Gelatin–Polyvinyl Alcohol Microspheres for Controlled and Sustained Release of BMP-2 and VEGF Enhance Osteogenic and Angiogenic Cell Differentiation

(Gel-PVA0%, Gel-PVA5%, and Gel-PVA10%, respectively). The microspheres were loaded with the model protein bovine serum albumin (BSA) first. The Gel-PVA10% microspheres demonstrated significantly higher loading capacity and encapsulation efficiency, as well as lower cumulative release rate, compared to the Gel-PVA5% ones when loaded with BSA. Thus, the microspheres with the Gel-PVA10% composition were selected for loading with BMP-2 and VEGF. Kinetic studies of BMP-2 and VEGF loaded into Gel-PVA10% microspheres indicated similar results to those with BSA. The microsphere concentration with the optimal cytocompatibility was 0.5 mg/mL, and it was applied for the assessment of the osteogenic differentiation using bone marrow-derived mesenchymal stem cells (MSCs), and for the angiogenic differentiation in Wharton jelly and adipose-derived MSCs. Alkaline phosphatase activity, collagen secretion, and calcium mineralization were significantly upregulated in the presence of BMP-2-loaded microspheres, while tubular formation and PECAM-1 secretion were significantly higher in VEGF-loaded microspheres compared to the unloaded control, demonstrating their effectiveness as drug delivery carriers.