Abstract
Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.
Highlights
Clinical interest in platelet-rich plasma (PRP) stems from its potential as a safe and attainable source of the wide range of growth factors (GFs) and cytokines required in physiological tissue repair
Various heparin-conjugated biomaterials have been utilized as a GF delivery vehicle (Jeon et al, 2006; Thomopoulos et al, 2010; Yang et al, 2010a, 2010b) by mimicking the physiological function of heparin sulfate (HS), which is abundant in the extracellular matrix (ECM)
Among the GFs contained in PRP, release of platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF), and FGF2 was evaluated since these GFs can bind to heparin in heparin-conjugated fibrin (HCF) (Yang et al, 2010a, 2010b) and are known to stimulate angiogenesis (Yang et al, 2010a), which promotes skin wound healing (Tonnesen et al, 2000)
Summary
Clinical interest in platelet-rich plasma (PRP) stems from its potential as a safe and attainable source of the wide range of growth factors (GFs) and cytokines required in physiological tissue repair. HCF can provide superior tissue regeneration properties to fibrin-based carriers by releasing bone morphogenic protein-2 (Yang et al, 2010b) and FGF2 (Yang et al, 2010a) for long time periods. We first examined the release kinetics of GFs contained in PRP from HCF and fibrin-based carriers. Among the GFs contained in PRP, release of PDGF-BB, VEGF, and FGF2 was evaluated since these GFs can bind to heparin in HCF (Yang et al, 2010a, 2010b) and are known to stimulate angiogenesis (Yang et al, 2010a), which promotes skin wound healing (Tonnesen et al, 2000). Activities of GFs released from the carriers were evaluated by determining the growth of human dermal fibroblasts (HDFs) cultured in the presence of GF delivery systems. Skin wound healing was evaluated based on histology, morphometric analysis, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR)
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