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

J Biomed Mater Res A. 2014 May;102(5):1275-85. doi: 10.1002/jbm.a.34789. Epub 2013 Jun 4.

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.

Keywords: bone marrow stromal cell; cartilage repair; regenerative medicine; sustained delivery; tissue engineering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Animals
  • Cattle
  • Cells, Immobilized / cytology
  • Cells, Immobilized / drug effects
  • Cells, Immobilized / metabolism
  • Chondrogenesis / drug effects*
  • Delayed-Action Preparations
  • Horses
  • Humans
  • Hydrogels / pharmacology*
  • Iodine Radioisotopes
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Peptides / pharmacology*
  • Sepharose
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Delayed-Action Preparations
  • Hydrogels
  • Iodine Radioisotopes
  • Peptides
  • Transforming Growth Factor beta1
  • Sepharose