Minnesota Dental Research Center for Biomaterials and Biomechanics, Department of Restorative Sciences, University of Minnesota, Moos Health Science Tower, 515, Delaware Street S.E. Minneapolis, MN 55455, United States of America.
Division of Pediatric Dentistry, School of Dentistry, University of Minnesota, Moos Health Science Tower, 515 Delaware Street S.E. Minneapolis, MN 55455, United States of America.
Biomater Adv. 2022 Apr;135:212735. doi: 10.1016/j.bioadv.2022.212735. Epub 2022 Apr 22.
Developing multifunctional nanostructures that promote bone repair while fighting infection is highly desirable in bone regenerative therapies. Previous efforts have focused on achieving one property or another by altering the chemical makeup of nanostructures or using growth factors or antibiotics. We present nanostructures with several simultaneous functional attributes including positive effects of strontium on bone formation and prevention of osteoclast differentiation along with incorporation of antimicrobial peptides (AMP) to prevent infection. To form these multifunctional nanostructures, mesoporous calcium silicate (CaMSN) was modified with high levels of strontium. For this, CaMSNs were either partially substituted (20 wt% Ca) or completely replaced with strontium (Sr) to form Sr-CaMSN or SrMSN. The mesoporous nature of these bioactive silicate nanostructures rendered a configuration for substantial AMP loading as well as their effective delivery. The physico-chemical and structural characterization of synthesized MSNs confirmed the mesoporous nature of the synthesized MSNs and their total surface area, pore size, pore volume and SBF-mediated bioactivity remained unaltered with the incorporation of Sr. However, biological evaluation confirmed that synthesized SrMSN upregulated osteogenic differentiation of mesenchymal stromal cells and significantly downregulated osteoclast differentiation. Also, the AMP-loaded MSNs prevented formation and growth of methicillin resistant Staphylococcus aureus (MRSA) biofilms. Thus, high Sr-containing AMP-loaded SrMSNs may combat MRSA-associated infection while promoting bone regeneration. The controlled availability of therapeutic Sr and AMP release as SrMSN degrade enables its potential application in bone tissue regeneration.
在骨再生治疗中，开发既能促进骨修复又能抗感染的多功能纳米结构是非常理想的。以前的研究主要集中在通过改变纳米结构的化学成分、使用生长因子或抗生素来实现一种或另一种性能。我们提出了具有几种同时具有功能属性的纳米结构，包括锶对骨形成的积极影响和防止破骨细胞分化，以及掺入抗菌肽（AMP）以预防感染。为了形成这些多功能纳米结构，介孔硅酸钙（CaMSN）被高浓度的锶进行了修饰。为此，CaMSNs 要么被部分取代（20wt%Ca），要么被锶（Sr）完全取代，形成 Sr-CaMSN 或 SrMSN。这些生物活性硅酸盐纳米结构的介孔性质为大量 AMP 的负载及其有效输送提供了一种配置。合成 MSNs 的物理化学和结构特性证实了合成 MSNs 的介孔性质及其总表面积、孔径、孔体积和 SBF 介导的生物活性在掺入 Sr 后保持不变。然而，生物学评价证实，合成的 SrMSN 上调了间充质基质细胞的成骨分化，并显著下调了破骨细胞分化。此外，负载 AMP 的 MSNs 阻止了耐甲氧西林金黄色葡萄球菌（MRSA）生物膜的形成和生长。因此，富含 Sr 的 AMP 负载的 SrMSN 可能在促进骨再生的同时对抗 MRSA 相关感染。随着 SrMSN 降解，治疗性 Sr 和 AMP 释放的可控性使其有可能应用于骨组织再生。
