Living joint prosthesis with in-situ tissue engineering for real-time and long-term osteoarticular reconstruction

The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge. Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate poor integration with host tissues. This often results in complications such as abnormal bone absorption and prosthetic loosening, which may necessitate secondary revisions. Here, we propose a paradigm-shifting "living prosthesis" strategy that combines a customized 3D-printed hollow titanium humeral prosthesis with engineered bone marrow condensations presenting bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β3 (TGF-β3) from encapsulated silk fibroin hydrogels. This innovative approach promotes <i>in situ</i> endochondral defect regeneration of the entire humeral head while simultaneously providing immediate mechanical support. In a rabbit model of total humerus resection, the designed "living prosthesis" achieved weight, macroscopic and microscopic morphologies that were comparable to those of undamaged native joints at 2 months post-implantation, with organized osteochondral tissues were regenerated both around and within the prosthesis. Notably, the "living prosthesis" displayed significantly higher osteo-integration than the blank metal prosthesis did, as evidenced by a 3-fold increase in bone ingrowth and a 2-fold increase in mechanical pull-out strength. Furthermore, the "living prosthesis" restored joint cartilage function, with rabbits exhibiting normal gait and weight-bearing capacity. The successful regeneration of fully functional humeral head tissue from a single implanted prosthesis represents technical advance in designing bioactive bone prosthesis, with promising implications for treating extreme-large osteochondral defects.