Subcutaneous surgical rat models for the evaluation of decellularised heart valve immunogenicity: A systematic review

Background: Tissue engineered heart valves are being designed as alternative valvular conduits to standard bioprostheses with the potential to meet the requirements of an ideal valvular prosthesis: non-thrombogenicity, non-immunogenicity, long-lasting, and capability of growth, repair, and remodelling upon implantation. Assessments of immunogenicity are required before in vivo testing in large animals may be undertaken. Rats are a cost-effective model that are widely used for such assessments. However, it is unclear whether the surgical rat models used for examining tissue immunogenicity are homogenous in their design. Methods: Systematic searches were conducted in the PubMed, Scopus, and Web of Science databases for articles in which the immunogenicity of decellularised heart valves was examined using subcutaneous surgical rat models. Assessments were made of the animal, surgical, and donor scaffold characteristics used in such models. The heterogeneity of the various characteristics was then evaluated qualitatively. Results: In total, 54 articles were qualitatively assessed in this systematic review. The donor scaffold characteristics were homogenous. Whereas, the animal and surgical characteristics were heterogenous and infrequently reported. The collective data suggest that an agreed subcutaneous rat model might consist of implanting four, 1 cm(2), decellularised heart valve samples in the dorsal aspect of 6-week-old, Sprague Dawley, rats. Conclusions: Rat subcutaneous implantation may be undertaken to assess the immunogenicity of decellularised heart valves before proceeding to in vivo studies in large animal models. There is significant heterogeneity in the characteristics of the subcutaneous rat models that have been used, to date. Most studies insufficiently report the techniques used.

Automated summary

This study systematically assessed the characteristics of subcutaneous surgical rat models used for evaluating the immunogenicity of decellularised heart valves. The results showed homogeneity in donor scaffold characteristics, while animal and surgical characteristics were heterogeneous and poorly reported. It suggests the need for a standardized subcutaneous rat model for studying the immunogenicity of decellularised heart valves.