Polymeric nanofibrous scaffolds laden with cell-derived extracellular matrix for bone regeneration

Bone tissue engineering aims to alleviate the shortage of available autograft material and the biological/mechanical incompatibility of allografts through fabrication of bioactive synthetic bone graft substitutes. However, these substitute grafting materials have insufficient biological potency that limits their clinical efficacy in regenerating large defects. Extracellular matrix, a natural tissue scaffold laden with biochemical and structural cues regulating cell adhesion and tissue morphogenesis, may be a versatile supplement that can extend its biological functionality to synthetic grafts. Embedding decellularized extracellular matrix (dECM) into synthetic polymers offers a promising strategy to enhance cellular response to synthetic materials, mitigate physical and mechanical limitations of dECMs, and improve clinical utility of synthetic bone grafts. Enriched with dECM biochemical cues, synthetic polymers can be readily fabricated into complex biocomposite grafts that mimic bone structure and stimulate endogenous cells to regenerate bone. In this study, cell-derived dECMs from osteoblast and endothelial cells were incorporated into polycaprolactone (PCL) solutions for electrospinning dual-layer nanofibrous scaffolds with osteogenic and vascular cues. The study examined the bioactivity of dECM scaffolds in osteoblast cultures for cell number, mineral deposits, and osteogenic markers, as well as regeneration of cortical bone defect in a rat femur. Scaffolds with osteoblast dECM had a significantly robust osteoblast proliferation, Alizarin Red staining/concentration, and osteopontin-positive extracellular deposits. Implanted scaffolds increased bone growth in femoral defects, and constructs with both osteogenic and vascular cues significantly improved cortical width. These findings demonstrate the potential to fabricate tailored biomimetic grafts with dECM cues and fibrous architecture for bone applications.