Growth Factor Therapy to Improve Soft Tissue Healing

David B. Hom; Gentry Thatcher; Robert Tibesar

doi:10.1055/s-2002-19826

Facial Plastic Surgery, Table of Contents

Facial Plast Surg 2002; 18(1): 041-052
DOI: 10.1055/s-2002-19826

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

Abstract

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.

KEYWORD

Growth factors - soft tissue - wound healing

Full Text

References

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