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一种新型巯基修饰透明质酸和弹性蛋白样多肽复合材料,用于椎间盘髓核组织工程。

A novel thiol-modified hyaluronan and elastin-like polypetide composite material for tissue engineering of the nucleus pulposus of the intervertebral disc.

机构信息

Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

出版信息

Spine (Phila Pa 1976). 2011 Jun;36(13):1022-9. doi: 10.1097/BRS.0b013e3181e7b705.

Abstract

STUDY DESIGN

Biomechanical, in vitro, and initial in vivo evaluation of a thiol-modified hyaluronan (TM-HA) and elastin-like polypeptide (ELP) composite hydrogel for nucleus pulposus (NP) tissue engineering.

OBJECTIVE

To investigate the utility of a TM-HA and ELP composite material as a potential tissue-engineering scaffold to reconstitute the NP in early degenerative disc disease (DDD) on the basis of both biomechanical and biologic parameters.

SUMMARY OF BACKGROUND DATA

DDD is a common ailment with enormous medical, psychosocial, and economic ramifications. Only end-stage surgical therapies are currently widely available. A less invasive, early stage therapy may provide a clinically relevant treatment option.

METHODS

TM-HA and ELP were combined in various concentrations and cross-linked using poly (ethylene glycol) diacrylate. Resulting materials were evaluated biomechanically using confined compression to determine biphasic material properties. In vitro cell culture with human intervertebral disc (IVD) cells seeded within TM-HA/ELP scaffolds was analyzed for cell viability and phenotype. The hydrogels' materials were evaluated in an established New Zealand White (NZW) rabbit model of DDD.

RESULTS

The addition of ELP to TM-HA-based hydrogels resulted in a stiffer construct, which is less stiff than native NP but has time-dependant loading characteristics that may be desirable when injected into the IVD. In vitro experiments demonstrated 70% cell viability at 3 weeks with apparent maintenance of phenotype on the basis of morphologic and immunohistochemical data. The addition of ELP had a positive desirable biomechanical effect but did not have a significant positive or negative biologic effect on cell activity. The in vivo feasibility study demonstrated favorable material characteristics and biocompatibility for application as a minimally invasive injectable NP supplement.

CONCLUSIONS

TM-HA-based hydrogels provide a hospitable environment for human IVD cells and have material characteristics, particularly when supplemented with ELPs that are attractive for potential application as an injectable NP supplement.

摘要

研究设计

巯基修饰透明质酸(TM-HA)和弹性蛋白样多肽(ELP)复合材料水凝胶的生物力学、体外和初步体内评估,用于治疗髓核(NP)组织工程。

研究目的

根据生物力学和生物学参数,研究 TM-HA 和 ELP 复合材料作为潜在组织工程支架,用于重建早期退变性椎间盘疾病(DDD)中 NP 的用途。

背景资料总结

DDD 是一种常见疾病,具有巨大的医疗、心理社会和经济影响。目前只有晚期手术治疗方法广泛可用。一种侵入性更小、早期的治疗方法可能提供一种具有临床相关性的治疗选择。

方法

将 TM-HA 和 ELP 以不同浓度组合,并使用聚乙二醇二丙烯酸酯交联。使用约束压缩法对所得材料进行生物力学评估,以确定双相材料特性。将人椎间盘(IVD)细胞接种在 TM-HA/ELP 支架内的体外细胞培养分析细胞活力和表型。在新西兰白兔(NZW)DDD 模型中评估水凝胶的材料。

结果

ELP 的添加使 TM-HA 基水凝胶的结构更硬,但硬度比天然 NP 低,但具有时变加载特性,这在注入 IVD 时可能是理想的。体外实验表明,第 3 周时细胞活力为 70%,根据形态学和免疫组织化学数据,表型明显维持。ELP 的添加对细胞活性具有积极的理想生物力学效应,但对细胞活性没有显著的积极或消极生物学效应。体内可行性研究表明,这种材料具有良好的特性和生物相容性,可作为一种微创可注射 NP 补充剂应用。

结论

基于 TM-HA 的水凝胶为人类 IVD 细胞提供了一个适宜的环境,并且具有材料特性,特别是在添加 ELP 后,更适合作为可注射 NP 补充剂的应用。

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