title: Biocompatibility of cross-linked hyaluronate (Gel-200) for the treatment of knee osteoarthritis.
abstract: OBJECTIVE
  To compare the biocompatibility and immunogenicity of two intra-articular hyaluronan formulations, Gel-200 (Gel-One(®)) and hylan G-F 20 (Synvisc(®) series).
  
  
  METHODS
  A comparison of the biocompatibility of Gel-200 and hylan G-F 20 was made using a rat subcutaneous air pouch model and the knee joint of normal rabbits. Immunogenicity was evaluated using a homologous passive cutaneous anaphylaxis (PCA) assay in guinea pigs.
  
  
  RESULTS
  In the air pouch model in rats, characteristic fibrous belts formed in the subcutaneous tissue. Injection of hylan G-F 20 into the air pouch induced granulomatous nodules primarily composed of macrophages, multinucleated giant cells, and eosinophils accompanied with the test material in the center of the nodules in the fibrous belt. Furthermore, the thickness of the fibrous belt in the hylan G-F 20 group increased significantly compared to the saline group. Injection of Gel-200 into the air pouch induced neither granulomatous inflammation nor significant thickening of fibrous belt, while foamy macrophages containing the test material were observed. Intra-articular injection of hylan G-F 20 into the rabbit knee joints induced granulomatous inflammation, eosinophil infiltration, and significant increase in the number of cells in the synovial fluid, while these findings were absent in the Gel-200 group. In the immunogenicity assay, hylan G-F 20 induced a positive PCA reaction, but the Gel-200 did not.
  
  
  CONCLUSIONS
  Gel-200 showed more favorable biocompatibility and less immunogenicity compared to hylan G-F 20. Gel-200 is expected to be a single injection hyaluronan product with less safety concerns for the treatment of knee osteoarthritis (OA) pain.
authors.affiliation: Central Research Laboratories, Research & Development Division, Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Central Research Laboratories, Research & Development Division, Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Central Research Laboratories, Research & Development Division, Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan. Electronic address: kei.urano@seikagaku.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Urano
authors.affiliation: Central Research Laboratories, Research & Development Division, Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Central Research Laboratories, Research & Development Division, Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hatanaka
authors.affiliation: Central Research Laboratories, Research & Development Division, Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nii
mesh_terms: D000818:Animals; D003432:Cross-Linking Reagents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007719:Knee Joint; D008297:Male; D008422:Materials Testing; D020370:Osteoarthritis, Knee / Q000188:drug therapy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003432:Cross-Linking Reagents; D006820:Hyaluronic Acid
keywords: Biocompatibility; Cross-linked hyaluronic acid; Gel-200; Osteoarthritis; Photo-gelation technology