三种可降解聚合物构建组织工程心脏瓣膜的可行性对照

Feasibility of three kinds of biodegradable polymer scaffolds for fabricating tissue engineering heart valve

目的:评价作为组织工程心脏瓣膜支架的聚乙醇酸/聚乳酸共聚物,聚羟基丁酸/聚羟基戊酸共聚物,聚羟基丁酯3种生物可吸收材料的组织相容性和皮下吸收情况。探讨应用生物可降解材料构建组织工程心脏瓣膜的可行性。方法:实验于2004-12/2005-10在解放军第二军医大学长海医院全军胸心外科研究所完成。①应用扫描电镜观察聚乙醇酸/聚乳酸共聚物,聚羟基丁酸/聚羟基戊酸共聚物,聚羟基丁酯3种材料的结构特点。②新西兰大白兔18只,在兔背胸腰段脊柱两侧各作3个切口,每只兔分别植入6块可吸收材料,每种材料6只。③分别于术后2,4,6,8,10和12周各取6块材料,进行大体和组织学观察,并测量纤维包裹组织的厚度。结果:15只兔全部进入结果分析。①3种材料的结构特点:扫描电镜下3种材料均呈网孔状泡沫结构,聚羟基丁酯孔径约110μm,聚羟基丁酸/聚羟基戊酸共聚物孔径约130μm,聚乙醇酸/聚乳酸共聚物孔径约170μm。②组织学检查结果:聚羟基丁酸/聚羟基戊酸共聚物和聚乙醇酸/聚乳酸共聚物2周包膜纤维疏松,与其下肌肉组织分界不清,网孔中有疏松纤维组织长入,炎细胞以中性粒细胞和淋巴细胞为主,可见多核巨细胞。10周聚羟基丁酸/聚羟基戊酸共聚物材料完全吸收,12周聚乙醇酸/聚乳酸共聚物材料完全吸收,均为胶原纤维所代替。聚羟基丁酯2周包膜结缔组织疏松,伴中性粒细胞、淋巴细胞、浆细胞浸润和成纤维细胞弥漫性增生,也可见多核巨细胞。8周时包膜增厚,以淋巴细胞浸润为主。10周材料包膜较8周薄,炎性细胞明显减少,成纤维细胞转变为梭形的纤维细胞。③包膜厚度测量结果:包埋后2,4,6,8,10周聚羟基丁酸/聚羟基戊酸共聚物和聚乙醇酸/聚乳酸共聚物材料厚度测量值均显著小于聚羟基丁酯。结论:聚乙醇酸/聚乳酸共聚物、聚羟基丁酸/聚羟基戊酸共聚物在组织相容性和降解率方面优于聚羟基丁酯,更适合于作为组织工程心脏瓣膜的支架材料。

AIM： To evaluate the histocompatibility and hypodermic absorbability of three biodegradable polymer scaffolds [polyglycolic acid/polylactic acid （PLGA）, poly-hydroxybutyrate/hydroxyvalerate （PHBV） and polyhydroxybutyrate （PHB）], and investigate the feasibility of applying biodegradable materials on constructing tissue engineering heart valve. METHODS： The experiment was carded out in Cardiothoracic Surgery Institute, Changhai Hospital of Second Military Medical University of Chinese PLA from December 2004 to October 2005. ①Constructive characteristics of three biodegradable polymer scaffolds ware observed by scanning electron microscope （SEM）.②A total of 18 New Zealand rabbits ware adopted to induce 3 incisions at beth sides of rabbit dorsal spine, and every 6 rabbits ware embedded with one kind of absorptive material, 6 pieces in each rabbit. ③The histocompatibility and absorbability of three biodegradable polymer scaffolds ware compared after hypodermic implantation for 2, 4, 6, 8 and 12 weeks In addition, thickness of polymer scaffolds was measured. RESULTS ： All 15 rabbits ware involved in the result analysis. ① Porous structure ware observed by SEM, the diameter of PHB was 110 um, PHBV was 130 p.m, and PLGA was 170 um.②After hypodermic implantation for 2 weeks, PHBV and PLGA had no obvious demarcation with muscular tissue, loose fibrous tissue ware present in porous polymers, neutrophilic granulocyte and lymphocyte penetrated in polymers, and multinuclear giant cells could be observed. PHBV and PLGA ware completely degraded at the 10^th and 12^th weeks, and substituted by collagen fibers. PHB presented loose connective tissue at the 2^nd week, accompanying neutrophil, lymphocyte, plasmacyte infiltration and fibroblast diffuse proliferation, together with appearance of multinuclear giant cells. At the 8^th week, membrane thickened and lymphocyte infiltration was dominant. At the 10^th week, membrane became thinner, inflammatory cells ware decreased obviously, and fibroblast transformed to fusiform fibrocyte. ③The thickness of PHBV and PLGA ware lighter than PHB after hypodermic implantation for 2, 4, 6, 8 and 10 weeks. CONCLUSION： The histocompatibility and absorbability of PLGA and PHBV is better than that of PHB. So PLGA and PHBV can be used to fabricate a biodegradable tissue engineering scaffold for heart valve.