title: Fundamental biomaterial properties of tough glycosaminoglycan-containing double network hydrogels newly developed using the molecular stent method.
abstract: 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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Higa
authors.affiliation: Department of Sports Medicine, Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan. Electronic address: nobukita@aol.com.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Laboratory of Soft and Wet Matter, Faculty of Advanced Life Science, Hokkaido University, Kita-10 Nishi-8, Sapporo 060-0810, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Department of Sports Medicine, Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Sports Medicine, Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Wada
authors.affiliation: Laboratory of Soft and Wet Matter, Faculty of Advanced Life Science, Hokkaido University, Kita-10 Nishi-8, Sapporo 060-0810, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nonoyama
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, 1 Senbaru, Nishihara-cho, Nakagami-gun, Okinawa 903-0213, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kanaya
authors.affiliation: Proteoglycan Signaling and Therapeutics Research Group, Faculty of Advanced Life Science, Hokkaido University, Kita-21, Nishi-11, Sapporo 001-0021, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.affiliation: Laboratory of Soft and Wet Matter, Faculty of Advanced Life Science, Hokkaido University, Kita-10 Nishi-8, Sapporo 060-0810, Japan.
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Gong
authors.affiliation: Department of Sports Medicine, Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002021:Buffers; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000737:chemistry; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels / Q000494:pharmacology*; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D008422:Materials Testing / Q000379:methods*; D055595:Mechanical Phenomena; D009132:Muscles / Q000187:drug effects; D011817:Rabbits; D013242:Sterilization; D040521:Subcutaneous Tissue / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D002021:Buffers; D024043:Collagen Type II; D006025:Glycosaminoglycans; D020100:Hydrogels; D014867:Water; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates
keywords: Chondrogenic differentiation; Chondroitin sulfate; Double-network hydrogel; Glycosaminoglycan; Sodium hyaluronate