A 3D-Printed BCP/PLGA-PEG-PLGA Scaffold for LNC000133-Loaded BMSC-Derived Exosome Delivery Promotes Repair of Steroid-Induced Osteonecrosis of the Femoral Head

Dysfunction of bone marrow mesenchymal stem cells (BMSCs) and impaired exosome-mediated intercellular communication are recognized as critical contributors to the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH), although the underlying mechanisms remain incompletely understood. Moreover, the development of novel biomaterials and therapeutic strategies capable of improving SONFH treatment remains an urgent clinical priority. Previous studies have demonstrated that LNC000133-modified exosomes derived from human BMSCs (hBMSCs) promote osteoblastic differentiation and enhance exosome uptake by osteoblasts, thereby exerting therapeutic effects in SONFH. Building on these findings, we developed a 3D-printed biphasic calcium phosphate (BCP)/poly (lactic-co-glycolic acid) (PLGA)- polyethylene glycol (PEG)-PLGA scaffold loaded with LNC000133-modified hBMSC-derived exosomes (LNC000133-Exos) to facilitate the clinical translation of this gene-based therapeutic approach for SONFH. The biological effects of this composite scaffold on hBMSCs were subsequently evaluated in vitro. Furthermore, the BCP/PLGA-PEG-PLGA scaffold loaded with LNC000133-Exos was applied for the treatment of SONFH in a rabbit model. Our results demonstrated that transplantation of the LNC000133-Exos-loaded BCP/PLGA-PEG-PLGA scaffold markedly enhanced bone repair and structural reconstruction within the necrotic region of the femoral head in vivo. Collectively, these findings indicate that the BCP/PLGA-PEG-PLGA scaffold and LNC000133 synergistically promote hBMSC proliferation and osteogenic differentiation while suppressing adipogenic differentiation, providing a strong theoretical foundation and a promising therapeutic strategy for targeted SONFH treatment.