Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
Acta Biomater. 2019 Sep 15;96:557-567. doi: 10.1016/j.actbio.2019.07.008. Epub 2019 Jul 5.
The development of smart interfaces that can guide tissue formation is of great importance in the field of regenerative medicine. Nanoparticles represent an interesting class of materials that can be used to enhance regenerative treatments by enabling close control over surface properties and directing cellular responses. Moreover, nanoparticles can be used to provide temporally controlled delivery of (multiple) biochemical compounds. Here, we exploited the cargo loading and surface functionalization properties of mesoporous silica nanoparticles (MSNs) to design films that can guide human mesenchymal stem cell (hMSC) differentiation towards the osteogenic lineage. We developed biocompatible MSN-based films that support stem cell adhesion and proliferation and demonstrated that these MSN films simultaneously allowed efficient local delivery of biomolecules without effecting film integrity. Films loaded with the osteogenesis-stimulating drug dexamethasone (Dex) were able to induce osteogenic differentiation of hMSCs in vitro. Dex delivery from the films led to increased alkaline phosphatase levels and matrix mineralization compared to directly supplementing Dex to the medium. Furthermore, we demonstrated that Dex release kinetics can be modulated using surface modifications with supported lipid bilayers. Together, these data demonstrate that MSN films represent an interesting approach to create biomaterial interfaces with controllable biomolecule release and surface properties to improve the bioactivity of biomaterials. STATEMENT OF SIGNIFICANCE: Engineering surfaces that can control cell and tissue responses is one of the major challenges in biomaterials-based regenerative therapies. Here, we demonstrate the potential of mesoporous silica nanoparticles (MSNs) as drug-delivering surface coatings. First, we show differentiation of mesenchymal stem cells towards the bone lineage when in contact with MSN films loaded with dexamethasone. Furthermore, we demonstrate that modification of MSNs with supported lipid bilayer allows control over drug release dynamics and cell shape. Given the range of loadable cargos and the tunability of release kinetics, MSN coatings can be used to mimic the sequential appearance of bioactive factors during tissue regeneration, which will ultimately lead to biomaterials with improved bioactivity.
开发能够引导组织形成的智能界面在再生医学领域非常重要。纳米颗粒是一类很有前途的材料，可以通过对表面特性进行精细控制并引导细胞反应，来增强再生治疗效果。此外，纳米颗粒还可用于提供（多种）生化化合物的时间控制释放。在这里，我们利用介孔硅纳米颗粒（MSNs）的负载和表面功能化特性，设计了能够引导人骨髓间充质干细胞（hMSC）向成骨谱系分化的薄膜。我们开发了具有生物相容性的基于 MSN 的薄膜，支持干细胞的黏附和增殖，并证明这些 MSN 薄膜同时能够在不影响薄膜完整性的情况下，有效地实现生物分子的局部递送。负载成骨刺激药物地塞米松（Dex）的薄膜能够在体外诱导 hMSC 的成骨分化。与直接向培养基中补充 Dex 相比，从薄膜中递送 Dex 可提高碱性磷酸酶水平和基质矿化。此外，我们证明可以通过用支撑脂质双层进行表面修饰来调节 Dex 的释放动力学。总之，这些数据表明，MSN 薄膜是一种很有前途的方法，可以制造具有可控生物分子释放和表面特性的生物材料界面，以提高生物材料的生物活性。
