Facial Plast Surg 2002; 18(1): 041-052
DOI: 10.1055/s-2002-19826
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Growth Factor Therapy to Improve Soft Tissue Healing

David B. Hom1 , Gentry Thatcher2 , Robert Tibesar3
  • 1Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Minnesota School of Medicine and Hennepin County Medical Center, Minneapolis, MN
  • 2Private practice, Boston, MA
  • 3Department of Otolaryngology, Mayo Medical School, Rochester, MN
Further Information

Publication History

Publication Date:
29 January 2002 (online)

ABSTRACT

The advent of new U.S. Food and Drug Administration-approved products containing growth factors to improve soft tissue healing signifies a new era for wound healing. Over the last decade, some clinical growth factor studies have been promising, whereas others have not shown any positive effect. What many of these studies have shown is that the state of a healing wound is not only dependent on its growth factor milieu but also on other variables (wound care, tissue oxygen state, bacteria count, and nutritional status of the patient). This article describes recent progress with growth factors on soft tissue structures (skin, mucosa, and nerve) relevant to the facial plastic and reconstructive surgeon.

REFERENCES

  • 1 May M. Nerve repair. In: May M, Schaitkin B, eds. The Facial Nerve New York: Thieme 2000 0: 571-609
  • 2 Sunderland S. Some anatomical and pathophysiological data relevant to facial nerve injury and repair. In: Fisch U, ed. Facial Nerve Surgery Birmingham: Aesculapius 1977
  • 3 Grabb W, Bernet S, Keopke G. Comparison of methods of peripheral nerve suturing in monkeys.  J Plast Reconstr . 1970;  46 31-38
  • 4 Grubel G. Factors influencing peripheral nerve suturing results.  Arch Orthoped Trauma Surg . 1983;  102 51-55
  • 5 Murray J, Willins M, Mountain R. A comparison of glue and a tube as an anastomotic agent to repair the divided branch of the buccal branch of the rat facial nerve.  Clin Otolaryngol . 1994;  19 190-192
  • 6 Barrs D. Facial nerve trauma: optimal timing for repair.  Laryngoscope . 1991;  101 835-848
  • 7 McQuarrie I. Acceleration of axonal regeneration in rat somatic motoneurons by using a conditioning lesion. In: Gorio A, Millesi H, Mingrino S, eds. Post-Traumatic Peripheral Nerve Regeneration: Experimental Basis and Clinical Implications New York: Raven Press 1981: 49-74
  • 8 Frostick S, Yin Q, Kemp G. Schwann cells, neurotrophic factors and peripheral nerve regeneration.  Microsurgery . 1998;  18 397-405
  • 9 Toriumi D, Woolford T, Teitlebaum B, Sanani K, O'Grady K. Growth factors in nerve regeneration.  Fac Plast Surg Clin North Am . 1997;  5 289-302
  • 10 He C, Chen Z, Chen Z. Enhancement of motor neuron regeneration by nerve growth factor.  Microsurgery . 1992;  13 151-154
  • 11 Birch R. Surgery for brachial plexus injury.  J Bone Joint Surg . 1993;  75B 346-348
  • 12 Utley D, Lewin S, Cheng E, Verity A, Sierra D, Terris D. Brain derived neurotrophic factor and collagen tubulization enhance functional recovery after peripheral nerve transection and repair.  Arch Head Neck Surg . 1996;  122 407-413
  • 13 Henderson C, Camus W, Mettling C. Neurotrophins promote motor neuron survival and are present in embryonic limb bud.  Nature . 1993;  363 266-270
  • 14 Lohof A, Ip N, Poo M. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF.  Nature . 1993;  363 350-352
  • 15 Xu X, Guenard V, Kleitman N, Aebischer P, Bunge M. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord.  Exp Neurol . 1995;  134 261-272
  • 16 Braun S, Croizat B, Lagrange M, Warter J, Poindron P. Neurotrophins increase motoneurons ability to innervate skeletal muscle fibers in rat spinal cord-human muscle co-culture.  J Neurol Sci . 1996;  136 17-23
  • 17 Arakawa Y, Sendetner M, Thoenen H. Survival effects of ciliary neurotrophic factor (CNTF) on chick embryonic motor neurons in culture: comparison with other neurotrophic factors and cytokines.  J Neurosci . 1990;  10 3507-3515
  • 18 Sahenk Z, Seharaseyon H, Mendell J. CNTF potentiates peripheral nerve regeneration.  Brain Res . 1994;  655 246-250
  • 19 Newman J, Verity A, Hawatmeh S, Fee W J, Terris D. Ciliary neurotropic factor enhances peripheral nerve regeneration.  Arch Otolaryngol Head Neck Surg . 1996;  122 399-403
  • 20 Lewin S, Utley D, Cheng E, Verity A, Terris D. Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone.  Laryngoscope . 1997;  107 992-999
  • 21 Helgren M, Squinto S, Davis H. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle.  Cell . 1994;  76 493-504
  • 22 Glazner G, Lupien S, Miller J, Ishii D. Insulin-like growth factor II correlates the rate of sciatic nerve regeneration in rats.  Neuroscience . 1993;  54 791-797
  • 23 Syroid D, Zorick T, Arbert-Enggela C, Kilpatrick T, Eckhart W, Lemke G. A role for insulin-like growth factor-I in the regulation of Schwann cell survival.  J Neurosci . 1999;  19 2059-2068
  • 24 Unsicker K, Grothe C, Ludecke G, Otto D, Westermann R. Fibroblast Growth Factors: Their Roles in the Central and Peripheral Nervous System.  New York: Academic Press 1993
  • 25 Ursicker K, Grothe C, Westermann R, Wewetzer K. Cytokines in neural regeneration.  Curr Opin Neurobiol . 1992;  2 671-678
  • 26 Grothe C, Wewetzer K. Fibroblast growth factor and its implications for developing and regenerating neurons.  Int J Dev Biol . 1996;  40 403-410
  • 27 Chen Y, Murakami S, Gyo K, Wakisaka H, Matsuda S, Sakanaka M. Effects of basic fibroblast growth factor (bFGF)-neutralizing antibody and platelet factor on facial nerve regeneration.  Exp Neurol . 1999;  155 274-283
  • 28 Kuzis K, Coffin J D, Eckenstein F P. Time course and age dependence of motor neuron death following facial nerve crush injury: role of fibroblast growth factor.  Exp Neurol . 1999;  157 77-87
  • 29 Spector J, Lee P, Derby A, Friedrich G, Neises G, Roufa D. Rabbit facial nerve regeneration in NGF-containing silastic tubes.  Laryngoscope . 1993;  103 548-558
  • 30 Madison R, Silva C D, Dikkes P, Chiu T, Sidman R. Increased rate of peripheral nerve regeneration using bioresorbable nerve guides and a laminin-containing gel.  Exp Neurol . 1985;  88 776-772
  • 31 Davison S P, McCaffrey T V, Porter M N, Manders E. Improved nerve regeneration with neutralization of transforming growth factor-β-1.  Laryngoscope . 1999;  109 631-635
  • 32 Eisma R, Allen J, Lafreniere D, Leonard G. Eosinophil expression of transforming growth factor-beta and its receptors in nasal polyposis: role of the cytokines in this disease process.  Am J Otolaryngol . 1997;  18 405-411
  • 33 Ellagard E, Oscarrson J, Bougoussa M. Serum level of placental growth hormone is raised in pregnancy rhinitis.  Arch Otolaryngol Head Neck Surg . 1998;  124 439-443
  • 34 Dohar J, Stool S. Respiratory mucosa wound healing and its management: an overview.  Otolaryngol Clin North Am . 1995;  28 897-912
  • 35 Cotton R, O'Connor D. Pediatric laryngotracheal reconstruction: 20 years experience.  Acta Otol Rhinol Laryngol . 1995;  49 367-372
  • 36 Walner D, Heffelfinger S C, Stern Y, Abrams M J, Miller M A, Cotton R T. Potential role of growth factors and extracellular matrix in wound healing after laryngotracheal reconstruction.  Otolaryngol Head Neck Surg . 2000;  122 363-366
  • 37 Yellon R, Szeremeta, Grandis J, Diguisseppe P, Dickman P. Subglottic injury, gastric juice corticosteroids and peptide growth factors in a porcine model.  Laryngoscope . 1998;  854-862
  • 38 Steed D. Modifying the wound healing response with exogenous growth factors.  Clin Plast Surg . 1998;  25 397-405
  • 39 Stahlman M, Orth D, Gray M. Immunohistochemical localization of epidermal growth factor in the developing human respiratory system and in acute and chronic lung disease in the neonate.  Lab Invest . 1989;  60 539-547
  • 40 Dillard D. Transforming growth factor and neutralizing antibodies in subglottic stenosis.  Ann Otol Rhinol Laryngol . 2001;  110 393-400
  • 41 Lowwen M, Walner D, Caldarelli D. Improved airway healing using transforming growth factor beta-3 in a rabbit model.  Wound Rep Reg . 2001;  9 44-49
  • 42 King J, Stringer S, Cheggini N. TGF-alpha protein receptor localization in laryngotracheal tissue.  Otolaryngol Head Neck Surg . 1993;  109 915-925
  • 43 Walner D, Cotton R, Willging P, Bove K, Toriumi D. Model for evaluating the effect of growth factors on the larynx.  Otolaryngol Head Neck Surg . 1999;  120 78-83
  • 44 Koempel J A G S E O G K T D M. The effect of platelet-derived growth factor on tracheal wound healing.  Int J Pediatr Otorhinolaryngol . 1998;  46 1-8
  • 45 Nogouchi S, Ohba Y, Oka T. Effect of salivary epidermal growth factor on wound healing of tongue in mice.  Am J Phys . 1991;  260 E620-E625
  • 46 Epstein J B, Gorsky M, Guglietta A, Le N, Sonis S T. The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy.  Cancer . 2000;  89 2258-2265
  • 47 Taicchman N, Cruchley A, Fletcher L. Vascular endothelial growth factor in normal human salivary gland and saliva: a possible role in the maintenance of mucosal homeostasis.  Lab Invest . 1998;  78 869-875
  • 48 Frank S, Hubner G, Breier G, Longaker M, Greenhalgh D, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes: implications for normal and impaired wound healing.  J Biol Chem . 1995;  276 12607-12613
  • 49 Stephens P, Davies K, Al-Khateeb T. A comparison of the ability of intra oral and extraoral fibroblasts to stimulate extracellular matrix reorganization in a model of wound contracture.  J Dent Res . 1996;  75 1358-1364
  • 50 Robson M, Mustoe T, Hunt T. The future of recombinant growth factors in wound healing.  Am J Surg . 1998;  176 80S-82S
  • 51 Robson M, Phillips L, Thomason A. Recombinant human platelet-derived growth factor-BB for the treatment of chronic pressure ulcers.  Ann Plast Surg . 1992;  29 193-201
  • 52 Robson M, Phillips L, Thomason A, Robson L. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers.  Lancet . 1992;  339 23-25
  • 53 Pierce G, Tarpley J, Tseng J. Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absences of PDGF in chronic nonhealing wounds.  J Clin Invest . 1995;  96 1336-1350
  • 54 Mustoe T, Cutler N, Allman R. A phase II study to evaluate recombinant platelet-derived growth factor-BB in the treatment of stage 3 and 4 pressure ulcers.  Arch Surg . 1994;  129 213-219
  • 55 Pierce G, Tarpley J, Allman R. Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB.  Am J Pathol . 1994;  145 1399-1410
  • 56 Steed D, Diabetic Ulcer Study Group. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers.  J Vasc Surg . 1995;  21 71-81
  • 57 Steed D, Donohoe D, Webster M, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers.  J Am Coll Surg . 1996;  183 61-64
  • 58 Wieman J, Smiel J, Nacht J. Efficacy and safety of recombinant human platelet derived growth factor-bb (Becaplermin) in patients with nonhealing lower extremity diabetic ulcers: a phase III randomized double blind study. American College of Surgeons 1997
  • 59 Wieman T. Clinical efficacy of becaplermin (rhPDGF-BB) gel.  Am J Surg . 1998;  176 74S-79S
  • 60 Wieman T, Smiell J, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet derived growth factor-bb (Becaplermin) in patients with chronic neuropathic diabetic ulcers: a phase III randomized placebo-controlled double-blind study.  Diabetes Care . 1998;  21 822-827
  • 61 Knighton D, Ciresi K, Fiegel V. Classification and treatment of chronic nonhealing wounds; successful treatment with autologous platelet-derived wound healing factors.  Ann Surg . 1986;  204 322-330
  • 62 Knighton D, Doucette M, Fiegel V, Ciresi K, Butler E, Austin L. The use of platelet derived wound healing formula in human clinical trials.  Prog Clin Biol Res . 1988;  266 319-329
  • 63 Atri S C, Misra J. Use of homologous platelet factors in achieving total healing of recalcitrant skin ulcers.  Surgery . 1990;  108 508-512
  • 64 Steed D, Goslen B, Hambley R. Clinical trials with purified platelet releasate.  Prog Clin Biol Res . 1991;  365 103-113
  • 65 Steed D L, Goslen J B, Holloway G A. CT-102 activated platelet supernatant, topical versus placebo: a randomized perspective double blind trial in healing of chronic diabetic foot ulcers.  Diabetes Care . 1992;  15 1598-1604
  • 66 Holloway G A, Steed D L, DeMarco M J. A randomized controlled dose response trial of activated platelet supernatant topical CT-102 (APST) in chronic non-healing wounds in patients with diabetes mellitus.  Wounds . 1993;  5 198-206
  • 67 Krupski W C, Reilly L M. A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report.  J Vasc Surg . 1991;  14 526-532
  • 68 Greaves M. Lack of effect of topically applied dermal growth factor (EFG) on epidermal growth in man in vivo.  Clin Exp Dermatol . 1980;  5 101-103
  • 69 Brown G, Nanney J, Griffen J. Enhancement of wound healing by topical treatment with epidermal growth factor.  N Engl J Med . 1989;  321 76-79
  • 70 Cohen I, Kelman R, Crossland M, Garrett A, Diegelmann R. Topical application of epidermal growth factor onto partial-thickness wounds in human volunteers does not enhance reepithelialization.  Plast Reconstr Surg . 1995;  96 251-254
  • 71 Brown G, Curtsinger L, Jurkiewicz M, Nahai F, Schultz G. Stimulation of healing of chronic wounds by epidermal growth factor.  Plast Reconstr Surg . 1991;  88 189-194
  • 72 Falanga V, Eaglstein W, Bucalo B. Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.  J Dermatol Surg Oncol . 1992;  18 604-606
  • 73 Robson M, Phillips L, Lawrence T. The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores.  Ann Surg . 1992;  216 401-408
  • 74  N. Synergen Press Release. Boulder, CO 1991
  • 75 Robson M. Exogenous growth factor application effect on human wound healing.  Prog Dermatol . 1996;  30 1-7
  • 76 Quinn T E, Thurman G B, Sundell A K, Zhang M, Hellerqvist C G. CM101, a polysaccharide antitumor agent, does not inhibit wound healing in murine models.  J Cancer Res Clin Oncol . 1995;  121 253-256
  • 77 DeVore R F, Hellerqvist C G, Wakefield G B. Phase I study of the antineovascularization drug CM101.  Clin Cancer Res . 1997;  3 365-372
  • 78 Thompson W D, Li W W, Maragoudakis M. The clinical manipulation of angiogenesis: pathology, side-effects, surprises, and opportunities with novel human therapies.  J Pathol . 2000;  190 330-337
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