自体心脏移植的最佳生物材料

T. Ozawa, Donald A. G. Mickle, R. Weisel, N. Koyama, S. Ozawa, Ren-Ke Li
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Cell-seeded patches were employed to replace a surgically created defect in the right ventricular outflow tract (RVOT) of rats (n=5 per group). Histology was studied at 8 weeks following implantation. ResultsIn vitro studies showed that the DNA content increased significantly (P <0.05) in all patches between 1 and 3 weeks after seeding. Histology and staining SMCs for anti-&agr;-smooth muscle actin (&agr;SMA) revealed better growth of cells in the interstices of the grafts with GEL and PCLA than the PGA graft. In vivo studies demonstrated that seeded SMCs survived at least 8 weeks after the patch implantation in all groups. PCLA scaffolds were replaced by more cells with larger &agr;SMA-positive areas and by more extracellular matrix with larger elastin-positive areas than with GEL and PGA. The patch did not thin and expanded significantly. The GEL and PGA patches thinned and expanded. All grafts had complete endothelialization on the endocardial surface. 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引用次数: 137

摘要

背景:修复先天性心脏缺陷的最佳心脏移植物将由自体细胞组成,并与儿童一起生长。生物可降解材料应允许细胞快速生长和延迟降解,炎症最小。我们比较了一种新材料,用针织聚乳酸织物(PCLA)增强的&egr;-己内酯-co-l-丙交酯海绵,明胶(GEL)和聚乙醇酸(PGA),这是以前评价的材料。方法将同种型大鼠主动脉平滑肌细胞(SMCs, 2×106)分别接种于GEL、PGA和PCLA贴片上培养(每组11个)。在播种后1周、2周和3周测量每个斑块的DNA含量。播种后2周进行组织学检查。采用细胞种子补片替代大鼠右心室流出道(RVOT)的手术缺损(每组n=5)。植入后8周进行组织学观察。结果体外研究表明,在播种后1 ~ 3周,各斑块的DNA含量均显著升高(P <0.05)。组织学和抗-&agr;-平滑肌肌动蛋白(&agr;SMA)的SMCs染色显示,与PGA移植物相比,GEL和PCLA移植物间质细胞生长更好。体内研究表明,在所有组中,有籽的SMCs在贴片植入后至少存活了8周。与GEL和PGA相比,PCLA支架被更多具有更大&agr; sma阳性区域的细胞和更多具有更大弹性蛋白阳性区域的细胞外基质所取代。贴片没有变薄,而且明显扩大。凝胶和PGA斑块变薄和扩大。所有移植物在心内膜表面都有完全的内皮化。结论smc种子生物可降解材料可用于修复RVOT。新型PCLA贴片在体外允许更好的细胞穿透,在体内不会变薄或扩张,也不会产生炎症反应。细胞种子PCLA贴片可以允许构建自体贴片来修复先天性心脏缺陷。
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Optimal Biomaterial for Creation of Autologous Cardiac Grafts
BackgroundThe optimal cardiac graft for the repair of congenital heart defects will be composed of autologous cells and will grow with the child. The biodegradable material should permit rapid cellular growth and delayed degradation with minimal inflammation. We compared a new material, &egr;-caprolactone-co-l-lactide sponge reinforced with knitted poly-l-lactide fabric (PCLA), to gelatin (GEL) and polyglycolic acid (PGA), which are previously evaluated materials. MethodsSyngenic rat aortic smooth muscle cells (SMCs, 2×106) were seeded onto GEL, PGA, and PCLA patches and cultured (n=11 per group). The DNA content in each patch was measured at 1, 2, and 3 weeks after seeding. Histological examination was performed 2 weeks after seeding. Cell-seeded patches were employed to replace a surgically created defect in the right ventricular outflow tract (RVOT) of rats (n=5 per group). Histology was studied at 8 weeks following implantation. ResultsIn vitro studies showed that the DNA content increased significantly (P <0.05) in all patches between 1 and 3 weeks after seeding. Histology and staining SMCs for anti-&agr;-smooth muscle actin (&agr;SMA) revealed better growth of cells in the interstices of the grafts with GEL and PCLA than the PGA graft. In vivo studies demonstrated that seeded SMCs survived at least 8 weeks after the patch implantation in all groups. PCLA scaffolds were replaced by more cells with larger &agr;SMA-positive areas and by more extracellular matrix with larger elastin-positive areas than with GEL and PGA. The patch did not thin and expanded significantly. The GEL and PGA patches thinned and expanded. All grafts had complete endothelialization on the endocardial surface. ConclusionsSMC-seeded biodegradable materials can be employed to repair the RVOT. The novel PCLA patches permitted better cellular penetration in vitro and did not thin or dilate in vivo and did not produce an inflammatory response. The cell-seeded PCLA patch may permit the construction of an autologous patch to repair congenital heart defects.
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