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

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

doi:10.3389/fbioe.2020.00752

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.

Highlights

Periarticular osteochondral structure usually includes three layers from the surface: articular cartilage, calcified cartilage, and the underlying subchondral bone, which can be further classified into cortical and trabecular bone. These well-organized anatomical structures closely integrate with each other and behave as a functional and structural unit supporting regular weight-bearing and joint motion (Bian et al, 2016; Goldring and Goldring, 2016). This unit could be damaged by several key reasons as follows: (1) vertical violence of peripheral joint; (2) severe degenerative osteoarthritis; and (3) osteonecrosis and sclerosis of peripheral joint caused by bone infarction
The injectability of the DN/bioactive glass (BG) gel was not influenced with the inorganic component, which allowed the molding of the composite hydrogel scaffolds
Using the bi-DN gel scaffold, we proved that the defects were repaired mostly at 24 weeks, with better quality in comparison with both glycol chitosan (GC)/Alg DN gel and the use of neat BG scaffold

Summary

Introduction

Periarticular osteochondral structure usually includes three layers from the surface: articular cartilage, calcified cartilage, and the underlying subchondral bone, which can be further classified into cortical and trabecular bone. These well-organized anatomical structures closely integrate with each other and behave as a functional and structural unit supporting regular weight-bearing and joint motion (Bian et al, 2016; Goldring and Goldring, 2016). This unit could be damaged by several key reasons as follows: (1) vertical violence of peripheral joint; (2) severe degenerative osteoarthritis; and (3) osteonecrosis and sclerosis of peripheral joint caused by bone infarction. The newly formed tissue regenerated via the existing repairing surgery is confirmed as a mixture of fibrous tissue and fibrocartilage mostly, and the subchondral bone cannot be sufficiently reconstructed (Mahmoud et al, 2017; McCarrel et al, 2017), which leads to the early good outcomes tending to deteriorate in long follow-up (Solheim et al, 2020)

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Conclusion