Original ResearchHuman immune-cell response towards diverse xenogeneic and allogeneic decellularized biomaterials

•A study, using a validated ex-vivo setting, was able to observe diverse species-specific immune response towards different processed biomaterials.•Neither effective decellularization nor cross-linking of xenogeneic tissue eliminates human cell-mediated response toward these biological grafts.•The absence of cell response demonstrated in human dermal or vascular material, is likely predictive for a less exaggerated immune reaction in vivo.

BackgroundImmunological knowledge on processed biological implants and mesh-prostheses is still mainly based on animal models, lacking information on the species-specific human immune response. We hypothesized that in contrast to human tissue even decellularized xenogenic specimens would lead to significant and tissue source dependent human immune reactions.MethodsSpecimens from processed allogenic and xenogenic pulmonary arteries, pericardium or dermis, were co-cultured with human peripheral blood mononuclear cells (PBMNC). Proliferative responses were measured in tritiated thymidine incorporation assays (n = 10). Stimulation indices (SI), calculated as counts-per-minute of co-cultured PBMNC divided by the cpm of basic cell proliferation, were compared.ResultsCompared to native porcine pulmonary artery tissue decellularization significantly reduced human PBMNC proliferation (mean SI: 48.7 vs. 18.0, p < 0.01), which was still higher compared to the human equivalent (SI: 0.7 vs. 1.7). Also the processed human dermal implant did not elicit immune response (SI: 1.5), whereas the decellularized and cross-linked porcine dermis lead to a significant human cell-proliferation (SI: 8.4, p < 0.01). Interestingly, both the processed human (SI: 15.2) and bovine pericardial patches (SI: 15.1) led to higher immune cell proliferation.ConclusionEven decellularized or cross-linked xenogenic cardiovascular and reconstructive biomaterials elicit increased human immune responses not seen in the majority of allogenic specimens tested.