The use of bioinspired alterations in the glycosaminoglycan content of collagen-GAG scaffolds to regulate cell activity

Rebecca A. Hortensius, Brendan A C Harley

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The design of biomaterials for regenerative medicine can require biomolecular cues such as growth factors to induce a desired cell activity. Signal molecules are often incorporated into the biomaterial in either freely-diffusible or covalently-bound forms. However, biomolecular environments invivo are often complex and dynamic. Notably, glycosaminoglycans (GAGs), linear polysaccharides found in the extracellular matrix, are involved in transient sequestration of growth factors via charge interactions. Biomaterials mimicking this phenomenon may offer the potential to amplify local biomolecular signals, both endogenously produced and exogenously added. GAGs of increasing sulfation (hyaluronic acid, chondroitin sulfate, heparin) were incorporated into a collagen-GAG (CG) scaffold under development for tendon tissue engineering. Manipulating the degree of GAG sulfation significantly impacts sequestration of growth factors from the media. Increasing GAG sulfation improved equine tenocyte metabolic activity in normal serum (10% FBS), low serum (1% FBS), and IGF-1 supplemented media conditions. Notably, previously reported dose-dependent changes in tenocyte bioactivity to soluble IGF-1 within the CG scaffold were replicated by using a single dose of soluble IGF-1 in scaffolds containing increasingly sulfated GAGs. Collectively, these results suggest that CG scaffold GAG content can be systematically manipulated to regulate the sequestration and resultant enhanced bioactivity of growth factor signals on cell behavior within the matrix.

Original languageEnglish (US)
Pages (from-to)7645-7652
Number of pages8
JournalBiomaterials
Volume34
Issue number31
DOIs
StatePublished - Oct 2013

Keywords

  • Biomimetic material
  • Collagen
  • Growth factors
  • Mesenchymal stem cell
  • Scaffold
  • Tendon

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