Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma

다국어 초록 (Multilingual 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.

참고문헌 (Reference)

1 Thomopoulos S, "bFGF and PDGF-BB for tendon repair: controlled release and biologic activity by tendon fibroblasts in vitro" 38 : 225-234, 2010

2 Rozman P, "Use of platelet growth factors in treating wounds and soft-tissue injuries" 16 : 156-165, 2007

3 Schnaper HW, "Type IV collagenase(s) and TIMPs modulate endothelial cell morphogenesis in vitro" 156 : 235-246, 1993

4 Tharakan S, "Transglutaminases, involucrin, and loricrin as markers of epidermal differentiation in skin substitutes derived from human sweat gland cells" 26 : 71-77, 2010

5 Moses MA, "The regulation of neovascularization of matrix metalloproteinases and their inhibitors" 15 : 180-189, 1997

6 Senger DR, "Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin" 149 : 293-305, 1996

7 Bhang SH, "Skin regeneration with fibroblast growth factor 2 released from heparin-conjugated fibrin" 33 : 845-851, 2011

8 Marui A, "Simultaneous application of basic fibroblast growth factor and hepatocyte growth factor to enhance the blood vessels formation" 41 : 82-90, 2005

9 Frechette JP, "Platelet-rich plasmas: growth factor content and roles in wound healing" 84 : 434-439, 2005

10 Baum CL, "Normal cutaneous wound healing: clinical correlation with cellular and molecular events" 31 : 674-686, 2005

11 Davidson J, "Mechanisms of accelerated wound repair using epidermal growth factor and basic fibroblast growth factor" 266 : 63-75, 1988

12 Raza SL, "Matrix metalloproteinases: pro- and anti-angiogenic activities" 5 : 47-54, 2000

13 Jeon O, "Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel" ELSEVIER SCI LTD 27 (27): 1598-1607, 2006

14 Brooks PC, "Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3" 85 : 683-693, 1996

15 Scott G, "Localization of basic fibroblast growth factor mRNA in melanocytic lesions by in situ hybridization" 96 : 318-322, 1991

16 Schultz GS, "Interactions between extracellular matrix and growth factors in wound healing" 17 : 153-162, 2009

17 김상민, "Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts" 생화학분자생물학회 42 (42): 38-46, 2010

18 Yang HS, "Heparin-conjugated fibrin as an injectable system for sustained delivery of bone morphogenetic protein-2" 16 : 1225-1233, 2010

19 Zhao B, "Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2" 281 : 23246-23253, 2006

20 Chu CL, "Heparan sulphate proteoglycans modulate fibroblast growth factor-2 binding through a lipid raft-mediated mechanism" 379 : 331-341, 2004

21 Iozzo RV, "Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena" 108 : 349-355, 2001

22 Bennett NT, "Growth factors and wound healing: Part II. Role in normal and chronic wound healing" 166 : 74-81, 1993

23 McCawley LJ, "Epidermal growth factor (EGF)- and scatter factor/hepatocyte growth factor (SF/HGF)- mediated keratinocyte migration is coincident with induction of matrix metalloproteinase (MMP)-9" 176 : 255-265, 1998

24 Froum SJ, "Effect of platelet-rich plasma on bone growth and osseointegration in human maxillary sinus grafts: three bilateral case reports" 22 : 45-53, 2002

25 Raghoebar GM, "Does platelet-rich plasma promote remodeling of autologous bone grafts used for augmentation of the maxillary sinus floor" 16 : 349-356, 2005

26 Tsay RC, "Differential growth factor retention by platelet-rich plasma composites" 63 : 521-528, 2005

27 Yang HS, "Delivery of basic fibroblast growth factor using heparin-conjugated fibrin for therapeutic angiogenesis" 16 : 2113-2119, 2010

28 Singer AJ, "Cutaneous wound healing" 341 : 738-746, 1999

29 Hebda PA, "Basic fibroblast growth factor stimulation of epidermal wound healing in pigs" 95 : 626-631, 1990

30 Enenstein J, "Basic FGF and TGF-beta differentially modulate integrin expression of human microvascular endothelial cells" 203 : 499-503, 1992

31 Hokugo A, "Augmented bone regeneration activity of platelet-rich plasma by biodegradable gelatin hydrogel" 11 : 1224-1233, 2005

32 Bir SC, "Angiogenic properties of sustained release platelet-rich plasma: characterization in vitro and in the ischemic hind limb of the mouse" 50 : 870-879, 2009

33 Senger DR, "Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins" 94 : 13612-13617, 1997

34 Tonnesen MG, "Angiogenesis in wound healing" 5 : 40-46, 2000