40 Development of an extracellular matrix hydrogel derived from decellularised tissues – a valuable tool for tissue engineering applications

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Abstract

Background

Irreversible intestinal failure (IIF) is a condition that can lead to significant morbidity and mortality and occurs as a result of anatomical or functional loss of the intestine. Many patients eventually require an intestinal transplant, which is unfortunately limited by poor survival (65% 1 year survival) and a scarcity of donor organs. Tissue engineering is an rapidly advancing field which we believe represents a highly promising potential solution to this problem. Stem cells isolated from the crypt of the intestine are an ideal cell source for this approach. However, they currently require 3D cell expansion in a commercially available hydrogel, Matrigel, which is currently not approved for clinical use. This represents a major road-block to the clinical translation of this otherwise extremely promising treatment option. To this end, our group have developed and optimised an extracellular matrix (ECM) hydrogel that is derived from decellularised intestinal tissue which has the potential to act as a Matrigel alternative.

Method

Piglet intestine is decellularised and formed into a gel using protocols developed by our group. These protocols were characterised using scanning electron microscopy (SEM), histology, immunohistochemistry, DNA and ECM quantification, rheology, spectrophotometry, angiogenic assays and proteomics. Cytocompatibility of intestinal stem cells in the gel was assessed with daily imaging, quantification and immunofluorescence.

Results

Results showed that a stable reproducible non-immunogenic gel is formed within 20 min post-application to 37°C, without the aid of any gelation agents. Proteomics showed a collagen-rich matrix with a plethora of other components including fibronectin, laminin myosin and fibrillin. Cell experiments demonstrated that the gel is biocompatible, non-cytotoxic and can facilitate cell viability with phenotypic morphology.

Conclusion

An ECM hydrogel derived from decellularised tissue represents a valuable tool for use in a many tissue engineering applications, primarily for 3D culturing of intestinal organoids. This discovery greatly widens the clinical potential for intestinal tissue engineering.

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