Curcumin-loaded porous scaffold: an anti-angiogenic approach to inhibit endochondral ossification

Bone marrow stem cells (BMSCs) are recognized for their robust proliferative capabilities and multidirectional differentiation potential. Ectopic endochondral ossification of BMSC-generated cartilage in subcutaneous environments is a concern associated with vascularization. Hence, devising a reliable strategy to inhibit vascularization is crucial. In this study, an anti-angiogenic drug, curcumin (Cur), was encapsulated into gelatin to create a porous Cur/Gelatin scaffold, with the aim of inhibiting vascular invasion and preventing endochondral ossification of BMSC-regenerated cartilage. In vitro wound healing tests demonstrated that a 30 μM Cur solution could inhibit the migration and growth of human umbilical vein endothelial cells without impeding BMSCs migration and growth. Compared to the gelatin scaffold, our findings verified that the Cur/Gelatin scaffold significantly inhibited vascular invasion after being subcutaneously implanted into rabbits for 12 weeks, as evidenced by gross observation and immunofluorescence CD31 staining. Moreover, both the porous gelatin and Cur/Gelatin scaffolds were populated with BMSCs and underwent in vitro chondrogenic cultivation to produce cartilage, followed by subcutaneous implantation in rabbits for 12 weeks. Histological examinations (including HE, Safranin-O/Fast Green, toluidine blue, and immunohistochemical COL II staining) revealed that the BMSC-generated cartilage in the gelatin group exhibited prominent endochondral ossification. In contrast, the BMSC-generated cartilage in the Cur/Gelatin group maintained cartilage features, such as cartilage matrix and lacunar structure. This study suggests that Cur-loaded scaffolds offer a reliable platform to inhibit endochondral ossification of BMSC-generated cartilage.