title: Sustained delivery of bioactive TGF-β1 from self-assembling peptide hydrogels induces chondrogenesis of encapsulated bone marrow stromal cells.
abstract: Tissue engineering strategies for cartilage defect repair require technology for local targeted delivery of chondrogenic and anti-inflammatory factors. The objective of this study was to determine the release kinetics of transforming growth factor β1 (TGF-β1) from self-assembling peptide hydrogels, a candidate scaffold for cell transplant therapies, and stimulate chondrogenesis of encapsulated young equine bone marrow stromal cells (BMSCs). Although both peptide and agarose hydrogels retained TGF-β1, fivefold higher retention was found in peptide. Excess unlabeled TGF-β1 minimally displaced retained radiolabeled TGF-β1, demonstrating biologically relevant loading capacity for peptide hydrogels. The initial release from acellular peptide hydrogels was nearly threefold lower than agarose hydrogels, at 18% of loaded TGF-β1 through 3 days as compared to 48% for agarose. At day 21, cumulative release of TGF-β1 was 32-44% from acellular peptide hydrogels, but was 62% from peptide hydrogels with encapsulated BMSCs, likely due to cell-mediated TGF-β1 degradation and release of small labeled species. TGF-β1 loaded peptide hydrogels stimulated chondrogenesis of young equine BMSCs, a relevant preclinical model for treating injuries in young human cohorts. Self-assembling peptide hydrogels can be used to deliver chondrogenic factors to encapsulated cells making them a promising technology for in vivo, cell-based regenerative medicine.
authors: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139.
authors: Paul W
authors: PW
authors: Kopesky
authors: Sangwon
authors: S
authors: Byun
authors: Eric J
authors: EJ
authors: Vanderploeg
authors: John D
authors: JD
authors: Kisiday
authors: David D
authors: DD
authors: Frisbie
authors: Alan J
authors: AJ
authors: Grodzinsky
mesh_terms: D000327:Adsorption; D000818:Animals; D002417:Cattle; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D003692:Delayed-Action Preparations; D006736:Horses; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D012685:Sepharose; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D007457:Iodine Radioisotopes; D010455:Peptides; D053773:Transforming Growth Factor beta1; D012685:Sepharose
keywords: bone marrow stromal cell; cartilage repair; regenerative medicine; sustained delivery; tissue engineering
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