) Synthesis and characteriza-
Asp 210:49–60. [Link] tion of nano-crystalline calcium phosphates with EDTA-
214-5 assisted hydrothermal method. Mater Des 31:1691–1694. h
[123] Zhang J, Jiang D, Zhang J et al (2010) Synthesis of orga- ttps://[Link]/10.1016/[Link].2009.01.048
nized hydroxyapatite (HA) using triton X-100. Ceram Int [135] Zhang W, Chai Y, Xu X et al (2014) Rod-shaped hydrox-
36:2441–2447. [Link] yapatite with mesoporous structure as drug carriers for
0.08.002 proteins. Appl Surf Sci 322:71–77. [Link]
[124] Iyyappan E, Wilson P (2013) Synthesis of nanoscale [Link].2014.10.064
hydroxyapatite particles using triton X-100 as an organic [136] Salarian M, Solati-Hashjin M, Shafiei SS et al (2009)
modifier. Ceram Int 39:771–777. [Link] Template-directed hydrothermal synthesis of dandelion-like
CERAMINT.2012.06.090 hydroxyapatite in the presence of cetyltrimethylammonium
[125] Zhao YF, Ma J (2005) Triblock co-polymer templating bromide and polyethylene glycol. Ceram Int
synthesis of mesostructured hydroxyapatite. Microporous 35:2563–2569. [Link]
Mesoporous Mater 87:110–117. [Link] 031
MICROMESO.2005.07.046 [137] Padmanabhan VP, Kulandaivelu R, Panneer DS et al (2019)
[126] Haung SM, Chen JC, Chang KC et al (2021) Synthesis of Surfactant assisted hydroxyapatite nanoparticles: drug
nanorod apatites with templates at critical micelle concen- loading and in vitro leaching kinetics and antimicrobial
trations and in vitro evaluation of cytotoxicity and antimi- properties. J Nanosci Nanotechnol 19:7198–7204. [Link]
crobial activity. J Asian Ceramic Soc 9:995–1006. [Link] [Link]/10.1166/jnn.2019.16665
[Link]/10.1080/21870764.2021.1932080 [138] Wang A, Yin H, Liu D et al (2007) Effects of organic
[127] Prakash VCA, Venda I, Thamizharasi V et al (2021) A new modifiers on the size-controlled synthesis of hydroxyapatite
attempt on synthesis of spherical nano hydroxyapatite nanorods. Appl Surf Sci 253:3311–3316. [Link]
powders prepared by dimethyl sulfoxide - poly vinyl 1016/[Link].2006.07.025
alcohol assisted microemulsion method. Mater Chem Phys [139] Arami H, Mohajerani M, Mazloumi M et al (2009) Rapid
259:124097. [Link] formation of hydroxyapatite nanostrips via microwave
124097 irradiation. J Alloys Compd 469:391–394. [Link]
[128] Prakash VCA, Venda I, Thamizharasi V (2022) Synthesis 10.1016/[Link].2008.01.116
and characterization of surfactant assisted hydroxyapatite [140] Lak A, Mazloumi M, Mohajerani MS et al (2008) Rapid
powder using microemulsion method. Mater Today Proc formation of mono-dispersed hydroxyapatite nanorods with
51:1788–1792. [Link] narrow-size distribution via microwave irradiation. J Am
[129] Sato K, Hotta Y, Nagaoka T et al (2006) Agglomeration Ceram Soc 91:3580–3584. [Link]
control of hydroxyapatite nano-crystals grown in phase- 2916.2008.02690.x
separated microenvironments. J Mater Sci 41:5424–5428. h [141] Liu J, Li K, Wang H et al (2004) Rapid formation of
ttps://[Link]/10.1007/S10853-006-0258-6/FIGURES/6 hydroxyapatite nanostructures by microwave irradiation.
[130] Sun Y, Guo G, Wang Z et al (2006) Synthesis of single- Chem Phys Lett 396:429–432. [Link]
crystal HAP nanorods. Ceram Int 32:951–954. [Link] plett.2004.08.094
org/10.1016/[Link].2005.07.023 [142] Amer W, Abdelouahdi K, Ramananarivo HR et al (2013)
[131] Ma X, Chen Y, Qian J et al (2016) Controllable synthesis of Synthesis of mesoporous nano-hydroxyapatite by using
spherical hydroxyapatite nanoparticles using inverse zwitterions surfactant. Mater Lett 107:189–193. [Link]
microemulsion method. Mater Chem Phys 183:220–229. h org/10.1016/[Link].2013.05.103
ttps://[Link]/10.1016/[Link].2016.08.021 [143] Langroudi MM, Saravani MG, Nouri A (2017) Surfactant-
[132] Nathanael AJ, Hong SI, Tae C et al (2016) Enhanced cell assisted synthesis of polyvinylpyrrolidone-hydroxyapatite
viability of hydroxyapatite nanowires by surfactant medi- composites as a bone filler. J Appl Biomater Funct Mater
ated synthesis and its growth mechanism. RSC Adv 15:e334–e340. [Link]
6:25070–25081. [Link] [144] Qiu C, Xiao X, Liu R (2008) Biomimetic synthesis of
[133] Nagata F, Toriyama M, Teraoka K et al (2001) Influence of spherical nano-hydroxyapatite in the presence of poly-
ethylamine on the crystal growth of hydroxyapatite crystals. ethylene glycol. Ceram Int 34:1747–1751. [Link]
10.1016/[Link].2007.06.001
 J Mater Sci

[145] Chen HT, Chang HF, Ko HH et al (2013) Effects of solute [156] Agalya P, Saravanan T, Kumar GS et al (2021) Surfactant-
and surfactant addition on the crystallization and mor- assisted microwave synthesis of luminescent/magnetic
phology of hydroxyapatite powders synthesized by bifunctional hydroxyapatite nanorods for dual-model
hydrolysis of calcium hydrogen phosphate dehydrate imaging. Optik 225:165564. [Link]
(DCPD). Metall Mater Trans A Phys Metall Mater Sci 2020.165564
44:1023–1033. [Link] [157] Tattanon T, Pongprayoon T, Arpornmaeklong P et al (2022)
Y/TABLES/1 Development of hydroxyapatite from cuttlebone and gela-
[146] Li Y, Tjandra W, Tam KC (2008) Synthesis and charac- tin-based hydrogel composite for medical materials.
terization of nanoporous hydroxyapatite using cationic J Polym Res 29:1–10. [Link]
surfactants as templates. Mater Res Bull 43:2318–2326. h 03224-X
ttps://[Link]/10.1016/[Link].2007.08.008 [158] Zhu L, Yang H, He Y (2022) Sodium dodecyl sulfate
[147] Govindan B, Latha BS, Nagamony P et al (2017) Designed assisted synthesis hydroxyapatite for effective adsorption of
synthesis of nanostructured magnetic hydroxyapatite based methylene blue. J Dispers Sci Technol. [Link]
drug nanocarrier for anti-cancer drug delivery toward the 1080/01932691.2022.2030237
treatment of human epidermoid carcinoma. Nanomaterials [159] Esteves AVM, Martins MI, Soares P et al (2022) Additive
7:138. [Link] manufacturing of ceramic alumina/calcium phosphate
[148] Kim J, Kim HS, Lee N et al (2008) Multifunctional uniform structures by DLP 3D printing. Mater Chem Phys
nanoparticles composed of a magnetite nanocrystal core 276:125417. [Link]
and a mesoporous silica shell for magnetic resonance and 021.125417
fluorescence imaging and for drug delivery. Angew Chem [160] Lin SC, Lin KG, Lo CC et al (1998) Enhanced biosurfac-
120:8566–8569. [Link] tant production by a Bacillus licheniformis mutant. Enzyme
[149] Ajithkumar G, Benjamin Y, Goral DE et al (2013) Multi- Microb Technol 23:267–273. [Link]
modal bioimaging using a rare earth doped Gd2O2S:Yb/Er 1-0229(98)00049-0
phosphor with upconversion luminescence and magnetic [161] Saikia RR, Deka S, Sarma H (2021) Biosurfactants from
resonance properties. J Mater Chem B 1:1561–1572. http bacteria and fungi. In: Biosurfactants for a sustainable
s://[Link]/10.1039/C3TB00551H future: production and applications in the environment and
[150] Jiang Z, Shan K, Song J et al (2019) Toxic effects of biomedicine. Wiley, USA, pp 293–315. [Link]
magnetic nanoparticles on normal cells and organs. Life Sci 1002/9781119671022.ch13
220:156–161. [Link] [162] De S, Malik S, Ghosh A et al (2015) A review on natural
[151] Tsoi KM, Dai Q, Alman BA, Chan WCW (2012) Are surfactants. RSC Adv 5:65757–65767. [Link]
quantum dots toxic? exploring the discrepancy between cell 1039/c5ra11101c
culture and animal studies. Acc Chem Res 46:662–671. h [163] Ritter SK (2004) Green innovations. Chem Eng News
ttps://[Link]/10.1021/AR300040Z 82:25–30. [Link]
[152] Lou L, Yu K, Zhang Z et al (2011) Functionalized mag- [164] Makkar R, Cameotra S (2002) An update on the use of
netic-fluorescent hybrid nanoparticles for cell labelling. unconventional substrates for biosurfactant production and
Nanoscale 3:2315–2323. [Link] their new applications. Appl Microbiol Biotechnol
C1NR10066A 58:428–434. [Link]
[153] Garcı́a RS, Stafford S, Gun’ko YK, (2018) Recent progress [165] Desai JD, Banat IM (1997) Microbial production of sur-
in synthesis and functionalization of multimodal fluores- factants and their commercial potential. Microbiol Mol Biol
cent-magnetic nanoparticles for biological applications. Rev 61:47–64. [Link]
Appl Sci 8:172. [Link] [166] Rahman PKSM, Gakpe E (2008) Production, characteri-
[154] Liu Z, Wang Q, Yao S et al (2014) Synthesis and charac- sation and applications of biosurfactants—review.
terization of Tb3?/Gd3? dual-doped multifunctional Biotechnol 7:360–370. [Link]
hydroxyapatite nanoparticles. Ceram Int 40:2613–2617. h 8.360.370
ttps://[Link]/10.1016/[Link].2013.10.070 [167] Ron EZ, Rosenberg E (2001) Natural roles of biosurfac-
[155] Chen F, Huang P, Zhu YJ et al (2011) The photolumines- tants. Minireview Environ Microbiol 3:229–236. [Link]
cence, drug delivery and imaging properties of multifunc- [Link]/10.1046/j.1462-2920.2001.00190.x
tional Eu3?/Gd3? dual-doped hydroxyapatite nanorods. [168] Khan A, Butt A (2016) Biosurfactants and their potential
Biomaterials 32:9031–9039. [Link] applications for microbes and mankind: an overview.
MATERIALS.2011.08.032
J Mater Sci

Middle East J Bus 11:9–18. [Link] biosurfactant surfactin. Int J Mol Sci 12:3821–3830. http
2015.92757 s://[Link]/10.3390/ijms12063821
[169] Akbari S, Abdurahman NH, Yunus RM et al (2018) Bio- [181] Balakrishnan S, Rajendran A, Kulandaivelu R et al (2019)
surfactants—a new frontier for social and environmental Saponin-mediated synthesis of hydroxyapatite by
safety: a mini review. Biotechnol Res Innov 2:81–90. h hydrothermal method: characteristics, bioactivity, and
ttps://[Link]/10.1016/[Link].2018.09.001 antimicrobial behavior. J Aust Ceram Soc 55:953–967. h
[170] Rodrigues L, Banat IM, Teixeira J et al (2006) Biosurfac- ttps://[Link]/10.1007/s41779-019-00307-9
tants: Potential applications in medicine. J Antimicrob [182] Ali AF, Alrowaili ZA, El-Giar EM et al (2021) Novel green
Chemother 57:609–618. [Link] synthesis of hydroxyapatite uniform nanorods via micro-
[171] Harshada K (2014) Biosurfactant: a potent antimicrobial wave-hydrothermal route using licorice root extract as
agent. J Microbiol Exp 1:173–177. [Link] template. Ceram Int 47:3928–3937. [Link]
6/jmen.2014.01.00031 [Link].2020.09.256
[172] Gupta S (2021) Biosurfactant-based antibiofilm nano [183] Gopi D, Bhuvaneshwari N, Indira J et al (2013) Synthesis
materials. In: Biosurfactants for a sustainable future. Wiley, and spectroscopic investigations of hydroxyapatite using a
USA, pp 269–292. [Link] green chelating agent as template. Spectrochim Acta A Mol
2.ch12 Biomol Spectrosc 104:292–299. [Link]
[173] Muntaha ST, Khan MN (2015) Natural surfactant extracted saa.2012.11.092
from Sapindus mukurossi as an eco-friendly alternate to [184] Rusted J (2020) Caffeine and cognitive performance:
synthetic surfactant—a dye surfactant interaction study. effects on mood or mental processing? In: Caffeine and
J Clean Prod 93:145–150. [Link] behavior: current views and research trends: current views
PRO.2015.01.023 and research trends, CRC Press, Boca Raton, pp 221–230.
[174] Song S, Zhu L, Zhou W (2008) Simultaneous removal of [Link]
phenanthrene and cadmium from contaminated soils by [185] Baldwin HA, File SE (1989) Caffeine-induced anxiogene-
saponin, a plant-derived biosurfactant. Environ pollut sis: The role of adenosine, benzodiazepine and noradren-
156:1368–1370. [Link] ergic receptors. Pharmacol Biochem Behav 32:181–186. h
06.018 ttps://[Link]/10.1016/0091-3057(89)90230-X
[175] KOSARIC N, (2001) Biosurfactants and their application [186] Subramanian R, Murugan P, Chinnadurai G et al (2019)
for soil bioremediation. Food Technol Biotechnol Experimental studies on caffeine mediated synthesis of
39:295–304 hydroxyapatite nanorods and their characterization. Mater
[176] Chhetri AB, Watts KC, Rahman MS et al (2009) Soapnut Res Exp 7:015022. [Link]
extract as a natural surfactant for enhanced oil recovery. 619a
Energy Sources A Recovery Util Environ Eff [187] Buitrago-Vásquez M, Ossa-Orozco CP (2018) Hydrother-
31:1893–1903. [Link] mal synthesis of hydroxyapatite nanorods using a fruit
15567030802462622 extract template. DYNA 85:283–288. [Link]
[177] Tmáková L, Sekretár S, Schmidt Š (2015) Plant-derived 446/dyna.v85n204.65773
surfactants as an alternative to synthetic surfactants: Sur- [188] Zhou R, Si S, Zhang Q (2012) Water-dispersible hydrox-
face and antioxidant activities. Chem Pap 70:188–196. h yapatite nanoparticles synthesized in aqueous solution
ttps://[Link]/10.1515/chempap-2015-0200 containing grape seed extract. Appl Surf Sci
[178] Zhao H, He W, Wang Y et al (2008) Biomineralization of 258:3578–3583. [Link]
large hydroxyapatite particles using ovalbumin as biosur- 1.119
factant. Mater Lett 62:3603–3605. [Link] [189] Klinkaewnarong J, Swatsitang E, Masingboon C et al
matlet.2008.04.007 (2010) Synthesis and characterization of nanocrystalline
[179] Gilman H, Hukins DWL, Hickey DS (1991) Characteri- HAp powders prepared by using aloe vera plant extracted
zation of the morphology of hydroxyapatite precipitated in solution. Curr Appl Phys 10:521–525. [Link]
the presence of proteins by texture analysis of scanning 1016/[Link].2009.07.014
electron micrographs. J Phys D Appl Phys 24:127. [Link] [190] Guifen Fu, Vary PS, Lin C-T (2005) Anatase TiO2
[Link]/10.1088/0022-3727/24/2/007 nanocomposites for antimicrobial coatings. J Phys Chem B
[180] Maity JP, Lin TJ, Cheng HPH et al (2011) Synthesis of 109:8889–8898. [Link]
brushite particles in reverse microemulsions of the [191] Aremu A, Kingsley EI, Talha BK et al (2019) Methanolic
leaf extract of Moringa oleifera improves the survivability
 J Mater Sci

rate, weight gain and histopathological changes of Wister cuttlebone assisted by the biosurfactant L-rhamnose mono-
rats infected with Trypanosoma brucei. Int J Vet Sci Med hydrate for biomedical materials. ChemEngineering 5:88. h
6:39–44. [Link] ttps://[Link]/10.3390/CHEMENGINEERING5040088
[192] Kalaiselvi V, Mathammal R, Vijayakumar S et al (2018) [201] Ghate P, Prabhu SD, Murugesan G et al (2022) Synthesis of
Microwave assisted green synthesis of Hydroxyapatite hydroxyapatite nanoparticles using Acacia falcata leaf
nanorods using Moringa oleifera flower extract and its extract and study of their anti-cancerous activity against
antimicrobial applications. Int J Vet Sci Med 6:286–295. h cancerous mammalian cell lines. Environ Res 214:113917.
ttps://[Link]/10.1016/[Link].2018.08.003 [Link]
[193] Sundrarajan M, Jegatheeswaran S, Selvam S et al (2015) [202] Bee SL, Bustami Y, Ul-Hamid A et al (2022) Green
The ionic liquid assisted green synthesis of hydroxyapatite biosynthesis of hydroxyapatite-silver nanoparticle
nanoplates by Moringa oleifera flower extract: a biomimetic nanocomposite using aqueous Indian curry leaf (Murraya
approach. Mater Des 88:1183–1190. [Link] koengii) extract and its biological properties. Mater Chem
6/[Link].2015.09.051 Phys 277:125455. [Link]
[194] Leong YK, Seah U, Chu SY et al (2001) Effects of Gum 2021.125455
Arabic macromolecules on surface forces in oxide disper- [203] Elizondo-Villarreal N, Verástegui-Dominguez LH, Qui-
sions. Colloids Surf A Physicochem Eng Asp jano-Briones JJ et al (2022) Agro-industrial waste as a
182:263–268. [Link] source of raw material: Eggshell and ash of agave salmiana
26-8 useful for the synthesis of hydroxyapatite. J Renew Mater
[195] Sreedhar B, Aparna Y, Sairam M et al (2007) Preparation 10:3559–3572. [Link]
and characterization of HAP/carboxymethyl chitosan [204] Vinayagam R, Pai S, Murugesan G et al (2022) Green
nanocomposites. J Appl Polym Sci 105:928–934. [Link] synthesized hydroxyapatite nanoadsorbent for the adsorp-
[Link]/10.1002/APP.26140 tive removal of AB113 dye for environmental applications.
[196] Mohan YM, Raju KM, Sambasivudu K et al (2007) Environ Res 212:113274. [Link]
Preparation of acacia-stabilized silver nanoparticles: A 2022.113274
green approach. J Appl Polym Sci 106:3375–3381. [Link] [205] Sodhani H, Hedaoo S, Murugesan G et al (2022) Adsorp-
[Link]/10.1002/APP.26979 tive removal of Acid Blue 113 using hydroxyapatite
[197] Sreedhar B, Devi DK, Neetha AS et al (2015) Green syn- nanoadsorbents synthesized using Peltophorum ptero-
thesis of gum-acacia assisted gold-hydroxyapatite nanos- carpum pod extract. Chemosphere 299:134752. [Link]
tructures - Characterization and catalytic activity. Mater org/10.1016/[Link].2022.134752
Chem Phys 153:23–31. [Link]
phys.2014.12.031 Publisher’s Note Springer Nature remains neutral with
[198] Nayar S, Guha A (2009) Waste utilization for the controlled regard to jurisdictional claims in published maps and
synthesis of nanosized hydroxyapatite. Mater Sci Eng, C institutional affiliations.
29:1326–1329. [Link]
[199] Liu Y, Layrolle P, de Bruijn J et al (2001) Biomimetic Springer Nature or its licensor (e.g. a society or other
coprecipitation of calcium phosphate and bovine serum partner) holds exclusive rights to this article under a
albumin on titanium alloy. J Biomed Mater Res publishing agreement with the author(s) or other rightsh-
57:327–335. [Link] older(s); author self-archiving of the accepted manuscript
57:3%3c327::aid-jbm1175%[Link];2-j version of this article is solely governed by the terms of
[200] Tattanon T, Arpornmaeklong P, Ummartyotin S et al (2021) such publishing agreement and applicable law.
Hydrothermal synthesis of biphasic calcium phosphate from