Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration

作者：David Chen, Josephine Y. Wu, Kelsey M. Kennedy, Keith Yeager, Jonathan Bernhard, Johnathan Ng, Brandon Zimmerman, Samuel T. Robinson, Krista M. Durney, Courtney Shaeffer, Olaia F. Vila, Catherine Takawira, Jeffrey M. Gimble, Xiao Guo, Gerard A. Ateshian, Mandi J. Lopez, Sidney B. Eisig, Gordana Vunjak‐Novakovic · 发表于：Science Translational Medicine · 年份：2020 · DOI：10.1126/scitranslmed.abb6683 · 被引用次数：57 · 研究领域：Periodontal Regeneration and Treatments、Osteoarthritis Treatment and Mechanisms、Dental Implant Techniques and Outcomes

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...