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Home / Equine Research Bank / Biomaterials / The use of bioinspired alterations in the glycosaminoglycan ...
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

    References

    This article includes 48 references
    1. Place ES, Evans ND, Stevens MM. Complexity in biomaterials for tissue engineering.. Nat Mater 2009;8:457–470.
      pubmed: 19458646
    2. Farrell E, O’Brien FJ, Doyle P, Fischer J, Yannas I, Harley BA. A collagen–glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes.. Tissue Eng 2006;12:459–468.
      pubmed: 16579679
    3. Caliari SR, Harley BA. Composite growth factor supplementation strategies to enhance tenocyte bioactivity in aligned collagen–GAG scaffolds.. Tissue Eng Part A 2013;19:1100–1112.
      pmc: PMC3609632pubmed: 23157454
    4. Gulotta LV, Rodeo SA. Growth factors for rotator cuff repair.. Clin Sports Med 2009;28:13–23.
      pubmed: 19064162
    5. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing.. Sports Med 2003;33:381–394.
      pubmed: 12696985
    6. Shen W, Chen X, Chen J, Yin Z, Heng BC, Chen W. The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration.. Biomaterials 2010;31:7239–7249.
      pubmed: 20615544
    7. Martin TA, Caliari SR, Williford PD, Harley BA, Bailey RC. The generation of biomolecular patterns in highly porous collagen–GAG scaffolds using direct photolithography.. Biomaterials 2011;32:3949–3957.
      pmc: PMC3947768pubmed: 21397322
    8. Alberti K, Davey RE, Onishi K, George S, Salchert K, Seib FP. Functional immobilization of signaling proteins enables control of stem cell fate.. Nat Methods 2008;5:645–650.
      pubmed: 18552855
    9. Klenkler BJ, Sheardown H. Characterization of EGF coupling to aminated silicone rubber surfaces.. Biotechnol Bioeng 2006;95:1158–1166.
      pubmed: 16817187
    10. Mann BK, Schmedlen RH, West JL. Tethered-TGF-beta increases extracellular matrix production of vascular smooth muscle cells.. Biomaterials 2001;22:439–444.
      pubmed: 11214754
    11. Hanson JA, Chang CB, Graves SM, Li Z, Mason TG, Deming TJ. Nanoscale double emulsions stabilized by single-component block copolypeptides.. Nature 2008;455:85–88.
      pubmed: 18769436
    12. Richardson TP, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery.. Nat Biotechnol 2001;19:1029–1034.
      pubmed: 11689847
    13. Sohier J, Vlugt TJH, Cabrol N, Van Blitterswijk C, de Groot K, Bezemer JM. Dual release of proteins from porous polymeric scaffolds.. J Control Release 2006;111:95–106.
      pubmed: 16455149
    14. Raman R, Sasisekharan V, Sasisekharan R. Structural insights into biological roles of protein–glycosaminoglycan interactions.. Chem Biol 2005;12:267–277.
      pubmed: 15797210
    15. Gama CI, Tully SE, Sotogaku N, Clark PM, Rawat M, Vaidehi N. Sulfation patterns of glycosaminoglycans encode molecular recognition and activity.. Nat Chem Biol 2006;2:467–473.
      pubmed: 16878128
    16. Rawat M, Gama CI, Matson JB, Hsieh-Wilson LC. Neuroactive chondroitin sulfate glycomimetics.. J Am Chem Soc 2008;130:2959–2961.
      pmc: PMC3034635pubmed: 18275195
    17. Spillmann D, Lindahl U. Glycosaminoglycan protein interactions – a question of specificity.. Curr Opin Struct Biol 1994;4:677–682.
      pubmed: 29455055
    18. Hudalla GA, Kouris NA, Koepsel JT, Ogle BM, Murphy WL. Harnessing endogenous growth factor activity modulates stem cell behavior.. Integr Biol (Camb) 2011;3:832–842.
      pmc: PMC3996706pubmed: 21720642
    19. Hempel U, Hintze V, Moller S, Schnabelrauch M, Scharnweber D, Dieter P. Artificial extracellular matrices composed of collagen I and sulfated hyaluronan with adsorbed transforming growth factor beta 1 promote collagen synthesis of human mesenchymal stromal cells.. Acta Biomaterialia 2012;8:659–666.
      pubmed: 22061106
    20. Zhang L, Furst EM, Kiick KL. Manipulation of hydrogel assembly and growth factor delivery via the use of peptide–polysaccharide interactions.. J Control Release 2006;114:130–142.
      pmc: PMC2606047pubmed: 16890321
    21. Sakiyama-Elbert SE, Hubbell JA. Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix.. J Control Release 2000;69:149–158.
      pubmed: 11018553
    22. Hudalla GA, Koepsel JT, Murphy WL. Surfaces that sequester serum-borne heparin amplify growth factor activity.. Adv Mater 2011;23:5415–5418.
      pmc: PMC4410730pubmed: 22028244
    23. Yannas IV, Lee E, Orgill DP, Skrabut EM, Murphy GF. Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin.. Proc Natl Acad Sci U S A 1989;86:933–937.
      pmc: PMC286593pubmed: 2915988
    24. Harley BA, Freyman TM, Wong MQ, Gibson LJ. A new technique for calculating individual dermal fibroblast contractile forces generated within collagen–GAG scaffolds.. Biophys J 2007;93:2911–2922.
      pmc: PMC1989727pubmed: 17586570
    25. Harley BA, Kim HD, Zaman MH, Yannas IV, Lauffenburger DA, Gibson LJ. Microarchitecture of three-dimensional scaffolds influences cell migration behavior via junction interactions.. Biophys J 2008;95:4013–4024.
      pmc: PMC2553126pubmed: 18621811
    26. Harley BA, Spilker MH, Wu JW, Asano K, Hsu HP, Spector M. Optimal degradation rate for collagen chambers used for regeneration of peripheral nerves over long gaps.. Cells Tissues Organs 2004;176:153–165.
      pubmed: 14745243
    27. O’Brien FJ, Harley BA, Yannas IV, Gibson LJ. The effect of pore size on cell adhesion in collagen–GAG scaffolds.. Biomaterials 2005;26:433–441.
      pubmed: 15275817
    28. Torres DS, Freyman TM, Yannas IV, Spector M. Tendon cell contraction of collagen–GAG matrices in vitro: effect of cross-linking.. Biomaterials 2000;21:1607–1619.
      pubmed: 10885733
    29. Ellis DL, Yannas IV. Recent advances in tissue synthesis in vivo by use of collagen–glycosaminoglycan copolymers.. Biomaterials 1996;17:291–299.
      pubmed: 8745326
    30. Harley BA, Leung JH, Silva EC, Gibson LJ. Mechanical characterization of collagen–glycosaminoglycan scaffolds.. Acta Biomater 2007;3:463–474.
      pubmed: 17349829
    31. James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options.. J Hand Surg Am 2008;33:102–112.
      pubmed: 18261674
    32. Liu Y, Ramanath HS, Wang DA. Tendon tissue engineering using scaffold enhancing strategies.. Trends Biotechnol 2008;26:201–209.
      pubmed: 18295915
    33. Wang JH. Mechanobiology of tendon.. J Biomech 2006;39:1563–1582.
      pubmed: 16000201
    34. Caliari SR, Harley BAC. The effect of anisotropic collagen–GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity.. Biomaterials 2011;32:5330–5340.
      pmc: PMC3947515pubmed: 21550653
    35. Caliari SR, Weisgerber DW, Ramirez MA, Kelkhoff DO, Harley BAC. The influence of collagen–glycosaminoglycan scaffold relative density and microstructural anisotropy on tenocyte bioactivity and transcriptomic stability.. J Mech Behav Biomed Mater 2012;11:27–40.
      pmc: PMC3947516pubmed: 22658152
    36. Caliari SR, Ramirez MA, Harley BA. The development of collagen–GAG scaffold-membrane composites for tendon tissue engineering.. Biomaterials 2011;32:8990–8998.
      pmc: PMC3947519pubmed: 21880362
    37. Olde Damink LHH, Dijkstra PJ, Van Luyn MJA, Van Wachem PB, Nieuwenhuis P, Feijen J. Cross-linking of dermal sheep collagen using a water-soluble carbodiimide.. Biomaterials 1996;17:765–773.
      pubmed: 8730960
    38. O’Brien FJ, Harley BA, Yannas IV, Gibson L. Influence of freezing rate on pore structure in freeze-dried collagen–GAG scaffolds.. Biomaterials 2004;25:1077–1086.
      pubmed: 14615173
    39. Kapoor A, Caporali EH, Kenis PJ, Stewart MC. Microtopographically patterned surfaces promote the alignment of tenocytes and extracellular collagen.. Acta Biomater 2010;6:2580–2589.
      pubmed: 20045087
    40. Taylor SE, Vaughan-Thomas A, Clements DN, Pinchbeck G, Macrory LC, Smith RK. Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems.. BMC Musculoskelet Disord 2009;10:27.
      pmc: PMC2651848pubmed: 19245707
    41. Pauly S, Klatte F, Strobel C, Schmidmaier G, Greiner S, Scheibel M. Characterization of tendon cell cultures of the human rotator cuff.. Eur Cell Mater 2010;20:84–97.
      pubmed: 20661865
    42. Park A, Hogan MV, Kesturu GS, James R, Balian G, Chhabra AB. Adipose-derived mesenchymal stem cells treated with growth differentiation factor-5 express tendon-specific markers.. Tissue Eng Part A 2010;16:2941–2951.
      pmc: PMC2928041pubmed: 20575691
    43. James R, Kumbar SG, Laurencin CT, Balian G, Chhabra AB. Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems.. Biomed Mater 2011;6:025011.
      pmc: PMC3206634pubmed: 21436509
    44. Costa MA, Wu C, Pham BV, Chong AK, Pham HM, Chang J. Tissue engineering of flexor tendons: optimization of tenocyte proliferation using growth factor supplementation.. Tissue Eng 2006;12:1937–1943.
      pubmed: 16889523
    45. Thomopoulos S, Harwood FL, Silva MJ, Amiel D, Gelberman RH. Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro.. J Hand Surg Am 2005;30:441–447.
      pubmed: 15925149
    46. Chamberlain LJ, Yannas IV, Hsu H-P, Strichartz G, Spector M. Collagen–GAG substrate enhances the quality of nerve regeneration through collagen tubes up to level of autograft.. Exper Neurol 1998;154:315–329.
      pubmed: 9878170
    47. Schubert M. Chondroitin from chondroitin sulfate.. In: Whistler R, BeMiller J, Wolfrom M, editors. Methods in carbohydrate chemistry: general polysaccharides. New York: Academic Press; 1965. pp. 109–110.
    48. Lim JJ, Temenoff JS. The effect of desulfation of chondroitin sulfate on interactions with positively charged growth factors and upregulation of cartilaginous markers in encapsulated MSCs.. Biomaterials 2013;34:5007–5018.
      pmc: PMC3671883pubmed: 23570717
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