Abstract
The ability of surgeons to accelerate wound healing through pharmacologic intervention is limited. The effects of locally applied, biosynthetic human epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) on tensile strength of experimental incisions were investigated. A single dose of EGF in saline failed to increase tensile strength over controls. Thus, EGF was incorporated into multilamellar liposomes, which prolonged the exposure of incisions to EGF (p less than 0.001). A single dose of EGF in multilamellar liposomes produced a 200% increase in wound tensile strength over controls between 7 and 14 days (p less than 0.05). Light and electron microscopy of the wounds revealed increased collagen formation and fibroblast proliferation. A single dose of TGB-beta in a collagen vehicle stimulated a 51% increase in wound tensile strength at 9 days (p less than 0.01). We conclude that addition of EGF and TGF-beta in appropriate vehicles stimulates early transient increases in wound tensile strength in normal rats.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aharonov A., Pruss R. M., Herschman H. R. Epidermal growth factor. Relationship between receptor regulation and mitogenesis in 3T3 cells. J Biol Chem. 1978 Jun 10;253(11):3970–3977. [PubMed] [Google Scholar]
- Arturson G. Epidermal growth factor in the healing of corneal wounds, epidermal wounds and partial-thickness scalds. A controlled animal study. Scand J Plast Reconstr Surg. 1984;18(1):33–37. doi: 10.3109/02844318409057400. [DOI] [PubMed] [Google Scholar]
- Assoian R. K., Grotendorst G. R., Miller D. M., Sporn M. B. Cellular transformation by coordinated action of three peptide growth factors from human platelets. 1984 Jun 28-Jul 4Nature. 309(5971):804–806. doi: 10.1038/309804a0. [DOI] [PubMed] [Google Scholar]
- Bangham A. D., Standish M. M., Watkins J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965 Aug;13(1):238–252. doi: 10.1016/s0022-2836(65)80093-6. [DOI] [PubMed] [Google Scholar]
- Bauer E. A., Silverman N., Busiek D. F., Kronberger A., Deuel T. F. Diminished response of Werner's syndrome fibroblasts to growth factors PDGF and FGF. Science. 1986 Dec 5;234(4781):1240–1243. doi: 10.1126/science.3022382. [DOI] [PubMed] [Google Scholar]
- Brightwell J. R., Riddle S. L., Eiferman R. A., Valenzuela P., Barr P. J., Merryweather J. P., Schultz G. S. Biosynthetic human EGF accelerates healing of Neodecadron-treated primate corneas. Invest Ophthalmol Vis Sci. 1985 Jan;26(1):105–110. [PubMed] [Google Scholar]
- Brown G. L., Curtsinger L., 3rd, Brightwell J. R., Ackerman D. M., Tobin G. R., Polk H. C., Jr, George-Nascimento C., Valenzuela P., Schultz G. S. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med. 1986 May 1;163(5):1319–1324. doi: 10.1084/jem.163.5.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buckley A., Davidson J. M., Kamerath C. D., Wolt T. B., Woodward S. C. Sustained release of epidermal growth factor accelerates wound repair. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7340–7344. doi: 10.1073/pnas.82.21.7340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cromack D. T., Sporn M. B., Roberts A. B., Merino M. J., Dart L. L., Norton J. A. Transforming growth factor beta levels in rat wound chambers. J Surg Res. 1987 Jun;42(6):622–628. doi: 10.1016/0022-4804(87)90005-9. [DOI] [PubMed] [Google Scholar]
- Darlak K., Franklin G., Woost P., Sonnenfeld E., Twardzik D., Spatola A., Schultz G. Assessment of biological activity of synthetic fragments of transforming growth factor-alpha. J Cell Biochem. 1988 Apr;36(4):341–352. doi: 10.1002/jcb.240360404. [DOI] [PubMed] [Google Scholar]
- Esch F., Baird A., Ling N., Ueno N., Hill F., Denoroy L., Klepper R., Gospodarowicz D., Böhlen P., Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511. doi: 10.1073/pnas.82.19.6507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greaves M. W. Lack of effect of topically applied epidermal growth factor (EGF) on epidermal growth in man in vivo. Clin Exp Dermatol. 1980 Mar;5(1):101–103. doi: 10.1111/j.1365-2230.1980.tb01675.x. [DOI] [PubMed] [Google Scholar]
- Grotendorst G. R., Martin G. R., Pencev D., Sodek J., Harvey A. K. Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. J Clin Invest. 1985 Dec;76(6):2323–2329. doi: 10.1172/JCI112243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haigler H. T., Carpenter G. Production and characterization of antibody blocking epidermal growth factor:receptor interactions. Biochim Biophys Acta. 1980 May 23;598(2):314–325. doi: 10.1016/0005-2736(80)90009-7. [DOI] [PubMed] [Google Scholar]
- Knighton D. R., Ciresi K. F., Fiegel V. D., Austin L. L., Butler E. L. Classification and treatment of chronic nonhealing wounds. Successful treatment with autologous platelet-derived wound healing factors (PDWHF). Ann Surg. 1986 Sep;204(3):322–330. doi: 10.1097/00000658-198609000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laato M., Niinikoski J., Lundberg C., Arfors K. E. Effect of epidermal growth factor (EGF) on experimental granulation tissue. J Surg Res. 1986 Sep;41(3):252–255. doi: 10.1016/0022-4804(86)90032-6. [DOI] [PubMed] [Google Scholar]
- Lawrence W. T., Norton J. A., Sporn M. B., Gorschboth C., Grotendorst G. R. The reversal of an Adriamycin induced healing impairment with chemoattractants and growth factors. Ann Surg. 1986 Feb;203(2):142–147. doi: 10.1097/00000658-198602000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mustoe T. A., Pierce G. F., Thomason A., Gramates P., Sporn M. B., Deuel T. F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987 Sep 11;237(4820):1333–1336. doi: 10.1126/science.2442813. [DOI] [PubMed] [Google Scholar]
- Pessa M. E., Bland K. I., Copeland E. M., 3rd Growth factors and determinants of wound repair. J Surg Res. 1987 Feb;42(2):207–217. doi: 10.1016/0022-4804(87)90120-x. [DOI] [PubMed] [Google Scholar]
- Postlethwaite A. E., Keski-Oja J., Moses H. L., Kang A. H. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 1987 Jan 1;165(1):251–256. doi: 10.1084/jem.165.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977 Feb 3;265(5593):421–424. doi: 10.1038/265421a0. [DOI] [PubMed] [Google Scholar]
- Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schreiber A. B., Winkler M. E., Derynck R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science. 1986 Jun 6;232(4755):1250–1253. doi: 10.1126/science.2422759. [DOI] [PubMed] [Google Scholar]
- Sporn M. B., Roberts A. B., Shull J. H., Smith J. M., Ward J. M., Sodek J. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983 Mar 18;219(4590):1329–1331. doi: 10.1126/science.6572416. [DOI] [PubMed] [Google Scholar]
- Szoka F., Jr, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4194–4198. doi: 10.1073/pnas.75.9.4194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thornton J. W., Hess C. A., Cassingham V., Bartlett R. H. Epidermal growth factor in the healing of second degree burns: a controlled animal study. Burns Incl Therm Inj. 1982 Jan;8(3):156–160. doi: 10.1016/0305-4179(82)90079-1. [DOI] [PubMed] [Google Scholar]
- Urdea M. S., Merryweather J. P., Mullenbach G. T., Coit D., Heberlein U., Valenzuela P., Barr P. J. Chemical synthesis of a gene for human epidermal growth factor urogastrone and its expression in yeast. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7461–7465. doi: 10.1073/pnas.80.24.7461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woost P. G., Brightwell J., Eiferman R. A., Schultz G. S. Effect of growth factors with dexamethasone on healing of rabbit corneal stromal incisions. Exp Eye Res. 1985 Jan;40(1):47–60. doi: 10.1016/0014-4835(85)90107-1. [DOI] [PubMed] [Google Scholar]