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Biomaterials2013; 34(31); 7645-7652; doi: 10.1016/j.biomaterials.2013.06.056

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

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 in vivo 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.
Copyright © 2013 Elsevier Ltd. All rights reserved.
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Publication Date: 2013-07-17 PubMed ID: 23871542PubMed Central: PMC4090944DOI: 10.1016/j.biomaterials.2013.06.056Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper focuses on how the alterations in the glycosaminoglycan content of collagen-GAG scaffolds can be used to regulate cell activity, specifically related to regenerative medicine and tissue engineering.

Research Objective and Methodology

  • This study revolves around the goal to design biomaterials for regenerative medicine. The researchers aimed to find a way to amplify local biomolecular signals, both produced internally (endogenously) and added externally (exogenously).
  • The team focused on glycosaminoglycans (GAGs), which are linear polysaccharides found in the extracellular matrix. These GAGs are known to sequester growth factors (signal molecules) transiently through charge interactions.
  • By incorporating GAGs of increasing sulfation (specifically, hyaluronic acid, chondroitin sulfate, and heparin) into a collagen-GAG (CG) scaffold, researchers aimed to develop a model for tendon tissue engineering.

Findings and Importance

  • The research found that manipulating the degree of GAG sulfation had a significant influence on the sequestration of growth factors from the media. In simpler terms, altering the level of GAG sulfation changed how effectively the growth factors could be stored and collected.
  • Increasing the GAG sulfation seemed to improve metabolic activity in equine tenocytes (a type of tendon cell) under different growth conditions such as normal serum, low serum, and insulin-like growth factor 1 (IGF-1) supplemented media conditions.
  • The experiment revealed that earlier reported dose-dependent changes in tenocyte bioactivity to soluble IGF-1 could be replicated through the use of increasingly sulfated GAGs in a CG scaffold.
  • Overall, the results indicate that modifying the GAG content in CG scaffolds could be a systematic technique for controlling the sequestration and enhanced bioactivity of growth factors. This may prove useful in specifying cell behavior within the extracellular matrix, a critical aspect in tissue engineering and regenerative medicine.

Cite This Article

APA
Hortensius RA, Harley BA. (2013). The use of bioinspired alterations in the glycosaminoglycan content of collagen-GAG scaffolds to regulate cell activity. Biomaterials, 34(31), 7645-7652. https://doi.org/10.1016/j.biomaterials.2013.06.056

Publication

Biomaterials
ISSN: 1878-5905
NlmUniqueID: 8100316
Country: Netherlands
Language: English
Volume: 34
Issue: 31
Pages: 7645-7652

Researcher Affiliations

Hortensius, Rebecca A
  • Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Harley, Brendan A C

    MeSH Terms

    • Animals
    • Biocompatible Materials / chemistry
    • Collagen / chemistry
    • Glycosaminoglycans / chemistry
    • Horses
    • Humans
    • Mesenchymal Stem Cells / cytology
    • Microscopy, Electron, Scanning
    • Real-Time Polymerase Chain Reaction
    • Tendons / cytology
    • Tissue Engineering / methods
    • Tissue Scaffolds / chemistry

    Grant Funding

    • R03 AR062811 / NIAMS NIH HHS

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