An Elastic Mineralized 3D Electrospun PCL Nanofibrous Scaffold for Drug Release and Bone Tissue Engineering

Complex shaped and critical-sized bone defects have been a clinical challenge for many years. Scaffold-based strategies such as hydrogels provide localized drug release while filling complex defect shapes, but ultimately possess weaknesses in low mechanical strength alongside a lack of macroporous and collagen-mimicking nanofibrous structures. Thus, there is a demand for mechanically strong, extracellular matrix (ECM) mimicking scaffolds that can robustly fit complex shaped critical sized defects and simultaneously provide localized, sustained, multiple growth factor release. We therefore developed a composite, bi-phasic PCL/hydroxyapatite (HA) 3D nanofibrous (NF) scaffold for bone tissue regeneration by using our innovative electrospun-based thermally induced self-agglomeration (TISA) technique. One intriguing feature of our ECM-mimicking TISA scaffolds is that they are highly elastic and porous even after evenly coated with minerals and can easily be pressed to fit different defect shapes. Furthermore, the bio-mimetic mineral deposition technique allowed us to simultaneously encapsulate different type of drugs, e.g., proteins and small molecules, on TISA scaffolds under physiologically mild conditions. Compared to scaffolds with physically surface-adsorbed phenamil, a BMP2 signaling agonist, incorporated phenamil composite scaffolds indicated less burst release and longer lasting sustained release of phenamil with subsequently improved osteogenic differentiation of cells in vitro. Overall, our study indicated that the innovative press-fit 3D NF composite scaffold may be a robust tool for multiple-drug delivery and bone tissue engineering.