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Collagen-fibril matrix properties modulate the kinetics of silica polycondensation to template and direct biomineralization

  • Jennifer L. Kahn (a1), Necla Mine Eren (a2), Osvaldo Campanella (a2), Sherry L. Voytik-Harbin (a3) and Jenna L. Rickus (a4)...

Fibrillar collagen networks template and direct biocompatible silica mineralization to produce hybrid materials for biomedical applications. Silica mineralization kinetics is critical for precision-tuning material properties, including mechanical strength, microstructure, and interface thickness. We investigated the effect of varying collagen template fibril volume fraction (0.2–0.8) and elasticity (G′ 200–1500 Pa) on silica mineralization rates. Measurement of the depletion of mono- and disilicic acids by silicomolybdic acid titration showed that silica condensation on collagen fibrils follows third-order kinetics. Resulting third-order rate constants increased linearly with storage modulus and quadratically with fibril volume fraction. A unique rheological approach used to probe the collagen template surface elasticity in real-time during silicification suggested a two-phase mechanism with high levels of surface-localized gelation in Phase 1 and high levels of bulk solution-localized gelation in Phase 2. These results provide a tool for controlling hybrid collagen-silica material properties by controlling local silica condensation rates.

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1. Jaroch, D., McLamore, E., Zhang, W., Shi, J., Garland, J., Banks, M.K., Porterfield, D.M., and Rickus, J.L.: Cell-mediated deposition of porous silica on bacterial biofilms. Biotechnol. Bioeng. 108, 22492260 (2011).
2. Jaroch, D.B., Lu, J., Madangopal, R., Stull, N.D., Stensberg, M., Shi, J., Kahn, J.L., Herrera-Perez, R., Zeitchek, M., Sturgis, J., Robinson, J.P., Yoder, M.C., Porterfield, D.M., Mirmira, R.G., and Rickus, J.L.: Mouse and human islets survive and function after coating by biosilicification. Am. J. Physiol.: Endocrinol. Metab. 305, E1230E1240 (2013).
3. Garcia, A.P., Sen, D., and Buehler, M.J.: Hierarchical silica nanostructures inspired by diatom algae yield superior deformability, toughness, and strength. Metall. Mater. Trans. A 42, 38893897 (2011).
4. Losic, D., Mitchell, J.G., and Voelcker, N.H.: Diatomaceous lessons in nanotechnology and advanced materials. Adv. Mater. 21, 29472958 (2009).
5. Zhao, D., Jianglin, F., Huo, Q., Melosh, N., Fredrickson, G.H., Chmelka, B.F., and Stucky, G.D.: Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 Angstrom pores. Science 279, 548552 (1998).
6. Beck, J.S., Vartuli, J.C., Roth, W.J., Leonowicz, M.E., Kresge, C.T., Schmitt, K.D., Chu, C.T-W., Olson, D.H., Sheppard, E.W., McCullen, S.B., Higgins, J.B., and Schlenker, J.L.: A new family of mesoporous molecular sieves prepared with liquid crystal templates. J. Am. Chem. Soc. 114, 1083410843 (1992).
7. Ellerby, L.M., Nishida, C.R., Nishida, F., Yamanaka, S.A., Dunn, B., Valentine, J.S., and Zink, J.I.: Encapsulation of proteins in transparent porous silicate glasses prepared by the sol-gel method. Science 255, 11131115 (1992).
8. Brinker, C.J. and Scherer, G.W.: Sol-gel Science: The Physics and Chemistry of Sol-gel Processing (Academic Press, Boston, 1990).
9. Iler, R.K.: The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties and Biochemistry of Silica (Wiley-Interscience, 1979).
10. Brinker, C.J., Sehgal, R., Hietala, S.L., Deshpande, R., Smith, D.M., Loy, D., and Ashley, C.S.: Sol-gel strategies for controlled porosity inorganic materials. J. Membr. Sci. 94, 85102 (1994).
11. Tobler, D.J., Shaw, S., and Benning, L.G.: Quantification of initial steps of nucleation and growth of silica nanoparticles: An in-situ SAXS and DLS study. Geochim. Cosmochim. Acta 73, 53775393 (2009).
12. Belton, D.J., Deschaume, O., Patwardhan, S.V., and Perry, C.C.: A solution study of silica condensation and speciation with relevance to in vitro investigations of biosilicification. J. Phys. Chem. B 114, 99479955 (2010).
13. Patwardhan, S.V., Emami, F.S., Berry, R.J., Jones, S.E., Naik, R.R., Deschaume, O., Heinz, H., and Perry, C.C.: Chemistry of aqueous silica nanoparticle surfaces and the mechanism of selective peptide adsorption. J. Am. Chem. Soc. 134, 62446256 (2012).
14. Coradin, T., Nassif, N., and Livage, J.: Silica-alginate composites for microencapsulation. Appl. Microbiol. Biotechnol. 61, 429434 (2003).
15. Wallace, A.F., DeYoreo, J.J., and Dove, P.M.: Kinetics of silica nucleation on carboxyl- and amine-terminated surfaces: Insights for biomineralization. J. Am. Chem. Soc. 131, 52445250 (2009).
16. Coradin, T. and Livage, J.: Effect of some amino acids and peptides on silicic acid polymerization. Colloids Surf., B 21, 329336 (2001).
17. Hecky, R.E., Mopper, K., Kilham, P., and Degens, E.T.: The amino acid and sugar composition of diatom cell-walls. Mar. Biol. 19, 323331 (1973).
18. Shimizu, K., Cha, J., Stucky, G.D., and Morse, D.E.: Silicatein alpha: Cathepsin L-like protein in sponge biosilica. Proc. Natl. Acad. Sci. U. S. A. 95, 62346238 (1998).
19. Sumper, M. and Brunner, E.: Learning from diatoms: Nature's tools for the production of nanostructured silica. Adv. Funct. Mater. 16, 1726 (2006).
20. Müller, W.E.G., Schröder, H.C., Burghard, Z., Pisignano, D., and Wang, X.: Silicateins-a novel paradigm in bioinorganic chemistry: Enzymatic synthesis of inorganic polymeric silica. Chem. Lett. 19, 57905804 (2013).
21. Birchall, J.D.: The essentiality of silicon in biology. Chem. Soc. Rev. 24, 351 (1995).
22. Ehrlich, H., Deutzmann, R., Brunner, E., Cappellini, E., Koon, H., Solazzo, C., Yang, Y., Ashford, D., Thomas-Oates, J., Lubeck, M., Baessmann, C., Langrock, T., Hoffmann, R., Wörheide, G., Reitner, J., Simon, P., Tsurkan, M., Ereskovsky, A.V., Kurek, D., Bazhenov, V.V., Hunoldt, S., Mertig, M., Vyalikh, D.V., Molodtsov, S.L., Kummer, K., Worch, H., Smetacek, V., and Collins, M.J.: Mineralization of the metre-long biosilicastructures of glass sponges is templatedon hydroxylated collagen. Nat. Chem. 2, 10841088 (2010).
23. Ono, Y., Kanekiyo, Y., Inoue, K., Hojo, J., Nango, M., and Shinkai, S.: Preparation of novel hollow fiber silica using collagen fibers as a template. Chem. Lett. 6, 475476 (1999).
24. Heinemann, S., Ehrlich, H., Knieb, C., and Hanke, T.: Biomimetically inspired hybrid materials based on silicified collagen. Int. J. Mater. Res. 98, 603608 (2007).
25. Kahn, J.L., Eren, N.M., Campanella, O., Voytik-Harbin, S.L., and Rickus, J.L.: Organic hydrogel templates for tunable mesoporous silica hybrid materials. MRS Proc. 1721, doi: 10.1556/opl.2015.38 (2015).
26. Niu, L-N., Jiao, K., Qi, Y-P., Yiu, C.K.Y., Ryou, H., Arola, D.D., Chen, J-H., Breschi, L., Pashley, D.H., and Tay, F.R.: Infiltration of silica inside fibrillar collagen. Angew. Chem. Int. Ed. 50, 1168811691 (2011).
27. Shoulders, M.D. and Raines, R.T.: Collagen structure and stability. Annu. Rev. Biochem. 78, 929958 (2009).
28. Ramshaw, J.A.M., Shah, N.K., and Brodsky, B.: Gly-X-Y tripeptide frequencies in collagen: a context for host–guest triple-helical peptides. J. Struct. Biol. 122, 8691 (1998).
29. Bailey, J.L., Critser, P.J., Whittington, C., Kuske, J.L., Yoder, M.C., and Voytik-Harbin, S.L.: Collagen oligomers modulate physical and biological properties of three-dimensional self-assembled matrices. Biopolymers 95, 7793 (2011).
30. Kreger, S.T., Bell, B.J., Bailey, J., Stites, E., Kuske, J., Waisner, B., and Voytik-Harbin, S.L.: Polymerization and matrix physical properties as important design considerations for soluble collagen formulations. Biopolymers 93, 690707 (2010).
31. Kadler, K.E., Holmes, D.F., Trotter, J.A., and Chapman, J.A.: Collagen fibril formation. Biochem. J. 316, 111 (1996).
32. Ramadass, S.K., Perumal, S., Gopinath, A., Nisal, A., Subramanian, S., and Madhan, B.: Sol–gel assisted fabrication of collagen hydrolysate composite scaffold: A novel therapeutic alternative to the traditional collagen scaffold. ACS Appl. Mater. Interfaces 6, 1501515025 (2014).
33. Jing, S., Jiang, D., Wen, S., Wang, J., and Yang, C.: Preparation and characterization of collagen/silica composite scaffolds for peripheral nerve regeneration. J. Porous Mater. 21, 699708 (2014).
34. Heinemann, S., Heinemann, C., Wenisch, S., Alt, V., Worch, H., and Hanke, T.: Calcium phosphate phases integrated in silica/collagen nanocomposite xerogels enhance the bioactivity and ultimately manipulate the osteblast/osteclast ratio in a human co-culture model. Acta Biomater. 9, 48784888 (2013).
35. Wang, X., Schloßmacher, U., Schröder, H.C., and Müller, W.E.G.: Biologically induced transition of bio-silica sol to mesoscopic gelatinous flocs: A biomimetic approach to a controlled fabrication of bio-silica structures. Soft Matter 9, 654664 (2013).
36. Niu, L-N., Jiao, K., Ryou, H., Diogenes, A., Yiu, C.K.Y., Mazzoni, A., Chen, J-H., Arola, D.D., Hargreaves, K.M., Pashley, D.H., and Tay, F.R.: Biomimetic silicification of demineralized hierarchical collagenous tissues. Biomacromolecules 14, 16611668 (2013).
37. Brightman, A.O., Rajwa, B.P., Sturgis, J.E., McCallister, M.E., Robinson, J.P., and Voytik-Harbin, S.L.: Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro. Biopolymers 54, 222234 (2000).
38. Marotta, M. and Martino, G.: Sensitive spectrophotometric method for the quantitative estimation of collagen. Anal. Biochem. 150, 8690 (1985).
39. ASTM F3089-14: Standard Guide for Characterization and Standardization of Polymerizable Collagen-Based Products and Associated Collagen-Cell Interactions (ASTM International, West Conshohocken, PA, 2014).
40. Coradin, T., Eglin, D., and Livage, J.: The silicomolybdic acid spectrophotometric method and its application to silicate/biopolymer interaction studies. Spectroscopy 18, 567576 (2004).
41. Harrison, C.C. and Loton, N.: Novel routes to designer silicas: Studies of the decomposition of (M+)2[Si(C6 H4O2)3]·xH2O. Faraday Trans. 91, 42874297 (1995).
42. Whittington, C.F., Brandner, E., Teo, K.Y., Han, B., Nauman, E., and Voytik-Harbin, S.L.: Oligomers modulate interfibril branching and mass transport properties of collagen matrices. Microsc. Microanal. 19, 13231333 (2013).
43. Nudelman, F., Pieterse, K., George, A., Bomans, P.H.H., Friedrich, H., Brylka, L.J., Hilbers, P.A.J., de With, G., and Sommerdijk, N.A.J.M.: The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nat. Mater. 9, 10041009 (2010).
44. Eglin, D., Shafran, K.L., Livage, J., Coradin, T., and Perry, C.C.: Comparative study of the influence of several silica precursors on collagen self-assembly and of collagen on “Si” speciation and condensation. J. Mater. Chem. 16, 42204230 (2006).
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