title: Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation.
abstract: Porcine small intestinal submucosa (SIS) has been recommended as a cell-free, biocompatible biomaterial for the repair of rotator cuff tendon tear. However, we have observed noninfectious edema and severe pain in patients who have undergone SIS implantation for tendon repair. The aim of this study was to conduct an independent assessment of the safety and efficacy of Restore SIS membrane. The Restore orthobiologic implant was examined by histology and the nested PCR technique using porcine immunoreceptor DAP12 gene to examine if SIS membrane contained porcine cells or DNA, respectively. The material was also implanted into mice and rabbits for the evaluation of biological reaction and inflammatory response. Restore SIS was found to contain multiple layers of porcine cells. Chloroacetate esterase staining showed that some of these cells were mast cells. Nested PCR of the DAP12 gene demonstrated that Restore SIS contained porcine DNA material. Subcutaneous implantation of Restore SIS membrane in mice, and in rabbits for rotator cuff tendon repair, showed that the membrane caused an inflammatory reaction characterized by massive lymphocyte infiltration. In conclusion, Restore SIS is not an acellular collagenous matrix, and contains porcine DNA. Our results contradict the current view that Restore SIS is a cell-free biomaterial, and that no inflammatory response is elicited by its implantation. We suggest that further studies should be conducted to evaluate the clinical safety and efficacy of SIS implant biomaterials.
authors.affiliation: School of Pathology and Surgery, Unit of Orthopaedics, University of Western Australia, 2nd Floor M-block QEII Medical Centre, Nedlands 6009, Australia. zheng@cyllene.uwa.edu.au
authors.forename: M H
authors.initials: MH
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Kirilak
authors.forename: C
authors.initials: C
authors.lastname: Willers
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Wood
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002265:Carboxylic Ester Hydrolases / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D003094:Collagen / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism; D007249:Inflammation; D007413:Intestinal Mucosa / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology*; D008214:Lymphocytes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008855:Microscopy, Electron, Scanning; D016133:Polymerase Chain Reaction; D019736:Prostheses and Implants; D011817:Rabbits; D011971:Receptors, Immunologic / Q000737:chemistry; D013552:Swine; D013710:Tendons / Q000473:pathology; D023822:Tissue Engineering; D014180:Transplantation; D014183:Transplantation, Heterologous
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001672:Biocompatible Materials; D017931:DNA Primers; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; D003094:Collagen; D004247:DNA; D002265:Carboxylic Ester Hydrolases; C019873:chloroacetate esterase