Topical Application of Recombinant Platelet-derived Growth Factor Increases the Rate of Healing and the Level of Proteins That Regulate This Response

Overview

Journal Int Wound J

Specialties Emergency Medicine
Orthopedics

Date 2013 Oct 15

PMID 24118782

Citations 9

Authors

Santosh Gowda

David A Weinstein

Timothy D Blalock

Kavita Gandhi

Bruce A Mast

Gloria Chin

Gregory S Schultz

Affiliations

Soon will be listed here.

Abstract

A bipedicle ischaemic rat skin flap model was used to study the effects of daily topical applications of platelet-derived growth factor (PDGF) on the healing of ischaemic wounds. Levels of tumour necrosis factor-alpha (TNFA), interleukin 1-beta (IL1B) and both the latent and active forms of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were measured. Full-thickness wounds were made on a total of 72 adult male Sprague-Dawley rats. Each group of 18 rats with normal and ischaemic wounds received either vehicle or 0·01% recombinant PDGF-BB. Additional applications were made on the wounds on a daily basis. Wound areas were measured at 0, 1, 3, 5, 7 9 and 13 days after wounding. Ischaemia caused a delay in wound healing as well as an increase in TNFA, IL1B and both the pro and active forms of MMP2 and MMP9. PDGF accelerated the rate of wound healing in both normal and ischaemic wounds and negated the effect of ischaemia. PDGF reduced the TNFA concentration in both normal and ischaemic wounds, and the rate of wound healing closely resembled the pattern of TNFA protein expression. PDGF also reduced both the magnitude and duration of the increases in IL1B and both the pro and active forms of MMP2 and MMP9 induced by ischaemia.

Citing Articles

Recent advances in decellularized biomaterials for wound healing.

Xiao H, Chen X, Liu X, Wen G, Yu Y Mater Today Bio. 2023; 19:100589.

PMID: 36880081 PMC: 9984902. DOI: 10.1016/j.mtbio.2023.100589.

Topical gel of mesenchymal stem cells-conditioned medium under TNF-α precondition accelerates wound closure healing in full-thickness skin defect animal model.

Putra A, Ibrahim S, Muradi Muhar A, Kuntardjo N, Dirja B, Pasongka Z J Med Life. 2022; 15(2):214-221.

PMID: 35419097 PMC: 8999092. DOI: 10.25122/jml-2019-0103.

Role of PDGF-A/B Ligands in Cardiac Repair After Myocardial Infarction.

Kalra K, Eberhard J, Farbehi N, Chong J, Xaymardan M Front Cell Dev Biol. 2021; 9:669188.

PMID: 34513823 PMC: 8424099. DOI: 10.3389/fcell.2021.669188.

Simvastatin combined with bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis through SDF-1α/CXCR4 pathway.

Ansari J, Ramhormozi P, Shabani R, Pazoki-Toroudi H, Yari A, Barati M Iran J Basic Med Sci. 2020; 23(6):751-759.

PMID: 32695291 PMC: 7351442. DOI: 10.22038/ijbms.2020.39782.9465.

Therapeutic effects of platelet derived growth factor overexpressed-mesenchymal stromal cells and sheets in canine skin wound healing model.

Kim N, Choi K, Lee E, Lee S, Oh J, Kim W Histol Histopathol. 2019; 35(7):751-767.

PMID: 31876285 DOI: 10.14670/HH-18-196.

References

Trengove N, Stacey M, Macauley S, Bennett N, Gibson J, Burslem F . Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen. 2000; 7(6):442-52. DOI: 10.1046/j.1524-475x.1999.00442.x. View

Weinstein D, Kirsner R . Refractory ulcers: the role of tumor necrosis factor-alpha. J Am Acad Dermatol. 2010; 63(1):146-54. DOI: 10.1016/j.jaad.2009.08.004. View

Alterescu V, Alterescu K . Pressure ulcers: assessment and treatment. Orthop Nurs. 1992; 11(2):37-49. DOI: 10.1097/00006416-199203000-00006. View

Singer A, Clark R . Cutaneous wound healing. N Engl J Med. 1999; 341(10):738-46. DOI: 10.1056/NEJM199909023411006. View

Murphy G, Willenbrock F, Crabbe T, OShea M, WARD R, Atkinson S . Regulation of matrix metalloproteinase activity. Ann N Y Acad Sci. 1994; 732:31-41. DOI: 10.1111/j.1749-6632.1994.tb24722.x. View

Steed D, Attinger C, Colaizzi T, Crossland M, Franz M, Harkless L . Guidelines for the treatment of diabetic ulcers. Wound Repair Regen. 2007; 14(6):680-92. DOI: 10.1111/j.1524-475X.2006.00176.x. View

Ladwig G, Robson M, Liu R, Kuhn M, Muir D, Schultz G . Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers. Wound Repair Regen. 2002; 10(1):26-37. DOI: 10.1046/j.1524-475x.2002.10903.x. View

Mustoe T, OShaughnessy K, Kloeters O . Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006; 117(7 Suppl):35S-41S. DOI: 10.1097/01.prs.0000225431.63010.1b. View

Bullen E, Longaker M, Updike D, Benton R, Ladin D, Hou Z . Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol. 1995; 104(2):236-40. DOI: 10.1111/1523-1747.ep12612786. View

10.

Cambou J, Aboyans V, Constans J, Lacroix P, Dentans C, Bura A . Characteristics and outcome of patients hospitalised for lower extremity peripheral artery disease in France: the COPART Registry. Eur J Vasc Endovasc Surg. 2010; 39(5):577-85. DOI: 10.1016/j.ejvs.2010.02.009. View

11.

Falanga V . Chronic wounds: pathophysiologic and experimental considerations. J Invest Dermatol. 1993; 100(5):721-5. DOI: 10.1111/1523-1747.ep12472373. View

12.

Chen C, Schultz G, Bloch M, Edwards P, Tebes S, Mast B . Molecular and mechanistic validation of delayed healing rat wounds as a model for human chronic wounds. Wound Repair Regen. 2000; 7(6):486-94. DOI: 10.1046/j.1524-475x.1999.00486.x. View

13.

Ihn H . Pathogenesis of fibrosis: role of TGF-beta and CTGF. Curr Opin Rheumatol. 2002; 14(6):681-5. DOI: 10.1097/00002281-200211000-00009. View

14.

Ruuls S, Sedgwick J . Unlinking tumor necrosis factor biology from the major histocompatibility complex: lessons from human genetics and animal models. Am J Hum Genet. 1999; 65(2):294-301. PMC: 1377927. DOI: 10.1086/302517. View

15.

Gabay C, Kushner I . Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999; 340(6):448-54. DOI: 10.1056/NEJM199902113400607. View

16.

Brown D, Kao W, Greenhalgh D . Apoptosis down-regulates inflammation under the advancing epithelial wound edge: delayed patterns in diabetes and improvement with topical growth factors. Surgery. 1997; 121(4):372-80. DOI: 10.1016/s0039-6060(97)90306-8. View

17.

Iversen M, Tell G, Riise T, Hanestad B, Ostbye T, Graue M . History of foot ulcer increases mortality among individuals with diabetes: ten-year follow-up of the Nord-Trøndelag Health Study, Norway. Diabetes Care. 2009; 32(12):2193-9. PMC: 2782976. DOI: 10.2337/dc09-0651. View

18.

Wysocki A, Staiano-Coico L, Grinnell F . Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol. 1993; 101(1):64-8. DOI: 10.1111/1523-1747.ep12359590. View

19.

Ito A, Sato T, Iga T, Mori Y . Tumor necrosis factor bifunctionally regulates matrix metalloproteinases and tissue inhibitor of metalloproteinases (TIMP) production by human fibroblasts. FEBS Lett. 1990; 269(1):93-5. DOI: 10.1016/0014-5793(90)81127-a. View

20.

Heldin C, Westermark B . Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999; 79(4):1283-316. DOI: 10.1152/physrev.1999.79.4.1283. View