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基于猪软骨的可注射交联软骨细胞外基质-PEG 水凝胶支架的构建及其在组织工程中的体内评估。

Development and In Vivo Assessment of an Injectable Cross-Linked Cartilage Acellular Matrix-PEG Hydrogel Scaffold Derived from Porcine Cartilage for Tissue Engineering.

机构信息

Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea.

Research Institute, Medipolymers, Woncheon Dong 332-2, Suwon, 16522, South Korea.

出版信息

Macromol Biosci. 2023 Jun;23(6):e2300029. doi: 10.1002/mabi.202300029. Epub 2023 Apr 13.

Abstract

The cartilage acellular matrix (CAM) derived from porcine cartilage, which does not induce significant inflammation and provides an environment conducive for cell growth and differentiation, is a promising biomaterial candidate for scaffold fabrication. However, the CAM has a short period in vivo, and the in vivo maintenance is not controlled. Therefore, this study is aimed at developing an injectable hydrogel scaffold using a CAM. The CAM is cross-linked with a biocompatible polyethylene glycol (PEG) cross-linker to replace typically used glutaraldehyde (GA) cross-linker. The cross-linking degree of cross-linked CAM by PEG cross-linker (Cx-CAM-PEG) according to the ratios of the CAM and PEG cross-linker is confirmed by contact angle and heat capacities measured by differential scanning calorimetry. The injectable Cx-CAM-PEG suspension exhibits controllable rheological properties and injectability. Additionally, injectable Cx-CAM-PEG suspensions with no free aldehyde group are formed in the in vivo hydrogel scaffold almost simultaneously with injection. In vivo maintenance of Cx-CAM-PEG is realized by the cross-linking ratio. The in vivo formed Cx-CAM-PEG hydrogel scaffold exhibits certain host-cell infiltration and negligible inflammation within and near the transplanted Cx-CAM-PEG hydrogel scaffold. These results suggest that injectable Cx-CAM-PEG suspensions, which are safe and biocompatible in vivo, represent potential candidates for (pre-)clinical scaffolds.

摘要

来源于猪软骨的脱细胞软骨细胞外基质(CAM)不会引起明显的炎症,并为细胞的生长和分化提供有利的环境,是一种很有前途的支架制造生物材料候选物。然而,CAM 在体内的半衰期较短,且体内的维持不受控制。因此,本研究旨在开发一种使用 CAM 的可注射水凝胶支架。通过将生物相容性的聚乙二醇(PEG)交联剂交联到 CAM 上来替代通常使用的戊二醛(GA)交联剂。通过差示扫描量热法测量的接触角和热容来确认根据 CAM 和 PEG 交联剂的比例交联的 CAM 的交联程度(Cx-CAM-PEG)。可注射的 Cx-CAM-PEG 悬浮液表现出可控制的流变学性质和可注射性。此外,在体内几乎与注射同时形成了没有游离醛基的可注射 Cx-CAM-PEG 水凝胶支架。通过交联比实现 Cx-CAM-PEG 的体内维持。体内形成的 Cx-CAM-PEG 水凝胶支架在移植的 Cx-CAM-PEG 水凝胶支架内及其附近显示出一定的宿主细胞浸润和可忽略不计的炎症。这些结果表明,体内安全且具有生物相容性的可注射 Cx-CAM-PEG 悬浮液是(预)临床支架的潜在候选物。

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