Tissue engineering toward temporomandibular joint disc regeneration

Abstract

Treatments for temporomandibular joint (TMJ) disc thinning and perforation, conditions prevalent in TMJ pathologies, are palliative but not reparative. To address this, scaffold-free tissue-engineered implants were created using allogeneic, passaged costal chondrocytes. A combination of compressive and bioactive stimulation regimens produced implants with mechanical properties akin to those of the native disc. Efficacy in repairing disc thinning was examined in minipigs. Compared to empty controls, treatment with tissue-engineered implants restored disc integrity by inducing 4.4 times more complete defect closure, formed 3.4-fold stiffer repair tissue, and promoted 3.2-fold stiffer intralaminar fusion. The osteoarthritis score (indicative of degenerative changes) of the untreated group was 3.0-fold of the implant-treated group. This tissue engineering strategy paves the way for developing tissue-engineered implants as clinical treatments for TMJ disc thinning.

Toward tissue-engineering of nasal cartilages

“…While the goal of engineering replacement cartilage is to achieve the functional properties of healthy native cartilage, complete biomimicry may not be necessary. For example, engineered temporomandibular joint (TMJ) disc implants with an FI of 0.42, or 42% of the native tissue's biochemical and mechanical properties, successfully resulted in healing of a native TMJ discs in an in vivo mini-pig model [111]. These results suggest that replacement tissues may not need to completely recapitulate the properties of native tissue to elicit regeneration.…”

“…Alternatively, costal cartilage may serve as an abundant source of chondrocytes whose isolation does not create further pathology or weakness in the cartilage structures of the nose. Passaged costal chondrocytes have shown the ability to form neocartilage which is capable of remodeling in vivo to promote healing [111]. While costal cartilage is used clinically as graft material, it often warps when cut into grafts.…”

“…While the goal of tissue-engineering is to create biomimetic tissues, recent work has suggested that complete biomimicry may not be necessary [111]. Recently, it was shown that neocartilage with and FI of 0.42 implanted into a partial thickness defect in a minipig temporomandibular joint disc elicited regeneration and halted osteoarthritic changes compared to empty defect controls [111].…”

Remaining Hurdles for Tissue-Engineering the Temporomandibular Joint Disc

“…Tissue-engineering uses scaffolds, cells, and various signals such as biochemical and mechanical stimuli (Figure 3). As discussed in this section, advances in materials engineering have resulted in a variety of scaffolds [34][35][36], while scaffold-free approaches, such as the selfassembling process [37][38][39], have also emerged in TMJ disc tissue-engineering. In terms of cell sources, primary chondrocytes, mesenchymal stem cells (MSCs), and cell expansion technologies are also reviewed below (Table 1).…”

“…Signals such as biochemical and mechanical stimuli for mechanical improvement of the TMJ disc (Table 1) are also discussed. This section also examines small animal models that have been used for examining the performance of these implants [36,[39][40][41][42][43].…”