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可生物降解的均聚物与多嵌段共聚物的体内生物相容性研究及其(微观)结构与一种已确立的生物材料的比较。

In vivo biocompatibility study of degradable homo- versus multiblock copolymers and their (micro)structure compared to an established biomaterial.

机构信息

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.

Department of Cardiology, Campus Virchow Klinikum, Charité, Berlin, Germany.

出版信息

Clin Hemorheol Microcirc. 2020;75(2):163-176. doi: 10.3233/CH-190748.

Abstract

Copolyetheresterurethane (PDC) is a biodegradable, shape-memory biomaterial, which has been shown to be of low toxicity and pro-angiogenic in vitro. In the present study we examined the in vivo compatibility of PDC as a compression molded film and as electrospun scaffolds and its well established constituent, the homopolymer poly(p-dioxanone) (PPDO), which were compared with the clinically used poly[(vinylidene fluoride)-co-hexafluoropropene] (PVDF) as reference material. The materials were implanted in the subcutaneous tissue of mice and the host responses were analyzed histologically 7 and 28 days after implantation.All materials induced a foreign body response (FRB) including the induction of foreign body giant cells and a peripheral fibrous capsule. PDC, PPDO and PVDF films showed no signs of degradation after 28 days. PDC films showed a significantly reduced associated macrophage layer and fibrous capsule on their surface. Few fragments of PDC and PPDO scaffolds were present at the implantation site, while PVDF scaffolds were still present in large amounts at day 28. Especially aligned electrospun PDC scaffold induced a significantly thinner fibrous and a slightly reduced inflammatory response after 28 days of implantation. In addition, only PDC aligned fibrous scaffold structures induced a significant increase in angiogenesis.In summary, PDC films outperformed PPDO and PVDF films in terms of compatibility, especially in capsule and macrophage layer thickness. Through microstructuring of PDC and PPDO into scaffolds an almost complete degradation was observed after 28 days, while their respective films remained almost unchanged. However, the capsule thickness of all scaffolds was comparable to the films after 28 days. Finally, the parallel arrangement of PDC fibers enabled a strong enhancement of angiogenesis within the scaffold. Hence, material chemistries influence overall compatibility in vivo, while angiogenesis could be influenced more strongly by microstructural parameters than chemical ones.

摘要

共聚醚酯氨酯(PDC)是一种可生物降解的形状记忆生物材料,体外研究表明其具有低毒性和促血管生成作用。在本研究中,我们研究了 PDC 压缩成型薄膜和电纺支架的体内相容性及其组成部分,即均聚物聚对二氧环己酮(PPDO),并与临床使用的聚[(偏二氟乙烯)-共-六氟丙烯](PVDF)作为参考材料进行了比较。将这些材料植入小鼠的皮下组织中,在植入后 7 天和 28 天分析组织学上的宿主反应。所有材料均诱导异物反应(FRB),包括异物巨细胞和外周纤维囊的诱导。PDC、PPDO 和 PVDF 薄膜在 28 天后均未显示出降解迹象。PDC 薄膜在其表面显示出明显减少的相关巨噬细胞层和纤维囊。在植入部位仅存在少量 PDC 和 PPDO 支架的碎片,而 PVDF 支架在第 28 天仍大量存在。特别是排列的 PDC 电纺支架在植入 28 天后,诱导的纤维和炎症反应明显变薄。此外,只有排列的 PDC 纤维支架结构诱导了血管生成的显著增加。总之,在相容性方面,PDC 薄膜优于 PPDO 和 PVDF 薄膜,特别是在胶囊和巨噬细胞层厚度方面。通过将 PDC 和 PPDO 微结构化为支架,在 28 天后几乎完全降解,而它们各自的薄膜几乎没有变化。然而,所有支架的胶囊厚度在 28 天后与薄膜相当。最后,PDC 纤维的平行排列使支架内的血管生成得到了强烈增强。因此,材料化学性质会影响体内整体相容性,而血管生成可能更多地受到微观结构参数的影响,而不是化学性质的影响。

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