Characterization of low-molecular-weight hyaluronic acid-based hydrogel and differential stem cell responses in the hydrogel microenvironments.
Hyaluronic acid is a natural glycosaminoglycan involved in biological processes. Low-molecular-weight hyaluronic acid (10 and 50 kDa)-based hydrogel was synthesized using derivatized hyaluronic acid. Hyaluronic acid was acrylated by two steps: (1) introduction of an amine group using adipic acid dihydrazide, and (2) acrylation by N-acryloxysuccinimide. Injectable hyaluronic acid-based hydrogel was prepared by using acrylated hyaluronic acid and poly(ethylene glycol) tetra-thiols via Michael-type addition reaction. Mechanical properties of the hydrogel were evaluated by varying the molecular weight of acrylated hyaluronic acid (10 and 50 kDa) and the weight percent of hydrogel. Hydrogel based on 50-kDa hyaluronic acid showed the shortest gelation time and the highest complex modulus. Next, human mesenchymal stem cells were cultured in cell-adhesive RGD peptide-immobilized hydrogels together with bone morphogenic protein-2 (BMP-2). Cells cultured in the RGD/BMP-2-incorporated hydrogels showed proliferation rates higher than that of control or RGD-immobilized hydrogels. Real-time RT-PCR showed that the expression of osteoblast marker genes such as CBFalpha1 and alkaline phosphatase was increased in hyaluronic acid-based hydrogel, and the expression level was dependent on the molecular weight of hyaluronic acid, RGD peptide, and BMP-2. This study indicates that low-molecular-weight hyaluronic acid-based hydrogel can be applied to tissue regeneration as differentiation guidance materials of stem cells.
Kim
Jungju
J
Biomedical Engineering, Brain Korea 21 Project for Biomedical Science, Korea University Medical College, Seoul, 136-705, Korea.
Park
Yongdoo
Y
Tae
Giyoong
G
Lee
Kyu Back
KB
Hwang
Chang Mo
CM
Hwang
Soon Jung
SJ
Kim
In Sook
IS
Noh
Insup
I
Sun
Kyung
K
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D015394:Molecular Structure; D008970:Molecular Weight; D009842:Oligopeptides / Q000378:metabolism; D012038:Regeneration; D013314:Stress, Mechanical
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D006820:Hyaluronic Acid