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

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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.

Funding

Irish Research Council (GOIPD/2014298)

EU BlueHuman Interreg Atlantic Area Project (EAPA_151/2016)

European Research Council, European Community’s Horizon 2020 research and innovation programme, ERC Advanced Grant agreement n◦ 788753 (ReCaP)

Health Research Board of Ireland under the Health Research Awards – Patient-Oriented Research Scheme (HRA-POR-2014-569)

History

Comments

The original article is available at https://www.sciencedirect.com

Published Citation

Sheehy EJ, et al. Mechanobiology-informed regenerative medicine: dose-controlled release of placental growth factor from a functionalized collagen-based scaffold promotes angiogenesis and accelerates bone defect healing. J Control Release. 2021 10;334:96-105.

Publication Date

1 April 2021

PubMed ID

33811984

Department/Unit

  • Tissue Engineering Research Group (TERG)
  • Anatomy and Regenerative Medicine
  • Amber (Advanced Material & Bioengineering Research) Centre
  • Physiology and Medical Physics

Research Area

  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation

Publisher

Elsevier BV

Version

  • Published Version (Version of Record)