In vivo evaluation of MMP sensitive high-molecular weight HA-based hydrogels for bone tissue engineering

• Published in: Journal of biomedical materials research. Part A Vol. 95A; no. 3; pp. 673 - 681
• Main Authors: Kim, Jungju, Kim, In Sook, Cho, Tae Hyung, Kim, Ho Chul, Yoon, So Jeong, Choi, Jaesoon, Park, Yongdoo, Sun, Kyung, Hwang, Soon Jung
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2010; Wiley-Blackwell
• Subjects: Animals; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Biological and medical sciences; Biotechnology; bone; Bone and Bones - cytology; Bone and Bones - pathology; Bone and Bones - physiology; Bone Regeneration - physiology; Cell Culture Techniques - methods; Cells, Cultured; Elasticity; Fundamental and applied biological sciences. Psychology; Gene Expression; Health. Pharmaceutical industry; Humans; hyaluronic acid; Hyaluronic Acid - chemistry; Hyaluronic Acid - metabolism; hydrogel; Hydrogels - chemistry; Hydrogels - metabolism; Industrial applications and implications. Economical aspects; Male; Materials Testing; matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Medical sciences; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Miscellaneous; Molecular Weight; Rats; Rats, Sprague-Dawley; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; tissue engineering; Tissue Engineering - methods; Viscosity; Enzyme; Tissue engineering; Metalloendopeptidases; Hydroxyapatite; Osteoarticular system; Polyelectrolyte; Peptidases; In vivo; Hydrolases; Glycosaminoglycan; Oside polymer; matrix metalloproteinase; Biomaterial; Hydrogel; Bone; Hyaluronic acid; Molecular mass; Biomedical engineering
• ISSN: 1549-3296; 1552-4965; 1552-4965
• DOI: 10.1002/jbm.a.32884

Hyaluronic acid (170 kDa)‐based hydrogel was synthesized using acrylated hyaluronic acid (HA) and matrix metalloproteinase (MMP) sensitive HA‐based hydrogels were then 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 by cell‐derived MMPs. Mechanical properties of these hydrogels were evaluated with different weight percentages (2.5 and 3.5 wt %) by measuring elastic modulus, viscous modulus, and swelling ratio. Human mesenchymal stem cells (hMSCs) were then cultured in MMP‐sensitive or insensitive HA‐based hydrogels and/or immobilized cell adhesive RGD peptides in vitro. Actin staining and image analysis proved that cells cultured in the MMP‐sensitive hydrogel with RGD peptides showed extensive cell spreading and sprouting. Gene expression analysis showed that bone specific genes such as alkaline phosphatase, osteocalcin, and osteopontin increased in MMP‐sensitive hydrogels as biomolecules such as BMPs and cells were added in the gels. For in vivo calvarial defect regeneration, five different samples (MMP insensitive hydrogel, MMP sensitive hydrogel, MMP sensitive hydrogel with BMP‐2, MMP sensitive hydrogel with hMSC, and MMP sensitive hydrogel with BMP‐2 and hMSC) were prepared. After 4 weeks of implantation, the Masson‐Trichrome staining and micro computed tomography scan results demonstrated that the MMP sensitive hydrogels with BMP‐2 and hMSCs have the highest mature bone formation. The MMP sensitive HA‐based hydrogel could become useful scaffolds in bone tissue engineering with improvements on tissue remodeling rates and regeneration activity. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.