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International Journal of Bioprinting
those of articular cartilage tissue, including hardness, play a vital role in articular cartilage regeneration. BFs can
viscoelasticity, compressive modulus, shear stress, etc. be loaded onto the scaffolds by direct blending or soaking,
Artificial scaffolds serve to bear loading and remain intact surface coating, embedding micro-nano particles, etc. to
after implantation into the cartilage defect, providing space enhance the scaffold performance, such as promoting cell
for cell differentiation, proliferation, and ECM secretion. As growth, differentiation, and proliferation, and benefiting
the local tissue regenerates, the artificial scaffold degrades ECM production and homeostasis . In previous research,
[68]
at an appropriate rate, leaving no toxic residue. A recent BFs used to promote cartilage regeneration included bone
review compared the properties and limitations of different morphogenetic proteins (BMP), fibroblast growth factor
biomaterials in cartilage tissue engineering . Scaffold (FGF), transforming growth factor beta (TGF-β), insulin
[30]
materials can be broadly categorized into two groups: growth factor (IGF), NEL-like molecule-1 (NELL-1),
natural biomaterials and synthetic biomaterials, both of platelet-derived growth factor (PDGF), epidermal
which are briefly discussed below. growth factor (EGF), SOX family of transcription factors,
There has been a wealth of research on natural interleukin 1 (IL-1), vascular endothelial growth factor
biomaterials in cartilage tissue engineering, including (VEGF), hepatocyte growth factor (HGF), connective
collagen, silk fibroin, fibrin, gelatin, sodium alginate tissue growth factor (CTGF), and tumor necrosis factor
[12,30,63,69]
(SA), hydroxyapatite (HA), hyaluronic acid (HyA), alpha (TNF-α) . Platelet-rich plasma (PRP) is a
agarose, chitosan, chondroitin sulfate, and decellularized common source of BFs, containing IGF-1, PDGF, FGF,
[12]
extracellular matrix (dECM) [12,30,63] . Despite ideal and TGF-β1 . PRP can also be incorporated into bioink
biocompatibility and cytocompatibility, natural to form a 3D-printed scaffold that serves to promote
biomaterials innately possess several flaws, such as chondrogenic differentiation of MSCs and deposition
[70]
poor mechanical properties, poor thermal stability, of ECM components . In addition, the combined
inappropriate degradation rate, etc. Several strategies application of multiple BFs exerts a synergistic effect in
have been proposed to overcome the obstacles. Compared promoting TMJ fibrocartilage regeneration, such as CTGF,
[72]
[71]
with the 3D-printed scaffolds with SA alone, those with BMP-2 and TGF-β3 , BMP-2 and TGF-β1 . In general,
the combination of SA and type I collagen exhibited screening for the optimal combination of seed cells, BFs,
higher mechanical strength and effectively suppressed the and scaffold materials is one of the research foci in TMJ
dedifferentiation tendency of chondrocytes . In addition, fibrocartilage tissue engineering, and further investigations
[64]
physical and chemical modifications have been adopted are needed (Figure 2).
as an effective approach to impart favorable 3D printing
properties to the natural biomaterials (collagen, HyA, 4. TMJ disc cartilage tissue engineering
chondroitin sulfate, and dECM) .
[12]
4.1. Anatomy
Common synthetic biomaterials include polyvinyl The TMJ disc is located in the joint capsule between the
alcohol (PVA), polyethylene glycol (PEG), polycaprolactone glenoid fossa and the mandibular condyle, ensuring that
(PCL), polyurethane (PU), polyglycolic acid (PGA), poly the mandibular condyle slides smoothly anteriorly and
(D, L-lactic-co-glycolic acid) (PLGA), and poly (lactic posteriorly during mouth opening and closing (Figure 3A).
acid) (PLA) [29,30,63] . Compared with natural biomaterials, The morphological appearance of the TMJ disc is a biconcave
synthetic biomaterials are gaining popularity due to their and roughly-oval fibrocartilaginous plate, with a medial–
advantages such as better printability, structural stability, lateral axis averaging 2.36 ± 0.0609 cm and an anterior–
controlled mechanical property, and degradation rate. posterior axis averaging 1.40 ± 0.149 cm (Figure 3B) .
[73]
However, some undesirable properties of synthetic The collagen fibers form a ring around the periphery of
materials, such as bioinert and slow degradation rate, are the disc and are aligned anteroposteriorly throughout the
not conducive to articular cartilage regeneration . Recent intermediate band (Figure 3C) . The TMJ disc can be
[15]
[1]
attempts to combine natural and synthetic biomaterials to divided into four sections: an anterior band (approximately
fabricate hybrid scaffolds provide an effective approach 2 mm thick), an intermediate band (approximately 1 mm
to improve scaffold performance [65-67] . For instance, the thick), a posterior band (approximately 3 mm thick), and
PCL scaffolds modified with chitosan hydrogel were more a posterior bilaminar region . Water, collagen, and GAG
[1]
conducive to the adhesion and proliferation of synovial are three major components of the TMJ disc, accounting
MSCs than PCL scaffolds . for 74.5 ± 4.2% wet weight, 62.0 ± 11.4% dry weight, and
[67]
3.2 ± 1.4% dry weight, respectively . The distribution
[74]
3.3. Bioactive factor characteristics of the three components and the different
Growth factors (GFs), mineral ions, and intracellular biomechanical properties in different regions were
signaling molecules are collectively referred to BFs, which mentioned in the previous research .
[74]
Volume 9 Issue 5 (2023) 263 https://doi.org/10.18063/ijb.761

