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. 2013 Oct;34(31):7645-52.
doi: 10.1016/j.biomaterials.2013.06.056. Epub 2013 Jul 17.

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

Rebecca A Hortensius  1 , Brendan A C Harley
Affiliations

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

Rebecca A Hortensius et al. Biomaterials. 2013 Oct.

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.

Keywords: Biomimetic material; Collagen; Growth factors; Mesenchymal stem cell; Scaffold; Tendon.

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Figures

Fig. 1
Fig. 1
SEM images of CG scaffold pore structure for each GAG variant (left to right): collagen:hyaluronic acid (C:HA), collagen:chondroitin sulfate (C:CS, standard), collagen:heparin (C:HP). Scale bar: 100 µm.
Fig. 2
Fig. 2
IGF-1 sequestration by CG scaffolds with varying degree of GAG sulfation. The degree of pull down is normalized to the no scaffold control. (*) Significance (p < 0.05) between scaffold groups.
Fig. 3
Fig. 3
Tenocyte metabolic activity as a function of scaffold GAG sulfation as well as media serum level. (A) Tenocyte metabolic activity in scaffolds cultured in media containing normal (10%) FBS concentrations. (B) Tenocyte metabolic activity under reduced (1%) FBS concentrations. (*) Significance (p < 0.05) between groups at a given time point.
Fig. 4
Fig. 4
Tenocyte gene expression levels for (A) collagen I (COL1A2) and (B) tenascin C (TNC) as a function of scaffold GAG sulfation at days 4, 7, and 14 of culture. Gene expression was normalized to tenocytes cultured in the C:HA scaffold variant at day 4. (*) Significance (p < 0.05) between GAG groups at a given time point.
Fig. 5
Fig. 5
Tenocyte response to IGF-1 supplementation (50 ng/mL in serum-free media) as a function of scaffold GAG content. Tenocyte response is reported as (A) total metabolic activity as well as gene expression levels (normalized to C:HA scaffolds at day 1) for (B) collagen I (COL1A2), (C) scleraxis (SCXB), and (D) tenascin-C (TNC). (*) Significance (p < 0.05) between groups at a given time point. (**) Significance (p < 0.01) between groups at a given time point.
Fig. 6
Fig. 6
(A) Metabolic activity and (B) normalized (to 2D control at day 4) scleraxis gene expression of hMSCs cultured in CG scaffolds with varying GAG content in serum-free media supplemented with 500 ng/mL GDF-5. (*) Significance (p < 0.05) between groups at a given time point.
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References

    1. Place ES, Evans ND, Stevens MM. Complexity in biomaterials for tissue engineering. Nat Mater. 2009;8:457–470. - PubMed
    1. Farrell E, O’Brien FJ, Doyle P, Fischer J, Yannas I, Harley BA, et al. A collagen–glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes. Tissue Eng. 2006;12:459–468. - PubMed
    1. 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 - PubMed
    1. Gulotta LV, Rodeo SA. Growth factors for rotator cuff repair. Clin Sports Med. 2009;28:13–23. - PubMed
    1. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med. 2003;33:381–394. - PubMed

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