摘要
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 in situ 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 im-plications for treating extreme-large osteochondral defects.
基金
supported by the National Key Research and Devel-opment Program of China(2023YFB3813000)
the National Natural Science Foundation of China(T2121004,92268203,82301016)
the Key Science and Technology Plan Projects in Jinhua City,2023-3-039.
