INTRODUCTION
Treatment options for disease- or trauma-related tissue degradation or injury include
replacement, regeneration, and repair. Autograft or allograft, which are innovative and life-
saving techniques, are used to do this. But they arise with serious issues related to tissue
rejections. Advances in tissue engineering and regenerative medicine can help to overcome
these limitations by creating biological replacements that aid in tissue function restoration.
[scaffold fabrication techniques]
Tissue engineering is a relatively new area of bioengineering that integrates the methods and
ideas of material science, cell biology, and engineering to build tissue substitutes that can
anatomically and physiologically mimic native tissues.10.
In the 1990s, Langer and Vacanti provided the first definition of the term "tissue engineering"
(TE) [3].
[ Polymeric nanocomposite scaffold in bone TE]
"Applying the principles and methods of engineering and life sciences to fundamentally
understand the structure–function relationship between normal and mammalian tissues, and
develop biological substitutes to restore, maintain, or improve tissue function" is the official
definition of "tissue engineering" as provided by the National Science Foundation (NSF).
That is, in tissue engineering, a variety of biomaterials (including polymers, ceramics and
inorganic substances), bioactive molecules and cells are integrated to induce and/or stimulate
differentiation signals, and promote tissue regeneration at the lesion or damaged site.11.
[application of nanomaterial in tissue engineering]
When surgery is required, the primary objective of tissue engineering is to create new,
functional tissues and regenerate tissue in vivo or in vitro in order to treat diseases [7]. Three
categories can be used to group broad tissue engineering strategies: (i) implanting single cells
or cell replacements into the body; (ii) supplying tissue that stimulates the release of
chemicals like growth factors. A growth factor is often defined as a protein or polypeptide
that can promote tissue growth (iii) place cells in or on different matrices in order to enhance
tissue growth [6]. Two main categories of tissue engineering exist: (a) Hard tissue
engineering, which deals with bone; (b) soft tissue engineering, which deals with skin, blood
vessels, tendon/ligament, cardiac patches, nerves, and skeletal muscle [8]
[ Polymeric nanocomposite scaffold in bone TE]
Extracellular matrix (ECM), which mostly consists of bioactive substances, structural
proteins, adhesive proteins, and proteoglycan-protein polysaccharide complexes, is the
substance to which cells are normally attached [9–11]. Porous biodegradable scaffolds with
growth factors and bioactive substances that resemble extracellular matrix (ECM) are made
possible by tissue engineering, and they aid in the regeneration and development of a variety
of tissues [nanomedicine as scaffold in TE]
The extracellular matrix (ECM) is a complex network of macromolecules that provides
structural and biochemical support to surrounding cells. A typical ECM is a well hydrated
nanocomposite which contains a variety of proteins and fibres, including signalling proteins,
proteoglycans, reticular fibres, adhesion proteins, collagen fibres, and elastic fibres, many of
which contribute to the rigidity of the ECM [37,45]. ECM contains growth factors and
mediates both cell–cell and cell-substrate interactions, making it a key component of native
microenvironments [41]. All the constituent parts of the ECM are necessary for maintaining
the biological, physical, and mechanical signalling that controls essential cell functions
including migration, differentiation, adhesion, migration, apoptosis, polarity, gene expression,
proliferation, and tissue morphogenesis [35,37,38,41]. [application of nanotech in 3D
printed TE scaffolds]
Scaffolds are designed to act as a 3D support structure to the surrounding tissue mimicking
ECM, with advantageous characteristics, including: (i) porous structure that promotes cell-
biomaterial interactions, cell adhesion, growth and migration, (ii) interconnected pores to
facilitate transport of mass, nutrients, and regulatory factors to allow cell survival,
proliferation, and differentiation, (iii) adequate mechanical properties as tensile strength and
elasticity, (iv) controlled degradation, and (v) minimal degree of inflammation or toxicity in
vivo. [ 133 ] Furthermore, scaffolds have desirable characteristics for cell transfer into a
defect site and to restrict cell loss, instead of simple injection of cells to the defects. [ 134]
[ Natural composite scaffolds in TE]
A perfect scaffold should be biocompatible to prevent unwanted host replies, biodegradable
with sufficient physical and mechanical characteristics [196,197]. The scaffold's interlinked
porosity facilitates cell spreading and nutrient, oxygen, waste and growth factors to be
transported, promoting the sustained development of tissue from the outskirts into the inner
part of the scaffold [198]. A scaffold should replace regenerative tissue while retaining the
shape and size of the final tissue structure [28,199]. [ Polymeric nanocomposite scaffold in
bone TE]
Commonly used processes for the production of such scaffolds are phase separation, foaming
and solvent casting/particulate leaching. [Effect of TiO2 Nanoparticles loading on Poly( L-
Lactic acid) ]
Research into new approaches to create such scaffolds has been intensified in recent years,
and tissue engineering combined with nanotechnology is now looked upon as a promising
alternative to the existing conventional repair strategies [1,2]. [carbon materials for TE of
bone]
Nanomaterials such as nanoclay, inorganic ceramics, and carbon-based nanomaterials
(CNMs) play a pivotal role in tissue engineering [10–16]. [chitosan carbon based scaffolds
in TE]
Similarly, CNMs, such as carbon nanotubes (CNTs), graphene, graphene oxide (GO), and
reduced graphene oxide (rGO), are widely considered as potential reinforcing agents for the
development of novel hybrid scaffolds with improved properties [20–22]. [chitosan carbon
based scaffolds in TE]
Furthemore, calcium phosphate–based ceramics, such as tricalcium phosphate, tetracalcium
phosphate, and hydroxyapatite, are used as reinforcing materials for the development of
chitosan-based scaffolds with the adequate mechanical, tensile, and compression strength
[2,19]. [chitosan carbon based scaffolds in TE]
These nanomaterials have diameters ranging from tens of nanometers to hundreds of
nanometers [19]. They possess unique structures and properties which make them promising
candidate materials for use in biomedical applications, such as tissue engineering and
regenerative medicine. [carbon materials for TE of bone]
Nanoceramics play an important role in tissue engineering, as they are ceramic materials
composed of nanodimensional grains/crystallites with at least one aspect of the element
below 100 nm. Also, nanoceramics show enhanced properties compared to their bulk
material, such as remarkable mechanical properties, including incredible strength, excellent
toughness, and high fatigue resistance.24 The cost-friendly and facile fabrication methods of
nanoceramics are the significant advantages researchers exploit for TE applications. These
nanoceramics can be widely used in bone tissue engineering due to their highly porous nature
and there would be improved cell migration and interaction between the bioceramic scaffold
and bone, post-implantation. Several impactful research works utilizing nanoceramics have
stated significant improvement in the scaffold’s mechanical strength, toughness and
resistance upon their incorporation. Despite their brittle nature, ceramics, including alumina,
ZrO2, TiO2, and bioglass, possess a high level of biocompatibility, and this attribute has been
exploited for use in the creation of natural bone substitutes, implants, and hip arthroplast .
Among those ceramic materials, titanium and its alloys have exhibited superior
biocompatibility and excellent corrosion resistance property. Fostad et al. reported TiO2
scaffolds with high mechanical strength and high porosity using the polymer sponge
method.40 Therefore, the mechanical strength of the nanoceramics can be optimized for
various TE applications. [Nanoceramics reinforced chitosan based scaffolds in bone TE]
Recent reviews suggest that the antimicrobial activity of TiO2 is highly selective depending
on the complexity of cell membrane/wall components. Microbial sensitivity towards TiO2
nanomaterials, for instance, increases as follow: viruses > Gram-negative bacteria > Gram-
positive bacteria > yeast > filamentous fungi [63]. By doping TiO2 nanomaterials with
metals, metal oxides, or non-metals, researchers tune the photophysics of TiO2 to modulate
its antimicrobial activity [64–68]. Apart from the photo-induced generation of ROS, TiO2
also acts as an antimicrobial agent in the absence of light, which suggest other mechanisms of
action unrelated to photocatalysis [58,69,70]. Whereas other nanomaterials such as zinc oxide
(ZnO) exhibit photo-induced antimicrobial activity [71–75], the susceptibility of UV
irradiation- and desiccation-resistant microorganisms to TiO2-based antimicrobial
technologies [58,76–78] highlights the uniqueness of TiO2 nanomaterials. Indeed, UV
irradiation and desiccation are some of the most widely used sterilisation techniques [79].
Therefore, the development of TiO2 nanomaterials offers a strategy to inactivate UV and
desiccation-resistant microorganisms on medical implants such as dental implants.
[Electrospinning TE and wound dressing scaffolds from polymer – TiO2
nanocomposites]
Due to its antimicrobial properties and quicker biodegeradability, earlier report suggests that
incorporation of TiO2 nanoparticles in scaffolds can improve adhesion of osteoblast cells on
the scaffolds [29]. Our recent report also suggests that incorporation of TiO2 nanorods can
also improve the cell adhesion, proliferation, angiogenic and wound healing potential of
electrospun polycaprolactone (PCL) scaffolds [30]. A study by Lin and co-workers have
shown that the loading of TiO2 nanoparticles in P(VDFTrFE) copolymer results in a
considerable improvement in dielectric properties compared to neat ferroelectric copolymer
[31]. Thus, incorporation of TNW in P(VDFTrFE) scaffolds may result in greater cell
adhesion and cell viability which are necessary for the success of an engineered bone
construct in tissue engineering. [Development of TiO2 Nanowire scaffolds in BTE]
Therefore, TiO2 particles have drawn more attention in the biomedical field. Nanosized
titanium can also promote protein absorption and osteoblast adhesion [24]. Thus, nano-TiO2
could be a potential material for bone repair applications.
[3D PCL Microsphere or TiO2 Nanotube composite scaffolds in Bone TE]
This review presents the various modifications of TiO2 nanoparticles to promote osteoblast
cell between the implant surface and its surrounding tissue.