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采用分子支架法新开发的含坚韧糖胺聚糖的双网络水凝胶的基本生物材料特性

Fundamental biomaterial properties of tough glycosaminoglycan-containing double network hydrogels newly developed using the molecular stent method.

作者信息

Higa Kotaro, Kitamura Nobuto, Kurokawa Takayuki, Goto Keiko, Wada Susumu, Nonoyama Takayuki, Kanaya Fuminori, Sugahara Kazuyuki, Gong Jian Ping, Yasuda Kazunori

机构信息

Department of Sports Medicine, Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan; Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, 1 Senbaru, Nishihara-cho, Nakagami-gun, Okinawa 903-0213, Japan.

Department of Sports Medicine, Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan.

出版信息

Acta Biomater. 2016 Oct 1;43:38-49. doi: 10.1016/j.actbio.2016.07.023. Epub 2016 Jul 15.

Abstract

UNLABELLED

The purpose of this study was to clarify fundamental mechanical properties and biological responses of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. This study discovered the following facts. First, these hydrogels had high mechanical performance comparable to the native cartilage tissue, and the mechanical properties were not affected by immersion in the saline solution for 12weeks. Secondly, the mechanical properties of the CS-DN gel were not significantly reduced at 12weeks in vivo, while the mechanical properties of the HA-DN gel were significantly deteriorated at 6weeks. Thirdly, the degree of inflammation around the HA-DN gel was the same as that around the negative control. The CS-DN gel showed a mild but significant foreign body reaction, which was significantly greater than the negative control and less than the positive control at 1week, while the inflammation was reduced to the same level as the negative control at 4 and 6weeks. Fourthly, these gels induced differentiation of the ATDC5 cells into chondrocytes in the culture with the insulin-free maintenance medium. These findings suggest that these tough hydrogels are potential biomaterials for future application to therapeutic implants such as artificial cartilage.

STATEMENT OF SIGNIFICANCE

The present study reported fundamental biomaterial properties of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. Both the HA- and CS-DN gels had high mechanical properties comparable to the cartilage tissue and showed the ability to induce chondrogenic differentiation of ATDC5 cells in vitro. They are potential biomaterials that may meet the requirements of artificial cartilage concerning the material properties. Further, these DN gels can be also applied to the implantable inducer for cell-free cartilage regeneration therapy.

摘要

未标注

本研究的目的是阐明使用分子支架法新开发的含透明质酸钠双网络(HA-DN)凝胶和含硫酸软骨素双网络(CS-DN)凝胶的基本力学性能和生物学反应。本研究发现了以下事实。首先,这些水凝胶具有与天然软骨组织相当的高力学性能,并且力学性能不受在盐溶液中浸泡12周的影响。其次,CS-DN凝胶的力学性能在体内12周时没有显著降低,而HA-DN凝胶的力学性能在6周时显著恶化。第三,HA-DN凝胶周围的炎症程度与阴性对照周围的相同。CS-DN凝胶显示出轻微但显著的异物反应,在1周时显著大于阴性对照且小于阳性对照,而在4周和6周时炎症降至与阴性对照相同的水平。第四,这些凝胶在无胰岛素维持培养基的培养中诱导ATDC5细胞分化为软骨细胞。这些发现表明,这些坚韧的水凝胶是未来应用于人工软骨等治疗性植入物的潜在生物材料。

意义声明

本研究报道了使用分子支架法新开发的含透明质酸钠双网络(HA-DN)凝胶和含硫酸软骨素双网络(CS-DN)凝胶的基本生物材料特性。HA-DN凝胶和CS-DN凝胶均具有与软骨组织相当的高力学性能,并在体外显示出诱导ATDC5细胞软骨分化的能力。它们是可能满足人工软骨材料性能要求的潜在生物材料。此外,这些DN凝胶还可应用于无细胞软骨再生治疗的可植入诱导剂。

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