Mechanobiology-informed regenerative medicine: Dose-controlled release of placental growth factor from a functionalized collagen-based scaffold promotes angiogenesis and accelerates bone defect healing

Leveraging the differential response of genes to mechanical loading may allow for identification novel therapeutics and we have recently established placental growth factor (PGF) as a mechanically augmented gene which promotes angiogenesis at higher doses osteogenesis lower doses. Herein, sought execute mechanobiology-informed approach regenerative medicine by designing functionalized scaffold dose-controlled delivery PGF hypothesized would be capable promoting regeneration critically-sized bone defects. Alginate microparticles collagen/hydroxyapatite scaffolds were shown effective PGF-delivery platforms, demonstrated their capacity promote in vitro. A release profile consisting an initial burst followed sustained was achieved incorporating PGF-loaded into already containing directly incorporated PGF. Although this PGF-functionalized only modest increase osteogenic vitro, robust observed after implantation rat calvarial defects, indicating that dose-dependent effect can harnessed alternative multi-drug systems both pro-angiogenic pro-osteogenic cues. This provides framework strategies aimed identifying evaluating scaffold-based applications.