Extracellular Matrix for Myocardial Repair


  • Stephen Badylak
  • Leslie Geddes
  • Leslie Geddes
  • Joe Obermiller




Objective: To evaluate the remodeling characteristics of an extracellular matrix (ECM) scaffold when used as a template for myocardial repair.

Background: Xenogeneic ECM has been shown to be an effective scaffold for the repair and reconstitution of several tissues, including lower urinary tract structures, dura mater, the esophagus, musculotendinous tissues, and blood vessels. These ECM scaffolds are completely degraded in vivo and induce a host cellular response that supports constructive remodeling rather than scar tissue formation.

Methods: Full-thickness circular defects measuring approximately 2.5 cm in diameter were created in the right ventricular anterior walls of 6 adult Yucatán pigs and 4 adult mongrel dogs. The defects were repaired with an ECM sheet 80 3m thick that was derived from either the porcine small intestinal submucosa or the porcine urinary bladder matrix. The animals lived for periods of 6 to 24 weeks before sacrifice.

Results: There was a complete replacement of the acellular scaffolds by a mixture of tissue types, including well-vascularized fibrous connective tissue, cartilage, adipose connective tissue, and myocardial tissue. The remodeled scaffold tissue showed spontaneous contractility and peak contractile force equivalent to 70% of the contractile force of the adjacent native myocardium.

Conclusions: We conclude that porcine ECM scaffolds alter the typical scar tissue healing response in myocardial tissue and instead support vascularization and the local development of multiple tissue types, including contractile myocardium.


Badylak S, Kokini K, Tullius B, Whitson B. 2001. Strength over time of a resorbable bioscaffold for body wall repair in a dog model. J Surg Res 99:282-7.nBadylak S, Meurling S, Chen M, Spievack A, Simmons-Byrd A. 2000. Resorbable bioscaffold for esophageal repair in a dog model. J Pediatr Surg 35:1097-103.nBadylak SF, Kropp B, McPherson T, Liang H, Snyder PW. 1998. Small intestinal submucosa: a rapidly resorbed bioscaffold for augmentation cystoplasty in a dog model. Tissue Eng 4:379-88.nBadylak SF, Lantz GC, Coffey AC, Geddes LA. 1989. Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res 47:74-80.nBadylak SF, Liang A, Record R, Tullius R, Hodde J. 1999. Endothelial cell adherence to small intestinal submucosa: an acellular bioscaffold. Biomaterials 20:2257-63.nChiu RCJ, Zibaitis A, Kao RL. 1995. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg 60:12-8.nClarke KM, Lantz GC, Salisbury SK, Badylak SF, Hiles MC, Voytik SL. 1996. Intestine submucosa and polypropylene mesh for abdominal wall repair in dogs. J Surg Res 60:107-14.nCobb MA, Badylak SF, Janas W, Boop FA. 1996. Histology after dural grafting with small intestinal submucosa. Surg Neurol 46:389-94.nCobb MA, Badylak SF, Janas W, Simmons-Byrd A, Boop FA. 1999. Porcine small intestinal submucosa as a dural substitute. Surg Neurol 51:99-104.nDahms SE, Piechota HJ, Dahiya R, Gleason CA, Hohenfellner M, Tanagho EA. 1998. Bladder acellular matrix graft in rats: its neurophysiologic properties and mRNA expression of growth factors TGF-alpha and TGF-beta. Neurourol Urodyn 17:37-54.nDahms SE, Piechota HJ, Dahiya R, Lue TF, Tanagho EA. 1998. Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human. Br J Urol 82:411-9.nDor V. 1997. Left ventricular aneurysms: the endoventricular patchplasty. Semin Thorac Cardiovasc Surg 9:123-30.nLantz GC, Badylak SF, Coffey AC, Geddes LA, Sandusky GE. 1992. Small intestinal submucosa as a superior vena cava graft in the dog. J Surg Res 53:175-81.nLeyh RG, Wilhelmi M, Rebe P, Haverich A, Mertschink H. 2002. In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation. Paper presented at: 38th Annual Meeting of the Society of Thoracic Surgeons; 2002 Jan; Fort Lauderdale, Fla. Li RK, Jia ZQ, Weisel RD, et al. 1996. Cardiomyocyte transplantation< improves heart function. Ann Thorac Surg 62:654-61.nLi RK, Tomita S, Weisel RD, Jia Z-Q, Tumiati L, Mickle DAG. 2002. Beneficial effect of autologous cell transplantation: direct comparison between bone marrow stromal cells and heart cells in porcine model.nPaper presented at: 38th Annual Meeting of the Society of Thoracic Surgeons; 2002 Jan; Fort Lauderdale, Fla.nLi RK, Yau TM, Sakai T, Mickle DA, Weisel RD. 1998. Cell therapy to repair broken hearts. Can J Cardiol 14:735-44.nMagovern JA. 2001. As originally published in 1993: right latissimusdorsi cardiomyoplasty augments left ventricular systolic performance. Updated in 2001. Ann Thorac Surg 71:2077-8.nMcPherson TB, Badylak SF. 1998. Characterization of fibronectin derived from porcine small intestinal submucosa. Tissue Eng 4:75-83.nMerguerian PA, Reddy PP, Barrieras DJ, et al. 2000. Acellular bladder matrix allografts in the regeneration of functional bladders: evaluation of large-segment (>24 cm) substitution in a porcine model. BJU Int 85:894-8.nMoreira LF, Stolf NA. 2001. Dynamic cardiomyoplasty: current status. Heart Fail Rev 6:201-12.nDowling RD, Koenig S, Laureano MA, Gray LA. 1999. Intermediate-term results of partial left ventriculectomy. J Card Surg 14:214-7.nFarza H, Yacoub M. 1995. Regulation of myocardial cell growth and multiplication. In: Yacoub M, Pepper J, editors. Annual of cardiac surgery. 8th ed. London, UK: Current Science. p 13-23.nFranco-Cereceda A, McCarthy PM, Blackstone EH, et al. 2001. Partial left ventriculectomy for dilated cardiomyopathy: is this the alternative to transplantation? J Thorac Cardiovasc Surg 121:837-9.nHodde JP, Badylak SF, Brightman AO, Voytik-Harbin SL. 1996. Glycosaminoglycan content of small intestinal submucosa: a bioscaffold for tissue replacement. Tissue Eng 2:209-17.nHodde JP, Badylak SF, Shelbourne KD. 1997. The effect of range of motion on remodeling of small intestinal submucosa (SIS) when used as an Achilles tendon repair material in the rabbit. Tissue Eng 3:27-37.nHodde JP, Record RD, Liang HA, Badylak SF. 2001. Vascular endothelial growth factor in porcine-derived extracellular matrix. Endothelium 8:11-24.nHodde J, Record R, Tullius R, Badylak S. 2002. Fibronectin peptides mediate HMEC adhesion to porcine-derived extracellular matrix. Biomaterials 23:1841-8.nKlug MG, Soonpaa MH, Koh GY, Field LJ. 1996. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest 98:216-24.nKnapp PM, Lingeman JE, Siegel YI, Badylak SF, Demeter RJ. 1994. Biocompatibility of small-intestinal submucosa in urinary tract as augmentation cystoplasty graft and injectable suspension. J Endourol 8:125-30.nKropp BP, Eppley BL, Prevel CD, et al. 1995. Experimental assessment of small intestine submucosa as a bladder wall substitute. Urology 46:396-400.nKropp BP, Ludlow JK, Spicer D, et al. 1998. Rabbit urethral regeneration using small intestinal submucosa onlay grafts. Urology 52:138-42.nKropp BP, Rippy MK, Badylak SF, et al. 1996. Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologic assessment in long term canine bladder augmentations. J Urol 155:2098-104.nLantz GC, Badylak SF, Coffey AC, Geddes LA, Blevins WE. 1990. Small intestinal submucosa as a small diameter arterial graft in the dog. J Invest Surg 3:217-27.nNational Institutes of Health. 1996. Guide for the care and use of laboratory animals. Bethesda, Md: National Institutes of Health. NIH publication nr NIH 85-23.nOhara K. 2000. Current surgical strategy for post-infarction left ventricular aneurysms from linear aneurysmectomy to Dor's operation. Ann Thorac Cardiovasc Surg 6:289-94.nPiechota HJ, Dahms SE, Nunes LS, Dahiya R, Lue TF, Tanagho EA. 1998. In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft. J Urol 159:1717-24.nProbst M, Dahiya R, Carrier S, Tanagho EA. 1997. Reproduction of functional smooth muscle tissue and partial bladder replacement. Br J Urol 79:505-15.nTaylor DA, Atkins BZ, Hungspreugs P, et al. 1998. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4:929-33.nTomita S, Li RK, Weisel RD, et al. 1999. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100:II247-56.nVoytik-Harbin SL, Brightman AO, Kraine M, Waisner B, Badylak SF. 1997. Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem 67:478-91.nBadylak SF, Park K, Peppas N, McCabe G, Yoder M. 2001. Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix. Exp Hematol 29:1310-8.nBadylak SF, Voytik SL, Kokini K, et al. 1995. The use of xenogeneic small intestinal submucosa as a biomaterial for Achilles tendon repair in a dog model. J Biomed Mater Res 29:977-85.nBirdi I, Bryan AJ, Mehta D, et al. 1997. Left ventricular volume reduction surgery. Int J Cardiol 62(suppl 1):S29-35.nBittira B, Kuang J-Q, Al-Khaldi A, Shun-Tim D, Chiu R. 2002. In vitro preprogramming of marrow stromal stem cells for myocardial regeneration. Paper presented at: 38th Annual Meeting of the Society of Thoracic Surgeons; 2002 Jan; Fort Lauderdale, Fla.nBuckberg GD. 1999. Commonality of ischemic and dilated cardiomyopathy: Laplace and ventricular restoration. J Card Surg 14:53-9. Calvano CJ, Moran ME, Parekh A, Desai PJ, Cisek LJ. 2000. Laparoscopic augmentation cystoplasty using the novel biomaterial Surgisis: small-intestinal submucosa. J Endourol 14:213-7.nCarlson BM, Faulkner JA. 1983. The regeneration of skeletal muscle fibers following injury: a review. Med Sci Sports Exerc 15:187-98.nChen F, Yoo JJ, Atala A. 1999. Acellular collagen matrix as a possible "off the shelf" biomaterial for urethral repair. Urology 54:407-10.n



How to Cite

Badylak, S., Geddes, L., Geddes, L., & Obermiller, J. (2005). Extracellular Matrix for Myocardial Repair. The Heart Surgery Forum, 6(2), E20-E26. https://doi.org/10.1532/hsf.917