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基于氧化葡聚糖和明胶的仿生自修复可注射纳米复合水凝胶,用于生长因子免费的骨再生。

Bioinspired self-healing injectable nanocomposite hydrogels based on oxidized dextran and gelatin for growth-factor-free bone regeneration.

机构信息

School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China.

College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China.

出版信息

Int J Biol Macromol. 2023 Nov 1;251:126145. doi: 10.1016/j.ijbiomac.2023.126145. Epub 2023 Aug 6.

DOI:10.1016/j.ijbiomac.2023.126145
PMID:37544566
Abstract

Hydrogels with great biocompatibility, biodegradability, and mechanical properties, combined with osteoconductivity, osteoinductivity, and osteointegration as biomaterials for bone regeneration without adding exogenous growth factors and cells are highly appealing but challenging. Here, inspired by organic-inorganic analogues of natural bone tissue and the adhesion chemistry of mussels, nanocomposite hydrogels with self-healing, injectable, adhesive, antioxidant, and osteoinductive properties (termed GO-PHA-CPs) were constructed by Schiff base cross-linking between dopamine-modified gelatin (Gel-DA) and oxidized dextran (ODex). Furthermore, the hydrogel network was enhanced by the introduction of polydopamine-functionalized nanohydroxyapatite (PHA) by improving the interfacial compatibility between the rigid inorganic particles and the flexible hydrogel matrix. Bioactive cod peptides (CPs) with osteogenic activity from Atlantic cod were further incorporated into the nanocomposite hydrogel. As a result, the multicomponent nanocomposite hydrogel favored the adhesion and spreading of MC3T3-E1 cells. The increased ALP activity suggested that GO-PHA-CPs hydrogels contributed to the osteogenic differentiation of MC3T3-E1 cells. The suitability of GO-PHA-CPs hydrogels for enhancing bone regeneration in vivo was further confirmed by the rat femoral defect model. Our results indicate that the multifunctional GO-PHA-CPs nanocomposite hydrogels without growth factors are a promising and effective candidate material for bone regeneration.

摘要

水凝胶具有良好的生物相容性、生物降解性和机械性能,结合骨传导性、骨诱导性和骨整合性,可作为无需添加外源性生长因子和细胞的骨再生生物材料,具有很大的吸引力,但也极具挑战性。在这里,受天然骨组织的有机-无机类似物和贻贝粘附化学的启发,通过多巴胺修饰明胶(Gel-DA)和氧化葡聚糖(ODex)之间的席夫碱交联,构建了具有自修复、可注射、粘附、抗氧化和骨诱导性能的纳米复合水凝胶(称为 GO-PHA-CPs)。此外,通过提高刚性无机颗粒和柔性水凝胶基质之间的界面相容性,引入了聚多巴胺功能化纳米羟基磷灰石(PHA)来增强水凝胶网络。进一步将具有成骨活性的大西洋 cod 生物活性肽(CPs)掺入纳米复合水凝胶中。结果表明,多组分纳米复合水凝胶有利于 MC3T3-E1 细胞的黏附和铺展。ALP 活性的增加表明 GO-PHA-CPs 水凝胶有助于 MC3T3-E1 细胞的成骨分化。大鼠股骨缺损模型进一步证实了 GO-PHA-CPs 水凝胶在增强体内骨再生中的适用性。我们的结果表明,这种无生长因子的多功能 GO-PHA-CPs 纳米复合水凝胶是一种很有前途和有效的骨再生候选材料。

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