Hydrogels functionalized with N-cadherin mimetic peptide enhance osteogenesis of hMSCs by emulating the osteogenic niche

Meiling Zhu; Sien Lin; Yuxin Sun; Qian Feng; Gang Li; Liming Bian

doi:10.1016/j.biomaterials.2015.10.072

Hydrogels functionalized with N-cadherin mimetic peptide enhance osteogenesis of hMSCs by emulating the osteogenic niche

Biomaterials. 2016 Jan:77:44-52. doi: 10.1016/j.biomaterials.2015.10.072. Epub 2015 Nov 2.

Authors

Meiling Zhu¹, Sien Lin², Yuxin Sun², Qian Feng¹, Gang Li², Liming Bian³

Affiliations

¹ 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.
² Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
³ 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: [email protected].

PMID: 26580785
DOI: 10.1016/j.biomaterials.2015.10.072

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.

Keywords: Bio-functionalization of biomaterials; Hyaluronic acid hydrogels; Mesenchymal stem cells; Tissue engineering.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Alkaline Phosphatase / metabolism
Amino Acid Sequence
Animals
Antigens, CD / biosynthesis
Antigens, CD / physiology
Cadherins / biosynthesis
Cadherins / physiology
Cell Adhesion
Cells, Cultured
Collagen Type I / metabolism
Core Binding Factor Alpha 1 Subunit / biosynthesis
Core Binding Factor Alpha 1 Subunit / genetics
Heterografts
Humans
Hyaluronic Acid / administration & dosage
Hyaluronic Acid / analogs & derivatives*
Hyaluronic Acid / pharmacology
Hydrogels
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / drug effects*
Mesenchymal Stem Cells / metabolism
Methacrylates / administration & dosage
Methacrylates / pharmacology*
Mice
Mice, Nude
Molecular Sequence Data
Oligopeptides / pharmacology
Osteocalcin / biosynthesis
Osteocalcin / genetics
Osteogenesis / drug effects*
Peptides / administration & dosage
Peptides / pharmacology*
Porosity
Stem Cell Niche*
Tissue Engineering / methods*
Transplantation, Heterotopic

Substances

Antigens, CD
CDH2 protein, human
Cadherins
Collagen Type I
Core Binding Factor Alpha 1 Subunit
Hydrogels
Methacrylates
Oligopeptides
Peptides
RUNX2 protein, human
Osteocalcin
arginyl-glycyl-aspartic acid
Hyaluronic Acid
Alkaline Phosphatase