title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, United States. Electronic address: jswoo@mednet.ucla.edu.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Woo
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Avenue, CHS 13-145, Los Angeles, CA, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Reemtsen
mesh_terms: D000293:Adolescent; D002114:Calcinosis / Q000209:etiology / Q000473:pathology*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005109:Extracellular Matrix / Q000473:pathology / Q000637:transplantation*; D005260:Female; D005355:Fibrosis; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology*; D006330:Heart Defects, Congenital / Q000473:pathology / Q000601:surgery*; D006346:Heart Septum / Q000473:pathology / Q000601:surgery*; D006351:Heart Valves / Q000473:pathology / Q000601:surgery*; D064593:Heterografts; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000637:transplantation*; D015141:Los Angeles; D008297:Male; D009336:Necrosis; D016896:Treatment Outcome
keywords: Congenital heart disease; CorMatrix; Small intestinal submucosa extracellular matrix