Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential.pdf (3.46 MB)

Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential

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posted on 03.06.2020, 08:16 by Ronaldo Jose Farias Correa Do Amaral, Noora M. A. Zayed, Elena I. Pascu, Brenton Cavanagh, Chris Hobbs, Francesco Santarella, Christopher R. Simpson, Ciara Murphy, Rukmani Sridharan, Arlyng Gyveth Gonzalez Vazquez, Barry O'Sullivan, Fergal O'Brien, Cathal J. Kearney
Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFβ) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.

Funding

Science Foundation Ireland (SFI) and the European Regional Development Fund under Grant 13/RC/2073

European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 713690

K has received funding for this project from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 758064

CK and FO'B have received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 659715; the Science Foundation Ireland (SFI) under Grant SFI/12/RC/2278

CH and the Advanced Microscopy Laboratory received funding from SFI AMBER, SFI PIYRA, ERC StG 2D Nanocaps, ERC CoG 3D2DPrint, Horizon2020 NMP Co-Pilot.

History

Comments

This article was first published in Frontiers in Bioengineering and Biotechnology at https://doi.org/10.3389/fbioe.2019.00371

Published Citation

Do Amaral RJFC, Zayed NMA, Pascu EI, Cavanagh B, Hobbs C, Santanarella F, Simpson CR, Murphy CM, Sridharan R, Gonzalez-Vazquez A, O’Sullivan B, O’Brien FJ, Kearney CJ. Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential. Frontiers in Bioengineering and Biotechnology. 2019;7:371.

Publication Date

03/12/2019

PubMed ID

31921799

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