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

Autor:	do Amaral RJFC; Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Centre for Research in Medical Devices (CURAM), National University of Ireland Galway, Galway, Ireland., Zayed NMA; Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates., Pascu EI; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland., Cavanagh B; Cellular and Molecular Imaging Core, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland., Hobbs C; Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.; Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin (TCD), Dublin, Ireland., Santarella F; Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland., Simpson CR; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland., Murphy CM; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland., Sridharan R; Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland., González-Vázquez A; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland., O'Sullivan B; Beaumont Hospital, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland., O'Brien FJ; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Centre for Research in Medical Devices (CURAM), National University of Ireland Galway, Galway, Ireland.; Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland., Kearney CJ; Kearney Lab, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.; Advanced Materials and Bioengineering Research (AMBER) Centre, Dublin, Ireland.; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2019 Dec 03; Vol. 7, pp. 371. Date of Electronic Publication: 2019 Dec 03 (Print Publication: 2019).
DOI:	10.3389/fbioe.2019.00371
Abstrakt:	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. (Copyright © 2019 do Amaral, Zayed, Pascu, Cavanagh, Hobbs, Santarella, Simpson, Murphy, Sridharan, González-Vázquez, O'Sullivan, O'Brien and Kearney.)
Databáze:	MEDLINE
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