title: Directing chondrogenesis of stem cells with specific blends of cellulose and silk.
abstract: Biomaterials that can stimulate stem cell differentiation without growth factor supplementation provide potent and cost-effective scaffolds for regenerative medicine. We hypothesize that a scaffold prepared from cellulose and silk blends can direct stem cell chondrogenic fate. We systematically prepared cellulose blends with silk at different compositions using an environmentally benign processing method based on ionic liquids as a common solvent. We tested the effect of blend compositions on the physical properties of the materials as well as on their ability to support mesenchymal stem cell (MSC) growth and chondrogenic differentiation. The stiffness and tensile strength of cellulose was significantly reduced by blending with silk. The characterized materials were tested using MSCs derived from four different patients. Growing MSCs on a specific blend combination of cellulose and silk in a 75:25 ratio significantly upregulated the chondrogenic marker genes SOX9, aggrecan, and type II collagen in the absence of specific growth factors. This chondrogenic effect was neither found with neat cellulose nor the cellulose/silk 50:50 blend composition. No adipogenic or osteogenic differentiation was detected on the blends, suggesting that the cellulose/silk 75:25 blend induced specific stem cell differentiation into the chondrogenic lineage without addition of the soluble growth factor TGF-β. The cellulose/silk blend we identified can be used both for in vitro tissue engineering and as an implantable device for stimulating endogenous stem cells to initiate cartilage repair.
authors.affiliation: School of Cellular and Molecular Medicine, Advanced Composites Centre for Innovation and Science (ACCIS), Aerospace Engineering, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Nandita
authors.initials: N
authors.lastname: Singh
authors.forename: Sameer S
authors.initials: SS
authors.lastname: Rahatekar
authors.forename: Krzysztof K K
authors.initials: KK
authors.lastname: Koziol
authors.forename: Th Sky
authors.initials: TS
authors.lastname: Ng
authors.forename: Avinash J
authors.initials: AJ
authors.lastname: Patil
authors.forename: Stephen
authors.initials: S
authors.lastname: Mann
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Hollander
authors.forename: Wael
authors.initials: W
authors.lastname: Kafienah
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation; D002482:Cellulose / Q000737:chemistry*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D052578:Ionic Liquids; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D047011:Silk / Q000737:chemistry*; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D001672:Biocompatible Materials; D024043:Collagen Type II; D052578:Ionic Liquids; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D047011:Silk; D002482:Cellulose