Non-releasing alginate hydrogels for analyte sensing and detoxification

藻酸盐水凝胶由于其高生物相容性、低毒性和易于凝胶化而广泛用于组织工程、药物递送和伤口愈合应用。在这项研究计划中，我们建议开发新的非释放海藻酸盐水凝胶分析物传感和解毒。在这些应用中，需要具有高配体密度和低配体释放速率的材料，因为检测或解毒发生在材料内部。事实上，配体释放降低了系统的活性，并可能导致局部或全身暴露于配体后的毒性。小分子和蛋白质通常从水凝胶中非常迅速地释放。因此，需要开发用于这些应用的非释放水凝胶的新策略。我建议使用共价结合的方法加载藻酸盐凝胶与生物活性货物和测试的水凝胶作为伤口敷料的慢性伤口。慢性伤口可以有几个起源，但共享的关键特征，即高活性氧（ROS）和高基质金属蛋白酶9水平，以及异常的pH值。这些新的水凝胶是高度通用的，并有望影响加拿大的生物技术景观的基础上，他们的能力，导致专利申请具有高许可潜力和/或创业公司的基础。

Alginate hydrogels are widely used in tissue engineering, drug delivery, and wound healing applications because of their high biocompatibility, low toxicity, and ease of gelation. In this research program, we propose to develop novel non-releasing alginate hydrogels for analyte sensing and detoxification. In these applications, materials with high ligand densities and low ligand release rates are needed, as the detection or detoxification occurs inside the material. Indeed, ligand release reduces the activity of the system and may lead to toxicity after local or systemic exposure to the ligand. Small molecules and proteins are generally released very rapidly from hydrogels. Therefore, new strategies for the development of non-releasing hydrogels for these applications are needed. I propose to use a covalent conjugation approach to load alginate gels with bioactive cargo and test the hydrogels as wound dressings for chronic wounds. Chronic wounds can have several origins but share key features, namely high reactive oxygen species (ROS) and high matrix metalloproteinase 9 levels, and abnormal pH. These new hydrogels are highly versatile and promise to impact the biotechnology landscape of Canada based on their capacity to lead to patent applications with high licensing potential and/or the foundation of startups.