A bilayer collagen scaffold with bevacizumab stabilizes chondrogenesis and promotes osteochondral regeneration

Abstract

Stem cell-based tissue engineering represents a promising therapeutic for osteochondral restoration. A bilayer scaffold with an appropriate niche can simultaneously induce stem cells for cartilage and bone regeneration. However, the engineered cartilage derived from stem cells tends to ossify due to vascular invasion. Bevacizumab possesses pronounced anti-angiogenic activity by inhibiting the vascular endothelial growth factor (VEGF) signaling pathway. Here, we prepared a bilayered collagen-based scaffold with bevacizumab loaded in the upper layer (Bev/collagen) to promote stable osteochondral regeneration. We show that this Bev/collagen scaffold possesses suitable bevacizumab release kinetics (nearly 100% at 7 weeks) to achieve the anti-angiogenic activity and prevents vascular invasion. When colonized with bone marrow stem cells, it also exhibited cytocompatibility to support in vitro cartilage regeneration. The engineered cartilage successfully maintained cartilaginous property in the upper layer after subcutaneous implantation in nude mice for 4 weeks and in situ transplantation in a rabbit osteochondral defect model for 8 weeks, resulting in satisfactory osteochondral regeneration. This study highlights a new avenue for osteochondral regeneration by leveraging anti-angiogenesis activity.