pubs.acs.org/Langmuir © 2009 American Chemical Society
Surface Signatures of Bioactivity: MD Simulations of 45S and 65S Silicate Glasses Antonio Tilocca*,† and Alastair N. Cormack‡ †
Department of Chemistry, University College London, London, U.K., and ‡New York State College of Ceramics, Alfred University, Alfred, New York 14802 Received July 13, 2009. Revised Manuscript Received August 14, 2009
The surface of a bioactive (45S) and a bioinactive (65S) glass composition has been modeled using shell-model classical molecular dynamics simulations. Direct comparison of the two structures allowed us to identify the potential role of specific surface features in the processes leading to integration of a bioglass implant with the host tissues, focusing in particular on the initial dissolution of the glass network. The simulations highlight the critical role of network fragmentation and sodium enrichment of the surface in determining the rapid hydrolysis and release of silica fragments in solution, characteristic of highly bioactive compositions. On the other hand, no correlation has been found between the surface density of small (two- and three-membered) rings and bioactivity, thus suggesting that additional factors need to be taken into account to fully understand the role of these sites in the mechanism leading to calcium phosphate deposition on the glass surface.
1. Introduction A growing number of medical applications is based on biomaterials related to, inspired by, or derived from the class of sodalime silicate glasses introduced by Hench in the early 1970s, with the most bioactive 45S Bioglass(R) composition as the core component of many current applications.1,2 Deteriorated or damaged hard (bone) and soft (muscle) tissue can be repaired through the close proximity of implanted bioglass particles or blocks, which promote local growth of new tissue through a complex sequence of chemical and cellular steps.3-6 The bioactive fixation starts at the glass surface, which partially dissolves upon contact with biological (body) fluids, releasing silicate, phosphate, sodium, and calcium ions in the environment surrounding the tissue.7 This partial dissolution is essential for tissue repair: the released ions promote nucleation and growth of a calcium phosphate bonding interface between glass and tissue and also activate genes which control cellular repair processes.6,8 Moreover, the rate of the initial dissolution is critical for the ability of a composition to bond to bone: more bioactive compositions generally show faster ion release immediately after contact with a biological medium.9,10 The biological activity of these materials is controlled by several factors, such as particle size,11 porosity/ surface area,12 and obviously glass composition: for instance, a 20% increase in the silica content of the highly bioactive 45S *Corresponding author. E-mail:
[email protected]. (1) Hench, L. L.; Andersson, O. H. In An Introduction to Bioceramics; Hench, L. L., Wilson, J., Eds.; World Scientific: Singapore, 1993. (2) Hench, L. L. Science 1984, 226, 630. (3) Tilocca, A. Proc. R. Soc. A 2009, 465, 1003. (4) Vallet-Regi, M.; Ragel, C. V.; Salinas, A. J. Eur. J. Inorg. Chem. 2003, 1029. (5) Cerruti, M.; Sahai, N. Rev. Min. Geochem. 2006, 64, 283. (6) Hench, L. L.; Polak, J. M. Science 2002, 295, 1014. (7) Hench, L. L. J. Am. Ceram. Soc. 1998, 81, 1705. (8) Xynos, I. D.; Edgar, A. J.; Buttery, L. D. K.; Hench, L. L.; Polak, J. M. J. Biomed. Mater. Res. 2001, 55, 151. (9) Sepulveda, P.; Jones, J. R.; Hench, L. L. J. Biomed. Mater. Res. 2002, 61, 301. (10) Arcos, D.; Greenspan, D.; Vallet-Regi, M. J. Biomed. Mater. Res. 2003, 65A, 344. (11) Brunner, T. J.; Grass, R. N.; Stark, W. J. Chem. Commun. 2006, 1384. (12) Leonova, E.; Izquierdo-Barba, I.; Arcos, D.; Lopez-Noriega, A.; Hedin, N.; Vallet-Regi, M.; Eden, M. J. Phys. Chem. C 2008, 112, 5552.
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results in complete loss of bioactivity of a 65S composition7,13 Whereas the level of bioactivity of a relatively wide range of compositions has been measured, a rational interpretation of the composition-activity dependence has not emerged as yet. For instance, experimental probes (vibrational, X-ray photoelectron and optical emission spectroscopy, scanning and transmission electron microscopy)9,14-19 can effectively characterize some of the chemical and morphological changes transforming the glass surface after contact with simulated body fluid (SBF). While the rate of these changes directly reflects and can be used to assign the biological activity of a composition, it is harder to unambiguously identify specific features (“bioactivity markers”) of a glass, which enhance or inhibit its activity. This kind of task requires an atomistic resolution which is often out of reach for standard techniques, in particular when amorphous multicomponent materials are concerned. State-of-the-art structural characterization techniques, such as high-energy diffraction20 and multinuclear solid-state nuclear magnetic resonance,12,21 have recently shown their strong potential for investigating structural features of bulk bioglasses, but they have not been systematically applied to these systems so far. Whereas obtaining high-resolution data of several compositions may still be too expensive for advanced experimental techniques, computational approaches represent today a convenient alternative for carrying out systematic studies of multicomponent glasses, as shown by many recent classical and (13) Fujibayashi, S.; Neo, M.; Kim, H.; Kokubo, T.; Nakamura, T. Biomaterials 2003, 24, 1349. (14) Cho, S.; Nakanishi, K.; Kokubo, T.; Soga, N.; Ohtsuki, C.; Nakamura, T. J. Biomed. Mater. Res. 1996, 33, 145. (15) Cerruti, M.; Greenspan, D.; Powers, K. Biomaterials 2005, 26, 1665. (16) Courtheoux, L.; Lao, J.; Nedelec, J.-M.; Jallot, E. J. Phys. Chem. C 2008, 112, 13663. (17) Peitl, O.; Zanotto, E. D.; Hench, L. L. J. Non-Cryst. Solids 2002, 292, 115. (18) Padilla, S.; Roman, J.; Carenas, A.; Vallet-Regi, M. Biomaterials 2005, 26, 475. (19) Banchet, V.; Michel, J.; Jallot, E.; Wortham, L.; Bouthors, S.; LaurentMaquin, D.; Balossier, G. Acta Biomater. 2006, 2, 349. (20) FitzGerald, V.; Pickup, D. M.; Greenspan, D.; Sarkar, G.; Fitzgerald, J. J.; Wetherall, K. M.; Moss, R. M.; Jones, J. R.; Newport, R. J. Adv. Funct. Mater. 2007, 17, 3746. (21) Coelho, C.; Azais, T.; Bonhomme-Coury, L.; Laurent, G.; Bonhomme, C. Inorg. Chem. 2007, 46, 1379.
Published on Web 09/03/2009
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ab initio simulations.22-25 In particular, molecular dynamics (MD) simulations26-28 have recently revealed interesting links between atomistic structural features of several bioglasses and their corresponding bioactive behavior.29-32 However, atomistic studies of bioglasses cannot be limited to the bulk structure only: further detailed investigations must directly focus on the interface itself, for instance to assess whether and how the bulk structure is reflected in features of the glass-tissue interface crucial for the success of bioglass implants. Given the high complexity of the problem, over the past few years we have been following a bottom-up approach, which involves modeling the bulk and then the dry surface of the reference 45S glass and probing the activity of key interaction sites at the surface, based on their interaction with gas-phase and liquid water.33,34 The latter computational studies required ab initio methods,35 in order to model the site reactivity with adequate accuracy, and allowed us to identify several surface sites that are presumably involved in the initial stages of the bioactive mechanism, such as undercoordinated Si, small rings, and nonbridging oxygen (NBO) atoms combined with modifier (Na+ and Ca2+) cations. A further important task is to assess the way in which these sites populate the surface of glass compositions of different bioactivity, in order to better understand their corresponding role and relevance in the bioactive process. Whereas an ab initio approach is essential to probe the reactivity of individual sites, the necessarily small size of the ab initio models limits the extent up to which one can compare the properties of surfaces of different compositions. On the other hand, classical MD with empirical force field, despite intrinsically limited for modeling reactivity, can provide an adequate structural picture of larger samples of oxide surfaces.36-39 The relatively short time scale of MD simulations does not allow us to model the full sequence of chemical stages leading to bioactive fixation, and even the “inorganic” steps (i.e., those leading to calcium phosphate deposition) are out of reach. The more (computationally) affordable approach adopted here focuses on examining the structure of the as-created dry surface of highly bioactive 45S and bioinactive 65S glasses: the comparison between the two samples, taking into account the recent ab initio data on the properties of individual sites,33,34 allows us to identify surface features that may affect the initial dissolution following soaking in a biological (aqueous) medium. As discussed above, it is well established that the rate of this process is critical for the subsequent reaction stages: the present results can thus represent a further important step toward building a bridge between atomistic properties and biological activity of glasses. (22) Ganster, P.; Benoit, M.; Delaye, J.-M.; Kob, W. J. Chem. Phys. 2004, 120, 10172. (23) Donadio, D.; Bernasconi, M.; Tassone, F. Phys. Rev. B 2004, 70, 214205. (24) Tilocca, A. Phys. Rev. B 2007, 76, 224202. (25) Pedone, A.; Malarasi, G.; Menziani, M. C.; Segre, U.; Cormack, A. N. J. Phys. Chem. C 2008, 112, 11034. (26) Tilocca, A.; de Leeuw, N. H. J. Phys. Chem. B 2006, 110, 25810. (27) Mead, R. N.; Mountjoy, G. J. Phys. Chem. B 2006, 110, 14273. (28) Tilocca, A. J. Chem. Phys. 2008, 129, 084504. (29) Tilocca, A.; Cormack, A. N.; de Leeuw, N. H. Chem. Mater. 2007, 19, 95. (30) Tilocca, A.; Cormack, A. N.; de Leeuw, N. H. Faraday Discuss. 2007, 136, 45. (31) Tilocca, A.; Cormack, A. N. J. Phys. Chem. B 2007, 111, 14256. (32) Tilocca, A.; Cormack, A. N. Nuovo Cimento B 2008, 123, 1415. (33) Tilocca, A.; Cormack, A. N. J. Phys. Chem. C 2008, 112, 11936. (34) Tilocca, A.; Cormack, A. N. ACS Appl. Mater. Interfaces 2009, 1, 1324. (35) Marx, D.; H€utter, J. In Modern Methods and Algorithms of Quantum Chemistry; Grotendorst, J., Ed.; John von Neumann Institute for Computing: Julich, 2000; NIC Series Vol. 1, p 301. (36) Kohler, A. E., Jr.; Garofalini, S. H. Langmuir 1994, 10, 4664. (37) Du, J.; Cormack, A. N. J. Am. Ceram. Soc. 2005, 88, 2532. (38) Zeitler, T. R.; Cormack, A. N. J. Cryst. Growth 2006, 294, 96. (39) Ganster, P.; Benoit, M.; Kob, W.; Delaye, J.-M. Surf. Sci. 2008, 602, 114.
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2. Computational Methods The present simulations employ a polarizable (shell-model)40 potential which has previously shown superior performances in the modeling of bulk multicomponent glasses compared to rigidion force fields.28,41 Whereas its accuracy cannot be comparable to that of ab initio methods, the inclusion of polarization effects ensures a sufficiently correct representation of distorted bonding and coordination environments typically formed on fractured glass surfaces. In other words, as long as the focus is on revealing differences between the as-created surface of the two compositions, shell-model classical MD can provide reliable answers. A modified version of the DL_POLY42 code was employed to perform the classical MD simulations. The shell-model ionic potential employed has been recently developed to model phosphosilicate glasses incorporating Na and Ca cation modifiers.28,29,41 The oxide ions are treated as polarizable core-shell units; shells interact with each other and with all other ions through short-range Buckingham terms, and Coulombic interactions act between all species, which bear full formal charges. Three-body screened harmonic potentials are used to control the intratetrahedral O-Si-O and O-P-O angles. The adiabatic shell method43 is used to control the relaxation of the core-shell units, complemented with a damping term to limit artificial heating of the core-shell springs and improve the stability of the MD trajectories.41 The complete list of potential parameters can be found in refs 29 and 41. Bulk models of melt-derived 45S (mol % composition 46.1 SiO2 : 24.35 Na2O : 26.9 CaO : 2.57 P2O5) and 65S (66.9 SiO2 : 14.47 Na2O : 15.98 CaO : 2.63 P2O5) glasses were generated through standard melt-and-quench MD.3 Each model contained around 1500 atoms in total, enclosed within a periodic cubic supercell with a ∼ 27 A˚ side. For both compositions, a random initial arrangement of ions in the supercell was heated up and held at 3500 K for 100 ps; the liquid precursor was then cooled down to 300 K with a linear cooling rate of 10 K/ps, in a 320 ps trajectory. The resulting glass structure was then used in a final production run of 200 ps. In order to prepare the surface calculations, the system was then relaxed in a constant-pressure MD run, which led to a small (∼2%) density decrease in each case, with respect to the initial (experimental) value. Starting from the volume-optimized bulk supercell, four surface samples were generated for each composition, by exposing different sections of the cubic cell. A slab geometry with 3D periodicity, but with the top and bottom faces exposed to vacuum, was obtained by elongating the c side by 20 A˚ and fixing all the atoms in the bottom 20% of the cell to their bulk positions; only the top surface was fully relaxed and therefore considered in the analysis. Each surface sample was relaxed in a short annealing run at 600 K, followed by a 100 ps trajectory at room temperature, the last 60 ps of which was included in the statistical analysis; the results were further averaged over the four slab samples of both compositions. Figure 1 illustrates the relaxed slab geometry for one of the samples of the 45S glass.
3. Results A top view of the surface models of 45S and 65S is shown in Figures 2 and 3, respectively. Previous work has suggested that surface features potentially important in the dissolution and (40) Dick, B. G.; Overhauser, A. W. Phys. Rev. 1958, 112, 90. (41) Tilocca, A.; de Leeuw, N. H.; Cormack, A. N. Phys. Rev. B 2006, 73, 104209. (42) Smith, W.; Forester, T. R. J. Mol. Graphics 1996, 14, 136. (43) Mitchell, P. J.; Fincham, D. J. J. Phys.: Condens. Matter 1993, 5, 1031.
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Figure 3. Top view of one of the samples of the 65S relaxed surface. Only the surface atoms are shown. Colors are as in Figure 2.
Figure 1. Slab model of 45S surface: the black borders outline the orthorhombic periodic supercell used in the simulation. Color codes are red (O), blue (Si), green (Na), gray (Ca), and yellow (P). Na and Ca atoms are represented as spheres and Si, P, and O atoms as wireframe.
Figure 2. Top view of a sample of the 45S relaxed surface. Only the surface atoms (that is, the atoms in the top 7 A˚ of the slab model) are shown. Atom colors are red (oxygen), blue (silicon), green (sodium), dark gray (calcium), and yellow (phosphorus). The square represents the simulation box. Letters denote surface features discussed in the text: (a) exposed NBO; (b) undercoordinated silicon (Si3c); (c) 2M ring; (d) 3M ring; (e) isolated SiO4 orthosilicate.
bioactive fixation process are exposed NBOs, undercoordinated silicon (Si3c) atoms, two- and three-membered small rings (2M and 3M, respectively), and isolated orthosilicate tetrahedra as (44) Morrow, B. A.; Cody, I. A.; Lee, L. S. M. J. Phys. Chem. 1976, 80, 2761. (45) Wallace, S.; West, J. K.; Hench, L. L. J. Non-Cryst. Solids 1993, 152, 101. (46) Grabbe, A.; Michalske, T. A.; Smith, W. L. J. Phys. Chem. 1995, 99, 4648. (47) Sahai, N.; Tossell, J. A. J. Phys. Chem. B 2000, 104, 4322. (48) Masini, P.; Bernasconi, M. J. Phys: Condens. Matter 2002, 14, 4133. (49) Fois, E.; Gamba, A.; Tabacchi, G.; Coluccia, S.; Martra, G. J. Phys. Chem. B 2003, 107, 10767. (50) Cerruti, M.; Bolis, V.; Magnacca, G.; Morterra, C. Phys. Chem. Chem. Phys. 2004, 6, 2468. (51) Wendt, S.; Frerichs, M.; Wei, T.; Chen, M. S.; Kempter, V.; Goodman, D. W. Surf. Sci. 2004, 565, 107.
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Figure 4. z-profiles of the total number (top panels) and fraction (bottom panels) of O, Si, Na, Ca, and P atoms in the slab models of (left panels) 45S and (right panels) 65S glass. The slab was divided in slices 2 A˚ thick along z, and the numbers of atoms found in each slice were time-averaged over the corresponding MD trajectory and further averaged over four different surface samples. Ni is the average number of atoms of species i, and N is the average total number of atoms of all species found in the slice; z = 0 marks the bulklike region in the center of the slab.
well as network modifier (Na and Ca) cations;38,44-57 examples of these features on the 45S surface are highlighted in Figure 2. It is important to note that these same sites were also exposed in our previous ab initio models of the 45S surface:33,34 a crucial task, which can be only achieved through classical MD, is to investigate their distribution on the bioactive and bioinactive glass surface, also in relation to the corresponding bulk structure. The distribution of the different species near to the surface can be highlighted through the z-profiles in Figure 4. Compositional changes (with respect to the bulklike values around the z = 0 center of the slab) (52) Rignanese, G.-M.; Charlier, J.-C.; Gonze, X. Phys. Chem. Chem. Phys. 2004, 6, 1920. (53) Cerruti, M.; Morterra, C.; Ugliengo, P. Chem. Mater. 2005, 17, 1416. (54) Leed, A. E.; Sofo, J. O.; Pantano, C. G. Phys. Rev. B 2005, 72, 155427. (55) Bolis, V.; Busco, C.; Aina, V.; Morterra, C.; Ugliengo, P. J. Phys. Chem. C 2008, 112, 16879. (56) Rimola, A.; Ugliengo, P. J. Chem. Phys. 2008, 128, 204702. (57) Adeagbo, W. A.; Doltsinis, N. L.; Klevakina, K.; Renner, J. ChemPhysChem 2008, 9, 994.
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Table 1. Concentration (Number Density, nm-3) of Relevant Sites in the Top Two Layers of the Surface Models of 45S and 65S site þ
Na Ca2þ Si3c NBO 2MR 3MR
45S
65S
7.0 2.3 0.13 11.75 0.17 0.58
4.3 2.48 0.64 10.67 0.32 1.18
Figure 6. z-profiles of the fraction of NBO, BO (top) and 3-, 4-, and 5-fold coordinated Si atoms (bottom) in the slab models of (left panels) 45S glass and (right panels) 65S glass. The z-profiles were calculated as in Figure 4. Figure 5. Side view of one of the samples of the 45S relaxed surface. Colors are as in Figure 2.
are evident in the top 5-6 A˚ of the slab (z > 9 A˚), in agreement with previous ab initio results for the 45S glass.33,34 The surface of both glasses is characterized by a significant enrichment in sodium, as also found in ab initio simulations of 45S:34 the Na fraction (fNa) sharply increases in the z >10 A˚ region, mainly at the expenses of the silicon content, which shows a corresponding decrease with respect to the fraction fSi in the bulk. In fact, the two bulk glasses contain equivalent Si and Na amounts (45S) or more Si than Na (65S), whereas on the surface the balance shifts abruptly toward Na, with a depletion in Si more marked for the bioinactive 65S. Table 1 shows that the actual surface concentration of Na is significantly higher on 45S, whereas the surface of the two compositions contains similar Ca amounts. In other words, as also evident from the z-profiles in Figure 4, Na replaces both Si and Ca on the 45S surface, but mostly Si on the 65S surface. The surface creation also results in the exposure of many NBOs, some of which protruding out of the surface, such as the one well visible in Figure 5. Whereas the bulk compositions already contain significant NBO amounts, the top panels of Figure 6 show that, as a result of the fracture of the surface, additional NBOs are created there from bridging Si-O-Si oxygens that have had one of their Si-O bonds cut. The BO f NBO conversion is more dramatic for the higher silica 65S, but because 45S already contains a significant (around 70%) NBO fraction in the bulk, after relaxation both surfaces contain similar amounts of NBOs (Table 1). At the same time, most exposed Si atoms on 45S recover bulklike (4-fold) coordination, whereas the higher silica content of bulk 65S results in less effective relaxation56 and a final higher surface density of undercoordinated Si3c (Figure 6), in agreement with previous simulations of modified silicate glasses.58 Further, medium-range structural features of the surface which are relevant to analyze the modifications occurring (58) Leed, A. E.; Pantano, C. G. J. Non-Cryst. Solids 2003, 325, 48.
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Figure 7. Qn distribution of (top) 45S and (bottom) 65S, calculated on the surface region and in the bulk glass (Qn denotes a silicon atom linked to n other Si through bridging oxygens). Surface distributions are averaged over four samples for each composition.
there are the distribution of Qn species (where Qn denotes a silicon atom linked to n other Si through bridging oxygens) and of Si-O-Si angles.30,32 The Qn distributions of the 45S and 65S surface are plotted together with the corresponding bulk distribution29 in Figure 7. The surface Qn distributions are found to reflect the bulk values rather closely, with an overall shift of the 45S distribution toward lower n, denoting a less interconnected glass network.29,30,32 Most Si tetrahedra are cross-linked to two other tetrahedra in 45S, whereas on average three tetrahedra are found linked to most Si in 65S. This bulk feature is maintained in the surface, showing that surface relaxation effectively tends to restore the original medium-range connectivity broken with fracture; however, a small fraction of tetrahedra in the surface escapes this process and is left less interconnected than in the bulk: a 3% of isolated SiO4 tetrahedra (Q0 orthosilicates), absent from the bulk, is found on the 45S surface, and a similar fraction of Q1 tetrahedra is introduced in the 65S surface. A corresponding Langmuir 2010, 26(1), 545–551
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Figure 8. (top) O-Si-O and (bottom) Si-O-Si angle distribution of (left) 45S and (right) 65S glass, calculated within the slab sections centered at the z values marked on the right side. The distributions, shifted vertically for clarity, were averaged over four surface samples for each composition.
decrease in the amount of more interconnected Qn species (to the higher n side of the main peak) is observed for both compositions. The O-Si-O and Si-O-Si angle distributions are shown in Figure 8. A new feature around 80°-90° appears in the intratetrahedral (O-Si-O) angle distribution of the surface (z >10 A˚), arising from edge-sharing two-membered (2M) rings.33 2M rings are not formed in the bulk of either 45S or 65S glasses,30 but ab initio studies have revealed that they are a common feature of the as-created bioglass surface, and despite the internal strain they are relatively stable against hydrolytic opening,33,56,34 which in principle makes them potential adsorption and nucleation sites for calcium phosphate in an advanced stage of the bioactive bonding mechanism.59 A corresponding feature, also absent from the bulk, develops in the intertetrahedral (Si-O-Si) angle distribution of the surface: the peak just above 90° in the z > 10 A˚ Si-O-Si distributions also arises from 2M rings. The increasing broadening of the main Si-O-Si peak at 130° going toward the surface denotes increasing distortion in the silicate network, needed to maintain a bulklike connectivity (as discussed above) after cutting several Si-O bonds at the surface. The sharp peak at 120° in the top section of the 65S Si-O-Si distribution arises from a relatively high concentration of 3M rings in this surface (Table 1).
4. Discussion Surface Fragmentation. Integration of bioglass implants with living tissues is achieved through hydrolysis and partial dissolution of the silicate network, with release of soluble species followed by deposition of a calcium phosphate bonding layer on the cation-depleted glass surface.7 Because higher bioactivity levels are generally associated with faster initial network degradation,10 it is important to focus on structural features of the ascreated surface which can affect the latter process. Comparing the more interconnected 65S surface structure (Figure 3) with the open and fragmented character of the 45S surface (Figure 2), one (59) Sahai, N.; Anseau, M. Biomaterials 2005, 26, 5763.
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can qualitatively visualize the 45S glass network being more easily attacked and partially dissolved by the solvent, whereas the 65S will offer a higher resistance and its initial dissolution will be slower; the Qn distributions in Figure 7 quantitatively substantiate this concept. Although both surfaces show a slightly higher fragmentation than their corresponding bulk, it is interesting to observe how the flexibility of the amorphous structure allows the exposed Si species to maintain most of their bulk connectivity. This entails that some structural features of the bulk, being reflected in the surface, are of central importance as they have a direct impact on the bioactivity (see also below). The small fraction of orthosilicate tetrahedra formed in the 45S surface (Figure 2e) as a consequence of the already low bulk 45S connectivity can be of critical importance, as these isolated species can be directly (i.e., without having to break chemical bonds) leached into the contact solution at a low energetic cost, and therefore accelerate the bioactive process, for instance by acting as nucleation sites for calcium phosphate precipitation.3,53 A similar mechanism would be in action for orthophosphate groups, which are already the dominating phosphorus species in the bulk of 45S31 and are therefore also expected to be leached relatively quickly. The roughness and fragmentation of the 45S surface are probably the most important factors leading to the rapid partial dissolution and the corresponding high bioactivity of this composition. Modifier Cations and Surface Hydrophilicity. In addition to these general effects, other specific surface features highlighted in Figure 2 are also known to affect the degradation of the glass network upon contact with an aqueous environment as well as some of the subsequent stages leading to integration of a bioglass implant with the host tissues: in particular, Naþ and Ca2þ, NBOs, Si3c, and small (2M and 3M) rings should all be taken into account.33,38,46,47,50,54-56,60 The higher Naþ concentration in the surface region of 45S reflects the higher sodium content of the bioactive composition: because the surface enrichment in Na turns out to be a feature shared by both compositions, it is the higher Na bulk fraction in 45S which ultimately determines a significantly higher Naþ concentration on its surface (Table 1). A sodium-enriched surface layer was previously identified in meltderived bioactive glasses;61 rapid release of sodium from this layer proceeds by exchange with protons from the aqueous contact solution, in the initial steps of the partial dissolution of meltderived bioglasses: the Naþ/Hþ ion exchange results in increased local alkalinity and further hydrolysis (breaking of Si-O-Si bonds) of the glass network, leading into the final stages of the bioactive fixation.7,19 As the predominant presence of sodium in our models of the dry surfaces is consistent with the initial stage of the general reaction mechanism of bioactive bonding, it seems natural to link the initial surface density of sodium to the bioactivity of these materials: in fact, previous FTIR-XPS measurements suggested that the presence of sodium enhances surface-water interactions on bioglasses,60 and our recent ab initio simulations of the 45S bioglass33,34 highlighted that (i) exposed Naþ ions strongly attract water molecules and promote their initial penetration inside the surface and (ii) Naþ ions stabilize OH- groups formed by water dissociation. The higher amount of sodium in 45S thus results in a more hydrophilic glass surface, whose initial attack by the contact solution will be faster and more effective than for 65S. This effect, combined with the marked fragmentation of the 45S glass (60) Cerruti, M.; Bianchi, C.; Bonino, F.; Damin, A.; Perardi, A.; Morterra, C. J. Phys. Chem. B 2005, 109, 14496. (61) Jallot, E.; Benhayoune, H.; Kilian, L.; Josset, Y.; Balossier, G. Langmuir 2001, 17, 4467.
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Figure 9. Central panel: radial distribution functions calculated for Si3c-NBO and Naþ -NBO pairs in the surface (z > 9 A˚) region of glass 65S. Top and bottom panels: corresponding cumulative coordination numbers.
network, promotes fast network dissolution, with release in solution of chainlike fragments and other soluble silica species, which are deemed to have a direct impact on the bioactivity by nucleating the precipitation of calcium phosphate and activating key cellular processes.3,53,8 On the other hand, the much slower dissolution of 65S, which ultimately results in loss of bioactivity for this composition,7,13,19 is consistent with the less hydrophilic character of the surface, as a consequence of the higher silica and lower sodium content. The similar Ca concentration on the two as-created surfaces reveals that the calcium amount in the glass composition does not seem to play an equally critical role in the initial dissolution stages. This is also consistent with the recent suggestion that dominant Ca2þ-H2O interactions leading to leaching of calcium ions in solution can only be established once most Naþ have been released from the surface34 and with the lower solubility of bioglass compositions where Na has been substituted by Ca.62 Silanol Formation. Bioactivity is often associated with a high surface density of silanol (Si-OH) groups.63 Shortly after contact with an aqueous medium, the glass surface will be hydroxylated, as a result of the initial hydrolysis of the glass network (discussed above) and of direct protonation of NBO sites found on the dry surface of both compositions. Protonation of NBOs by water dissociation in principle requires the additional participation of a Lewis acid (electron acceptor) such as an Si3c or a modifier cation (Figure 5), as in the generic HO-H þ M...NBO f M...OH þ NBO-H scheme, where M is Si3c or Na/Ca.54,33,34,64 Figure 9, which summarizes the local environment of NBOs with respect to Si3c and Naþ on the 65S surface, strongly supports the participation of NBO...Naþ pairs in this process, whereas the association between Si3c surface sites and NBOs is less marked: the top panel of the figure denotes strong NBO-Naþ association on the surface, only slightly weaker with respect to the bulk, where NBOs are always combined with charge-balancing modifier cations;65,66 the bottom panel denotes the presence of five NBOs within 5 A˚ of every Naþ versus only two NBOs within the same range of every Si3c.67 (62) Aina, V.; Magnacca, G.; Cerrato, G.; Bonino, F.; Malarasi, G.; Morterra, C. Nuovo Cimento B 2008, 123, 1517. (63) Kokubo, T. J. Non-Cryst. Solids 1990, 120, 138. (64) Ma, Y.; Foster, A. S.; Nieminen, R. M. J. Chem. Phys. 2005, 122, 144709. (65) Greaves, G. N. J. Non-Cryst. Solids 1985, 71, 203–217. (66) Greaves, G. N.; Sen, S. Adv. Phys. 2007, 56, 1. (67) These include NBOs directly bonded to Si3c which are less reactive toward water than nonbonded NBOs.37,64
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Despite the low availability of electron donors associated with Si3c’s, water dissociation leading to hydroxylation of these sites in solution can still proceed through proton transfer mediated by additional water molecules.34,64,68-70 On the basis of these considerations, we can assume that most exposed NBOs and Si3c sites formed on both dry surfaces will be protonated/hydroxylated immediately upon soaking; the NBO and Si3c densities of Table 1 then translate into a slightly higher (11.9 and 11.3 nm-3 on 45S and 65S, respectively) initial surface density of silanol groups on the hydrated 45S and 65S compositions. Whereas this small difference alone cannot explain the much faster dissolution of the bioactive glass, one has to take into account that surface hydroxylation, although necessary, is not itself sufficient to lead to network dissolution/breakup: the features discussed in the previous two sections, namely, a significant network fragmentation with isolated silicate groups and a higher Naþ concentration, appear essential, in combination with a relatively high initial Si-OH density, to promote the rapid initial degradation of the hydrated 45S surface compared to the much slower dissolution of bioinactive 65S.13,19 For instance, the affinity of hydroxyl groups for Naþ provides pathways for adsorption, dissociation, and penetration of water inside the surface, with corresponding release of Naþ as well as silicate fragments. Small Rings. A more subtle effect involves the small (2M and 3M) rings exposed on the surface: the transition from bioactive to bioinactive glass is accompanied by a transformation of the bulk structure from predominantly chainlike to ringlike.30,3 This entails that a higher surface density of small rings will characterize the surface of the bioinactive composition, as confirmed by Figure 3 and Table 1. This observation is apparently at odds with the suggestion that small rings can effectively favor the deposition of the calcium phosphate bonding interface, crucial for the bioactive fixation.59 In other words, the almost double surface density of small (2M and 3M) rings on the surface of bioinactive 65S does not support hypotheses where these rings play a critical part in the bioactive process.33,45,59,71 However, Cho et al.13 showed that the presence of small rings on the surface before soaking does not necessarily lead to bioactivity: instead, it is a specific structural unit formed from these rings upon soaking, possibly involving protonation of the ring oxygens,59 which is actually responsible for calcium phosphate nucleation. This opens the possibility that the small rings on 45S might represent a more favorable site for this process than the more abundant rings in the 65S surface: the higher connectivity of the 65S silica network would make rings less accessible, thus reducing their ability to adsorb and nucleate calcium phosphate.
5. Conclusions In this work we have attempted to link the structure of the ascreated surface of two glass compositions to the corresponding bioactivity (or lack thereof), based on general aspects as well as specific surface sites whose possible relation to the bioactivity has been previously suggested, either on experimental or theoretical grounds. In particular, we have focused on the possible effect that the structure of the dry surface can have on the first dissolution stages occurring immediately upon contact of the glass with a physiological fluid. Because the most significant difference in the z-profiles of the as-created 45S and 65S surfaces concerns the (68) 265. (69) (70) (71)
Hass, K. C.; Schneider, W. F.; Curioni, A.; Andreoni, W. Science 1998, 282, Odelius, M. Phys. Rev. Lett. 1999, 82, 3919. Tilocca, A.; Selloni, A. J. Phys. Chem. B 2004, 8, 4743. West, J. K.; Hench, L. L. J. Non-Cryst. Solids 1993, 152, 101.
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much higher sodium fraction of the bioactive composition, this suggests a link between substantial sodium amounts in the exposed surface and a more effective bioactive fixation in meltderived soda-lime bioglasses. This effect is obviously absent in sodium-free bioactive glasses obtained through the sol-gel route, whose high bioactivity arises from the combination of higher surface area and hydrophilicity, which considerably extends the range of bioactivity and also entails that other effects should be taken into account to fully understand their properties.4,72 Because a similar surface density of silanol groups can be predicted to be formed upon hydration of both bioactive 45S and bioinactive 65S, the faster initial dissolution of 45S must arise from the combined effect of a relatively high Si-OH concentration with the significant surface roughness, fragmentation, and sodium content of 45S. The lack of correlation between the surface density of small rings and glass bioactivity, highlighted by the present simulations, does not rule out the participation of these sites to the bioactive process.45,59 However, further work is needed to elucidate this issue: a possible interpretation is that the small rings on the 65S dry surface (at variance with the rings on 45S) are not available to nucleate calcium phosphates, likely because the higher network connectivity makes them less accessible upon immersion. It is important to note that the various structural units identified on the bioglass surfaces in this work, that is, NBO, (72) Li, R.; Clark, A. E.; Hench, L. L. J. Appl. Biomater. 1991, 2, 231.
Langmuir 2010, 26(1), 545–551
Article
Si3c, small rings, Na and Ca cations (with surface enrichment in Na), are consistent with previous ab initio calculations,33,34 thus confirming the validity of classical MD simulations to study the structure of the dry surface of complex multicomponent glasses. The structural flexibility inherent to the amorphous nature of Hench’s glasses entails that relaxation of an as-created fractured surface quickly restores the bulklike environment to a significant extent. Therefore, a number of bulk structural features will be reflected in the surface and can be effective guidelines to interpret the glass bioactivity. In particular, our simulations indicate that a high bulk fraction of modifier Na cations will be further enhanced at the surface and, in association with exposed NBOs, boosts the process of dissolution of the glass network. On the other hand, other specific surface features which can also be qualitatively predicted based on the bulk structure, such as the surface density of small rings, do not show the expected correlation with bioactivity. Further work is needed to assess hypotheses about the reasons for the latter effect, which reflects the complex nature of these biomaterials and the difficult task of rationalizing their special properties. Acknowledgment. A.T. thanks the UK’s Royal Society for financial support (University Research Fellowship). Computer resources on the HECToR national supercomputing services were provided via the UK’s HPC Materials Chemistry Consortium and funded by EPSRC grant EP/F067496/1.
DOI: 10.1021/la902548f
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