Externally-Activated Smart Materials and Devices as On-Demand Biomaterials

能够对环境变化做出可逆反应的智能材料在开发多个领域的一系列新的、反应迅速的技术和设备方面具有巨大的潜力。然而，这些智能反应在许多靶向应用中的有效和安全的激活(特别是在体内，环境的细微变化可能导致显著的局部毒性)仍然是翻译的障碍。因此，拟议的Discovery研究的目标是利用我们在设计多种长度尺度的智能聚合物方面的专业知识，开发可通过非侵入性刺激(振荡磁场或超声波)从外部激活的新材料和设备，从而能够动态控制通过智能材料的扩散和/或与智能材料的表面相互作用。研究将集中在三个主题上，围绕应用聚合物、材料和界面工程的基本原理来设计具有目标应用特性的智能材料：*(1)为了解决当前按需输送工具存在的问题，将探索使用“硬”聚合物的玻璃化转变而不是水凝胶的体积相转变来减少“关”状态的释放，虽然相变材料将与热敏材料相结合，以避免不安全的过热，并即使在短的激活步骤之后也能实现长时间的开启。*(2)为了克服用于局部输送药物或成像部位的纳米颗粒的快速循环清除(从而降低靶向效率)，将开发可注射颗粒为基础的输送载体，该载体可被外部激活以根据需要在超声波或磁场激活时释放特定浓度的完整纳米颗粒。*(3)为了模拟天然细胞外基质的动态性质，智能多孔水凝胶纳米复合支架将被设计，其中我们开发的在多个长度尺度上控制凝胶孔隙率的新方法(反应电纺和反应冷冻铸造)将与这两种激活剂相结合，使远程控制的孔隙率变化和可触发的化学物质即使在远程刺激被移除后也能“锁定”新的孔结构。*总体而言，这项工作有望导致新的智能材料的开发，这些材料可以安全可靠地被非侵入性刺激激活，实现脉动/时间触发的药物输送(治疗癌症和激素失调的关键)，动态的细胞环境，更好地模拟自然组织不断演变的性质，以及传感器，可以保护脆弱的传感元件，直到需要报告事件。这种研究将在具有科学和经济重要性的新兴领域(生物医学装置、纳米技术)的技术开发和HQP培训方面对加拿大产生重大好处。

Smart materials that can reversibly respond to changes in their environment have significant potential for developing a range of new, responsive technologies and devices across multiple fields. However, the effective and safe activation of these smart responses in many targeted applications (particularly in vivo in which subtle changes in the environment can lead to significant local toxicity) remains a barrier to translation. As such, the objective of the proposed Discovery research is to leverage our expertise in designing smart polymers on multiple length scales to develop new materials and devices that can be externally activated via a non-invasive stimulus (oscillating magnetic fields or ultrasound), enabling dynamic control over diffusion through and/or surface interactions with smart materials. Research will focus on three themes, centred around applying fundamentals of polymer, material, and interfacial engineering to design smart materials with targeted application properties:****** (1) To address existing issues with current on-demand delivery vehicles, the use of the glass transition of “hard” polymers instead of the volume phase transition of hydrogels will be explored to reduce “off” state release, while phase change materials will be combined with thermoresponsive materials to avoid unsafe overheating and enable prolonged “on” times even after short activation steps.****** (2) To overcome the rapid circulation clearance (and thus poor targeting efficiency) of nanoparticles intended to locally deliver drug or image disease sites, injectable particle-based delivery vehicles will be developed that can be externally activated to release specific concentrations of intact nanoparticles on-demand as activated by ultrasound or magnetic fields.****** (3) To mimic the dynamic nature of native extracellular matrices, smart porous hydrogel nanocomposite scaffolds will be designed in which new approaches we have developed to control gel porosity on multiple length scales (reactive electrospinning and reactive freeze casting) will be combined with both activation agents to enable remote-controlled porosity changes and triggerable chemistries to “lock in” the new pore structures achieved even after the remote stimulus is removed.****** Collectively, this work is anticipated to lead to the development of new smart materials that can be safely and reliably activated by non-invasive stimuli, enabling pulsatile/time-triggered drug delivery (key for treating cancer and hormone irregularities), dynamic cell environments that better mimic the constantly-evolving nature of native tissues, and sensors that can protect a fragile sensing element until a reporting event is desired. Such research would have significant benefits to Canada in terms of both technology development as well as HQP training in emerging areas of scientific and economic importance (biomedical devices, nanotechnology).