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 language | English (US) |
|---|---|
| Pages (from-to) | 7645-7652 |
| Number of pages | 8 |
| Journal | Biomaterials |
| Volume | 34 |
| Issue number | 31 |
| DOIs | |
| State | Published - Oct 2013 |
Bibliographical note
Funding Information:The authors would like to acknowledge Dr. Allison Stewart (Veterinary Sciences, UIUC) for the equine tenocytes, Karen Doty (Veterinary Sciences, UIUC) for sectioning for pore size analysis, Dr. Sandra McMasters (SCS, UIUC) for culture media preparation, and the IGB Core Facilities for assistance with real-time PCR. This research was carried out in part in the Frederick Seitz Materials Research Laboratory Central Facilities, University of Illinois, which is partially supported by the U.S. Department of Energy under grants DE-FG02-07ER46453 and DE-FG02-07ER46471 . This material is based upon work supported by the National Science Foundation under Grant No. 1105300. We are grateful for the funding for this study provided by the NSF Graduate Research Fellowship DGE 11-44245 FLLW (RAH) , the Chemical and Biomolecular Engineering Dept. (BAH) , and the Institute for Genomic Biology (BAH) at the University of Illinois at Urbana-Champaign.
Keywords
- Biomimetic material
- Collagen
- Growth factors
- Mesenchymal stem cell
- Scaffold
- Tendon