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

目前使用的生物瓣膜有一些局限性，如钙化和。功能退化，并通过细胞内生来恢复活力是不可能的。为了克服这些障碍，我们开发了一种免疫原性最低的组织工程瓣膜，它由一种无固定的、脱细胞的猪瓣支架组成，能够在植入后在体内自发恢复活力。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方法有效地去除了猪主动脉组织中的细胞碎片。在一项初步研究中，脱细胞组织植入大鼠皮下14天和60天后，显示出最小的炎细胞渗透和钙化。将脱细胞猪瓣作为活体瓣膜置换术模型植入犬的肺动脉瓣部位。术后2个月内中膜细胞自发内皮化和再生，6个月内超声心动图显示瓣膜功能良好，无返流现象。最低免疫原性去细胞猪瓣膜被证明有效地减轻了术后钙化，并通过原位再细胞化、细胞内长入和组织重塑为修复假体提供了合适的基质。我们还发现，我们的脱细胞瓣膜含有结合纤维连接蛋白和肝细胞生长因子的融合蛋白，可能会加速原位再细胞化。

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.