Curcumin-loaded nanofilm generating avascular niche to stabilize in vivo ectopic chondrogenesis of BMSC

Abstract

Bone marrow stem cells (BMSCs) engineered cartilage (BEC) represent a promising substitute for cartilage repairment. However, the in vitro-generated BEC was prone to endochondral ossification after in vivo ectopic implantation, significantly hindering its clinical translation. Increasing evidence suggested that vascularization essentially led to endochondral ossification of BEC in the subcutaneous microenvironment. Herein, a potent antiangiogenic agent of curcumin (Cur) was successfully laden into a polycaprolactone (PCL) to prepare a Cur/PCL nanofilm. The in vitro findings of this study showed that after co-culturing with human umbilical vein endothelial cells, Cur was sustained-released from Cur/PCL and suppressed the formation of tubes. Further, the Cur/PCL nanofilm was cytocompatible when recolonized with BMSCs. BMSCs were seeded into a porous polyglycolic acid scaffold and underwent 4 weeks of in vitro chondrogenic culture to successfully produce BEC. Thereafter, the BEC is encapsulated by the Cur/PCL nanofilm and subcutaneously implanted into nude mice for 4 weeks. The localized and sustained Cur release could inhibit vascular invasion via the antagonization of vascular endothelial growth factor signal, and stabilizes the cartilaginous phenotype. The results confirmed that Cur/PCL nanofilms protected BEC from vascularization and endochondral ossification in vivo, thus, indicating that the encapsulation of BEC using an anti-angiogenic nanofilm could be used as a novel strategy for modulating the in vivo ectopic BEC stability to repair cartilage defects.