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Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.

ABSTRACT: Decellularized tissues have been widely used as scaffolds for biomedical applications due to their presentation of adhesion peptide sequences and growth factors, which facilitate integration with surrounding tissue. One of the most commonly used decellularized tissues is derived from porcine small intestinal submucosa (SIS). In some applications, SIS is crosslinked to modulate the mechanical properties or degradation rate of the scaffold. Despite the widespread use of SIS, there has been no mechanistic characterization of blood reactions with SIS, or how crosslinking affects these reactions. Therefore, we characterized the effect of SIS and carbodiimide-crosslinked SIS (cSIS) on plasma coagulation, including targeted assessments of the intrinsic and extrinsic coagulation pathways, and thrombus formation using flowing whole blood. SIS inhibited plasma coagulation initiated by recalcification, as well as low concentrations of thrombin or tissue factor. SIS prolonged the activated partial thromboplastin time by 14.3 ± 1.54s, indicating inhibition of the intrinsic coagulation pathway. Carbodiimide crosslinking abrogated all anticoagulant effects of SIS, as did heparinase I and III treatment, suggesting that heparin and heparan sulfate are predominantly responsible for SIS anticoagulant effects. Inhibiting contact activation of the intrinsic pathway prevented cSIS-mediated coagulation. When tubular SIS devices were connected to a nonhuman primate arteriovenous shunt loop, which enables whole blood to flow across devices without the use of anticoagulants, SIS demonstrated remarkably limited platelet accumulation and fibrinogen incorporation, while cSIS initiated significantly higher platelet and fibrinogen accumulation. These results demonstrate that SIS is a thromboresistant material and crosslinking markedly reduces the hemocompatibility of SIS.

SUBMITTER: Glynn JJ

PROVIDER: S-EPMC4308447 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.

Glynn Jeremy J JJ Polsin Elizabeth G EG Hinds Monica T MT

Acta biomaterialia 20141125

Decellularized tissues have been widely used as scaffolds for biomedical applications due to their presentation of adhesion peptide sequences and growth factors, which facilitate integration with surrounding tissue. One of the most commonly used decellularized tissues is derived from porcine small intestinal submucosa (SIS). In some applications, SIS is crosslinked to modulate the mechanical properties or degradation rate of the scaffold. Despite the widespread use of SIS, there has been no mech ...[more]

PMID: 25463505

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Project description:Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients' quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients' quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

Dataset Information

Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.

Publications

Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.

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