title: Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration.
abstract: Regenerative medicine strategies for restoring articular cartilage face significant challenges to recreate the complex and dynamic biochemical and biomechanical functions of native tissues. As an approach to recapitulate the complexity of the extracellular matrix, collagen-mimetic proteins offer a modular template to incorporate bioactive and biodegradable moieties into a single construct. We modified a Streptococcal collagen-like 2 protein with hyaluronic acid (HA) or chondroitin sulfate (CS)-binding peptides and then cross-linked with a matrix metalloproteinase 7 (MMP7)-sensitive peptide to form biodegradable hydrogels. Human mesenchymal stem cells (hMSCs) encapsulated in these hydrogels exhibited improved viability and significantly enhanced chondrogenic differentiation compared to controls that were not functionalized with glycosaminoglycan-binding peptides. Hydrogels functionalized with CS-binding peptides also led to significantly higher MMP7 gene expression and activity while the HA-binding peptides significantly increased chondrogenic differentiation of the hMSCs. Our results highlight the potential of this novel biomaterial to modulate cell-mediated processes and create functional tissue engineered constructs for regenerative medicine applications.
authors.affiliation: Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, Victoria 3169, Australia.
authors.forename: Paresh A
authors.initials: PA
authors.lastname: Parmar
authors.affiliation: Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
authors.forename: Lesley W
authors.initials: LW
authors.lastname: Chow
authors.affiliation: Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: St-Pierre
authors.affiliation: Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
authors.forename: Christine-Maria
authors.initials: CM
authors.lastname: Horejs
authors.affiliation: CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, Victoria 3169, Australia.
authors.forename: Yong Y
authors.initials: YY
authors.lastname: Peng
authors.affiliation: CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, Victoria 3169, Australia.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Werkmeister
authors.affiliation: CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, Victoria 3169, Australia.
authors.forename: John A M
authors.initials: JA
authors.lastname: Ramshaw
authors.affiliation: Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom; Institute of Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom. Electronic address: m.stevens@imperial.ac.uk.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis; D002358:Cartilage, Articular / Q000166:cytology / Q000254:growth & development*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology; D002809:Chondroitin Sulfates / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D020783:Matrix Metalloproteinase 7 / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry; D012038:Regeneration / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D020100:Hydrogels; D009842:Oligopeptides; C423453:Scl2 protein, Streptococcus; D002809:Chondroitin Sulfates; D003094:Collagen; C046617:arginyl-glycyl-aspartyl-serine; D020783:Matrix Metalloproteinase 7
keywords: Bioactivity; Biodegradation; Biomimetic material; Cartilage tissue engineering; Hydrogel; Mesenchymal stem cell