Histologic examination of decellularized porcine intestinal submucosa extracellular matrix (CorMatrix) in pediatric congenital heart surgery

Abstract

Background

CorMatrix is a decellularized porcine small intestinal submucosa extracellular matrix that has gained attention as a promising alternative to current materials used in cardiac repair. While animal models demonstrate integration of CorMatrix material with host tissue, the histologic characteristics of CorMatrix used in humans are less well-characterized. In this retrospective study, we report our experience with CorMatrix material used in pediatric congenital heart surgery and describe the histology of CorMatrix material and of surrounding native tissue in explanted specimens.

Methods

Records were reviewed of all pediatric patients implanted with CorMatrix from a single institution (2011–2014). Histologic examinations were performed on CorMatrix and other tissues removed. Explanted samples of CorMatrix and adherent tissues were evaluated for inflammation (acute and chronic), fibrosis, necrosis, degenerative changes, eosinophil response, foreign-body giant cell reaction, neovascularization, and calcification of tissues on a semiquantitative basis (0, none; 1, mild; 2, moderate; 3, marked). Presence of degeneration within CorMatrix and necrosis of surrounding tissue were noted.

Results

CorMatrix was utilized in 532 pediatric heart reconstruction procedures since 2011. Twelve explanted CorMatrix specimens from 11 pediatric patients including 4 valves (2 mitral and 2 aortic) and 8 outflow/septal/conduit patches were identified and evaluated. Six cases (5 patients) demonstrated clinical evidence of graft failure prior to surgery (n= 6, 1%). Chronic inflammation was seen in adjacent native tissue in 11/12 cases and consisted predominantly of a mixed population of lymphocytes, macrophages, and plasma cells. Acute inflammation was seen in three cases (3/12). Fibrosis of the surrounding native tissue was seen in all CorMatrix specimens. Eosinophils were present in 6/12 cases. Calcification in surrounding tissue was present in 3/12 cases. Giant cell reaction in adjacent native tissue was seen in 8/12 cases. Neovascularization was seen in surrounding native tissue in 5/12 cases. Degeneration of CorMatrix material was seen in 9/12 cases. Necrosis of surrounding tissue was also identified in 5/12 cases. CorMatrix was not resorbed and no cases demonstrated any remodeling of CorMatrix material by integration of native mesenchymal cells or myocytes.

Conclusion

CorMatrix may be associated with a marked inflammatory response, including a foreign-body giant cell reaction and fibrosis of the surrounding native tissue. Degenerative changes of CorMatrix material are also seen in a majority of explanted specimens. No histologic differences were seen between patients with clinical evidence of graft failure versus patients requiring graft removal due to other factors. Additionally, no cases showed evidence of tissue integration or recellularization of patch material. Our overall clinical experience with CorMatrix demonstrates a favorable outcome for pediatric patients undergoing cardiac reconstructive surgery. However, there is no histologic evidence that CorMatrix acts as a scaffold for reconstitution of the native cardiovascular structures.

Introduction

CorMatrix (CorMatrix Cardiovascular Inc., Alpharetta, Georgia) is a decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM), currently approved by the Federal Drug Administration for cardiovascular and peripheral vasculature repair. Use of CorMatrix has gained considerable attention as a promising alternative to other materials currently used for cardiac reconstruction, including processed allografts (pulmonary and aortic allografts), xenografts (bovine pericardium and porcine aortic valves), and synthetic materials such as polytetrafluoroethylene (Gore-Tex, W. L. Gore & Associates Inc., Flagstaff, Arizona), polyester (Dacron, DuPont, Wilmington, Delaware), and mechanical valves. Although the current materials have greatly improved long-term outcomes in cardiac surgical candidates, patients continue to face adverse outcomes secondary to graft degeneration, calcification, stenosis, and lack of growth, with inflammatory response, cicatrization, and aneurysm formation [1], [2], [3].

CorMatrix as well as other decellularized biologic scaffolds appear advantageous in cardiac repair as they avoid sensitization associated with homograft materials as xenogeneic and allogeneic cellular antigens are recognized as foreign by the host [4], [5], [6]. Decellularized biologic scaffolds also possess the theoretical potential for growth by providing a scaffold for host cells to reconstruct related tissues. These characteristics are especially ideal in the repair of congenital heart defects, where growth accommodation is desirable. Patch remodeling and integration into surrounding native tissue have been shown in multiple cardiac surgery animal models [7], [8]. Preliminary experiences with CorMatrix, predominantly in congenital heart surgery, have also demonstrated overall favorable outcomes, although these case series are limited by small sample size and lack of long-term follow-up [9], [10], [11], [12].

The histologic findings of explanted CorMatrix in human cardiac surgery have been reported in adult patient case reports (CorMatrix implanted for pericardial closure [13] and aortic root repair [14]), and pediatric [9], [11], [15] and adult [12], [16], [17] case series, including a case series of pediatric CorMatrix valvuloplasty specimens [14]. In this present study, we report the histologic characteristics of explanted CorMatrix specimens used for pediatric cardiac reconstruction at our institution and compare these results with previous studies.