State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
AO Research Institute Davos, Davos, Switzerland.
Acta Biomater. 2023 Mar 15;159:173-187. doi: 10.1016/j.actbio.2023.01.042. Epub 2023 Jan 26.
Currently, no effective disc reconstruction treatment strategy is clinically available for temporomandibular joint (TMJ) disc-related diseases. To address this, we developed a prosthesis construct with laser-drilled decellularized natural disc reinforced by polycaprolactone, which mimics the natural morphology, and structural, biomechanical and biological property of the TMJ disc. The construct demonstrated good biocompatibility, safety and immunological tolerance both in vitro, and in a rat subcutaneous model. During 6 months implantation in an allogeneic rabbit TMJ disc reconstruction model, the disc prosthesis maintained its integrity, collagen fiber-orientation, mechanical property, joint structural stability and prevented articular cartilage and bone from damage. Furthermore, the "upgraded" disc prosthesis obtained from decellularized porcine disc was implanted into a goat TMJ disc reconstruction model. The xenograft prosthesis, with strength and viscoelasticity similar to a natural TMJ disc, was able to restore the structure and function of TMJ up to 20 weeks. These results demonstrate the translational feasibility of an allogeneic or xenogeneic decellularized disc prosthesis for treatment of advanced TMJ disc-related diseases. STATEMENT OF SIGNIFICANCE: This study makes a significant contribution to TMJ disc disease treatment both in theory and in clinics, because: (1) it provided an innovative approach to prepare an artificial TMJ disc with decent mechanical properties and long-term condyle-protecting effect; (2) it specified an advanced decellularized method for fibrocartilage decellularization and xenograft application; (3) it developed a facile and reproducible TMJ disc reconstruction model not only for middle size animal but also for large animal study; (4) the comprehensive and unreported biomechanical tests on the natural TMJ discs would act as a valuable reference for further research in the field of artificial TMJ disc materials or TMJ disc tissue engineering; (5) it suggested a potential treatment for patients with severe TMJ diseases that were commonly met but difficult to treat in clinics.
目前,临床上尚无有效的颞下颌关节(TMJ)盘相关疾病的盘重建治疗策略。为此,我们开发了一种由聚己内酯增强的激光钻孔去细胞天然盘假体,该假体模拟了 TMJ 盘的自然形态、结构、生物力学和生物学特性。该假体在体外和大鼠皮下模型中表现出良好的生物相容性、安全性和免疫耐受性。在同种异体兔 TMJ 盘重建模型中植入 6 个月期间,盘假体保持完整,胶原纤维取向、力学性能、关节结构稳定性,并防止关节软骨和骨损伤。此外,从去细胞猪盘获得的“升级”盘假体被植入山羊 TMJ 盘重建模型。异种移植物假体具有与天然 TMJ 盘相似的强度和粘弹性,能够恢复 TMJ 的结构和功能,最长可达 20 周。这些结果表明,同种异体或异种去细胞盘假体用于治疗晚期 TMJ 盘相关疾病具有转化可行性。
本研究在理论和临床方面都为 TMJ 盘疾病的治疗做出了重要贡献,原因如下:(1)它提供了一种创新的方法来制备具有良好机械性能和长期保护髁突作用的人工 TMJ 盘;(2)它指定了一种先进的纤维软骨去细胞化和异种移植应用的去细胞化方法;(3)它开发了一种简便且可重复的 TMJ 盘重建模型,不仅适用于中型动物,也适用于大型动物研究;(4)对天然 TMJ 盘进行的全面且未报告的生物力学测试将为人工 TMJ 盘材料或 TMJ 盘组织工程领域的进一步研究提供宝贵参考;(5)它为临床上常见但难以治疗的严重 TMJ 疾病患者提供了一种潜在的治疗方法。