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Proangiogenic Potential of a Collagen/Bioactive Glass Substrate

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Abstract

Purpose

Previous attempts to stimulate angiogenesis have focused on the delivery of growth factors and cytokines, genes encoding for specific angiogenic inductive proteins or transcription factors, or participating cells. While high concentrations of bioactive glasses have exhibited osteogenic potential, recent studies have demonstrated that low concentrations of particular bioactive glasses are angiogenic. We hypothesized that a well known bioactive glass (Bioglass® 45S5) possesses proangiogenic potential over a limited range of concentrations.

Materials and Methods

Varying amounts of Bioglass were loaded into absorbable collagen sponges. The proangiogenic potential of Bioglass was determined by examining the capacity of the soluble products to induce endothelial cell proliferation, tubule formation in a co-culture, and upregulate vascular endothelial growth factor (VEGF) production.

Results

We determined a range of Bioglass concentrations which exhibit proangiogenic potential. Furthermore, we demonstrated that the proangiogenic capacity of this material is related to the soluble dissolution products of Bioglass and the subsequent production of cell-secreted angiogenic factors by stimulated cells.

Conclusions

These studies suggest that this bioactive glass possesses a robust proangiogenic potential, and this strategy may provide an alternative to recombinant inductive growth factors.

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References

  1. P. Carmeliet. Manipulating angiogenesis in medicine. J. Intern. Med. 255:538–561 (2004).

    Article  PubMed  Google Scholar 

  2. M. Nomi, A. Atala, P. D. Coppi, and S. Soker. Principals of neovascularization for tissue engineering. Mol. Aspects. Med. 23:463–483 (2002).

    PubMed  CAS  Google Scholar 

  3. L. L. Hench, R. J. Splinter, W. C. Allen, and T. K. Greenlee. Bonding mechanisms at the interface of ceramic prosthetic materials. J. Biomed. Mater. Res. 5:117–141 (1971).

    Article  Google Scholar 

  4. L. L. Hench, I. D. Xynos, and J. M. Polak. Bioactive glasses for in situ tissue regeneration. J. Biomater. Sci. Polym. Ed. 15:543–562 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. E. J. Schepers, and P. Ducheyne. Bioactive glass particles of narrow size range for the treatment of oral bone defects: a 1–24 month experiment with several materials and particle sizes and size ranges. J. Oral. Rehabil. 24:171–181 (1997).

    Article  PubMed  CAS  Google Scholar 

  6. T. B. Lovelace, J. T. Mellonig, R. M. Meffert, A. A. Jones, P. V. Nummikoski, and D. L. Cochran. Clinical evaluation of bioactive glass in the treatment of periodontal osseous defects in humans. J. Periodontol. 69:1027–1035 (1998).

    PubMed  CAS  Google Scholar 

  7. R. Mengel, D. Schreiber, and L. Flores-de-Jacoby. Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis: results of a 5-year clinical and radiological study. J. Periodontol. 77:1781–1787 (2006).

    Article  PubMed  Google Scholar 

  8. M. Marcolongo, P. Ducheyne, J. Garino, and E. Schepers. Bioactive glass fiber/polymeric composites bond to bone tissue. J. Biomed. Mater. Res. 39:161–170 (1998).

    Article  PubMed  CAS  Google Scholar 

  9. J. A. Roether, A. R. Boccaccini, L. L. Hench, V. Maquet, S. Gautier, and R. Jerjme. Development and in vitro characterisation of novel bioresorbable and bioactive composite materials based on polylactide foams and Bioglass for tissue engineering applications. Biomaterials 23:3871–3878 (2002).

    Article  PubMed  CAS  Google Scholar 

  10. J. Yao, S. Radina, P. S. Leboy, and P. Ducheyne. The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering. Biomaterials 26:1935–1943 (2005).

    Article  PubMed  CAS  Google Scholar 

  11. C. R. Perry. Bone repair techniques, bone graft, and bone graft substitutes. Clin. Orthop. Relat. Res. 360:71–86 (1999).

    Article  PubMed  Google Scholar 

  12. J. K. Leach, and D. J. Mooney. Bone engineering by controlled delivery of osteoinductive molecules and cells. Expert. Opin. Biol. Ther. 4:1015–1027 (2004).

    Article  PubMed  CAS  Google Scholar 

  13. I. D. Xynos, A. J. Edgar, L. D. Buttery, L. L. Hench, and J. M. Polak. Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem. Biophys. Res. Commun. 276:461–465 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. I. D. Xynos, A. J. Edgar, L. D. Buttery, L. L. Hench, and J. M. Polak. Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. J. Biomed. Mater. Res. 55:151–157 (2001).

    Article  PubMed  CAS  Google Scholar 

  15. M. Bosetti, and M. Cannas. The effect of bioactive glasses on bone marrow stromal cells differentiation. Biomaterials 26:3873–3879 (2005).

    Article  PubMed  CAS  Google Scholar 

  16. S. Hattar, A. Asselin, D. Greenspan, M. Oboeuf, A. Berdal, and J. M. Sautier. Potential of biomimetic surfaces to promote in vitro osteoblast-like cell differentiation. Biomaterials 26:839–848 (2005).

    Article  PubMed  CAS  Google Scholar 

  17. E. Bergeron, M. E. Marquis, I. Chretien, and N. Faucheux. Differentiation of preosteoblasts using a delivery system with BMPs and bioactive glass microspheres. J. Mater. Sci. Mater. Med. 18:255–263 (2007).

    Article  PubMed  CAS  Google Scholar 

  18. H. Keshaw, A. Forbes, and R. M. Day. Release of angiogenic growth factors from cells encapsulated in alginate beads with bioactive glass. Biomaterials 26:4171–4179 (2005).

    Article  PubMed  CAS  Google Scholar 

  19. J. K. Leach, D. Kaigler, Z. Wang, P. H. Krebsbach, and D. J. Mooney. Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration. Biomaterials 27:3249–3255 (2006).

    Article  PubMed  CAS  Google Scholar 

  20. R. M. Day. Bioactive glass stimulates the secretion of angiogenic growth factors and angiogenesis in vitro. Tissue Eng. 11:768–777 (2005).

    Article  PubMed  CAS  Google Scholar 

  21. W. H. Zhu, and R. F. Nicosia. The thin prep rat aortic ring assay: A modified method for the characterization of angiogenesis in whole mounts. Angiogenesis 5:81–86 (2002).

    Article  PubMed  CAS  Google Scholar 

  22. D. Donovan, N. J. Brown, E. T. Bishop, and C. E. Lewis. Comparison of three in vitro human ‘angiogenesis’ assays with capillaries formed in vivo. Angiogenesis 4:113–121 (2001).

    Article  PubMed  CAS  Google Scholar 

  23. S. Ivanovski, H. Li, T. Daley, and P. M. Bartold. An immunohistochemical study of matrix molecules associated with barrier membrane-mediated periodontal wound healing. J. Periodontal. Res. 35:115–126 (2000).

    Article  PubMed  CAS  Google Scholar 

  24. A. B. Ennett, D. Kaigler, and D. J. Mooney. Temporally regulated delivery of VEGF in vitro and in vivo. J. Biomed. Mater. Res. Part A 79A:176–184 (2006).

    Article  CAS  Google Scholar 

  25. R. R. Chen, and D. J. Mooney. Polymeric growth factor delivery strategies for tissue engineering. Pharm. Res. 20:1103–1112 (2003).

    Article  PubMed  CAS  Google Scholar 

  26. S. R. Peyton, and A. J. Putnam. Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion. J. Cell Physiol. 204:198–209 (2005).

    Article  PubMed  CAS  Google Scholar 

  27. R. K. Willits, and S. L. Skornia. Effect of collagen gel stiffness on neurite extension. J. Biomater. Sci. Polym. Ed. 15:1521–1531 (2004).

    Article  PubMed  CAS  Google Scholar 

  28. N. Yamamura, R. Sudo, M. Ikeda, and K. Tanishita. Effects of the mechanical properties of collagen gel on the in vitro formation of microvessel networks by endothelial cells. Tissue Eng. 13:1443–1453 (2007).

    Article  PubMed  CAS  Google Scholar 

  29. T. Yeung, P. C. Georges, L. A. Flanagan, B. Marg, M. Ortiz, M. Funaki, N. Zahir, W. Ming, V. Weaver, and P. A. Janmey. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil. Cytoskeleton. 60:24–34 (2005).

    Article  PubMed  Google Scholar 

  30. S. X. Hsiong, P. Carampin, H. J. Kong, K. Y. Lee, and D. J. Mooney. Differentiation stage alters matrix control of stem cells. J. Biomed. Mater. Res. A (in press) (2007). DOI 10.1002/jbm.a.31521

  31. A. J. Engler, S. Sen, H. L. Sweeney, and D. E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126:677–689 (2006).

    Article  PubMed  CAS  Google Scholar 

  32. C. B. Khatiwala, S. R. Peyton, M. Metzke, and A. J. Putnam. The regulation of osteogenesis by ECM rigidity in MC3T3-E1 cells requires MAPK activation. J. Cell Physiol. 211:661–672 (2007).

    Article  PubMed  CAS  Google Scholar 

  33. C. B. Khatiwala, S. R. Peyton, and A. J. Putnam. Intrinsic mechanical properties of the extracellular matrix affect the behavior of pre-osteoblastic MC3T3-E1 cells. Am. J. Physiol. Cell Physiol. 290:C1640–1650 (2006).

    Article  PubMed  CAS  Google Scholar 

  34. P. Carmeliet. Angiogenesis in health and disease. Nat. Med. 9:653–660 (2003).

    Article  PubMed  CAS  Google Scholar 

  35. T. P. Richardson, M. C. Peters, A. B. Ennett, and D. J. Mooney. Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19:1029–1034 (2001).

    Article  PubMed  CAS  Google Scholar 

  36. C. R. Ozawa, A. Banfi, N. L. Glazer, G. Thurston, M. L. Springer, P. E. Kraft, D. M. McDonald, and H. M. Blau. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J. Clin. Invest. 113:516–527 (2004).

    PubMed  CAS  Google Scholar 

  37. W. Helen, C. L. R. Merry, J. J. Blaker, and J. E. Gough. Three-dimensional culture of annulus fibrosus cells within PDLLA/Bioglass(R) composite foam scaffolds: Assessment of cell attachment, proliferation and extracellular matrix production. Biomaterials 28:2010–2020 (2007).

    Article  PubMed  CAS  Google Scholar 

  38. B. R. McAuslan, and W. Reilly. Endothelial cell phagokinesis in response to specific metal ions. Exp. Cell Res. 130:147–157 (1980).

    Article  PubMed  CAS  Google Scholar 

  39. K. S. Raju, G. Alessandri, M. Ziche, and P. M. Gullino. Ceruloplasmin, copper ions, and angiogenesis. J. Natl. Cancer Inst. 69:1183–1188 (1982).

    PubMed  CAS  Google Scholar 

  40. C. K. Sen, S. Khanna, M. Venojarvi, P. Trikha, E. C. Ellison, T. K. Hunt, and S. Roy. Copper-induced vascular endothelial growth factor expression and wound healing. Am. J. Physiol. Heart Circ. Physiol. 282:H1821–1827 (2002).

    PubMed  CAS  Google Scholar 

  41. M. Frangoulis, P. Georgiou, C. Chrisostomidis, D. Perrea, I. Dontas, N. Kavantzas, A. Kostakis, and O. Papadopoulos. Rat epigastric flap survival and VEGF expression after local copper application. Plast. Reconstr. Surg. 119:837–843 (2007).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge financial support from the American Cancer Society and the Dean, UC Davis School of Medicine [notice ACS IRG-95-125-07] and David Fyhrie for use of mechanical testing equipment.

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  1. Department of Biomedical Engineering, University of California, Davis, 451 Health Sciences Drive, Davis, California, 95616, USA

    Ann Leu & J. Kent Leach

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  1. Ann Leu
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Correspondence to J. Kent Leach.

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Leu, A., Leach, J.K. Proangiogenic Potential of a Collagen/Bioactive Glass Substrate. Pharm Res 25, 1222–1229 (2008). https://doi.org/10.1007/s11095-007-9508-9

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