title: Steric Interference of Adhesion Supports In-Vitro Chondrogenesis of Mesenchymal Stem Cells on Hydrogels for Cartilage Repair.
abstract: Recent studies suggest the presence of cell adhesion motifs found in structural proteins can inhibit chondrogenesis. In this context, the current study aims to determine if a polyethylene glycol (PEG)-modified fibrinogen matrix could support better chondrogenesis of human bone marrow mesenchymal stem cells (BM-MSC) based on steric interference of adhesion, when compared to a natural fibrin matrix. Hydrogels used as substrates for two-dimensional (2D) BM-MSC cultures under chondrogenic conditions were made from cross-linked PEG-fibrinogen (PF) and compared to thrombin-activated fibrin. Cell morphology, protein expression, DNA and sulfated proteoglycan (GAG) content were correlated to substrate properties such as stiffness and adhesiveness. Cell aggregation and chondrogenic markers, including collagen II and aggrecan, were observed on all PF substrates but not on fibrin. Shielding fibrinogen's adhesion domains and increasing stiffness of the material are likely contributing factors that cause the BM-MSCs to display a more chondrogenic phenotype. One composition of PF corresponding to GelrinC™--a product cleared in the EU for cartilage repair--was found to be optimal for supporting chondrogenic differentiation of BM-MSC while minimizing hypertrophy (collagen X). These findings suggest that semi-synthetic biomaterials based on ECM proteins can be designed to favourably affect BM-MSC towards repair processes involving chondrogenesis.
authors.affiliation: The Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Goldshmid
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Shachaf
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Kupershmit
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Offra
authors.initials: O
authors.lastname: Sarig-Nadir
authors.affiliation: The Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Wechsler
mesh_terms: D015415:Biomarkers; D002356:Cartilage / Q000502:physiology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D020219:Chondrogenesis; D003094:Collagen / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009024:Morphogenesis; D012038:Regeneration
chemical_list: D015415:Biomarkers; D020100:Hydrogels; D005337:Fibrin; D005340:Fibrinogen; D003094:Collagen