title: Hydrogels functionalized with N-cadherin mimetic peptide enhance osteogenesis of hMSCs by emulating the osteogenic niche.
abstract: N-cadherin is considered to be the key factor in directing cell-cell interactions during mesenchymal condensation, which is essential to osteogenesis. In this study, hyaluronic acid (HA) hydrogels are biofunctionalized with an N-cadherin mimetic peptide to mimic the pro-osteogenic niche in the endosteal space to promote the osteogenesis of human mesenchymal stem cells (hMSCs). Results show that the conjugation of the N-cadherin peptide in the HA hydrogels enhances the expression of the osteogenic marker genes in the seeded hMSCs. Furthermore, the biofunctionalized HA hydrogels promote the alkaline phosphatase activity, type I collagen deposition, and matrix mineralization by the seeded hMSCs under both in vitro and in vivo condition. We postulate that the biofunctionalized hydrogels emulates the N-cadherin-mediated homotypic cell-cell adhesion among MSCs and the "orthotypic" interaction between the osteoblasts and MSCs. These findings demonstrate that the biofunctionalized HA hydrogels provide a supportive niche microenvironment for the osteogenesis of hMSCs.
authors.affiliation: Division of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Sien
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Division of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Division of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, People's Republic of China. Electronic address: lbian@mae.cuhk.edu.hk.
authors.forename: Liming
authors.initials: L
authors.lastname: Bian
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D064593:Heterografts; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D016062:Porosity; D055153:Stem Cell Niche; D023822:Tissue Engineering / Q000379:methods*; D016042:Transplantation, Heterotopic
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D020100:Hydrogels; D008689:Methacrylates; D009842:Oligopeptides; D010455:Peptides; C493709:RUNX2 protein, human; D015675:Osteocalcin; C047981:arginyl-glycyl-aspartic acid; D006820:Hyaluronic Acid; D000469:Alkaline Phosphatase
keywords: Bio-functionalization of biomaterials; Hyaluronic acid hydrogels; Mesenchymal stem cells; Tissue engineering