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

JOURNAL OF CONTROLLED RELEASE

卷:334

Article

Sheehy, Eamon J.^1,2,3,4  Miller, Gregory J.^1,2  Amado, Isabel^1,2  Raftery, Rosanne M.^1,2  Chen, Gang⁵  Cortright, Kai^1,2  Vazquez, Arlyng Gonzalez^1,2  O'Brien, Fergal J.^1,2,3,4 

[1] Royal Coll Surgeons Ireland, Dept Anat & Regenerat Med, Tissue Engn Res Grp TERG, Dublin, Ireland

[2] Trinity Coll Dublin, Trinity Biomed Sci Inst, Trinity Ctr Biomed Engn, Dublin, Ireland

[3] Royal Coll Surgeons Ireland, Adv Mat & Bioengn Res Ctr AMBER, Dublin, Ireland

[4] Trinity Coll Dublin, Dublin, Ireland

[5] Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Ctr Study Neurol Disorders, Microsurg Res & Training Facil MRTF, Dublin, Ireland

关键词: Drug delivery;    Vascularization;    Osteogenesis;    PGF;    Alginate;    Microparticles;    Hydroxyapatite;   

DOI  :  10.1016/j.jconrel.2021.03.031

来源: Elsevier

【 摘 要 】

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 multidrug 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.

【 授权许可】

Free