title: Engineering cell matrix interactions in assembled polyelectrolyte fiber hydrogels for mesenchymal stem cell chondrogenesis.
abstract: Cell-cell and cell-matrix interactions are important events in directing stem cell chondrogenesis, which can be promoted in matrix microenvironments presenting appropriate ligands. In this study, interfacial polyelectrolyte complexation (IPC) based hydrogels were employed, wherein the unique formation of submicron size fibers facilitated spatial orientation of ligands within such hydrogels. The influence of aligned, collagen type I (Col I) presentation in IPC hydrogel on chondrogenic differentiation of human mesenchymal stem cells (MSC) was investigated. Early morphological dynamics, onset of N-cadherin/β-catenin mediated chondrogenic induction and differentiation were compared between MSCs encapsulated in IPC-Col I and IPC-control (without Col I) hydrogels, and a conventional Col I hydrogel. MSCs in IPC-Col I hydrogel aligned and packed uniformly, resulting in enhanced cell-cell interactions and cellular condensation, facilitating superior chondrogenesis and the generation of mature hyaline neocartilage, with notable downregulation of fibrocartilaginous marker. Inhibition study using function blocking β1-integrin antibodies reversed the aforementioned outcomes, indicating the importance of coupling integrin mediated cell-matrix interactions and N-cadherin/β-catenin mediated downstream signaling events. This study demonstrated the significance of oriented ligand presentation for MSC chondrogenesis, and the importance of facilitating an orderly sequence of differentiation events, initiated by proximal interactions between MSCs and the extracellular matrix for robust neocartilage formation.
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore 119288, Singapore.
authors.forename: Deepak
authors.initials: D
authors.lastname: Raghothaman
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Meng Fatt
authors.initials: MF
authors.lastname: Leong
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Tze Chiun
authors.initials: TC
authors.lastname: Lim
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Jerry K C
authors.initials: JK
authors.lastname: Toh
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. Electronic address: awan@ibn.a-star.edu.sg.
authors.forename: Andrew C A
authors.initials: AC
authors.lastname: Wan
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore 119288, Singapore; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore 117510, Singapore. Electronic address: lsiyz@nus.edu.sg.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 11, 1E Kent Ridge Road, Singapore 119288, Singapore; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore 117510, Singapore; Mechanobiology Institute (MBI), National University of Singapore, T-Lab, #10-01, 5A Engineering Drive 1, Singapore 117411, Singapore. Electronic address: eng_hin_lee@nuhs.edu.sg.
authors.forename: Eng Hin
authors.initials: EH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D024042:Collagen Type I / Q000494:pharmacology; D004573:Electrolytes / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D019012:Integrin beta1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D024042:Collagen Type I; D004573:Electrolytes; D020100:Hydrogels; D019012:Integrin beta1
keywords: Cell encapsulation; Cell–matrix interactions; Chondrogenesis; Interfacial polyelectrolyte complexation; Mesenchymal stem cells