Sustained delivery of bioactive TGF-β1 from self-assembling peptide hydrogels induces chondrogenesis of encapsulated bone marrow stromal cells

• Main Authors: Kopesky, Paul Wayne (Contributor), Byun, Sangwon (Contributor), Vanderploeg, Eric J. (Contributor), Kisiday, John D. (Author), Frisbie, David D. (Author), Grodzinsky, Alan J. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Center for Biomedical Engineering (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor)
• Format: Article
• Language: English
• Published: John Wiley & Sons, Inc., 2013-07-25T20:46:43Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (NIH EB003805)
National Institutes of Health (U.S.) (NIH AR60331)
National Institutes of Health (U.S.). Molecular, Cell, and Tissue Biomechanics (Training Grant Fellowship)
Arthritis Foundation (postdoctoral fellowship)