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

• Published in: Journal of controlled release 2021-06, Vol.334, p.96-105
• Main Authors: Sheehy, Eamon J., Miller, Gregory J., Amado, Isabel, Raftery, Rosanne M., Chen, Gang, Cortright, Kai, Vazquez, Arlyng Gonzalez, O'Brien, Fergal J.
• Format: Article
• Language: English
• Subjects: Alginate; Drug delivery; Hydroxyapatite; Microparticles; Osteogenesis; PGF; Vascularization
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.03.031

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