Biocompatibility and Immunophenotypic Characterization of a Porcine Cholecyst–derived Scaffold Implanted in Rats

Abstract

Comparative histomorphological assessment of local response to implanted reference biomaterial, also called biocompatibility testing/evaluation, in an appropriate animal model is a widely practiced safety evaluation procedure performed on biomaterials before clinical use. Standardized protocols and procedures, originally designed for testing synthetic materials, available for the testing/evaluation do not account for the immunogenic potential of a candidate biomaterial. Therefore, it is appropriate to supplement the routine biocompatibility test reports with adjunct data that may provide insight into the immunogenic potential of candidate biomaterials, especially when testing biomaterials that are derived from mammalian sources. This article presents expanded safety evaluation data of a porcine cholecyst-derived scaffold (CDS) intended as a xenogeneic graft. The biocompatibility was tested in rat subcutaneous model in comparison with a reference material and the CDS was found biocompatible. However, when studied by immunohistochemistry and real-time reverse transcription polymerase chain reaction for the number and/or polarization of M1 macrophage, M2 macrophage, cytotoxic T-cell, helper T cell, TH1 cell, and TH2 cell, the CDS appeared to induce a differential local immunopathological tissue reaction despite the similarity in biocompatibility with the reference material. The adjunct data collected were useful for objectively assessing the safety of CDS as a xenograft.

Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials

“…For all materials in both animal models, T-helper cell densities increased by day 7 with the decellularized materials becoming T-helper cell dominant compared to NDM (Figure 4B, C). This transition for the decellularized materials from a cytotoxic to a T-helper cell response has been previously observed [32] and suggests only NDM was being rejected as expected. Comparing the T-helper versus cytotoxic T-cell response between the decellularized materials, no significant differences were observed in the Balb/c mice and in the Hu-mice when the whole biomaterial was examined (Figure 4B).…”

Comparison of High‐Hydrostatic‐Pressure Decellularized Versus Freeze‐Thawed Porcine Menisci

“…The areas of the border between subcutaneous lesion and implanted meniscus were selected in parallel with the implanted meniscus as the high‐power fields. The numbers of giant cells per high‐power field were presented as mean ± standard deviation, as described in a previous report …”

Regenerative immunology: the immunological reaction to biomaterials

“…The composition of cellular infiltrates varies depending on the source and processing of the scaffold. Both neutrophilic and giant cell infiltrations have been seen after implantation of porcine and human scaffolds into rats . Mononuclear cells invade the peri‐implant space as early as at 24 h of implantation, and this process can continue for several months leading to chronic inflammation and encapsulation or scar formation .…”