Synthesis and characterization of matrix metalloprotease sensitive-low molecular weight hyaluronic acid based hydrogels.
Hyaluronic acid is a naturally derived glycosaminoglycan (GAG) involved in biological processes. A low molecular weight hyaluronic acid (50 kDa)-based hydrogel was synthesized using acrylated hyaluronic acid. Matrix metalloproteinase (MMP) sensitive hyaluronic acid-based hydrogels were prepared by conjugation with two different peptides: cell adhesion peptides containing integrin binding domains (Arg-Gly-Asp: RGD) and a cross-linker with MMP degradable peptides to mimic the remodeling characteristics of natural extracellular matrices (ECMs) by cell-derived MMPs. Mechanical properties of these hydrogels were evaluated with different molecular weights of acrylated hyaluronic acid (10 kDa and 50 kDa) cross-linked by MMP sensitive peptides by measuring elastic modulus, viscous modulus, swelling ratio and degradation rate. The MMP sensitive hydrogel based on the 50 kDa hyaluronic acid showed a 31.5-fold shorter gelation time, 4.7-fold higher storage modulus and 0.51-fold smaller swelling ratio than those of the hydrogel based on the 10 kDa. Degradation rate was dependent on MMP sensitivity of the peptide cross-linker. MMP sensitive hyaluronic acid based hydrogels were degraded faster than MMP insensitive-hyaluronic acid-based hydrogels. Human mesenchymal stem cells (MSCs) were cultured in MMP-sensitive or insensitive hyaluronic acid-based hydrogels (50 kDa hyaluronic acid) and/or immobilized cell adhesive RGD peptides. Cells cultured in the MMP-sensitive hydrogel with RGD peptides showed dramatic cell spreading compared with that of the control, which remained round. This MMP-sensitive low molecular weight hyaluronic acid-based hydrogel could be useful in tissue engineering by improving tissue defect regeneration and tissue remodeling.
Kim
Jungju
J
Biomedical Engineering, Brain Korea 21 Project for Biomedical Science, Korea University Medical College, Seoul, Korea.
Park
Yongdoo
Y
Tae
Giyoong
G
Lee
Kyu Back
KB
Hwang
Soon Jung
SJ
Kim
In Sook
IS
Noh
Insup
I
Sun
Kyung
K
D000179:Acrylates / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000378:metabolism; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism; D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism; D008970:Molecular Weight; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D023822:Tissue Engineering; D014783:Viscosity
D000179:Acrylates; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D009842:Oligopeptides; D010455:Peptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; D045726:Metalloproteases; D020782:Matrix Metalloproteinases