Delivery of epidermal growth factor receptor inhibitor via a customized collagen scaffold promotes meniscal defect regeneration in a rabbit model

摘要

Graphical abstract Display Omitted Abstract Meniscal injury is one of the most common knee joint injuries, which remains an intractable challenge in clinical practice to date. Aberrant epidermal growth factor receptor (EGFR) activation levels in both human and mice menisci following injury, prompted us to investigate the functional role of EGFR by utilizing an inducible cartilage-specific EGFR-deficient mouse model. We demonstrated that conditional EGFR deletion in mice resulted in increased partial meniscectomy-induced ECM production within the meniscus, which is comparable to utilization of the small molecule EGFR inhibitor, gefitinib, to block EGFR activity. Here, we combined intra-articular delivery of gefitinib with an implanted customized collagen scaffold to substitute for lost meniscal tissue, as well as to promote meniscal regeneration and prevent osteoarthritis (OA) progression in a rabbit meniscectomy model. Statement of Significance The main novelty of this study is the finding of a new application for small molecule EGFR inhibitor in meniscal injury therapy. This study also highlights the importance of using a customized collagen scaffold to provide robust mechanical strength and effectively promote meniscus regeneration. In summary, our study finds that intra-articular delivery of gefitinib together with implantation of a customized, multi-layer collagen scaffold not only enhanced meniscal regeneration, but also protected articular cartilage from degeneration in rabbit model. These results provide valuable insight for meniscal tissue engineering studies and clinical practice.