A Review of Collagen and Collagen-based Wound Dressings

Author(s): 
David Brett, BS, BS, MS; From the Wound Management Division, Smith & Nephew Inc., St. Petersburg, FL.

Abstract: Collagen is a key component of a healing wound. In this review, a general description of the wound healing process is provided focusing on collagen’s unique role. The mode of action (MoA) of collagen-based dressings is also addressed. Due to a number of potential stimuli (local tissue ischemia, bioburden, necrotic tissue, repeated trauma, etc.), wounds can stall in the inflammatory phase contributing to the chronicity of the wound. One key component of chronic wounds is an elevated level of matrix metalloproteinases (MMPs). At elevated levels, MMPs not only degrade nonviable collagen but also viable collagen. In addition, fibroblasts in a chronic wound may not secrete tissue inhibitors of MMPs (TIMPs) at an adequate level to control the activity of MMPs. These events prevent the formation of the scaffold needed for cell migration and ultimately prevent the formation of the extracellular matrix (ECM) and granulation tissue. Collagen based wound dressings are uniquely suited to address the issue of elevated levels of MMPs by acting as a ‘sacrificial substrate’ in the wound. It has also been demonstrated that collagen breakdown products are chemotactic for a variety of cell types required for the formation of granulation tissue. In addition, collagen based dressings have the ability to absorb wound exudates and maintain a moist wound environment.



Address correspondence to:
David Brett, BS, BS, MS
Wound Management Division
Smith & Nephew
920 Lake Carillon Dr., Suite 110
St. Petersburg, FL 33716
Phone: 727-399-3496
E-mail: dave.brett@smith-nephew.com





Collagen

   Proteins are natural polymers and make up almost 15% of the human body. The building blocks of all proteins are amino acids. Collagen is the major protein of the extracellular matrix (ECM) and is the most abundant protein found in mammals, comprising 25% of the total protein and 70% to 80% of skin (dry weight). Collagen acts as a structural scaffold in tissues. The central feature of all collagen molecules is their stiff, triple-stranded helical structure.1 Types I, II, and III are the main types of collagen found in connective tissue and constitute 90% of all collagen in the body.

   Function of collagen in wound healing. Previously, collagens were thought to function only as a structural support; however, it is now evident that collagen and collagen-derived fragments control many cellular functions, including cell shape and differentiation, 2,3 migration, 4 and synthesis of a number of proteins. 5 Findings suggest that cell contact with precise extracellular matrix molecules influence cell behavior by regulating the quantity and quality of matrix deposition. Type I collagen is the most abundant structural component of the dermal matrix; migrating keratinocytes likely interact with this protein. Collagenase (via formation of gelatin) may aid in dissociating keratinocytes from collagen-rich matrix and thereby promote efficient migration over the dermal and provisional matrices. Cellular functions are regulated by the ECM. The information provided by ECM macromolecules is processed and transduced into the cells by specialized cell surface receptors. 5 Evidence demonstrates that the receptors play a major function in contraction of wounds, 6,7 migration of epithelial cells, 8 collagen deposition, 9 and induction of matrix-degrading collagenase. Although keratinocytes will adhere to denatured collagen (gelatin), collagenase production is not turned on in response to this substrate. 10 Keratinocytes have been known to recognize and migrate on Type I collagen substratum, resulting in enhanced collagenase production. 11 Collagen plays a key role in each phase of wound healing.

   Hemostasis (duration = minutes).




References: 

1. Jeffrey J. Metalloproteinases and tissue turnover. WOUNDS. 1995;7(Suppl A):13A–22A.
2. Montesano R, Orci L, Vasselli P. In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. J Cell Biol. 1983;97(5 Pt 1):1648–1652.
3. Madri JA, Marx M. Matrix composition, organization, and soluble factors: modulators of microvascular cell differentiation in vitro. Kidney Int. 1992;41(3):560–565.
4. Albini A, Adelmann-Grill BC. Collagenolytic cleavage products of collagen Type I as chemoattractants for human dermal fibroblasts. Eur. J Cell Biol. 1985;36(1):104–107.
5. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992;69(1):11–25.
6. Klein CE, Dressel D, Steinmayer T, et al. Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collage I fibrils. J Cells Biol. 1991;115(5):1427–1436.
7. Schiro JA, Chan BM, Roswit WT, et al. Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell. 1991;67(2):403–410.
8. Scharffetter-Kochanek K, Klein CE, Heinen G, et al. Migration of human keratinocyte cell line (HaCaT) to interstitial collagen Type I is mediated by the alpha 2 beta 1-integrin receptor. J Invest Dermatol. 1992;98(1):3–11.
9. Krieg T. Collagen in the Healing Wound. WOUNDS. 1995;7(Suppl A):5A–12A.
10. Subdeck BD, Parks WC, Welgus HG, Pentland AP. Collagen-stimulated induction of keratinocyte collagenase is mediated via tyrosine kinase and protein kinase C activities. J Biol Chem. 1994;269(47):30022–30029.
11. Petersen MJ, Woodley DT, Stricklin GP, O’Keefe EJ. Enhanced synthesis of collagenase by human keratinocytes cultured on Type I or Type IV collagen. J Invest Dermatol. 1990;94(3):341–346.
12. Schultz G, Mast B. Molecular analysis of the environment of healing and chronic wounds: cytokines, proteases and growth factors. WOUNDS. 1998;10(6 suppl):1F–9F.
13. Sibbald RG, Williamson D, Orsted HL, et al. Preparing the wound bed—debridement, bacterial balance, and moisture balance. Ostomy Wound Manage. 2000;46(11)14–35.
14. Falanga V. Classifications for wound bed preparation and stimulation of chronic wounds. Wound Repair Regen. 2000;8(5):347–352.
15. Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003;11(Suppl 1):1–28.
16. Doillon CJ, Silver FH. Collagen-based wound dressing: effects of hyaluronic acid and fibronectin on wound healing. Biomaterials. 1986;7(1):3–8.
17. Doillon CJ, Silver FH, Olson RM, Kamath CY, Berg RA. Fibroblast and epidermal cell-Type I collagen interactions: cell culture and human studies. Scanning Microsc. 1988;2(2):985–992.
18. Burton JL, Etherington DJ, Peachey RD. Collagen sponge for leg ulcers. Br J Dermatol. 1978;99(6):681–685.
19. Doillon CJ, Whyne CF, Berg RA, Olson RM, Silver FH. Fibroblast-collagen sponge interactions and spatial deposition of newly synthesized collagen fibers in vitro and in vivo. Scan Electron Microsc. 1984;(Pt 3):1313–1320.
20. Palmieri B. Heterologous collagen in wound healing: a clinical study. Int J Tissue React. 1992;14(Suppl):21–25.
21. Parks WC. The production, role, and regulation of matrix metalloproteinases in the healing epidermis. WOUNDS. 1995;7(Suppl A):23–37.
22. Mignatti P, Rifkin DB, Welgus HG, Parks WC. Proteinases and tissue remodeling. In: Clark RAF, ed. The Molecular and Cellular Biology of Wound Repair. 2nd ed. New York, NY: Plenum Press; 1996:427–474.






















Post new comment

  • Lines and paragraphs break automatically.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Use to create page breaks.

More information about formatting options

Image CAPTCHA
Enter the characters shown in the image.