Small Intestinal Submucosa Extracellular Matrix Research Articles

Effect of porcine small intestinal submucosa extracellular matrix in promoting vitality and functional gene expression of hepatocyte

To investigate the effect of porcine small intestinal submucosa extracellular matrix (PSISM) on the vitality and gene regulation of hepatocyte so as to lay the experimental foundation for the application of PSISM in liver tissue engineering. The experiment was divided into two parts: ① BRL cells were cultured with 50, 100, and 200 μg/mL PSISM-medium which were prepared by adding PSISM into the H-DMEM-medium containing 10%FBS in groups A1, B1, and C1, and simple H-DMEM-medium served as a control (group D1); ② BRL cells were seeded on 1%, 2%, and 3% PSISM hydrogel which were prepared by dissolving PSISM in sterile PBS solution containing 0.1 mol/L NaOH in groups A2, B2, and C2, and collagen type I gel served as a control (group D2). At 1, 3, and 5 days after culture, the morphology and survival of liver cells were detected by the Live/Dead fluorescent staining. The cell vitality was tested by cell counting kit-8 (CCK-8) assay. And the relative expressions of albumin (ALB), cytokeratin 18 (CK18), and alpha-fetoprotein (AFP) in hepatocytes were determined by real-time fluorescent quantitative PCR (RT-qPCR). The Live/Dead fluorescent staining showed the cells survived well in all groups. CCK-8 results displayed that the absorbance ( A) value of group C1 was significantly higher than that of group D1 at 5 days after culture with PSISM-medium, and there was no significant difference between groups at other time points ( P>0.05). After cultured with PSISM hydrogels, the A values of groups A2, B2, and C2 were significantly higher than those of group D2 at 3 and 5 days ( P<0.05), the A value of group A2 was significantly higher than that of groups B2 and C2 at 5 days ( P<0.05), but there was no significant difference between groups at other time points ( P>0.05). RT-qPCR showed that the relative expressions of ALB and CK18 mRNA significantly increased and the relative expression of AFP mRNA significantly decreased in groups A1, B1, and C1 when compared with group D1 ( P<0.05). The relative expression of CK18 mRNA in group C1 was significantly lower than that in groups A1 and B1 ( P<0.05). The relative expressions of ALB and CK18 mRNA were significantly higher and the relative expression of AFP mRNA was significantly lower in groups A2, B2, and C2 than group D2 ( P<0.05); the relative expression of CK18 mRNA in group A2 was significantly higher than that in group B2 ( P<0.05), and the relative expression of AFP mRNA in group A2 was significantly lower than that in group C2 ( P<0.05), but no significant difference was found between other groups ( P>0.05). PSISM has good compatibility with hepatocyte and can promote the vitality and functional gene expression of hepatocyte. PSISM is expected to be used as culture medium supplement or cell carrier for liver tissue engineering.

Manufacture and preparation of human placenta-derived mesenchymal stromal cells for local tissue delivery

BackgroundIn this study we describe the development of a Current Good Manufacturing Practice (CGMP)-compliant process to isolate, expand and bank placenta-derived mesenchymal stromal cells (PMSCs) for use as stem cell therapy. We characterize the viability, proliferation and neuroprotective secretory profile of PMSCs seeded on clinical-grade porcine small intestine submucosa extracellular matrix (SIS-ECM; Cook Biotech). MethodsPMSCs were isolated from early gestation placenta chorionic villus tissue via explant culture. Cells were expanded, banked and screened. Purity and expression of markers of pluripotency were determined using flow cytometry. Optimal loading density and viability of PMSCs on SIS-ECM were determined using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell proliferation and fluorescent live/dead assays, respectively. Growth factors secretion was analyzed using enzyme-linked immunosorbent assays (ELISA). ResultsPMSCs were rapidly expanded and banked. Viable Master and Working Cell Banks were stable with minimal decrease in viability at 6 months. All PMSCs were sterile, free from Mycoplasma species, karyotypically normal and had low endotoxin levels. PMSCs were homogeneous by immunophenotyping and expressed little to no pluripotency markers. Optimal loading density on SIS-ECM was 3–5 × 105 cells/cm2, and seeded cells were >95% viable. Neurotrophic factor secretion was detectable from PMSCs seeded on plastic and SIS-ECM with variability between donor lots. DiscussionPMSCs from early gestation placental tissues can be rapidly expanded and banked in stable, viable cell banks that are free from contaminating agents, genetically normal and pure. PMSC delivery can be accomplished by using SIS-ECM, which maintains cell viability and protein secretion. Future work in vivo is necessary to optimize cell seeding and transplantation to maximize therapeutic capabilities.

Small intestinal submucosa tricuspid valve tube graft shows growth potential, remodelling and physiological valve function in a porcine model†.

Tricuspid valve reconstruction using small intestinal submucosal extracellular matrix (ECM) designed as a tube graft is possible in severe valve pathology. Using cardiac magnetic resonance imaging (MRI) and digital photograph imaging, valves were evaluated after 6 months in a porcine model. Ten 60 kg pigs received a tricuspid valve tube graft. A baseline MRI was performed after 2 weeks ( n = 8). A follow-up MRI was performed in three of five 6 months' survivors to assess function and haemodynamics of the tricuspid tube graft. Valves were explanted in five animals for gross examination. No statistical comparisons were made due to low numbers. : Compared to the original tube graft, leaflet area and leaflet height decreased after 6 months (32 ± 0 vs 14.7 ± 4 cm 2 and 3.2 ± 0 vs 1.7 ± 0.3 cm, respectively). Both imaging modalities showed septal dehiscence in all tube grafts after 6 months causing haemodynamically severe paravalvular regurgitation. Cardiac MRI showed a significant remodelling of the right ventricular and annular dimensions. The cardiac output decreased (67 ± 16 vs 34 ± 5 ml/min/kg), while right ventricular stroke volume increased from 64.4 ± 14.6 to 107 ± 63.9 ml. This corresponded to a paravalvular regurgitant volume increasing from 7.2 ± 7.3 to 71.7 ± 69.6 ml. The ECM tube grafts seemed to remodel over time with loss of redundant ECM material. However, tube graft dehiscence caused severe tricuspid paravalvular regurgitation and heart failure. These data suggest that surgical reinforcement, e.g. adjunct annuloplasty, should be considered to improve durability.

不同组织来源的胶原蛋白生物材料物理性能对比研究

本文对比考察了四种不同来源的胶原蛋白植入材料的物理性能，主要包括形貌、粗糙度、孔隙率、亲水性、力学强度以及变性温度等性质。实验结果表明，脱细胞猪小肠粘膜下层生物材料(VIDASIS)的物理性能与进口同类产品无显著差异。 In this paper, physical properties of different tissue-derived collagen biomaterials were studied, including morphology, roughness, porosity, hydrophilicity, mechanical strength and denaturation temperature. Results demonstrated that physical property of porcine small intestinal submucosa extracellular matrix (VIDASIS) was almost the same with other domestic and foreign products.

A Gingiva-Derived Mesenchymal Stem Cell-Laden Porcine Small Intestinal Submucosa Extracellular Matrix Construct Promotes Myomucosal Regeneration of the Tongue.

In the oral cavity, the tongue is the anatomic subsite most commonly involved by invasive squamous cell carcinoma. Current treatment protocols often require significant tissue resection to achieve adequate negative margins and optimal local tumor control. Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, and swallowing functions remains one of the major challenges in head and neck oncologic surgery. We investigated the in vitro feasibility of fabricating a novel combinatorial construct using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human gingiva-derived mesenchymal stem cells (GMSCs) as a GMSC/SIS-ECM tissue graft for the tongue reconstruction. We developed a rat model of critical-sized myomucosal defect of the tongue that allowed the testing of therapeutic effects of an acellular SIS-ECM construct versus a GMSC/SIS-ECM construct on repair and regeneration of the tongue defect. We showed that the GMSC/SIS-ECM construct engrafted at the host recipient site, promoted soft tissue healing, and regenerated the muscular layer, compared to the SIS-ECM alone or nontreated defect controls. Furthermore, our results revealed that transplantation of the GMSC/SIS-ECM construct significantly increased the expression of several myogenic transcriptional factors and simultaneously suppressed the expression of type I collagen at the wounded area of the tongue. These compelling findings suggest that, unlike the tongue contracture and fibrosis of the nontreated defect group, transplantation of the combinatorial GMSC/SIS-ECM constructs accelerates wound healing and muscle regeneration and maintains the overall tongue shape, possibly by both enhancing the function of endogenous skeletal progenitor cells and suppressing fibrosis. Together, our findings indicate that GMSC/SIS-ECM potentially served as a myomucosal graft for tongue reconstruction postsurgery of head and neck cancer.

CorMatrix valved conduit in a porcine model: long-term remodelling and biomechanical characterization.

Porcine small intestinal submucosa extracellular matrix (CorMatrix; CorMatrix Cardiovascular, Rosewell, GA) is a relatively novel tissue substitute used in cardiovascular applications. We investigated the biological reaction and remodelling of CorMatrix as a tri-leaflet valved conduit in a pig model. We hypothesized that CorMatrix maintains a durable architecture as a valved conduit and remodels to resemble surrounding tissues. We fashioned the valved conduit using a 7 × 10 cm 4-ply CorMatrix sheet and placed it in the thoracic aorta of seven landrace pigs for 3, 4, 5 and 6 months. Biodegradation, replacement by native tissue, strength and durability were examined by histology, immunohistochemistry and mechanical testing. Four pigs, one per time frame, completed the study. The conduit lost its original architecture as a tri-leaflet valve due to cusp immobility, subsequent attachment to the wall segment and consequent maintenance of a thick arterial wall-like structure. Scaffold resorption was incomplete, with disorganized inconsistent spatial and temporal degradation even at 6 months. Fibrosis, scarring and calcification started at 4 months and chronic inflammation persisted. The partially remodelled scaffold did not resemble the aortic wall, suggesting impaired remodelling. Mechanical testing showed progressive weakening of the tissues over time, which were liable to breakage. CorMatrix is biodegradable; however, it failed to remodel in a structured and anatomical fashion in an arterial environment. Progressive mechanical and remodelling failure in this scenario might be explained by the complexity of the conduit design and the host's chronic inflammatory response, leading to early fibrosis and calcification.

Erratum: Experimental Aortic Valve Cusp Extension with CorMatrix in a Porcine Model.

Background We tested the feasibility of using porcine small intestinal submucosal extracellular matrix (CorMatrix) for aortic valve (AV) repair in porcine model examining its resorption and remodeling potential. Methods The non-coronary cusp was replaced with CorMatrix in four animals for 120 days. Valve function was assessed by echocardiography. Explants were examined by histology, immunohistochemistry, and collagen assessment. Results CorMatrix was almost totally replaced with tissue resembling the native cusp with a partial two-layer architecture. However, function was lost due to thickening and calcification. Conclusions Tested in high-pressure AV position in a pig model, CorMatrix degrades and remodels, but also loses function.

Experimental Aortic Valve Cusp Extension with CorMatrix in a Porcine Model.

Background We tested the feasibility of using porcine small intestinal submucosal extracellular matrix (CorMatrix) for aortic valve (AV) repair in porcine model examining its resorption and remodeling potential. Methods The non-coronary cusp was replaced with CorMatrix in four animals for 120 days. Valve function was assessed by echocardiography. Explants were examined by histology, immunohistochemistry, and collagen assessment. Results CorMatrix was almost totally replaced with tissue resembling the native cusp with a partial two-layer architecture. However, function was lost due to thickening and calcification. Conclusions Tested in high-pressure AV position in a pig model, CorMatrix degrades and remodels, but also loses function.

Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications.

In this study, we investigate the translational potential of a novel combined construct using an FDA-approved decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) seeded with human or porcine mesenchymal stem cells (MSCs) for cardiovascular indications. With the emerging success of individual component in various clinical applications, the combination of SIS-ECM with MSCs could provide additional therapeutic potential compared to individual components alone for cardiovascular repair. We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes. Additionally, we evaluated the ability of porcine MSCs to modulate recipient graft-specific response towards SIS-ECM in a porcine cardiac patch in vivo model. Specifically, we determined: 1) in vitro loading-capacity of human MSCs on SIS-ECM, 2) effect of cell seeding on SIS-ECM structure, compositions and mechanical properties, 3) effect of SIS-ECM seeding on human MSC phenotypes and differentiation potential, and 4) optimal orientation and dose of porcine MSCs seeded SIS-ECM for an in vivo cardiac application. In this study, histological structure, biochemical compositions and mechanical properties of the FDA-approved SIS-ECM biomaterial were retained following MSCs repopulation in vitro. Similarly, the cellular phenotypes and differentiation potential of MSCs were preserved following seeding on SIS-ECM. In a porcine in vivo patch study, the presence of porcine MSCs on SIS-ECM significantly reduced adaptive T cell response regardless of cell dose and orientation compared to SIS-ECM alone. These findings substantiate the clinical translational potential of combined SIS-ECM seeded with MSCs as a promising therapeutic candidate for cardiac applications.

Small intestinal submucosa extracellular matrix (CorMatrix®) in cardiovascular surgery: a systematic review.

Extracellular matrix (ECM) derived from small intestinal submucosa (SIS) is widely used in clinical applications as a scaffold for tissue repair. Recently, CorMatrix® porcine SIS-ECM (CorMatrix Cardiovascular, Inc., Roswell, GA, USA) has gained popularity for 'next-generation' cardiovascular tissue engineering due to its ease of use, remodelling properties, lack of immunogenicity, absorbability and potential to promote native tissue growth. Here, we provide an overview of the biology of porcine SIS-ECM and systematically review the preclinical and clinical literature on its use in cardiovascular surgery. CorMatrix® has been used in a variety of cardiovascular surgical applications, and since it is the most widely used SIS-ECM, this material is the focus of this review. Since CorMatrix® is a relatively new product for cardiovascular surgery, some clinical and preclinical studies published lack systematic reporting of functional and pathological findings in sufficient numbers of subjects. There are also emerging reports to suggest that, contrary to expectations, an undesirable inflammatory response may occur in CorMatrix® implants in humans and longer-term outcomes at particular sites, such as the heart valves, may be suboptimal. Large-scale clinical studies are needed driven by robust protocols that aim to quantify the pathological process of tissue repair.

CRT-500.03 Examining the Remodeling of CorMatrix as a Trileaflet Valve Conduit in Heterotopic Position in Growing Pig Model

Porcine small intestinal submucosa extracellular matrix, CorMatrix (CorMatrix Cardiovascular, Roswell, GA) is potentially suitable tissue substitute for cardiovascular use. We investigate the biological reaction and remodeling of CorMatrix, as a tri-leaflet valve conduit in growing pig model. We

SIS-ECM BIOMATERIAL DECREASES HUMAN CARDIAC MYOFIBROBLAST ACTIVATION AND ATTENUATES LOCAL MATRIX REMODELING

SIS-ECM BIOMATERIAL DECREASES HUMAN CARDIAC MYOFIBROBLAST ACTIVATION AND ATTENUATES LOCAL MATRIX REMODELING

Small intestinal submucosa-derived extracellular matrix bioscaffold significantly enhances angiogenic factor secretion from human mesenchymal stromal cells

IntroductionThe in vivo therapeutic effect of mesenchymal stromal cells (MSCs) is currently believed to be tightly linked to their paracrine secretion ability. However, insufficient or imprecise cell delivery, low cell survival and retention post-transplant, along with harsh donor site microenvironments, are major barriers to the clinical success of MSC therapies. Here we tested a small intestinal submucosa (SIS)-derived extracellular matrix (ECM) bioscaffold augmented with MSCs, with the hypothesis that they will facilitate the precise delivery of increased numbers of MSCs therefore improving cell viability and retention.MethodsIn this study, we evaluated the secretion of angiogenic factors from three human MSC lines cultured on SIS ECM. We used human antibody array and enzyme-linked immunosorbent assay to measure the level of angiogenic factors released from MSCs when cultured on SIS ECM or regular tissue culture plastic. We tested MSCs cultured for three different time points.ResultsWe found that the SIS ECM culture environment can significantly enhance the release of several angiogenic factors when compared to MSCs cultured on standard tissue culture plastic. Specifically, vascular endothelial growth factor and interleukin-8 secretion was significantly increased at 24, 48 and 72 hours postseeding onto SIS ECM whereas vascular endothelial growth factor release for cells cultured on plastic surface remained the same during these time points. We also observed significant donor to donor variation in cytokine production.ConclusionsThis study demonstrates that MSCs transplanted onto a SIS ECM may greatly increase their therapeutic potential through an increase in pro-angiogenic cytokine release.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0165-3) contains supplementary material, which is available to authorized users.

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

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. 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. 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. 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.

Invited Commentary

Rosario-Quinones and colleagues report [1Rosario-Quinones F. Magid M.S. Yau J. Pawale A. Nguyen K. Tissue reaction to porcine intestinal submucosa (CorMatrix) implants in pediatric cardiac patients: a single-center experience.Ann Thorac Surg. 2015; 99: 1373-1378Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar] their experience of using CorMatrix during pediatric cardiac surgery. Six of 25 patients required reoperation and pathology demonstrated inflammation and fibrosis with transient peripheral eosinophilia. It is difficult to know how to interpret these findings. The small intestinal submucosa-extracellular matrix (SIM-ECM) technology has been used in greater than 2,000,000 patients and constructive remodeling has been reported in greater than 800 scientific papers. CorMatrix has been used for reconstruction of all 4 cardiac valves, aorta and pulmonary arteries, septal defect closure, outflow tract repairs, and pericardial reconstruction. In general, clinical reports are few and the concern has been inflammation and fibrosis [2Zaidi A.H. Nathan M. Emani S. et al.Preliminary experience with porcine intestinal submucosa(CorMatrix) for valve reconstruction in congenital heart disease: histologic evaluation of explanted valves.J Thorac Cardiovasc Surg. 2014; 148 (2216-4, 2225.e1)Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar]. Negative results reported have ranged from explanted pathology to abnormal imaging (computed tomography, magnetic resonance imaging, and echocardiography) to contraction and thickening noted at reoperation. Techniques of implantation are also variable; continuous versus interrupted suture, circumferential suture lines, eg, mid-leaflet augmentation or blood vessel reconstruction versus an exposed free edge with semilunar leaflet reconstruction, and finally anastomosis to a freshly cut normal endocardium that may be important for porcine scaffold cellularization. Despite concerning reports, CorMatrix implants now exceed 120,000 patients and feedback by many surgeons have been positive (Drs Emile Bacha, James Tweddell, ∗Drs Bacha and Tweddell are both on the Medical Advisory Board for CorMatrix.∗Drs Bacha and Tweddell are both on the Medical Advisory Board for CorMatrix. Patrick McConnell, Frank Scholl and John Kupferschmid, personal communications, February 2 and 3, 2015). Favorable comments include “soft and pliable,” “looks like the native tissue of what was reconstructed,” and “cannot differentiate between CorMatrix and adjacent native tissue.” There are some patients who react adversely to bioprosthetic valves and have early deterioration. Whether this is similar to the negative findings reported with CorMatrix is not clear. It should be emphasized that adherence to proper preparation protocols is essential as inadvertent rinsing of a bioprosthetic valve with antibiotic solution can adversely affect the leaflets [3Hu J.E. Gilmer L. Hopkins R. Wolfinbarger Jr., L. Effects of antibiotics on cellular viability in porcine heart valve tissue.Cardiovasc Res. 1990; 24 ([Erratum]): 168Crossref Scopus (16) Google Scholar]. There is a need for a prosthetic that will remodel, grow, and not calcify. Current materials include synthetic, cross-linked, or glutaraldehyde-treated and all are non-growing. Basic science evidence has demonstrated CorMatrix to be capable of in vivo remodeling and probable growth of new heart muscle [4Yanagawa R. Rao V. Yau T.M. Cusimano R.J. Potential myocardial regeneration with CorMatrix ECM: a case report.J Thorac Cardiovasc Surg. 2014; 147: e41-e43Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar]. It may well be that multiple ECM products will be required and that one design does not fit all needs. Regenerative medicine is the future for many cardiovascular diseases. The negative findings in this review add to the other small series of worrisome anecdotes. The discrepancy between favorable opinions by other surgeons who use CorMatrix enthusiastically contributes to the confusion as to what its role is and should be. More comprehensive follow-up or prospective study is required to determine its place in clinical practice. Tissue Reaction to Porcine Intestinal Submucosa (CorMatrix) Implants in Pediatric Cardiac Patients: A Single-Center ExperienceThe Annals of Thoracic SurgeryVol. 99Issue 4PreviewDecellularized porcine small intestine submucosa (CorMatrix, Atlanta, GA) patches have been used in the repair of congenital heart malformations. Tissue reaction to the material may create hemodynamic dysfunction and necessitate explantation. We reviewed our series of congenital cardiac patients who had a reoperation after the implantation of CorMatrix patches. Full-Text PDF

Healing Rate and Autoimmune Safety of Full-Thickness Wounds Treated With Fish Skin Acellular Dermal Matrix Versus Porcine Small-Intestine Submucosa

A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care.

PIN44 - Cost-Effectiveness Of Small Intestinal Submucosa Extracellular Matrix On Wound Closure In Patients With Difficult-To-Heal Wound Of Mixed Arterial/Venous And Venous Etiology

Determine the cost-effectiveness of small intestinal submucosa extracellular matrix (SISEM) relative to standard of care (SC) on wound closure for the treatment of mixed arterial/venous (A/V) or venous (VLUs) leg ulcers. A 2-stage Markov model was used to predict the expected costs and outcomes of wound closure for SISEM and SC. Outcome data used in the analysis were taken from an 8-week randomized clinical trial that directly compared SISEM and SC. Patients were followed for 6 months to assess wound closure. Forty-eight patients completed the study; 25 for SISEM and 23 for SC. SC was defined as a standard moist wound dressing. Transition probabilities for the Markov states were estimated from the clinical trial. The economic outcome of interest was direct cost per ulcer-free week. Resource utilization was based on the treatment regimen used in the clinical trial. Costs were derived from standard cost references. The payer’s perspective was taken. SISEM-treated wounds healed, on average, after 5.4 weeks of treatment, compared to 8.3 weeks for SC wounds (p=0.02). Furthermore, complete wound closure was significantly higher for patients treated with SISEM (p<0.05), with 20 wounds closed in the SISEM group (80%) and 15 wounds closed in the SC group (65%). After 6 months, patients treated with SISEM had substantially higher ulcer-free weeks compared to SC (20.0 versus 16.8, respectively). Expected direct costs per patient were $2,360 for SISEM and $1,326 for SC. The incremental cost-effectiveness ratio (ICER) for SISEM was $349 (approximately $50/day), indicating that for each $349 paid for SISEM therapy patients gained one additional ulcer-free week. SISEM yielded better outcomes at a slightly higher cost in patients with mixed A/V and VLUs. SISEM is an effective treatment for wound healing and should be considered for use in the management of mixed A/V and VLUs.

PDB65 - Cost-effectiveness of small intestinal submucosa extracellular matrix on wound closure in patients with diabetic foot ulcer

Determine the cost-effectiveness of small intestinal submucosa extracellular matrix (SISEM)* relative to human fibroblast-derived dermal substitute (HF-DDS)†on wound closure for the treatment of diabetic foot ulcers (DFUs). A 2-stage Markov model was used to predict the expected costs and outcomes of wound closure for SISEM and HF-DDS. Outcome data used in the analysis were taken from a 12-week randomized clinical trial that directly compared SISEM and HF-DDS. Twenty-six patients completed the study; 13 for SISEM and 13 for HF-DDS. The primary outcome of interest was ulcer-free days. Transition probabilities for the Markov states were estimated from the clinical trial. Resource utilization was based on the treatment regimen used in the clinical trial. Costs were derived from standard cost references and medical supply wholesalers. The economic perspective taken was that of the payer. No cost discounting was performed due to the short duration of the study. Ten wounds closed in the SISEM group (77%), with an average time to closure of 36 days, while 11 wounds closed in the HF-DDS group (85%), with an average closure time of 41 days. No significant difference was found in the time to closure or in the percentage of wound closure between the two groups (p=0.73). Expected direct costs per patient for DFU were $2,949 for SISEM and $5,282 for HF-DDS. Patients treated with HF-DDS incurred total treatment costs that were approximately 1.8 times higher than those treated with SISEM. The estimated cost per ulcer-free day was more than 1.5 times higher HF-DDS vs. SISEM. SISEM yielded similar outcomes at a lower cost in patients with DFU. Health care providers should consider SISEM as a cost-saving alternative to HF-DDS. *OASIS®, Smith & Nephew Biotherapeutics, Fort Worth, Texas †Dermagraft®, Shire Regenerative Medicine Inc., San Diego, California

Short-term experience using Cormatrix as aortic leaflet replacement or extension in pediatric patients

Objectives: The preservation and repair of aortic valve has emerged over the last years. The greatest benefit to avoid valve prosthesis can be expected for the congenital population. Currently used biological patch materials are associated with limited longevity. A recently introduced new patch, made of decellularized porcine small intestinal submucosa extracellular matrix (CorMatrix®) presents promising characteristics.

Effects and Mechanistic Correlates of Using a Liquefied, Injectable Porcine Submucosa Extracellular Matrix, With Or Without Angiogenic Cells, in a Myocardial Scar Model

We examined possible effects and mechanisms involved in cardiac remodeling and vasculomyogenesis after injection of a clinically approved, porcine-derived small intestinal submucosa-extracellular matrix (SIS-ECM) injectable material, with and without circulating angiogenic cells (CACs), in a mouse model of post-infarction myocardial scar.