Spherical bioactive glass with enhanced rates of hydroxyapatite deposition and hemostatic activity
Spherical bioactive glass with enhanced rates of hydroxyapatite deposition and hemostatic activity
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DOI：
10.1002/smll.200600177
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发表时间：
2006-11-01
期刊：
影响因子：
13.3
通讯作者：
Stucky, Galen D.
中科院分区：
文献类型：
--
作者：
Ostomel, Todd A.;Shi, Qihui;Stucky, Galen D.
生物活性玻璃，可以用一般化学式SiO2ÀCaOÀP2O5ÀMO （M= Na， Mg等）来描述，用于骨骼和牙齿重建，因为它们能够结合软硬组织，对宿主的炎症和毒性最小。[1,2]虽然氧化物材料的医疗应用主要用于承重植入物，但最近人们对多孔无机材料感兴趣，这些材料可以与柔软的生物组织/流体（例如血液）相结合[4,5]。人们普遍需要开发可用于急救人员的新材料，以防止受创伤的人大量失血大出血占战场死亡人数的50%以上，因此美国军方花费了大量精力开发速效止血剂，其中最主要的是一种基于沸石的[7]复合材料，可以倒在伤口上，以稳定可能流血致死的受害者我们的实验室是第一个确定止血生物活性玻璃作为速效止血剂[9]的实验室，它的凝血活性与目前美国士兵使用的沸石基止血剂相当，但没有在使用过程中可能灼伤健康组织的负面热副作用。止血生物活性玻璃，由于其Si/Ca比、高表面积和多孔性，与用于骨修复的传统生物玻璃不同。[10,11]由于生物矿化[12]和凝血[13]都是表面介导的现象，我们研究了改变生物活性玻璃颗粒形状对羟基磷灰石体外沉积率和止血效果的影响。高表面积无机氧化物是一种有吸引力的骨和牙齿修复剂材料，现在是新发现的止血剂。与类似的不规则生物活性玻璃相比，球形生物活性玻璃颗粒的羟基磷灰石沉积速率和止血活性都得到了增强。介孔生物活性玻璃微球（MBGMs）的孔隙度、Si/Ca比和形态可以定制，以引发可预测的生物反应，因此它们适用于各种伤口愈合场景。我们之前已经报道了高表面积介孔生物活性玻璃颗粒的制备，证明了羟基磷灰石在模拟体液（SBFs）中的沉积速度加快该合成依赖于溶胶-凝胶化学技术，其中Si， Ca和P无机前体（正硅酸四乙酯，硝酸钙和磷酸三乙酯）被控制地凝聚在结构导向模板（P123，三嵌段共聚物；（聚乙烯氧化物）20（聚丙烯氧化物）70（聚乙烯氧化物）20）周围。尽管羟基磷灰石在介孔生物活性玻璃上的体外沉积率令人鼓舞，但蒸发诱导的协同组装过程[10,15,16]是耗时的，并且需要最后的研磨步骤来制备用于配制水泥的不规则形状生物活性玻璃的细粉末一致性。两亲分子（如表面活性剂和嵌段共聚物）在气溶胶内的协同组装是一种强大而灵活的合成有序介孔二氧化硅颗粒的方法，可用于催化、控制药物释放、分离和能量转换。[17-19]我们扩展了先前的溶胶-凝胶法制备介孔生物活性玻璃[14]，将这种气溶胶法制备球形生物活性玻璃颗粒。P摩尔含量均保持在4%。
Bioactive glasses, which can be described by the general chemical formula SiO2ÀCaOÀP2O5ÀMO (M= Na, Mg, etc.), are used for bone and dental reconstruction because of their ability to bond to both soft and hard tissue with minimal inflammation and toxicity for the host.[1, 2] Although the medical application of oxide materials has been primarily for load-bearing implants,[3] there is a recent interest in porous inorganic materials that can interface with soft biological tissue/fluid,[4, 5] for example, blood. There is a widespread need for the development of new materials that can be applied by first-aid responders to prevent lethal amounts of blood loss from traumatically injured individuals.[6] Massive hemorrhage accounts for over 50% of battlefield fatalities, and consequently the United States military has expended great efforts to develop rapid-acting hemostatic agents, the leader of which is a zeolite-based [7] composite that can be poured onto a wound to stabilize a victim who might otherwise bleed to death.[8] Our laboratory was the first to identify hemostatic bioactive glass as a rapid-acting hemostatic agent [9] that demonstrates clotting activity comparable to the zeolite-based hemostatic agent currently used by United States soldiers but without the negative thermal side effect that tended to burn healthy tissue during application. Hemostatic bioactive glass, as a function of its Si/Ca ratio, high surface area, and porosity, is distinct from the traditional bioglass used for bone repair.[10, 11] Because both biomineralization [12] and blood clotting [13] are surface-mediated phenomena, we investigated the effect of changing the shape of the bioactive glass particles on the in vitro rates of hydroxyapatite deposition and hemostatic efficacy. High-surfacearea inorganic oxides are attractive materials for bone and tooth repair agents and now as newly identified hemostatic agents. Both the rates of hydroxyapatite deposition and hemostatic activity are enhanced for spherical bioactive glass particles compared to the analogous irregular bioactive glass. The porosity, Si/Ca ratio, and morphology of mesoporous bioactive glass microspheres (MBGMs) can be tailored to elicit a predictable biological response and they are therefore suitable for a variety of wound-healing scenarios. We have previously reported the preparation of highsurface area mesoporous bioactive glass particles that demonstrated accelerated deposition rates of hydroxyapatite in simulated body fluids (SBFs).[14] This synthesis relied on sol–gel chemistry techniques in which Si, Ca, and P inorganic precursors (tetraethyl orthosilicate, calcium nitrate, and triethyl phosphate) were controllably condensed around a structure-directing template (P123, triblock copolymer;(polyethylene oxide) 20 (polypropylene oxide) 70 (polyethylene oxide) 20). Despite the encouraging in vitro deposition rates of hydroxyapatite on mesoporous bioactive glass, the evaporation-induced cooperative-assembly process [10, 15, 16] is time consuming and requires a final grinding step to prepare the fine powder consistency of irregular-shaped bioactive glass that was used to formulate cements. Cooperative assembly of amphiphilic molecules (eg, surfactants and block copolymers) within aerosols is a powerful and flexible method for synthesizing ordered mesoporous silica particles, which can be used for catalysis, con-ACHTUNGTRENNUNGtrolled drug release, separation, and energy conversion.[17–19] We have extended our previous sol–gel preparation of mesoporous bioactive glass [14] to incorporate this aerosol method for the preparation of spherical bioactive glass particles. The P molar content was maintained at 4% for all …