title: In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration.
abstract: Encapsulation of nucleus pulposus (NP) cells within in situ forming hydrogels is a novel biological treatment for early stage intervertebral disc degeneration. The procedure aims to prolong the life of the degenerating discs and to regenerate damaged tissue. In this study we developed an injectable oxidized hyaluronic acid-gelatin-adipic acid dihydrazide (oxi-HAG-ADH) hydrogel. High molecular weight (1900 kDa) hyaluronic acid was crosslinked with various concentrations of gelatin to synthesize the hydrogels and their viscoelastic properties were analyzed. Interactions between the hydrogels, NP cells, and the extracellular matrix (ECM) were also evaluated, as were the effects of the hydrogels on NP cell gene expression. The hydrogels possess several clinical advantages, including sterilizability, low viscosity for injection, and ease of use. The viscoelastic properties of the hydrogels were similar to native tissue, as reflected in the complex shear modulus (∼11-14 kPa for hydrogels, 11.3 kPa for native NP). Cultured NP cells not only attached to the hydrogels but also survived, proliferated, and maintained their round morphology. Importantly, we found that hydrogels increased NP cell expression of several crucial ECM-related genes, such as COL2A1, AGN, SOX-9, and HIF-1A.
authors.affiliation: Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Su
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Amit
authors.initials: A
authors.lastname: Gefen
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
mesh_terms: D000272:Adipates / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D002152:Calorimetry, Differential Scanning; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D004548:Elasticity; D005780:Gelatin / Q000138:chemical synthesis / Q000737:chemistry*; D005786:Gene Expression Regulation; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008970:Molecular Weight; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012038:Regeneration; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014783:Viscosity
chemical_list: D000272:Adipates; D020100:Hydrogels; D012333:RNA, Messenger; D005780:Gelatin; D006820:Hyaluronic Acid; C010011:adipic dihydrazide