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Tissue engineering. Part A2013; 19(9-10); 1100-1112; doi: 10.1089/ten.TEA.2012.0497

Composite growth factor supplementation strategies to enhance tenocyte bioactivity in aligned collagen-GAG scaffolds.

Abstract: Biomolecular environments encountered in vivo are complex and dynamic, with combinations of biomolecules presented in both freely diffusible (liquid-phase) and sequestered (bound to the extracellular matrix) states. Strategies for integrating multiple biomolecular signals into a biomimetic scaffold provide a platform to simultaneously control multiple cell activities, such as motility, proliferation, phenotype, and regenerative potential. Here we describe an investigation elucidating the influence of the dose and mode of presentation (soluble, sequestered) of five biomolecules (stromal cell-derived factor 1α [SDF-1α], platelet-derived growth factor BB [PDGF-BB], insulin-like growth factor 1 [IGF-1], basic fibroblast growth factor [bFGF], and growth/differentiation factor 5 [GDF-5]) on the recruitment, proliferation, collagen synthesis, and genomic stability of equine tenocytes within an anisotropic collagen-GAG scaffold for tendon regeneration applications. Critically, we found that single factors led to a dose-dependent trade-off between driving tenocyte proliferation (PDGF-BB, IGF-1) versus maintenance of a tenocyte phenotype (GDF-5, bFGF). We identified supplementation schemes using factor pairs (IGF-1, GDF-5) to rescue the tenocyte phenotype and gene expression profiles while simultaneously driving proliferation. These results suggest coincident application of multi-biomolecule cocktails has a significant value in regenerative medicine applications where control of cell proliferation and phenotype are required. Finally, we demonstrated an immobilization strategy that allows efficient sequestration of bioactive levels of these factors within the scaffold network. We showed sequestration can lead to a greater sustained bioactivity than soluble supplementation, making this approach particularly amenable to in vivo translation where diffusive loss is a concern and continuous biomolecule supplementation is not feasible.
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Publication Date: 2013-01-04 PubMed ID: 23157454PubMed Central: PMC3609632DOI: 10.1089/ten.TEA.2012.0497Google Scholar: Lookup
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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 addresses the development of biomimetic scaffolds that use combinations of biomolecules to control aspects of cell activity, specifically focusing on tenocytes. The aim is to advance tendon regeneration applications, by revealing how five biomolecules affect tenocyte bioactivity within a specially designed collagen-GAG scaffold, and finding optimal multi-biomolecule combinations and delivery methods.

Experiment design and objectives

  • The researchers sought to investigate how the dosage and mode of delivery (soluble or sequestered) of five biomolecules influence tenocyte activities. They used anisotropic collagen-GAG scaffolds in these experiments, which are designed for tendon regeneration.
  • The biomolecules investigated were stromal cell-derived factor 1α (SDF-1α), platelet-derived growth factor BB (PDGF-BB), insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF), and growth/differentiation factor 5 (GDF-5).
  • The aim was to understand the effect of these biomolecules on recruitment, proliferation, collagen synthesis, and genomic stability of equine tenocytes within the scaffolds.

Key Findings

  • Single biomolecules had a dose-dependent effect on tenocytes, with a trade-off between promoting tenocyte proliferation (PDGF-BB, IGF-1) and maintaining the tenocyte phenotype (GDF-5, bFGF). Essentially, certain factors promoted cell growth while others retained cell identity, but not both together.
  • By using dual supplementation schemes (IGF-1, GDF-5), the researchers were able to strike a balance between proliferation and phenotype maintenance. This showed that multi-biomolecule blends could significantly benefit regenerative medicine applications, particularly where cell proliferation and phenotype control are required.

Sequestration Strategy

  • The team also developed a strategy for immobilizing these biomolecules within the scaffold framework. This approach led to more sustained bioactivity than soluble supplementation, indicating its potential for in vivo applications.
  • This method of embedding biomolecules is valuable in real-world conditions where continuous biomolecule supplementation is not feasible and there are concerns about diffusive loss.

Impact on regenerative medicine

  • This study suggests that using a cocktail of biomolecules, rather than single factors, could significantly augment tissue regeneration efforts.
  • The findings also highlight the potential of scaffold sequestration as an effective biomolecule delivery method, which could make subsequent clinical application of these findings more feasible.

Cite This Article

APA
Caliari SR, Harley BA. (2013). Composite growth factor supplementation strategies to enhance tenocyte bioactivity in aligned collagen-GAG scaffolds. Tissue Eng Part A, 19(9-10), 1100-1112. https://doi.org/10.1089/ten.TEA.2012.0497

Publication

Tissue engineering. Part A
ISSN: 1937-335X
NlmUniqueID: 101466659
Country: United States
Language: English
Volume: 19
Issue: 9-10
Pages: 1100-1112

Researcher Affiliations

Caliari, Steven R
  • Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Harley, Brendan A C

    MeSH Terms

    • Animals
    • Biomechanical Phenomena
    • Cell Proliferation / drug effects
    • Cells, Cultured
    • Chemokine CXCL12 / chemistry
    • Chemokine CXCL12 / pharmacology
    • Collagen / chemistry
    • Fibroblast Growth Factor 2 / chemistry
    • Fibroblast Growth Factor 2 / pharmacology
    • Growth Differentiation Factor 5 / chemistry
    • Growth Differentiation Factor 5 / pharmacology
    • Horses
    • Insulin-Like Growth Factor I / chemistry
    • Insulin-Like Growth Factor I / pharmacology
    • Platelet-Derived Growth Factor / chemistry
    • Platelet-Derived Growth Factor / pharmacology
    • Tendons / cytology
    • Tissue Engineering / methods
    • Tissue Scaffolds / chemistry

    Grant Funding

    • T32 GM070421 / NIGMS NIH HHS
    • T32GM070421 / NIGMS NIH HHS

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