Non-releasing alginate hydrogels for analyte sensing and detoxification

海藻酸盐水凝胶因其生物相容性高、毒性低、易于凝胶化而被广泛应用于组织工程、药物输送和伤口愈合等领域。在这项研究计划中，我们建议开发用于分析物传感和解毒的新型不释放藻酸盐水凝胶。在这些应用中，需要具有高配体密度和低配体释放率的材料，因为检测或解毒发生在材料内部。事实上，配体的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会很快从水凝胶中释放出来。因此，需要开发用于这些应用的非释放水凝胶的新策略。我建议使用共价偶联的方法将生物活性物质负载到藻酸盐凝胶中，并测试水凝胶作为慢性伤口敷料的作用。慢性创面可以有几个来源，但有共同的关键特征，即高活性氧类(ROS)和高基质金属蛋白酶9水平，以及异常的pH。这些新型水凝胶用途广泛，有望影响加拿大的生物技术格局，因为它们有能力导致具有高许可潜力的专利申请和/或初创企业的基础。

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.