Nanofibers and Nanosurfaces
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2.1 Cartilage Regeneration
Cartilage plays an integral role as connective tissue in vertebrates. As cartilage lacks a
lymphatic and blood vessel system and has meagre percent of chondrocytes (approximately 1–5% of chondrocyte of a total matrix), regeneration of cartilage becomes a
strenuous process [28, 29]. Due to confinement of chondrocytes within lacunae and
low metabolic activity, reparation of cartilage to its natural form after the damage
becomes unattainable. Surgical interventions to repair cartilage using microfracture and mosaicplasty have been the conventional line of treatment for chondral
defects [30]. However, restoration of the damaged cartilage using a biomaterial scaffold, which epitomizes extracellular matrix (ECM) along with cells has been a more
promising approach in cartilage repair than conventional methods. Apart from microarchitecture, studies show that progenitor cells’ fate can be influenced by the pore size
of the scaffold [31]. The broader mean pore size of 300 μm has unveiled enhanced
cell proliferation, chondrogenic markers than lower mean pore sizes (94 & 130 μm)
in Collagen-hyaluronic acid (CHyA) scaffolds [22]. Cells seeded in gradient scaffold
showed enhanced chondrogenesis with higher expression of GAG and ECM deposition than non-gradient scaffold [22]. Consequently, pore size plays a crucial role
in cartilage regeneration by enhancing and inducing chondrogenesis along with the
orientation of the fibres [32, 33]. Chondrocytes cultured on aligned nanofibers tend
to secrete more GAG and collagen type 2 then random nanofibers demonstrating that
orientation played an essential role in enhancing chondrogenesis [32, 34].
Cartilage is predominantly made up of collagen, proteoglycan and water; Collagen
type II accounts for about 80% of the total volume of cartilage. To mimic the natural
structure of cartilage, researchers in the past have tried fabricating electrospun mats
made up of collagen type 2 extracted from chicken cartilage [35]. However, there
is a lack of clear understanding as there are scarce reports on the in-vitro and invivo assessment of collagen type II Mats. Jiang et al. demonstrated a growth factor
free chondrogenesis of mesenchymal stem cells using composite electrospun fibres
of poly(ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I.
Interestingly, in the absence of collagen 1, the PCL-PTHF nanofibers on its own failed
to induce chondrogenesis. The difference in modulus of collagen free nanofiber may
have attributed to this behaviour.
On the other hand, a softer and low modulus (4.3Mpa) PCL-PTHF-collagen
nanofiber was able to block NF-kappa B signalling leading to chondrogenesis [36].
The nanofibers’ microenvironment and modulus have shown to regulate chondrogenesis in progenitor cells [17]. A co-axial P(LLA-CL) & collagen type 1 loaded
with rhTGF-β3 was evaluated for cartilage regeneration in trachea repair. The inner
core comprised of rhTGF-β3, while the outer layer was a blend of P(LLA-CL) &
collagen. On differentiating, stem cells on core-shell nanofiber, which was a blend of
P(LLA-CL), an approximately 0.3-fold increase in the expression of collagen type
II and a 0.1-fold increase in Sox 9 was observed. Implying that the expression of
chondrogenic genes is upregulated on the addition of collagen [37].
111
2.1 Cartilage Regeneration
Cartilage plays an integral role as connective tissue in vertebrates. As cartilage lacks a
lymphatic and blood vessel system and has meagre percent of chondrocytes (approximately 1–5% of chondrocyte of a total matrix), regeneration of cartilage becomes a
strenuous process [28, 29]. Due to confinement of chondrocytes within lacunae and
low metabolic activity, reparation of cartilage to its natural form after the damage
becomes unattainable. Surgical interventions to repair cartilage using microfracture and mosaicplasty have been the conventional line of treatment for chondral
defects [30]. However, restoration of the damaged cartilage using a biomaterial scaffold, which epitomizes extracellular matrix (ECM) along with cells has been a more
promising approach in cartilage repair than conventional methods. Apart from microarchitecture, studies show that progenitor cells’ fate can be influenced by the pore size
of the scaffold [31]. The broader mean pore size of 300 μm has unveiled enhanced
cell proliferation, chondrogenic markers than lower mean pore sizes (94 & 130 μm)
in Collagen-hyaluronic acid (CHyA) scaffolds [22]. Cells seeded in gradient scaffold
showed enhanced chondrogenesis with higher expression of GAG and ECM deposition than non-gradient scaffold [22]. Consequently, pore size plays a crucial role
in cartilage regeneration by enhancing and inducing chondrogenesis along with the
orientation of the fibres [32, 33]. Chondrocytes cultured on aligned nanofibers tend
to secrete more GAG and collagen type 2 then random nanofibers demonstrating that
orientation played an essential role in enhancing chondrogenesis [32, 34].
Cartilage is predominantly made up of collagen, proteoglycan and water; Collagen
type II accounts for about 80% of the total volume of cartilage. To mimic the natural
structure of cartilage, researchers in the past have tried fabricating electrospun mats
made up of collagen type 2 extracted from chicken cartilage [35]. However, there
is a lack of clear understanding as there are scarce reports on the in-vitro and invivo assessment of collagen type II Mats. Jiang et al. demonstrated a growth factor
free chondrogenesis of mesenchymal stem cells using composite electrospun fibres
of poly(ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I.
Interestingly, in the absence of collagen 1, the PCL-PTHF nanofibers on its own failed
to induce chondrogenesis. The difference in modulus of collagen free nanofiber may
have attributed to this behaviour.
On the other hand, a softer and low modulus (4.3Mpa) PCL-PTHF-collagen
nanofiber was able to block NF-kappa B signalling leading to chondrogenesis [36].
The nanofibers’ microenvironment and modulus have shown to regulate chondrogenesis in progenitor cells [17]. A co-axial P(LLA-CL) & collagen type 1 loaded
with rhTGF-β3 was evaluated for cartilage regeneration in trachea repair. The inner
core comprised of rhTGF-β3, while the outer layer was a blend of P(LLA-CL) &
collagen. On differentiating, stem cells on core-shell nanofiber, which was a blend of
P(LLA-CL), an approximately 0.3-fold increase in the expression of collagen type
II and a 0.1-fold increase in Sox 9 was observed. Implying that the expression of
chondrogenic genes is upregulated on the addition of collagen [37].