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载有 TGF-β3 的纳米粒子的海藻酸钠-聚丙烯酰胺水凝胶用于软骨修复:生物降解性、生物相容性和蛋白质吸附。

An alginate-poly(acrylamide) hydrogel with TGF-β3 loaded nanoparticles for cartilage repair: Biodegradability, biocompatibility and protein adsorption.

机构信息

Department of Bioengineering, Faculty of Engineering, Ege University, 35100 Izmir, Turkey.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Marmara University, 34668 Istanbul, Turkey.

出版信息

Int J Biol Macromol. 2021 Mar 1;172:381-393. doi: 10.1016/j.ijbiomac.2021.01.069. Epub 2021 Jan 18.

DOI:10.1016/j.ijbiomac.2021.01.069
PMID:33476613
Abstract

Current implantable materials are limited in terms of function as native tissue, and there is still no effective clinical treatment to restore articular impairments. Hereby, a functionalized polyacrylamide (PAAm)-alginate (Alg) Double Network (DN) hydrogel acting as an articular-like tissue is developed. These hydrogels sustain their mechanical stability under different temperature (+4 °C, 25 °C, 40 °C) and humidity conditions (60% and 75%) over 3 months. As for the functionalization, transforming growth factor beta-3 (TGF-β3) encapsulated (NP) and empty poly(lactide-co-glycolide) (PLGA) nanoparticles (PLGA NPs) are synthesized by using microfluidic platform, wherein the mean particle sizes are determined as 81.44 ± 9.2 nm and 126 ± 4.52 nm with very low polydispersity indexes (PDI) of 0.194 and 0.137, respectively. Functionalization process of PAAm-Alg hydrogels with ester-end PLGA NPs is confirmed by FTIR analysis, and higher viscoelasticity is obtained for functionalized hydrogels. Moreover, cartilage regeneration capability of these hydrogels is evaluated with in vitro and in vivo experiments. Compared with the PAAm-Alg hydrogels, functionalized formulations exhibit a better cell viability. Histological staining, and score distribution confirmed that proposed hydrogels significantly enhance regeneration of cartilage in rats due to stable hydrogel matrix and controlled release of TGF-β3. These findings demonstrated that PAAm-Alg hydrogels showed potential for cartilage repair and clinical application.

摘要

目前的植入材料在功能上与天然组织相比存在局限性,仍然没有有效的临床治疗方法来恢复关节损伤。因此,开发了一种具有功能化的聚丙烯酰胺(PAAm)-海藻酸钠(Alg)双网络(DN)水凝胶,作为类似关节的组织。这些水凝胶在 3 个月内可以在不同的温度(+4°C、25°C、40°C)和湿度条件(60%和 75%)下保持其机械稳定性。至于功能化,通过微流控平台合成了包封转化生长因子β-3(TGF-β3)的纳米颗粒(NP)和空的聚(乳酸-共-乙醇酸)(PLGA)纳米颗粒(PLGA NPs),其平均粒径分别确定为 81.44±9.2nm 和 126±4.52nm,具有非常低的多分散指数(PDI)分别为 0.194 和 0.137。通过傅里叶变换红外(FTIR)分析证实了 PAAm-Alg 水凝胶与酯端 PLGA NPs 的功能化过程,并且功能化水凝胶具有更高的粘弹性。此外,通过体外和体内实验评估了这些水凝胶的软骨再生能力。与 PAAm-Alg 水凝胶相比,功能化配方表现出更好的细胞活力。组织学染色和评分分布证实,由于稳定的水凝胶基质和 TGF-β3 的控制释放,所提出的水凝胶显著增强了大鼠软骨的再生。这些发现表明 PAAm-Alg 水凝胶具有用于软骨修复和临床应用的潜力。

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