Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration
Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration
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DOI：
10.1126/scitranslmed.abb6683
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发表时间：
2020-10-14
影响因子：
17.1
通讯作者：
Vunjak-Novakovic, Gordana
中科院分区：
文献类型：
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作者：
Chen, David;Wu, Josephine Y.;Vunjak-Novakovic, Gordana
关节疾病可能对生活质量有害。在颅颌面区域，尤其是颞下颌关节（TMJ），对精确地功能性重建类似天然的软骨和骨组织存在未满足的需求。当前的手术方法缺乏精确性且存在并发症，常常需要多次手术。一些研究试图在不涉及软骨的情况下改进颅颌面骨移植，但软骨对颞下颌关节功能至关重要。在尤卡坦小型猪模型中针对与人尺寸相当的颞下颌关节，我们构建了自体的、在生物学和解剖学上匹配的软骨 - 骨移植物，用于修复髁突 - 升支单元（RCU），这是一种承受复杂载荷力的几何形状复杂的结构。利用图像引导的微铣削技术，从脱细胞骨基质中制造出解剖学上精确的支架，并注入自体脂肪来源的软骨生成和骨生成祖细胞。所得到的构建体在植入前在双灌注生物反应器中培养5周。植入6个月后，生物工程化的髁突 - 升支单元保持了其预先设定的解剖结构，并在下方的骨上再生出全厚度、分层且机械性能良好的软骨，其程度优于仅由自体骨构建的移植物或无细胞支架。对植入细胞的追踪以及并行的生物反应器研究使我们对软骨和骨再生的进程有了更多的了解。这项研究证明了使用解剖学上精确的、自体的、有活性的软骨 - 骨移植物进行颞下颌关节再生以实现功能性、个性化全关节置换的可行性。纳入相邻组织，如软结缔组织和颞下颌关节盘，可进一步扩展工程化髁突 - 升支单元与宿主的功能整合。
Joint disorders can be detrimental to quality of life. There is an unmet need for precise functional reconstruction of native-like cartilage and bone tissues in the craniofacial space and particularly for the temporomandibular joint (TMJ). Current surgical methods suffer from lack of precision and comorbidities and frequently involve multiple operations. Studies have sought to improve craniofacial bone grafts without addressing the cartilage, which is essential to TMJ function. For the human-sized TMJ in the Yucatan minipig model, we engineered autologous, biologically, and anatomically matched cartilage-bone grafts for repairing the ramus-condyle unit (RCU), a geometrically intricate structure subjected to complex loading forces. Using image-guided micromilling, anatomically precise scaffolds were created from decellularized bone matrix and infused with autologous adipose-derived chondrogenic and osteogenic progenitor cells. The resulting constructs were cultured in a dual perfusion bioreactor for 5 weeks before implantation. Six months after implantation, the bioengineered RCUs maintained their predefined anatomical structure and regenerated full-thickness, stratified, and mechanically robust cartilage over the underlying bone, to a greater extent than either autologous bone-only engineered grafts or acellular scaffolds. Tracking of implanted cells and parallel bioreactor studies enabled additional insights into the progression of cartilage and bone regeneration. This study demonstrates the feasibility of TMJ regeneration using anatomically precise, autologous, living cartilage-bone grafts for functional, personalized total joint replacement. Inclusion of the adjacent tissues such as soft connective tissues and the TMJ disc could further extend the functional integration of engineered RCUs with the host.