Press-Fit 3D Electrospun Porous Nanofibrous Scaffolds for Bone Tissue Engineering

Objectives: To repair critical-sized and complex-shaped bone defects has presented many clinical challenges to biomaterials development including but not limited to: chemical composition, mechanical properties, and capability for sustained drug release. Biomaterials-based drug delivery systems commonly utilized for repairing irregular-shaped defects are made of materials such as hydrogels, which however possess poor mechanical strength and lack macro-porous structures required for support of cell/tissue growth, leading to a desire for mechanically strong and highly porous materials capable of drug release for bone repair. Our previous studies indicated that the thermally induced self-assembled (TISA) 3D electrospun nanofibrous (NF) scaffolds are efficient for critical-sized defect repair, with high elasticity and mechanical properties well suited for bone tissue engineering. The elasticity of TISA scaffolds could be retained after coating with hydroxyapatite (HA), suggesting this technique could possess press-fit characteristics, fitting complex-shaped defects while providing sustained release from HA-incorporated drug.
Methods: TISA-generated PCL scaffolds were coated via simulated body fluid, where the small molecule phenamil, a BMP2 activator, was used to compare sustained release profile versus physically adsorbed drug. Scaffolds were characterized by SEM for morphological structures, and AFM for local mechanical properties. Sustained release profiles of encapsulated phenamil were compared to physically adsorbed phenamil and measured by absorbance. In addition to phenamil, we also demonstrated that protein (e.g., Bovine Serum Albumin) could be sustained release using the same strategy.
Results: Ubiquitous coating of HA on electrospun nanofibers was examined by SEM, indicating the ability of encapsulated drug to penetrate completely within scaffolds, and the resulting release curves demonstrated sustained release up to 21 days, compared to quick burst release of physically adsorbed drug.
Conclusions: Osteogenic differentiation of C2C12 cells showed a significant increase in alkaline phosphatase activity and early marker Runx2 gene expression, indicating this composite scaffold may represent an excellent approach to promote critical-sized defect bone repair.