An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering.

An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering.
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用于软骨组织工程的可注射酶交联羧甲基化支链淀粉/硫酸软骨素水凝胶

DOI:
10.1038/srep20014
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发表时间:
2016-01-28
期刊:
影响因子:
4.6
通讯作者:
Yan D
Yan D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen F;Yu S;Liu B;Ni Y;Yu C;Su Y;Zhu X;Yu X;Zhou Y;Yan D

文献摘要

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在本研究中,在生理条件下,在辣根过氧化物酶(HRP)和过氧化氢(H2 O2)的存在下,成功地开发了用于软骨组织工程(CTTE)的酶促交联的可注射和可生物降解的水凝胶系统,所述水凝胶系统包括羧甲基普鲁兰-酪胺(CMP-TA)和硫酸软骨素-酪胺(CS-TA)缀合物。HRP交联方法使这种可注射系统可行,微创,易于转化为再生医学应用。机械稳定的水凝胶系统的物理化学性质可以通过改变聚合物的重量比和浓度以及交联剂的浓度来调节。此外,包裹在CMP-TA/CS-TA水凝胶中的猪耳软骨细胞的细胞行为表明该水凝胶系统具有良好的细胞相容性。具体而言,与CMP-TA水凝胶相比,这些CMP-TA/CS-TA复合水凝胶具有增强的细胞增殖和增加的软骨ECM沉积,这显著促进软骨形成。此外,通过使用小鼠皮下植入模型,组织学分析表明水凝胶系统表现出可接受的组织相容性。总之,本文提出的新型可注射普鲁兰多糖/硫酸软骨素复合水凝胶有望成为用于软骨组织再生的有用生物材料支架。
In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP-TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue.