Enhanced function of chondrocytes in a chitosan-based hydrogel to regenerate cartilage tissues by accelerating degradability of the hydrogel via a hydrolysable crosslinker Shohei Ishikawa, 1 Kazutoshi Iijima , 2† Daisuke Matsukuma, 3 Michihiro Iijima, 4 Shigehito Osawa , 3 Hidenori Otsuka 1,2,5 1 Department of Science, Graduate School of Chemical Sciences, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan 2 Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, 12-1 Ichigayafunagawara-machi, Shinjuku- ku, Tokyo 162-0826, Japan 3 Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan 4 Department of Materials Chemistry and Bioengineering, Oyama National College of Technology, 771 Nakakuki, Oyama, Tochigi 323-0806, Japan 5 Water Frontier Science & Technology Research Center, Research Institute for Science and Technology, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601, Japan Correspondence to: S. Osawa (E-mail: osawa-s@rs.tus.ac.jp) and H. Otsuka (E-mail: h.otsuka@rs.kagu.tus.ac.jp) ABSTRACT: Chitosan-based hydrogels as scaffolds for culturing chondrocytes were prepared using linkers with and without hydrolysable poly(DL-lactide) (PLA) segments. The evaluation of the cultured chondrocytes in them indicated that the accelerated degradation of the hydrogel via hydrolysis of the PLA slightly promoted production of the sulfated glycosaminoglycan and drastically improved that of col- lagen from the encapsulated chondrocytes, which are the chondrospecific extracellular matrix components. Furthermore, the accelerated degradability significantly upregulated the gene expression for Collagen II production and downregulated that for Collagen I production of the encapsulated chondrocytes. Because major component of the articular cartilage tissue is Collagen II-rich hyaline cartilage, these results suggest the degradation of the scaffolds is an important parameter in cartilage tissue regeneration and the accelerated degradabil- ity may have benefits on promotion of cartilage tissue regeneration especially from the viewpoint of hyaline cartilage-like collagen pro- duction. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48893. KEYWORDS: biodegradable; biomaterials; biomedical applications; gels Received 4 September 2019; accepted 2 December 2019 DOI: 10.1002/app.48893 INTRODUCTION In an aging population, cartilage diseases, including osteoarthritis, are increased drastically. 1 As an alternative to the widely per- formed treatment involving the use of an artificial joint, implan- tation of autologous chondrocytes to regenerate articular cartilage has received much attention as an effective and noninvasive ther- apy. 2 This technique is expected to allow the filling of defective cartilage tissue without surgery; however, implanted chondrocytes immediately dedifferentiate and lose their functions, resulting in the formation of fibrocartilage tissues as unfavorable cartilage tissue. 3 For achieving a high therapeutic effect, it is important to regenerate cartilage, not as fibrocartilage, but as the original hya- line cartilage with high resilience and shock absorbing properties. Therefore, it is necessary to design a scaffold for implanting cho- ndrocytes such that they are highly functionalized in forming hyaline cartilage tissues. Such scaffolds should mimic the environment provided by the extracellular matrix (ECM) of tissues in order to achieve the intended regeneration. 4 The hyaline cartilage has a high water content. Hydrogels have a crosslinked polymer network that Additional Supporting Information may be found in the online version of this article. † Present address: Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan. © 2019 Wiley Periodicals, Inc. 48893 (1 of 8) J. APPL. POLYM. SCI. 2019, DOI: 10.1002/APP.48893