TY - JOUR
T1 - In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration
AU - Chen, Yu Chun
AU - Su, Wen Yu
AU - Yang, Shu Hua
AU - Gefen, Amit
AU - Lin, Feng Huei
N1 - Funding Information:
This study was financially supported by National Health Research Institutes ( 00A1-MEPP01-014 ). The authors would like to thank the DNA Sequence Core Laboratory of NHRI for use of the Applied Biosystems 7900 Real-time PCR System, and the Industrial Technology Research Institute for the use of the HAKKE rheometer.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Gelatin
KW - Gene expression
KW - Hyaluronic acid
KW - Nucleus pulposus
KW - Viscoelastic properties
UR - http://www.scopus.com/inward/record.url?scp=84872072044&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2012.09.039
DO - 10.1016/j.actbio.2012.09.039
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C2 - 23041783
AN - SCOPUS:84872072044
SN - 1742-7061
VL - 9
SP - 5181
EP - 5193
JO - Acta Biomaterialia
JF - Acta Biomaterialia
IS - 2
ER -