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使用由己内酯和 D,L-丙交酯共聚物组成的弹性心脏补片进行右心室流出道置换的长期疗效和结局。

Long term efficacy and fate of a right ventricular outflow tract replacement using an elastomeric cardiac patch consisting of caprolactone and D,L-lactide copolymers.

机构信息

Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

Acta Biomater. 2021 Mar 15;123:222-229. doi: 10.1016/j.actbio.2021.01.022. Epub 2021 Jan 18.

DOI:10.1016/j.actbio.2021.01.022
PMID:33476828
Abstract

For decades, researchers have investigated the ideal material for clinical use in the cardiovascular field. Several substitute materials are used clinically, but each has drawbacks. Recently we developed biodegradable and elastic poly(ε-caprolactone-co-D,L-lactide) (P(CL-DLLA)) copolymers by adjusting the CL/DLLA composition, and evaluated the long-term efficacy and outcomes of these copolymers when used for right ventricular outflow tract (RVOT) replacement. This P(CL-DLLA) material was processed into a circular patch and used to replace a surgical defect in the RVOT of adult rats. Control rats were implanted with expanded polytetrafluoroethylene (ePTFE). Histologic evaluation was performed at 8, 24, and 48 weeks post-surgery. All animals survived the surgery with no aneurysm formation or thrombus. In all periods, ePTFE demonstrated fibrous tissue. In contrast, at 8 weeks P(CL-DLLA) showed infiltration of macrophages and fibroblast-like cells into the remaining material. At 24 weeks, P(CL-DLLA) was absorbed completely, and muscle-like tissue was present with positive staining for α-sarcomeric actinin and cardiac troponin T (cTnT). At 48 weeks, the cTnT-positive area had increased. The biodegradable and elastic P(CL-DLLA) induced cardiac regeneration throughout the 48-week study period. Future application of this material as a cardiovascular scaffold seems promising. STATEMENT OF SIGNIFICANCE: Biomaterials for reconstruction of tissue deficiencies in cardiovascular surgery require having suitable mechanical properties for cardiac tissue and biodegradation resulting in native tissue growth. Several biodegradable polymers such as poly-ε-caprolactone (PCL) and polylactic acid (PLA) have excellent biocompatibility and already been widely used clinically. In general, PCL and PLA are quite mechanically rigid. Meanwhile, significant elasticity is required in the high-pressure environment of the heart while the material is being replaced by new tissue. The present study provides a novel four-armed crosslinked poly(ε-caprolactone-co-D,L-lactide) (i.e., P(CL-DLLA)) material for cardiac patch, which was demonstrated properties including tissue-compatible, super-elastic nature, that made it suitable for long-term, in vivo RVOT repair. This super-elastic biomaterial could be useful for reconstruction of various muscular tissues deficiencies.

摘要

几十年来,研究人员一直在研究心血管领域临床应用的理想材料。临床上已经使用了几种替代材料,但每种材料都有其缺点。最近,我们通过调整 CL/DLLA 组成,开发了可生物降解和弹性的聚(ε-己内酯-co-D,L-丙交酯)(P(CL-DLLA))共聚物,并评估了这些共聚物用于右心室流出道(RVOT)置换时的长期疗效和结果。这种 P(CL-DLLA)材料被加工成圆形补丁,用于替代成年大鼠 RVOT 的手术缺损。对照大鼠植入膨体聚四氟乙烯(ePTFE)。术后 8、24 和 48 周进行组织学评估。所有动物均存活,无动脉瘤形成或血栓形成。在所有时期,ePTFE 均显示出纤维组织。相比之下,在 8 周时,P(CL-DLLA)显示巨噬细胞和成纤维细胞样细胞浸润到剩余材料中。在 24 周时,P(CL-DLLA)完全吸收,并且存在肌肉样组织,α-横纹肌肌动蛋白和心肌肌钙蛋白 T(cTnT)呈阳性染色。在 48 周时,cTnT 阳性区域增加。可生物降解和弹性的 P(CL-DLLA)在整个 48 周的研究期间诱导了心脏再生。这种材料作为心血管支架的未来应用似乎很有前景。意义声明:心血管手术中组织缺陷重建的生物材料需要具有适合心脏组织的机械性能和生物降解性,以促进原生组织生长。几种可生物降解的聚合物,如聚己内酯(PCL)和聚乳酸(PLA)具有极好的生物相容性,已经在临床上广泛使用。一般来说,PCL 和 PLA 的机械强度相当高。然而,当材料被新组织取代时,心脏处于高压环境,因此需要具有显著的弹性。本研究提供了一种新型四臂交联聚(ε-己内酯-co-D,L-丙交酯)(即 P(CL-DLLA))心脏补片材料,其具有组织相容性和超弹性等特性,使其适合长期体内 RVOT 修复。这种超弹性生物材料可用于重建各种肌肉组织缺陷。

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