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Biomaterials2011; 32(23); 5330-5340; doi: 10.1016/j.biomaterials.2011.04.021

The effect of anisotropic collagen-GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity.

Abstract: Current surgical and tissue engineering approaches for treating tendon injuries have shown limited success, suggesting the need for new biomaterial strategies. Here we describe the development of an anisotropic collagen-glycosaminoglycan (CG) scaffold and use of growth factor supplementation strategies to create a 3D platform for tendon tissue engineering. We fabricated cylindrical CG scaffolds with aligned tracks of ellipsoidal pores that mimic the native physiology of tendon by incorporating a directional solidification step into a conventional lyophilization strategy. By modifying the freezing temperature, we created a homologous series of aligned CG scaffolds with constant relative density and degree of anisotropy but a range of pore sizes (55-243 μm). Equine tendon cells showed greater levels of attachment, metabolic activity, and alignment as well as less cell-mediated scaffold contraction, when cultured in anisotropic scaffolds compared to an isotropic CG scaffold control. The anisotropic CG scaffolds also provided critical contact guidance cues for cell alignment. While tendon cells were randomly oriented in the isotropic control scaffold and the transverse (unaligned) plane of the anisotropic scaffolds, significant cell alignment was observed in the direction of the contact guidance cues in the longitudinal plane of the anisotropic scaffolds. Scaffold pore size was found to significantly influence tendon cell viability, proliferation, penetration into the scaffold, and metabolic activity in a manner predicted by cellular solids arguments. Finally, the addition of the growth factors PDGF-BB and IGF-1 to aligned CG scaffolds was found to enhance tendon cell motility, viability, and metabolic activity in dose-dependent manners. This work suggests a composite strategy for developing bioactive, 3D material systems for tendon tissue engineering.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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Publication Date: 2011-05-07 PubMed ID: 21550653PubMed Central: PMC3947515DOI: 10.1016/j.biomaterials.2011.04.021Google 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 researchers have developed a biomaterial strategy for repairing tendon injuries, using collagen-glycosaminoglycan scaffolds and supplementing with growth factors. This strategy showed improved cell attachment, activity, alignment and reduced scaffold contraction compared to current methods.

Creation of Collagen-Glycosaminoglycan Scaffolds

  • The researchers designed collagen-glycosaminoglycan (CG) scaffolds shaped like cylinders, with aligned ellipsoidal pores imitating the structure of natural tendons.
  • This involved adding a step of directional solidification to the usual lyophilization (freeze-drying) process.
  • The freezing temperature was adjusted to create a series of CG scaffolds with unchanging relative density and degree of anisotropy (directional dependence), but with varying pore sizes ranging between 55 and 243µm.

Anisotropic Scaffolds vs Isotropic Scaffolds

  • Equine tendon cells showed improved attachment, metabolic activity, and alignment as well as reduced contraction when cultured in anisotropic (directionally dependent) scaffolds compared to an isotropic (uniform in all directions) CG scaffold control.
  • The anisotropic CG scaffolds provided important contact guidance cues promoting cell alignment.
  • Cells in the isotropic control scaffold and the transverse plane of the anisotropic scaffolds were randomly oriented. However in the longitudinal plane of the anisotropic scaffolds, cells showed significant alignment following the direction of contact guidance cues.

Impact of Scaffold Pore Size and Growth Factors

  • Cell viability, proliferation, scaffold penetration, and metabolic activity were found to be significantly influenced by the size of the scaffold pores, and this influence was predictable based on cellular solids arguments.
  • The researchers added growth factors PDGF-BB and IGF-1 to the aligned CG scaffolds and observed enhanced cell motility, viability, and metabolic activity in a dose-dependent manner, suggesting a critical role played by the growth factors in promoting cell functions.

Concluding Remarks

  • This study introduces a composite strategy that combines anisotropic CG scaffolds and supplementation of growth factors for the development of bioactive, 3-dimensional systems for tendon tissue engineering.
  • The positive influence of scaffold anisotropy and pore size as well as the growth factors on cell viability, metabolic activity, proliferation, and alignment highlight this approach as a potential improvement over current tendon injury treatment methods.

Cite This Article

APA
Caliari SR, Harley BA. (2011). The effect of anisotropic collagen-GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity. Biomaterials, 32(23), 5330-5340. https://doi.org/10.1016/j.biomaterials.2011.04.021

Publication

Biomaterials
ISSN: 1878-5905
NlmUniqueID: 8100316
Country: Netherlands
Language: English
Volume: 32
Issue: 23
Pages: 5330-5340

Researcher Affiliations

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

    MeSH Terms

    • Animals
    • Anisotropy
    • Becaplermin
    • Cell Adhesion
    • Cell Proliferation
    • Cell Survival / drug effects
    • Chemotaxis / drug effects
    • Chondroitin Sulfates / chemistry
    • Collagen Type I / chemistry
    • Connective Tissue Cells / cytology
    • Connective Tissue Cells / drug effects
    • Connective Tissue Cells / metabolism
    • Horses
    • Insulin-Like Growth Factor I / pharmacology
    • Intercellular Signaling Peptides and Proteins / pharmacology
    • Microscopy, Electron, Scanning
    • Platelet-Derived Growth Factor / pharmacology
    • Porosity
    • Proto-Oncogene Proteins c-sis
    • Surface Properties
    • Temperature
    • Tendons / cytology
    • Tissue Engineering / methods
    • Tissue Scaffolds / chemistry

    Grant Funding

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

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