Self-crosslinked oxidized alginate/gelatin hydrogel as injectable, adhesive biomimetic scaffolds for cartilage regeneration

Self-crosslinked oxidized alginate/gelatin hydrogel as injectable, adhesive biomimetic scaffolds for cartilage regeneration
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DOI:
10.1016/j.actbio.2014.04.031
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发表时间:
2014-08-01
期刊:
影响因子:
9.7
通讯作者:
Banerjee, Rinti
Banerjee, Rinti
中科院分区:
工程技术1区
文献类型:
--
作者:
Balakrishnan, Biji;Joshi, Nitin;Banerjee, Rinti

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模仿细胞外基质特性的生物聚合物水凝胶在促进细胞迁移和增殖以促进组织再生方面具有巨大潜力。作者此前报道,在硼砂存在下,通过高碘酸盐氧化藻酸盐和明胶的自交联,可以制备快速胶凝、可生物降解、可注射的水凝胶,而不使用任何有毒的交联剂。本文研究了这种水凝胶作为微创可注射、细胞吸引和粘附支架的适用性,用于软骨组织工程治疗骨关节炎。时间和频率扫描流变学分析证实凝胶在 20 秒内形成。水凝胶与软骨组织结合良好,爆破压力为 70 +/- 3 mmHg,表明其具有粘合性质。水凝胶引起的炎症和氧化应激反应可以忽略不计,这是控制和治疗骨关节炎的先决条件。封装在基质内的原代鼠软骨细胞的扫描电子显微镜图像显示细胞附着在水凝胶基质上。软骨细胞在基质内表现出活力、增殖和迁移,同时保持其表型(如 II 型胶原蛋白和聚集蛋白聚糖的表达所示)和功能性(如随着时间的推移糖胺聚糖 (GAG) 沉积增强所示)。基质内软骨细胞的 DNA 含量和 GAG 沉积可以通过掺入生物活性信号分子(例如地塞米松、硫酸软骨素、血小板衍生生长因子 (PDGF-BB))以及这三种药物的组合来调节。结果表明,自交联氧化藻酸盐/明胶水凝胶可能是一种有前途的可注射、细胞吸引的粘合基质,用于骨关节炎管理和治疗中新软骨的形成。 (C) 2014 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Biopolymeric hydrogels that mimic the properties of extracellular matrix have great potential in promoting cellular migration and proliferation for tissue regeneration. The authors reported earlier that rapidly gelling, biodegradable, injectable hydrogels can be prepared by self-crosslinking of periodate oxidized alginate and gelatin in the presence of borax, without using any toxic crosslinking agents. The present paper investigates the suitability of this hydrogel as a minimally invasive injectable, cell-attractive and adhesive scaffold for cartilage tissue engineering for the treatment of osteoarthritis. Time and frequency sweep rheology analysis confirmed gel formation within 20 s. The hydrogel integrated well with the cartilage tissue, with a burst pressure of 70 +/- 3 mmHg, indicating its adhesive nature. Hydrogel induced negligible inflammatory and oxidative stress responses, a prerequisite for the management and treatment of osteoarthritis. Scanning electron microscopy images of primary murine chondrocytes encapsulated within the matrix revealed attachment of cells onto the hydrogel matrix. Chondrocytes demonstrated viability, proliferation and migration within the matrix, while maintaining their phenotype, as seen by expression of collagen type II and aggrecan, and functionality, as seen by enhanced glycosoaminoglycan (GAG) deposition with time. DNA content and GAG deposition of chondrocytes within the matrix can be tuned by incorporation of bioactive signaling molecules such as dexamethasone, chondroitin sulphate, platelet derived growth factor (PDGF-BB) and combination of these three agents. The results suggest that self-crosslinked oxidized alginate/gelatin hydrogel may be a promising injectable, cell-attracting adhesive matrix for neo-cartilage formation in the management and treatment of osteoarthritis. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.