PART I: A New Biomaterial Derived from Small Intestine Submucosa and Developed into a Wound Matrix Device

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Author(s): 
Marie Brown-Etris, RN, CWOCN;1 William D. Cutshall, MD;2 Michael C. Hiles, PhD3

Introduction

Biomaterials have become critical components in the development of effective new medical therapies for wound care. As limitations of previous generations of biologically derived materials are overcome, many new and impressive applications for biomaterials are being examined. A new biomaterial was first discovered in 1987 at Purdue University (West Lafayette, Indiana) when researchers were evaluating various biological materials as blood conduits. This biomaterial was derived from small intestine submucosa (SIS). The SIS biomaterial has since been developed into several medical products currently used by healthcare providers in the clinical setting.1,2

Initial investigations leading to the evaluation of SIS as an implantable biomaterial began with the use of sections of whole small intestine. However, the sections of small intestine tissue proved to be too active enzymatically to retain sutures. Subsequent implantation studies used intestine with various layers removed. In the end, the most successful graft was composed solely of the thin, translucent, but resilient, submucosal layer that remained after removing the mucosal and muscular layers. The submucosal layer of the small intestine is approximately 0.15 to 0.25mm thick and consists primarily of a collagen-based extracellular matrix (ECM) containing relatively few resident connective tissue cells.3 This layer provides structural support, stability, and biochemical signals to the rapidly regenerating mucosal cell layer. The naturally cross-linked collagen network of the submucosal layer also gives strength to the whole intestine. For these reasons, SIS biomaterial was derived from this intestinal layer and used initially for vascular graft studies.4,5 Currently, SIS biomaterial is harvested from a porcine source and minimally processed to lyse all resident cells and remove cellular debris as described elsewhere.6,7 SIS biomaterial is sterilized using a proprietary method that includes treatment with ethylene oxide. This sequential processing method allows long-term storage of the acellular sheet of ECM without destroying its ability to support wound healing and tissue repair.8

Following the initial discovery and evaluation, this naturally occurring ECM-based biomaterial was tested in a number of pre-clinical studies to evaluate its biocompatibility and persistence upon implantation. The SIS biomaterial is biocompatible in all host species tested. In addition, the biomaterial was remodeled gradually into new tissue by the host. This phenomenon was particularly remarkable because the new tissue generated by the host was specific to the site of implantation rather than a generalized fibrotic tissue. For example, when SIS was implanted in place of a blood vessel, within four months the biomaterial had been incorporated and replaced by new tissue, which appeared nearly identical to the original vessel.4 Even though the conduit had been formed from a single layer of the thin SIS biomaterial, a multilayered vessel was formed, which was several times thicker than the original SIS. The implanted graft supported the development of new artery tissue with an intimal lining of endothelial cells and a supporting outer layer of muscle tissue. This regeneration of tissue structures following implantation has been termed "smart remodeling" by researchers.5 A biomaterial with such properties was anticipated to provide a suitable covering for dermal wounds, and a pre-clinical animal study has specifically demonstrated the potential effectiveness of SIS as a biological-derived dressing in the clinical setting.9

In this review, we report the results of a pilot study showing the initial clinical experiences with the wound matrix device (WMD)* developed from the SIS biomaterial.

References: 

References

1. Parmenter MA. Limb salvage of severe wounds: Experiences using a novel extracellular matrix. Abstract: ACFAS & PRS Joint Annual Meeting and Scientific Seminar, New Orleans, LA: February 7, 2001.
2. Knoll LD. Use of porcine small intestinal submucosal graft in the surgical management of Peyronie’s disease. Urology 2001; 57:753–7.
3. Badylak SF, Lantz GC, Coffey A, Geddes LA. Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res 1989; 47:74–80.
4. Lantz GC, Badylak SF, Hiles MC, et al. Small intestinal submucosa as a vascular graft: A Review. J Invest Surgery 1993; 6:297–310.
5. Badylak SF. Small intestinal submucosa (SIS): A biomaterial conducive to smart tissue remodeling. In: Bell E (ed). Tissue Engineering: Current Perspectives. Cambridge, MA: Burkhauser Publishers, 1993; 179–89.
6. Badylak SF, Kropp B, McPherson T, et al. Small intestional submucosa: A rapidly resorbed bioscaffold for augmentation cystoplasty in a dog model. Tissue Eng 1998; 4(4):379–87.
7. Voytik-Harbin SL, Brightman AO, Waisner BZ, et al. Small intestinal submucosa: A tissue-derived extracellular matrix which promotes tissue-specific growth and differentiation of cells in vitro. Tissue Eng 1998;4:157–74.
8. Hodde JP, Hiles MC. Bioactive FGF-2 in sterilized extracellular matrix. Abstract: Symposium on Advanced Wound Care. Las Vegas, NV: April 30, 2001.
9. Prevel CD, Eppley BL, Summerlin DJ, et al. Small intestinal submucosa: Utilization as a wound dressing in full-thickness rodent wounds. Ann Plast Surg 1995; 35:381–8.
10. Brown-Etris M. Measuring healing in wounds. Adv Wound Care 1995; 8(4):53–8.
11. Calvin M. Cutaneous wound repair. Wounds 1998;10(1):12–32.
12. Winter GD. Formation of scab and the rate of epithelialization of superficial wounds in the skin of the domestic pig. Nature 1962;200:377–8.
13. Leipziger LS, Glushko V, DiBernardo B, et al. Dermal wound repair: Role of collagen matrix implants and synthetic polymer dressings. J Am Acad Dermatol 1985;12(2):409–19.
14. Bromber BE, Song IC, Mohn MP. The use of pig skin as a temporary biologic dressing. Plast Reconstr Surg 1965; 36:80–90.
15. Elliot R, Hoehn J. Use of commercial porcine skin for wound dressings. Plast Reconstr Surg 1973;52(4):401–5.
16. Shettigar UG, Jagannathan R, Natarajan R. Collagen film for burn wound dressings reconstituted from animal intestines. Artif Organs 1982;6:256–60.
17. Greenfield E, Jordan B. Advances in burn wound care. Crit Care Nurs Clin North Am 1996; 8:203–15.
18. Eaglstein WH, Falanga V. Tissue engineering and the development of Apligraf, a human skin equivalent. Adv Wound Care 1998;11(4 Suppl):1–8.
19. Lantz GC, Badylak SF, Coffey AC, et al. Small intestinal submucosa as a small-diameter arterial graft in the dog. J Invest Surg 1990;3(3):217–27.
20. Lantz GC, Badylak SF, Coffey AC, et al. Small intestinal submucosa as a superior vena cava graft in the dog. J Surg Res 1992;53(2):175–81.
21. Sandusky GE Jr, Badylak SF, Morff RJ, et al. Histologic findings after in-vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid artery in dogs. Am J Pathol 1992;140(2):317–24.
22. Sandusky GE, Lantz GC, Badylak SF. Healing comparison of small intestine submucosa and ePTFE grafts in the canine carotid artery. J Surg Res 1995;58(4):415–20.
23. Hiles MC, Badylak SF, Lantz GC, et al. Mechanical properties of xenogeneic small-intestinal submucosa when used as an aortic graft in the dog. J Biomed Mater Res 1995;29(7):883–91.
24. Knapp PM, Lingeman JE, Siegel YI, et al. Biocompatibility of small-intestinal submucosa in urinary tract augmentation cystoplasty graft and injectable suspension. J Endourology 1995;8:125–30.
25. Kropp BP, Eppley BL, Prevel CD, et al. Experimental assessment of small intestinal submucosa as a bladder wall substitute. Urology 1995; 46:396–400.
26. Kropp BP, Ripply MK, Badylak SF, et al. Regenerative urinary bladder augmentation using small intestinal submucosa: Urodynamic and histopathological assessment in long term canine bladder augmentation. J Urol 1996; 155:2098–104.
27. Vaught JD, Kropp BP, Sawyer BD, et al. Detrusor regeneration in the rat using porcine small intestinal submucosal grafts: Functional innervation and receptor expression. J Urol 1996;155(1):374–8.
28. Kropp BP, Ludlow JK, Spicer D, et al. Rabbit urethral regeneration using small intestinal submucosa onlay grafts. Urology 1998; 52:138–42.
29. Prevel CD, Eppley BL, Summerlin DJ, et al. Small intestinal submucosa (SIS): Utilization for repair of rodent abdominal wall defects. Ann Plast Surg 1995;35:374–80.
30. Clark KM, Lantz GC, Salisbury SK, et al. Intestinal submucosa and polypropelene mesh for abdominal wall repair in dogs. J Surg Res 1996;60:107–14.
31. Badylak SF, Tulleius R, Kokini K, et al. The use of xenogenic small intestinal submucosa as a biomaterial for achille’s tendon repair in a dog model. J Biomat Matter Res 1995;29:977–85.
32. Hodde J, Badylak SF, Shelbourne KD. The effect of range of motion upon remodeling of small intestinal submucosa (SIS) when used as an achilles tendon repair material in the rabbit. Tissue Eng 1997;3(1):27–37.
33. Aiken SW, Badylak SF, Toombs JP, et al. Small intestinal submucosa as an intra-articular ligamentous graft material: A pilot study in dogs. VCOT 1994;7:124–8.
34. Badylak S, Arnoczky S, Plouhar P, et al. Naturally occurring extracellular matrix as a scaffold for musculoskeletal repair. Clin Orthop 1999;367(Suppl):S333–43.
35. Cobb MA, Badylak SF, Janas W, Boop FA. Histology after dural grafting with small intestinal submucosa. Surg Neurol 1996;46(4):389–93.
36. Cobb MA, Badylak SF, Janas W, et al. Porcine small intestinal submucosa as a dural substitute. Surg Neurol 1999;51(1):99–104.
37. Suckow MA, Voytik-Harbin SL, Terril LA, Badylak SF. Enhanced bone regeneration using porcine small intestinal submucosa. J Invest Surg 1999;12(5):277–87.
38. Dalla Vecchia L, Engum S, Kogon B, et al. Evaluation of small intestine submucosa and acellular dermis as diaphragmatic prostheses. J Pediatr Surg 1999;34(1):167–71.
39. Prevel CD, Eppley BL, McCarty M, et al. Experimental evaluation of small intestinal submucosa as a microvascular graft material. Microsurgery 1994;15(8):586–91.
40. Badylak SF, Coffey AC, Lantz GC, et al. Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model. J Vasc Surg 1994;19(3):465–72.
41. Badylak SF, Wu CC, Simmons-Byrd A. Infection resistance of a multi-laminate ECM scaffold material in a dog model. Tissue Eng 2001; (in press).
42. McPherson JM, Sawamura SJ, Condell RA, et al. The effects of heparin on the physicochemical properties of reconstituted collagen. Coll Relat Res 1988;8(1):65–82.
43. Murphy GF, Orgill DP, Yannas IV. Partial dermal regeneration is induced by biodegradable collagen-glycosaminoglycan grafts. Lab Invest 1990;62(3):305–13.
44. Allman AJ, McPherson TB, Badylak SF, et al. Xenogeneic extracellular matrix grafts elicit a Th2-restricted dominant immune response. Immunology (submitted for publication).
45. Voytik-Harbin SL. Personal communication.
46. McGrath JA, Eady RA. Heparan sulphate proteoglycan and wound healing in skin. J Pathol 1997;183(3):251–2.
47. Kosir MA, Quinn CC, Wang W, Tromp G. Matrix glycosaminoglycans in the growth phase of fibroblasts: More of the story in wound healing. J Surg Res 2000;92(1):45–52.
48. Hodde JP, Badylak SF, Brightman AO, Voytik-Harbin SL. Glycosaminoglycan content of small intestinal submucosa: A bioscaffold for tissue replacement. Tissue Eng 1996;2:209–17.
49. McPherson TB, Badylak SF. Characterization of fibronectin derived from porcine small intestinal submucosa. Tissue Eng 1998;4:75–83.
50. Voytik-Harbin SL, Brightman AO, Kraine MR, et al. Identification of extractable growth factors from small intestinal submucosa. J Cellular Biochem 1997;67:478–91.
51. Hodde JP, McPherson TB, Savaiano JK, Badylak SF. Vascular endothelial growth factor in SIS. Second SIS Symposium. Orlando, FL: 1998;92.
52. Voytik-Harbin SL, Brightman AO, Waisner BZ, et al. Application and evaluation of the alamar Blue assay for cell growth and survival of fibroblasts. In-Vitro Cell Dev Biol Anim 1998;34(3):239–46.
53. Kajio T, Kawahara K, Kato K. Stabilization of basic fibroblast growth factor with dextran sulfate. FEBS Lett 1992;306(2–3):243–6.
54. Coltrini D, Rusnati M, Zoppetti G, et al. Biochemical bases of the interaction of human basic fibroblast growth factor with glycosaminoglycans. New insights from trypsin digestion studies. Eur J Biochem 1993;214(1):51–8.
55. Hiles MC, Badylak SF, Geddes LA, et al. Porosity of porcine small-intestinal submucosa for use as a vascular graft. J Biomed Mater Res 1993;27(2):139–44.
56. Ferrand BK, Kokini K, Badylak SF, et al. Directional porosity of porcine small-intestinal submucosa. J Biomed Mater Res 1993;27(10):1235–41.
57. Whitson BA, Cheng BC, Kokini K, et al. Multilaminate resorbable biomedical device under biaxial loading. J Biomed Mater Res 1998;43(3):277–81.
58. Roeder R, Wolfe J, Lianakis N, et al. Compliance, elastic modulus, and burst pressure of small-intestine submucosa (SIS), small-diameter vascular grafts. J Biomed Mater Res 1999;47(1):65–70.
59. Peel SAF, Chen H, Renlund R, et al. Formation of a SIS-cartilage composite graft in vitro and its use in the repair of articular cartilage defects. Tissue Eng 1998;4(2):143–55.
60. Badylak SF, Record R, Lindberg K, et al. Small intestinal submucosa: A substrate for in-vitro cell growth. J Biomater Sci Polym Ed 1998;9(8):863–78.
61. Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression? J Theor Biology 1982; 99:31–68.
62. Badylak S, Liang A, Record R, et al. Endothelial cell adherence to small intestinal submucosa: An acellular bioscaffold. Biomaterials 1999;20(23–24):2257–63.
63. Brown-Etris M, Pribble J, LaBrecque J. Evaluation of two wound measurement methods in a multi-center, controlled study. Wounds 1994;6:54–61.
64. Nakagawa S, Pawelek P, Grinnell F. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness. Exper Cell Res 1989;182:572–82.
65. Roskelly CD, Srebrow A, Bissell MJ. A hierarchy of ECM-mediated signaling regulates tissue-specific gene expression. Curr Opin Cell Biol 1995;7:736–47.
66. Robotin-Johnson MC, Swanson PE, Johnson DC, et al. An experimental model of small intestinal submucosa as a growing vascular graft. J Thorac Cardiovasc Surg 1998;116(5):805–11.
67. Niezgoda JA, Parmenter MA. A clinical study to evaluate small intestine submucosa (SIS) as a treatment for full-thickness diabetic ulcers. Abstract: Symposium for Advanced Wound Care. Las Vegas, NV: April 30, 2001.
68. Brown-Etris M, Milne C, Edvalson J, Mlynek L. A clinical study to evaluate small intestine submucosa (SIS) as a treatment for full-thickness pressure ulcers. Abstract: Symposium for Advanced Wound Care. Las Vegas, NV: April 30, 2001.

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