Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Delft, The Netherlands.
Tissue Eng Part A. 2020 Dec;26(23-24):1226-1242. doi: 10.1089/ten.tea.2020.0010. Epub 2020 Apr 14.
Bone tissue engineering strategies have been developed to address the limitations of the current gold standard treatment options for bone-related disorders. These systems consist of an engineered scaffold that mimics the extracellular matrix and provides an architecture to guide the natural bone regeneration process, and incorporated growth factors that enhance cell recruitment and ingress into the scaffold and promote the osteogenic differentiation of stem cells and angiogenesis. In particular, the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) has been widely studied as a potent agent to improve bone regeneration. A key challenge in growth factor delivery is that the growth factors must reach their target sites without losing bioactivity and remain in the location for an extended period to effectively aid in the formation of new bone. Protein incorporation into nanoparticles can both protect protein bioactivity and enable its sustained release. In this study, a poly(methyl methacrylate-co-methacrylic acid) nanoparticle-based system was synthesized incorporating a custom poly(ethylene glycol) dimethacrylate crosslinker. It was demonstrated that the nanoparticle degradation rate can be controlled by tuning the number of hydrolytically degradable ester units along the crosslinker. We also showed that the nanoparticles had high affinity for a model protein for BMP-2, and optimal conditions for maximum protein loading efficiency were elucidated. Ultimately, the proposed system and its high degree of tunability can be applied to a wide range of growth factors and tissue engineering applications. Impact Statement In this study, we developed a novel method of synthesizing nanoparticles with tunable degradation rates through the incorporation of a custom synthesized, hydrolytically degradable crosslinker. In addition, we demonstrated the affinity of the synthesized nanoparticles for a model protein for bone morphogenetic protein 2 (BMP-2). The tunability of these nanoparticles can be used to develop complex tissue engineering systems, for example, for the delivery of multiple growth factors involved at different stages of the bone regeneration process.
骨组织工程策略的发展旨在解决与骨相关疾病当前金标准治疗选择的局限性。这些系统由模仿细胞外基质的工程支架组成，为引导自然骨再生过程提供了一种结构，并结合了生长因子，这些生长因子增强了细胞募集和进入支架的能力，并促进了干细胞的成骨分化和血管生成。特别是骨形成蛋白 2（BMP-2）等成骨生长因子已被广泛研究作为改善骨再生的有效药物。生长因子传递的一个关键挑战是，生长因子必须到达其靶位而不失活，并在延长的时间内保持在该位置，以有效帮助新骨的形成。将蛋白质纳入纳米颗粒既可以保护蛋白质的生物活性，又可以实现其持续释放。在这项研究中，合成了一种基于聚（甲基丙烯酸甲酯-共-甲基丙烯酸）的纳米颗粒系统，其中包含了一种定制的聚乙二醇二甲基丙烯酸酯交联剂。研究表明，通过调整交联剂上可水解的酯单元的数量，可以控制纳米颗粒的降解速率。我们还表明，纳米颗粒对 BMP-2 的模型蛋白具有很高的亲和力，并阐明了实现最大蛋白加载效率的最佳条件。最终，所提出的系统及其高度的可调性可应用于广泛的生长因子和组织工程应用。 影响说明 在这项研究中，我们通过掺入定制合成的可水解交联剂，开发了一种通过控制降解率来合成具有可调降解率的纳米颗粒的新方法。此外，我们还证明了合成纳米颗粒对骨形态发生蛋白 2（BMP-2）模型蛋白的亲和力。这些纳米颗粒的可调性可用于开发复杂的组织工程系统，例如，用于递送在骨再生过程的不同阶段涉及的多种生长因子。
