Host immune response to tissue engineering tissues or organs directly determines the graft survival and the integration with host. Our and other previous studies have successfully regenerated the organs/tissues based on allogeneic native decellularized matrix (aNDM). But the very limited aNDM clinically hinders the artificial organs/tissues application to resolve the native organs/tissues loss with high incidence. However, the xenogeneic NDM will induce host immune rejection leading to the transplantation failure. This study constructed the xenogeneic (porcine) NDM (xNDM) which carried the immunoregulator Rosiglitazone (xNDM-RSG), a synthetic highly selective agonist of peroxisome proliferator-activated receptor-γ (PPARγ), evaluated xNDM's physical and chemical characterization, immunomodulatory properties, and its effect on the tissue regeneration. Results showed that the xNDM-RSG did not affect the proliferation and differentiation of odontogenic stem cells. In addition, the xNDM-RSG could also effectively decrease the expression of IL-1 and TNFα, and increase the expression of IL-10 and TGFβ to enable a favorable immunomodulation and promote the ligament-to-bone regeneration by PPARγ to induce the alternative activated macrophages (M2 macrophages) antagonizing classically activated macrophages (M1 macrophages). Meanwhile the xNDM-RSG obviously reduces the implants absorption and promotes the regenerated ligament-to-bone expressing the key proteins (ALP, OPN, DSP) which are relative to the native dental and bone. This study demonstrated that protein adsorption could aggravate the immune inflammatory reaction, whereas, xNDM-RSG could effectively control the host immune response to accelerate tissue reparation and regeneration by facilitating the macrophage polarization, which highlighted a new strategy for improving the transplantation survival of the artificial organ or tissue based on the xenogeneic decellularized biomaterials.

宿主对组织工程组织或器官的免疫反应直接决定了移植物的存活以及与宿主的整合。我们和其他先前的研究已经成功地基于同种异体天然脱细胞基质（aNDM）再生了器官/组织。但是非常有限的aNDM在临床上阻碍了人工器官/组织的应用以解决高发生率的天然器官/组织的损失。但是，异种NDM将诱导宿主免疫排斥反应，从而导致移植失败。这项研究构建了异种（猪）NDM（xNDM），它携带了免疫调节剂罗格列酮（xNDM-RSG），一种过氧化物酶体增殖物激活受体-γ（PPARγ）的合成高选择性激动剂，评估了xNDM的理化特性，免疫调节特性，及其对组织再生的影响。结果表明，xNDM-RSG不会影响牙源性干细胞的增殖和分化。此外，xNDM-RSG还可以有效降低IL-1和TNFα的表达，并增加IL-10和TGFβ的表达，从而实现良好的免疫调节，并促进PPARγ诱导韧带到骨的再生，从而诱导替代激活的巨噬细胞（M2巨噬细胞）对抗经典激活的巨噬细胞（M1巨噬细胞）。同时，xNDM-RSG明显减少了植入物的吸收并促进了再生的韧带到骨表达的关键蛋白（ALP，OPN，DSP），这些蛋白相对于天然牙齿和骨骼。这项研究表明，蛋白质吸附可加剧免疫炎症反应，而