Modified hyaluronic acid hydrogels with chemical groups that facilitate adhesion to host tissues enhance cartilage regeneration

被引:265
作者
Chen, Jiaqing [1 ]
Yang, Jiabei [1 ]
Wang, Li [1 ]
Zhang, Xuewei [1 ]
Heng, Boon Chin [2 ]
Wang, Dong-An [3 ]
Ge, Zigang [1 ]
机构
[1] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China
[2] Peking Univ, Sch Stomatol, Beijing 100081, Peoples R China
[3] City Univ Hong Kong, Coll Engn, Dept Biomed Engn, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
Cartilage regeneration; Hydrogel; Adhesion; Schiff base reaction; Hyaluronic acid; Aldehyde; ARTICULAR-CARTILAGE; SYNOVIAL-FLUID; CROSS-LINKING; CHONDROITIN SULFATE; INFLAMMATION; BIOMATERIAL; DEGRADATION; ALDEHYDE; REPAIR; BIOCOMPATIBILITY;
D O I
10.1016/j.bioactmat.2020.11.020
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
Stable integration of hydrogel implants with host tissues is of critical importance to cartilage tissue engineering. Designing and fabricating hydrogels with high adhesive strength, stability and regeneration potential are major challenges to be overcome. This study fabricated injectable adhesive hyaluronic acid (HA) hydrogel modified by aldehyde groups and methacrylate (AHAMA) on the polysaccharide backbone with multiple anchoring mechanisms (amide bond through the dynamic Schiff base reaction, hydrogen bond and physical interpenetration). AHAMA hydrogel exhibited significantly improved durability and stability within a humid environment (at least 7 days), together with higher adhesive strength (43 KPa to skin and 52 KPa to glass), as compared to commercial fibrin glue (nearly 10 KPa) and HAMA hydrogel (nearly 20 KPa). The results showed that AHAMA hydrogel was biocompatible and could be easily and rapidly prepared in situ. In vitro cell culture experiments showed that AHAMA hydrogel could enhance proliferation (1.2-folds after 3 days) and migration (1.5-folds after 12 h) of bone marrow stem cells (BMSCs), as compared to cells cultured in a culture dish. Furthermore, in a rat osteochondral defect model, implanted AHAMA hydrogel significantly promoted integration between neo-cartilage and host tissues, and significantly improved cartilage regeneration (modified O'Driscoll histological scores of 16.0 +/- 4.1 and 18.3 +/- 4.6 after 4 and 12-weeks of post-implantation in AHAMA groups respectively, 12.0 +/- 2.7 and 12.2 +/- 2.8 respectively in HAMA groups, 9.8 +/- 2.4 and 11.5 +/- 2.1 respectively in untreated groups). Hence, AHAMA hydrogel is a promising adhesive biomaterial for clinical cartilage regeneration and other biomedical applications.
引用
收藏
页码:1689 / 1698
页数:10
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