Page 277 - IJB-9-5

International Journal of Bioprinting

HA biphasic scaffold. The PGA/PLA scaffold seeded with between the scaffold and the natural tissue, and potential
chondrocytes and the PCL/HA scaffold seeded with bone immune response induced by the scaffold, etc. [30,92,93]
MSCs formed a biphasic scaffold (Figure 5E–G). Scanning Several recent reviews have discussed potential solutions
electron micrographs showed a difference in microscopic to these challenges, such as hybrid scaffolds composed of
structure between the two phases of the scaffold. Twelve synthetic and natural materials, chemical or non-chemical
weeks after subcutaneous implantation into the dorsum modification of biomaterials, etc. [30,92,93]
in mice, smooth, continuous, cartilage-like tissue with Some additional barriers in TMJ tissue engineering are
approximately 1.2-mm thickness covered the surface of the related to the anatomical structure and location of the TMJ.
scaffold. Histological examination revealed the regenerated Although the PCL scaffolds that mimic the organization of
cartilage and the interface between the regenerated the collagen fibers of the TMJ disc have been constructed
cartilage and the subchondral bone. Notably, the auricular by 3D printing techniques, the mechanism by which the
chondrocytes seeded in the PGA/PLA scaffold may have internal structure of the PCL scaffold regulates cellular
been responsible for the reduction of the bone formation behavior and regenerates articular disc tissue remained
in the microchannels of the PCL/HA scaffolds as bone unclear. The internal structure of the scaffolds has been
mesenchymal stem cells (BMSCs) have the capacity of demonstrated to affect the mechanical stability of the
biphasic differentiation. Therefore, further research is PCL scaffold in vitro, and therefore, further in vivo
needed to focus on reducing the effect of chondrocytes studies are needed . In addition, the immunological
[65]
(including both auricular and articular chondrocytes) on implications associated with 3D-printed TMJ tissue-
BMSCs to enhance osteochondral interface formation. engineered products have not been fully investigated in
Recent research on 3D-printed gelatin scaffolds large animal models. Furthermore, given the proximity
has provided new guidance on scaffold fabrication for of the TMJ to the brain, stringent safety guidelines need
[90]
mandibular condylar engineering. Helgeland et al. to be established to facilitate the translation of 3D-printed
compared the chemical, mechanical, biological, and TMJ tissue-engineered products from research to clinical
physical properties of the 3D-printed gelatin scaffolds applications and to reduce the risk of medical accidents .
[94]
crosslinked with dehydrothermal (DHT), ribose glycation, Another challenge is that the existing research on TMJ
and both. Compared with the DHT-crosslinked and tissue engineering has employed 3D-printed scaffolds
ribose-crosslinked scaffolds, dual-crosslinked scaffolds to repair either the TMJ disc or the mandibular condyle
showed the largest degree of crosslinking, moderate only. However, in clinical practice, it is common for
compressive modulus, lowest swelling ratio, highest osteoarthritis to cause fibrocartilage defects in both the
resistance to hydrolytic and enzymatic degradation, TMJ disc and mandibular condyle at the same time . It is
[7]
greatest cell proliferation, and lowest expression of the therefore necessary to establish animal models (e.g., goats,
hypertrophy-related collagen 10 gene (COL10). In another minipigs) with articular defects in both the TMJ disc and
study by Helgeland et al. , when 3D-printed gelatin mandibular condyle, based on which the synergistic effects
[91]
scaffolds were crosslinked by genipin, the stability, swelling, of the 3D-printed scaffolds used to repair the TMJ disc and
and mechanical properties of gelatin were improved. mandibular condyle need to be investigated.
Unfortunately, the aforementioned improvement in
3D-printed gelatin scaffolds was only demonstrated in 6.2. Critical need for support and guidance in TMJ
vitro, so in vivo studies are needed to further evaluate the tissue engineering
effect of modified 3D-printed gelatin scaffolds. Partly due to the lack of financial and academic support
for TMJ tissue engineering, attempts to promote TMJ
6. Challenges and prospects fibrocartilage regeneration using 3D-printed scaffolds
have been relatively limited so far. There is a large gap
6.1. Current challenges between knee and TMJ tissue engineering in terms of
3D printing is currently at an early stage of development research funding, academic publications, and research
in TMJ tissue engineering, and as such, a large number of translation, despite similarities in the incidence of knee and
challenges remain unresolved, which can be divided into TMJ osteoarthritis . There is a lack of sufficient primary
[95]
the general cartilage tissue-engineering challenges and the research in TMJ tissue engineering, resulting in a paucity of
TMJ-specific local challenges. TMJ tissue-engineered products and human clinical trials.
General challenges faced by 3D-printed scaffolds The limited number of human clinical trials results in the
used for articular cartilage regeneration at different sites low availability of marketed TMJ products and little to no
include a mismatch between the mechanical properties of commercial support for TMJ products. This exacerbates
the scaffold and the natural cartilage, lack of integration the lack of industrial guidance and research funding for the

Volume 9 Issue 5 (2023) 269 https://doi.org/10.18063/ijb.761