Remaining Hurdles for Tissue-Engineering the Temporomandibular Joint Disc

Abstract

The temporomandibular joint (TMJ) disc, a fibrocartilaginous structure between the mandible and temporal bone, is implicated in temporomandibular disorders (TMDs). TMDs symptomatically affect approximately 25% of the population, of which 70% have internal derangement of the disc. Treatments lack efficiency, motivating novel therapies, including tissue-engineering toward TMJ disc regeneration. Recent developments in scaffold-based or scaffold-free approaches, cell sources, and biochemical and mechanical stimulation have resulted in constructs exhibiting native tissue mechanics. Safety and efficacy of tissue-engineered implants have shown promising results in orthotopic animal studies. However, many hurdles need to be overcome in tissue-engineering approaches, and clinical and regulatory pathways. Future studies present an opportunity for clinicians and researchers to work together toward safe and effective clinical trials.

Keywords: temporomandibular joint disc.

Figure 1:. TMJ disc anatomy.

(A) Depending on the open or closed position of the joint, the TMJ disc is situated between the mandibular condyle and the articular eminence-mandibular fossa region. In this sagittal view, the disc is held in place by disc attachments, present at all angles (e.g., lateral, medial, posterior, anterior), surrounding the disc. The joint is separated into two joint capsules delineated by the TMJ disc. (B) The disc is regionally composed of two bands in the anterior and posterior portions of the disc. The middle portion of the disc is referred to as the intermediate zone. S – superior, I – inferior, A – anterior, P – posterior, M – medial, L – lateral.

Figure 2:. Internal derangement of the TMJ disc.

(A) A healthy closed jaw position is shown. (B) The most common type of internal derangement is shown, where the disc is displaced anteriorly. Progression of the joint in this configuration often causes (C) disc thinning and (D) eventual disc perforation.

Figure 3:. Tissue-engineering paradigm of TMJ disc constructs.

Combination of an appropriate cell source and scaffold-based or scaffold-free approaches can be used for fabrication of a TMJ disc construct (upper panels). Via the application of various biochemical and mechanical stimuli, an enhanced, biomimetic construct can be tissue-engineered (lower panels). ACs – hyaline articular chondrocytes, MSCs – mesenchymal stem cells, MCs – knee meniscus cells, LBL – layer-by-layer, 3D – three-dimensional, C-ABC – chondroitinase ABC, LOXL2 – lysyl oxidase-like 2, TGF-β – transforming growth factor beta.

Figure 4:. Toward the path to translation.

(A) Constructs should be tailored for human discal pathologies and size, potentially increasing in both area and thickness. (B) Prior to translation through regulatory bodies such as the FDA, animal studies must be performed in proper large animals, such as the minipig. (C) Novel surgical procedures for disc repair and disc replacement need to be developed as well. (D) Additional studies also need to be performed to examine local and systemic responses to tissue-engineered TMJ discs in the orthotopic environment. Upon overcoming these hurdles, the TMJ disc tissue-engineering field will be closer to human clinical trials.

Figure 5:. The intralaminar fenestration surgical technique.

(A-B) Through a preauricular incision, the TMJ was exposed. (C-E) Surgeons fileted the disc open with a scalpel, and (F-G) created a one-sided thinning defect via a biopsy punch. (H) A tissue-engineered disc was placed between the two laminae and (I) sutured back together. Sutures attached to the side of the disc instead of on the articulating surfaces allowed for continued loading of the TMJ disc while healing; this placement avoided possible stress concentrations and resulting degeneration. (J) The lateral attachment is recreated by use of an anchoring system. From Vapniarsky, et al., 2018 [39]. Reprinted with permission from AAAS.