CAREER: Stimuli-responsive biomaterials for wound healing and drug delivery

伤口愈合和关节炎治疗是人们关心的两个领域。新型的“智能”水凝胶将被开发用于可移动伤口敷料和关节炎治疗，这种水凝胶可以对环境做出反应并改变其硬度。这项工作每年将改善数百万患者的治疗效果。除了实际应用，这些材料将提供工具和方法，每个人都可以使用这些工具和方法来合理设计水凝胶材料，并将有助于动态纳米材料，药物输送和生物传感等更广泛领域的发展。教育部分整合了生物材料的研究工作和几个教育计划，1）为锡拉丘兹市学区（SCSD）的高中生开发研究培训计划; 2）为参加锡拉丘兹大学预备役军官训练团（ROTC）的本科生提供研究培训; 3）为锡拉丘兹的米尔顿·J·鲁宾斯坦科学技术博物馆（MOST）设计一个生物材料的外展模型。通过这些多管齐下的外展计划，不同年龄组的学生将被包容性地参与，特别强调培训妇女，代表性不足的少数民族和难民。教育计划不仅将为未来的生物化学家提供培训基地，而且还将产生有价值的成果，以推进研究领域。技术摘要本提案的目标是设计基于肽的、智能的、刺激响应的生物相容性抗微生物材料，其响应于氧化还原状态和pH的变化而改变其刚度。多种性质的协同组合是至关重要的，因为自我修复对于通过注射器递送水凝胶是必不可少的，抗微生物性质和细胞相容性对于实际应用是至关重要的，并且氧化还原转换允许在加入温和的还原剂或响应于活性氧物质（ROS）释放药物时除去凝胶。为了实现这一目标，将设计三类具有自愈特性的刺激响应材料：1）氧化还原敏感肽水凝胶; 2）将成纤维细胞递送到伤口床中的pH响应水凝胶; 3）响应pH和ROS变化的水凝胶。这项工作将产生用于伤口护理和关节炎治疗的水凝胶材料，并将为功能材料的合理设计提供工具和方法。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Non-technical abstractWound healing and arthritis treatment are two areas that people care about. New classes of “smart” hydrogels that respond to environment and change their stiffness will be developed for removable wound dressings and arthritis treatment. This work will improve healing outcome for millions of patients each year. In addition to practical applications, these materials will provide tools and methods that could be used by everyone to rationally design hydrogel materials and will contribute to development of the wider fields of dynamic nanomaterials, drug delivery and biosensing. The educational component integrates research efforts and several education programs in biomaterials by 1) developing a research training program for high school students from Syracuse City School District (SCSD); 2) providing research training for undergraduate students that participate in Reserve Officer Training Corps (ROTC) at Syracuse University and 3) designing an outreach model of biomaterials for the Milton J. Rubinstein Museum of Science and Technology (MOST) in Syracuse. Through these multi-prong outreach programs, students across different age groups will be inclusively engaged with a particular emphasis on training women, underrepresented minorities, and refugees. Educational programs will not only provide a training ground for future biochemists but will also generate valuable results to advance the research field. Technical abstractThe goal of this proposal is to design peptide-based, smart, stimuli-responsive biocompatible antimicrobial materials that change their stiffness in response to changes in redox state and pH. Synergistic combination of multiple properties is critically important because self-healing is essential for delivery of the hydrogel via a syringe, antimicrobial properties and cytocompatibility are critical for practical applications, and redox switching allows the removal of the gel upon addition of a mild reductant or drug release in response to reactive oxygen species (ROS). Toward this goal, three classes of stimuli-responsive materials with self-healing properties will be designed: 1) redox-sensitive peptide hydrogels; 2) pH-responsive hydrogel to deliver fibroblast cells into wound bed; 3) hydrogels that respond to both changes in pH and ROS. This work will generate hydrogel materials for wound care and arthritis treatment and will provide tools and methods for rational design of functional materials.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.