Effect of nano-sized bioactive glass particles on the angiogenic properties of collagen based composites

Abstract

Angiogenesis is essential for tissue regeneration and repair. A growing body of evidence shows that the use of bioactive glasses (BG) in biomaterial-based tissue engineering (TE) strategies may improve angiogenesis and induce increased vascularization in TE constructs. This work investigated the effect of adding nano-sized BG particles (n-BG) on the angiogenic properties of bovine type I collagen/n-BG composites. Nano-sized (20–30 nm) BG particles of nominally 45S5 Bioglass® composition were used to prepare composite films, which were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The in vivo angiogenic response was evaluated using the quail chorioallantoic membrane (CAM) as an model of angiogenesis. At 24 h post-implantation, 10 wt% n-BG containing collagen films stimulated angiogenesis by increasing by 41 % the number of blood vessels branch points. In contrast, composite films containing 20 wt% n-BG were found to inhibit angiogenesis. This experimental study provides the first evidence that addition of a limited concentration of n-BG (10 wt%) to collagen films induces an early angiogenic response making selected collagen/n-BG composites attractive matrices for tissue engineering and regenerative medicine.

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References

  1. 1.

    Boccaccini AR, Erol M, Stark WJ, Mohn D, Hong Z, Mano JF. Polymer/bioactive glass nanocomposites for biomedical applications: A review. Compos Sci Technol. 2010;70:1764–76.

    Article  CAS  Google Scholar 

  2. 2.

    Silva SS, Mano JF, Reis RL. Potential applications of natural origin polymer-based systems in soft tissue regeneration. Crit Rev Biotechnol. 2010;30:200–21.

    Article  CAS  Google Scholar 

  3. 3.

    Wu C, Zhang Y, Zhou Y, Fan W, Xiao Y. A comparative study of mesoporous glass/silk and non-mesoporous glass/silk scaffolds: physiochemistry and in vivo osteogenesis. Acta Biomater. 2011;7:2229–36.

    Article  CAS  Google Scholar 

  4. 4.

    Misra SK, Mohn D, Brunner TJ, Stark WJ, Philip SE, Roy I, Salih V, Knowles JC, Boccaccini AR. Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass composites. Biomaterials. 2008;29:1750–61.

    Article  CAS  Google Scholar 

  5. 5.

    Misra SK, Ansari T, Mohn D, Valappil SP, Brunner TJ, Stark WJ, Roy I, Knowles JC, Sibbons PD, Jones EV, Boccaccini AR, Salih V. Effect of nanoparticulate bioactive glass particles on bioactivity and cytocompatibility of poly(3-hydroxybutyrate) composites. J R Soc Interface. 2010;7:453–65.

    Article  CAS  Google Scholar 

  6. 6.

    Dorj B, Park JH, Kim H-W. Robocasting chitosan/nanobioactive glass dual-pore structured scaffolds for bone engineering. Mater Letters. 2012;73:119–22.

    Article  CAS  Google Scholar 

  7. 7.

    Hong Z, Reis RL, Mano JF. Preparation and in vitro characterization of scaffolds of poly(l-lactic acid) containing bioactive glass ceramic nanoparticles. Acta Biomater. 2008;4:1297–306.

    Article  CAS  Google Scholar 

  8. 8.

    Lovett M, Lee K, Edwards A, Kaplan DL. Vascularization strategies for tissue engineering. Tissue Eng Part B Rev. 2009;15:353–70.

    Article  CAS  Google Scholar 

  9. 9.

    Vila OF, Bagó JR, Navarro M, Alieva M, Aguilar E, Engel E, Planell J, Rubio N, Blanco J. Calcium phosphate glass improves angiogenesis capacity of poly(lactic acid) scaffolds and stimulates differentiation of adipose tissue-derived mesenchymal stromal cells to the endothelial lineage. J Biomed Mater Res. 2012;. doi:10.1002/jbm.a.34391.

    Google Scholar 

  10. 10.

    Grieb G, Groger A, Piatkowski A, Markowicz M, Steffens GC, Pallua N. Tissue substitutes with improved angiogenic capabilities: an in vitro investigation with endothelial cells and endothelial progenitor cells. Cells Tissues Organs. 2010;191:96–104.

    Article  CAS  Google Scholar 

  11. 11.

    Gorustovich AA, Roether JA, Boccaccini AR. Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng Part B Rev. 2010;16:199–207.

    Article  CAS  Google Scholar 

  12. 12.

    Hoppe A, Güldal NS, Boccaccini AR. A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. Biomaterials. 2011;32:2757–74.

    Article  CAS  Google Scholar 

  13. 13.

    Leu A, Leach JK. Proangiogenic potential of a collagen/bioactive glass substrate. Pharm Res. 2008;25:1222–9.

    Article  CAS  Google Scholar 

  14. 14.

    Day RM, Boccaccini AR, Shurey S, Roether JA, Forbes A, Hench LL, Gabe SM. Assessment of polyglycolic acid mesh and bioactive glass for soft-tissue engineering scaffolds. Biomaterials. 2004;25:5857–66.

    Article  CAS  Google Scholar 

  15. 15.

    Gerhardt LC, Widdows KL, Erol MM, Burch CW, Sanz-Herrera JA, Ochoa I, Stämpfli R, Roqan IS, Gabe S, Ansari T, Boccaccini AR. The pro-angiogenic properties of multi-functional bioactive glass composite scaffolds. Biomaterials. 2011;32:4096–108.

    Article  CAS  Google Scholar 

  16. 16.

    Wahl DA, Czernuszka JT. Collagen-hydroxyapatite composites for hard tissue repair. Eur Cell Mater. 2006;11:43–56.

    CAS  Google Scholar 

  17. 17.

    Glowacki J, Mizuno S. Collagen scaffolds for tissue engineering. Biopolymers. 2008;89:338–44.

    Article  CAS  Google Scholar 

  18. 18.

    Ramshaw JA, Peng YY, Glattauer V, Werkmeister JA. Collagens as biomaterials. J Mater Sci Mater Med. 2009;20(Suppl 1):S3–8.

    Article  CAS  Google Scholar 

  19. 19.

    Liao S, Ngiam M, Chan CK, Ramakrishna S. Fabrication of nano-hydroxyapatite/collagen/osteonectin composites for bone graft applications. Biomed Mater. 2009;4:025019.

    Article  Google Scholar 

  20. 20.

    Parenteau-Bareil R, Gauvin R, Berthod F. Collagen-based biomaterials for tissue engineering applications. Materials. 2010;3:1863–87.

    Article  CAS  Google Scholar 

  21. 21.

    Ko Y-G, Kawazoe N, Tateishi T, Chen G. Preparation of novel collagen sponges using an ice particulate template. J Bioact Comp Polym. 2010;25:360–73.

    Article  CAS  Google Scholar 

  22. 22.

    Walton RS, Brand DD, Czernuszka JT. Influence of telopeptides, fibrils and crosslinking on physicochemical properties of type I collagen films. J Mater Sci Mater Med. 2010;21:451–61.

    Article  CAS  Google Scholar 

  23. 23.

    Francis ME, Uriel S, Brey EM. Endothelial cell-matrix interactions in neovascularization. Tissue Eng Part B Rev. 2008;14:19–32.

    Article  CAS  Google Scholar 

  24. 24.

    Allen P, Melero-Martin J, Bischoff J. Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks. J Tissue Eng Regen Med. 2011;5:e74–86.

    Article  CAS  Google Scholar 

  25. 25.

    Koch S, Yao Ch, Grieb G, Prével P, Noah EM, Steffens GC. Enhancing angiogenesis in collagen matrices by covalent incorporation of VEGF. J Mater Sci Mater Med. 2006;17:735–41.

    Article  CAS  Google Scholar 

  26. 26.

    Chiu LL, Weisel RD, Li RK, Radisic M. Defining conditions for covalent immobilization of angiogenic growth factors onto scaffolds for tissue engineering. J Tissue Eng Regen Med. 2011;5:69–84.

    Article  CAS  Google Scholar 

  27. 27.

    Singh S, Wu BM, Dunn JC. Delivery of VEGF using collagen-coated polycaprolactone scaffolds stimulates angiogenesis. J Biomed Mater Res A. 2012;100:720–7.

    Google Scholar 

  28. 28.

    Hong S-J, Yu H-S, Noh K-T, Oh S-A, Kim H-W. Novel scaffolds of collagen with bioactive nanofiller for the osteogenic stimulation of bone marrow stromal cells. J Biomater Appl. 2010;24:733–50.

    Article  CAS  Google Scholar 

  29. 29.

    Marelli B, Ghezzi CE, Mohn D, Stark WJ, Barralet JE, Boccaccini AR, Nazhat SN. Accelerated mineralization of dense collagen-nano bioactive glass hybrid gels increases scaffold stiffness and regulates osteoblastic function. Biomaterials. 2011;32:8915–26.

    Article  CAS  Google Scholar 

  30. 30.

    Joo NY, Knowles JC, Lee GS, Kim JW, Kim HW, Son YJ, Hyun JK. Effects of phosphate glass fiber-collagen scaffolds on functional recovery of completely transected rat spinal cords. Acta Biomater. 2012;8:1802–12.

    Article  CAS  Google Scholar 

  31. 31.

    Brunner TJ, Grass RN, Stark WJ. Glass and bioglass nanopowders by flame synthesis. Chem Commun (Camb). 2006;13:1384–6.

    Article  Google Scholar 

  32. 32.

    Villiger W, Bremer A. Ultramicrotomy of biological objects: from the beginning to the present. J Struct Biol. 1990;104:178–88.

    Article  CAS  Google Scholar 

  33. 33.

    Parsons-Wingerter P, Lwai B, Yang MC, Elliot KE, Milaninia A, Redlitz A, Clark JI, Sage EH. A novel assay of angiogenesis in the quail chorioallantoic membrane: stimulation by bFGF and Inhibition by angiostatin according to fractal dimension and grid intersection. Microvasc Res. 1998;55:201–14.

    Article  CAS  Google Scholar 

  34. 34.

    Brooks PC, Montgomery AM, Cheresh DA. Use of the 10-day-old chick embryo model for studying angiogenesis. Methods Mol Biol. 1999;129:257–69.

    CAS  Google Scholar 

  35. 35.

    Ribatti D. Chicken chorioallantoic membrane angiogenesis model. Methods Mol Biol. 2012;843:47–57.

    Article  CAS  Google Scholar 

  36. 36.

    Baiguera S, Macchiarini P, Ribatti D. Chorioallantoic membrane for in vivo investigation of tissue-engineered construct biocompatibility. J Biomed Mater Res B Appl Biomater. 2012;100:1425–34.

    Google Scholar 

  37. 37.

    Chiu LL, Radisic M. Scaffolds with covalently immobilized VEGF and Angiopoietin-1 for vascularization of engineered tissues. Biomaterials. 2010;31:226–41.

    Article  CAS  Google Scholar 

  38. 38.

    Borselli C, Ungaro F, Oliviero O, d’Angelo I, Quaglia F, La Rotonda MI, Netti PA. Bioactivation of collagen matrices through sustained VEGF release from PLGA microspheres. J Biomed Mater Res A. 2010;92:94–102.

    Google Scholar 

  39. 39.

    Keshaw H, Thapar N, Burns AJ, Mordan N, Knowles JC, Forbes A, Day RM. Microporous collagen spheres produced via thermally induced phase separation for tissue regeneration. Acta Biomater. 2010;6:1158–66.

    Article  CAS  Google Scholar 

  40. 40.

    Yao C, Markowicz M, Pallua N, Noah EM, Steffens GC. The effect of cross-linking of collagen matrices on their angiogenic capability. Biomaterials. 2008;29:66–74.

    Article  CAS  Google Scholar 

  41. 41.

    Steffens GC, Yao C, Prével P, Markowicz M, Schenck P, Noah EM, Pallua N. Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor. Tissue Eng. 2004;10:1502–9.

    CAS  Google Scholar 

  42. 42.

    Irvine SM, Cayzer J, Todd EM, Lun S, Floden EW, Negron L, Fisher JN, Dempsey SG, Alexander A, Hill MC, O’Rouke A, Gunningham SP, Knight C, Davis PF, Ward BR, May BC. Quantification of in vitro and in vivo angiogenesis stimulated by ovine forestomach matrix biomaterial. Biomaterials. 2011;32:6351–61.

    Article  CAS  Google Scholar 

  43. 43.

    Haag J, Baiguera S, Jungebluth P, Barale D, Del Gaudio C, Castiglione F, Bianco A, Comin CE, Ribatti D, Macchiarini P. Biomechanical and angiogenic properties of tissue-engineered rat trachea using genipin cross-linked decellularized tissue. Biomaterials. 2012;33:780–9.

    Article  CAS  Google Scholar 

  44. 44.

    Oh SJ, Jeltsch MM, Birkenhäger R, McCarthy JE, Weich HA, Christ B, Alitalo K, Wilting J. VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev Biol. 1997;188:96–109.

    Article  CAS  Google Scholar 

  45. 45.

    González-Iriarte M, Carmona R, Pérez-Pomares JM, Macías D, Medina MA, Quesada AR, Muñoz-Chápuli R. A modified chorioallantoic membrane assay allows for specific detection of endothelial apoptosis induced by antiangiogenic substances. Angiogenesis. 2003;6:251–4.

    Article  Google Scholar 

  46. 46.

    Lazarovici P, Gazit A, Staniszewska I, Marcinkiewicz C, Lelkes PI. Nerve growth factor (NGF) promotes angiogenesis in the quail chorioallantoic membrane. Endothelium. 2006;13:51–9.

    Article  CAS  Google Scholar 

  47. 47.

    Saito A, Miyazaki H, Fujie T, Ohtsubo S, Kinoshita M, Saitoh D, Takeoka S. Therapeutic efficacy of an antibiotic-loaded nanosheet in a murine burn-wound infection model. Acta Biomater. 2012;8:2932–40.

    Article  CAS  Google Scholar 

  48. 48.

    Sharma AK, Bury MI, Fuller NJ, Rozkiewicz DI, Hota PV, Kollhoff DM, Webber MJ, Tapaskar N, Meisner JW, Lariviere PJ, DeStefano S, Wang D, Ameer GA, Cheng EY. Growth factor release from a chemically modified elastomeric poly(1,8-octanediol-co-citrate) thin film promotes angiogenesis in vivo. J Biomed Mater Res, Part A. 2012;100A:561–70.

    Article  CAS  Google Scholar 

  49. 49.

    Hoang MV, Whelan MC, Senger DR. Rho activity critically and selectively regulates endothelial cell organization during angiogenesis. Proc Natl Acad Sci U S A. 2004;101:1874–9.

    Article  CAS  Google Scholar 

  50. 50.

    Oates MR, Duncan CM, Hunt JA. The angiogenic potential of three-dimensional open porous synthetic matrix materials. Biomaterials. 2007;28:3679–86.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Research Council of Argentina (Grant PIP CONICET 0184 to A.A.G.). The authors thank the German research council (Deutsche Forschungsgemeinschaft, DFG) for partial financial support of this work.

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Correspondence to Alejandro A. Gorustovich.

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Vargas, G.E., Haro Durand, L.A., Cadena, V. et al. Effect of nano-sized bioactive glass particles on the angiogenic properties of collagen based composites. J Mater Sci: Mater Med 24, 1261–1269 (2013). https://doi.org/10.1007/s10856-013-4892-7

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Keywords

  • Vascular Endothelial Growth Factor
  • Composite Film
  • Bioactive Glass
  • Transmission Electron Microscopy Investigation
  • Collagen Film