Biphasic Double-Network Hydrogel With Compartmentalized Loading of Bioactive Glass for Osteochondral Defect Repair

Bingchuan Liu; Yanran Zhao; Tengjiao Zhu; Shan Gao; Kaifeng Ye; Fang Zhou; Dong Qiu; Xing Wang; Yun Tian; Xiaozhong Qu

doi:10.3389/fbioe.2020.00752

Biphasic Double-Network Hydrogel With Compartmentalized Loading of Bioactive Glass for Osteochondral Defect Repair

Front Bioeng Biotechnol. 2020 Jul 2:8:752. doi: 10.3389/fbioe.2020.00752. eCollection 2020.

Authors

Bingchuan Liu^{1

2}, Yanran Zhao³, Tengjiao Zhu^{1

2}, Shan Gao^{1

2}, Kaifeng Ye^{1

2}, Fang Zhou^{1

2}, Dong Qiu^{4

5}, Xing Wang^{4

5}, Yun Tian^{1

2}, Xiaozhong Qu³

Affiliations

¹ Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
² Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education, Peking University Third Hospital, Beijing, China.
³ Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing, China.
⁴ Beijing National Laboratory for Molecular Science, State Key Laboratory of Polymer Physics and Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry Chinese Academy of Sciences, Beijing, China.
⁵ University of Chinese Academy of Sciences, Beijing, China.

Abstract

Periarticular injury usually causes the defects of superficial cartilage and the underlying subchondral bone. Although some efficacious outcomes have been achieved by the existing therapeutic methods both in clinics and research, like symptomatic treatment, microfracture surgery, and tissue engineering technology, they still present specific disadvantages and complications. To improve this situation, we designed a biphasic (bi-) scaffold aiming to repair the structure of cartilage and subchondral bone synchronously. The scaffold consisted of a superior double-network (DN) hydrogel layer and a lower bioactive glass (BG) reinforced hydrogel layer, and the DN hydrogel included glycol chitosan (GC) and dibenzaldhyde functionalized poly(ethylene oxide) network, and sodium alginate (Alg) and calcium chloride (CaCl₂) network. To investigate its effectiveness, we applied this biphasic scaffold to repair osteochondral full-thickness defects in rabbit models. We set up six observation groups in total, including Untreated group, Microfracture group, BG only group, DN gel group, bi-DN gel group, and bi-DN/TGF-β gel group. With a follow-up period of 24 weeks, we evaluated the treatment effects by gross observation, micro-CT scan and histological staining. Besides, we further fulfilled the quantitative analysis of the data from ICRS score, O'Driscoll score and micro-CT parameters. The results revealed that neat GC/Alg DN hydrogel scaffold was only conductive to promoting cartilage regeneration and neat BG scaffold merely showed the excellent ability to reconstruct subchondral bone. While the biphasic scaffold performed better in repairing osteochondral defect synchronously, exhibiting more well-integrated cartilage-like tissue with positive staining of toluidine blue and col II immunohistochemistry, and more dense trabecular bone connecting closely with the surrounding host bone. Therefore, this method possessed the clinical application potential in treating articular injury, osteochondral degeneration, osteochondral necrosis, and sclerosis.

Keywords: biphasic scaffold; double-network hydrogel; dynamic cross linking; experimental research; osteochondral repair.