The Use of Extracellular Matrix in Cardiovascular Surgery
By Sanghun Kim, MD and Hong Liu, MD
University of California Davis Health System, Sacramento, California
Although there were several attempts at development of biomaterials for orthopedic applications as early as 1970’s, initial reference to the term “tissue engineering” can be trace back to a meeting held by National Science Foundation in late 1980’s.1 At a later meeting by the same organization, it was defined as “the application of the principles and methods of engineering and the life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve functions.”2 Since then interest in tissue engineering for cardiovascular applications has gradually gained momentum over the last few decades leading to development of biomaterials for use in cardiovascular medicine. Recently focus has shifted from merely replacing a portion of tissue with biomaterials to regenerating new tissue after implantation of bioengineered scaffold. This year’s Earl Wynands lecture at SCA’s 34th Annual Meeting will be delivered by Dr. Charles Vacanti on the topic of tissue engineering in the 21st century.
Importance of extracellular matrix was not appreciated by scientists and engineers in early stages of tissue engineering. However, it has taken a major role in recent years with the understanding that there is interplay between cells and the surrounding structures. Rather than merely occupying space around cells as a static entity, it has been shown that proteins within the framework communicate with cells and regulate growth, proliferation, differentiation, and migration of tissue at cellular level.3 In fact, it has been shown that extracellular matrix constantly undergoes remodeling through degradation and reassembly by the surrounding cells.4 In pre-clinical studies, the dynamic relationship between cells and extracellular matrix has been shown in wound healing, tissue regeneration, angiogenesis, and tumor invasions. For clinical applications, extracellular matrix has been successfully harvested from many mammalian tissue types including skin, dermis, fascia lata, small intestine submucosa, and pericardium. These materials are processed through proprietary methods developed by tissue engineering laboratories and are commercially available under different trade names. For uses in cardiovascular medicine, a few biotechnology firms have made strides and a select number of products are clinically used.
CorMatrix ECM is available from CorMatrix Cardiovascular, Inc (Alpharetta, GA) and has been approved for usage in pericardial closure, cardiac tissue repair, and carotid repair by Food and Drug Administration. It is bioengineered acellular porcine extracellular matrix harvested from small intestine submucosa that is primarily composed of structural protein collagen.5 Based on laboratory research done by Badylak and his team of biomedical engineers from Purdue University, use of this material and processing method have been licensed to Cormatrix Cardiovascular, Inc (Alpharetta, GA) and Cook Biotech, Inc (West Lafayette, IN) for development of surgical implants for tissue regeneration and remodeling.
Initially developed as a possible solution to prevent complications from placement of vascular grafts used in surgery, Cormatrix ECM was shown to be effective as arterial grafts in carotid artery in an animal model in its ability to withstand forces and remodeling without causing calcification.6 Animal studies show that it can also act as a scaffold for repair and reconstitution of several tissue types including connective tissue, blood vessels, and myocardial tissue. The remodeled tissue showed functional cardiomyocytes with spontaneous contractility.7 Original scaffold is completely degraded after implantation over several months and induces a host cellular response that results in constructive remodeling instead of scar tissue formation.7
There are currently two preliminary studies that show promising results from using Cormatrix ECM in cardiovascular surgery in humans.8,9 In a retrospective study of 111 patients who received pericardial repair and reconstruction using Cormatrix ECM after coronary artery bypass graft surgery, there was decreased incidence of post operative atrial fibrillation with similar rate of other post operative complications.8 Although this finding led to statistically insignificant decrease in length of hospital stay, further research is warranted to investigate long term morbidity and mortality related to its use. In another study of 26 pediatric patients with congenital heart disease who required complex cardiac surgery in Europe, there was no incidence of surgical complications related to use of Cormatrix ECM both immediately after the surgery and up to a year after the surgery.9 Since it was used as a vascular graft to repair pulmonary artery, ascending aorta, aortic arch, right ventricular outflow tract as well as a tissue graft for pulmonic, tricuspid, mitral, and aortic valve reconstruction in the study, this finding is very promising if follow up studies can show that there is vascular and myocardial tissue reconstruction with minimal adverse side effects due to host response during remodeling period.
There are also several anecdotal reports on use of Cormatrix ECM for cardiac surgery.10 It has been used in atrial septal repair after removal of atrial myxoma, aortic root enlargement in a case of patient prosthesis mismatch, and pericardial closure after left ventricular assist device implantation. It has met the functional role in surgical repairs without obvious immediate complications. In addition, its use for pericardial reconstruction is advocated for purported benefit to patients that may require another open heart surgery by preventing formation of adhesion between heart and sternum.
Although further studies are required to objectively assess utility of Cormatrix ECM for routine use in cardiac surgery, current literature suggests that there is a promising outlook for bioengineered extracellular matrix. Future studies evaluating long term effects in the human body would determine success of this product in clinical medicine.
- Vacanti CA. History of tissue engineering and a glimpse into its future. Tissue Eng. 2006 May;12(5):1137-42.
- Skalak R, Fox CF. Tissue engineering. Granlibakken, Lake Tahoe: Proc wrkshop; New York: Liss; 1988. p 26 –29.
- Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater. 2009 Jan;5(1):1-13. Epub 2008 Oct 2.
- Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci. 2008 Feb 1;121(Pt 3):255-64.
- Badylak SF, Kropp B, McPherson T, Liang H, Snyder PW. Small intestional submucosa: a rapidly resorbed bioscaffold for augmentation cystoplasty in a dog model. Tissue Eng. 1998 Winter;4(4):379-87.
- Fallon A, Goodchild T, Wang R, Matheny RG. Remodeling of Extracellular Matrix Patch used for Carotid Artery Repair. J Surg Res. 2011 Nov 26.
- Badylak S, Obermiller J, Geddes L, Matheny R. Extracellular matrix for myocardial repair. Heart Surg Forum. 2003;6(2):E20-6.
- Boyd WD, Johnson WE 3rd, Sultan PK, Deering TF, Matheny RG. Pericardial reconstruction using an extracellular matrix implant correlates with reduced risk of postoperative atrial fibrillation in coronary artery bypass surgery patients. Heart Surg Forum. 2010 Oct;13(5):E311-6.
- Quarti A, Nardone S, Colaneri M, Santoro G, Pozzi M. Preliminary experience in the use of an extracellular matrix to repair congenital heart diseases. Interact Cardiovasc Thorac Surg. 2011 Dec;13(6):569-72.
- http://www.cormatrix.com/index accessed March 1st 2012