Minimally-immunogenic Decellularized Porcine Valve Provides In-situ Recellularization in a Stentless Bioprosthetic Valve

目前使用的生物假体瓣膜存在诸如钙化和。功能退化，通过细胞向内生长来恢复活力是不可能的。为了克服这些障碍，我们开发了一种最低免疫原性的组织工程瓣膜，它由一个非固定的、去细胞化的猪瓣膜支架组成，能够在植入后在体内自发地恢复活力。用洗涤剂对猪主动脉根部组织进行脱细胞。组织学检查表明，新开发的洗涤剂处理有效地去除了猪主动脉组织中的细胞碎片。在初步研究中，大鼠皮下植入脱细胞组织14天和60天，炎症细胞浸润和钙化程度最低。将脱细胞猪瓣膜植入犬肺瓣膜位置，作为活体瓣膜置换模型。在本研究中，患者在2个月内观察到自发性再内皮化和内侧细胞再生，超声心动图观察到瓣膜功能良好，无反流，持续6个月。最小免疫原性脱细胞猪瓣膜被证明可以有效减轻植入后的钙化，并通过原位再细胞化、细胞长入和组织重塑为修复假体提供合适的基质。我们还发现，我们的脱细胞瓣膜含有融合蛋白结合纤维连接蛋白和肝细胞生长因子可能加速原位再细胞化。

CurRently used bioprosthetic valves have limitations such as.calcification and. functional deterioration, and revitalization through cellular ingrowth is impossible. To overcome these obstacles, we have developed a minimally immunogenic tissue-engineered valve that consists of an unfixed, decellularized porcine valve scaffold capable of being spontaneously revitalized in vivo after implantation. Porcine aortic root tissue was decellularized using detergents. Histological examination showed that the newly developed detergent treatment effectively removed cellular debris from the porcine aortic tissue. In a preliminary study, Decellularized tissue implanted subdermally in rats for 14 and 60 days showed minimal inflammatory cell infiltration and calcification. As an in vivo valve replacement model, the decellularized porcine valve was implanted in the pulmonary valve position in dogs. In this series, spontaneous reendothelialization and repopulation of the medial cells were observed within 2 months, and good valve function without regurgitation was observed by echocardiography up to 6 months. The minimally immunogenic decellularized porcine valve proved effective in mitigating postimplant calcification and provided a suitable matrix for revitalizing prostheses through in situ recellularization, cellular ingrowth, and tissue remodeling. We also find that our decellularized valve containing a fusion protein combined fibronectin and hepatocyte growth factor might accelerate in situ recellularization.