Oxygen-Mediated Initiation of Thiol-ene Adhesives and Sealants

描述（由申请人提供）：已经出现了几种用于组织粘合剂和密封剂的材料和方法;然而，仍然需要大量的研究关注，以充分实现可以以液体形式应用于伤口部位并原位固化的材料的潜力，从而减轻对缝线或绷带的需求。虽然自由基介导的聚合是用于制造用于生物应用的材料的有吸引力的手段，但由于它们在室温下不使用溶剂快速固化的能力，大多数自由基介导的聚合对氧抑制敏感。在所提出的工作中，氧引发而不是抑制聚合，因此引发反作用。我们提出了新的，氧介导的硫醇-烯聚合系统，以解决目前的方法在医疗程序的原位聚合的缺点。这种引发硫醇-烯聚合的方法类似于氰基丙烯酸酯聚合，其中液体单体在其包装中保持稳定，但在应用于伤口部位时迅速固化。然而，与氰基丙烯酸酯不同，硫醇-烯材料的化学和机械性能容易变化。 最初，将开发用于氧介导的自由基生成的方法以引发硫醇-烯聚合。随后，硫醇烯树脂，利用这些氧介导的引发方案的生物医学粘合剂和密封剂，将制定和基准对商业材料。最后，将进行聚合建模，以针对应用限制（例如聚合引起的厚度和温度上升）指导和优化配方开发。 公共卫生相关性：该项目旨在开发硫醇烯生物医学粘合剂和密封剂，这些粘合剂和密封剂在暴露于氧气时会发生反应。利用硫醇-烯体系，其表现出上级机械性能、生物相容性和在环境条件下快速固化的能力，预计将大大改善现有材料的实用性和功效。

DESCRIPTION (provided by applicant): Several materials and approaches for tissue adhesives and sealants have emerged; however, substantial research attention is still required to fully realize the potential of materials that can be applied to a wound site in liquid form and solidify in situ, alleviating the need for sutures or bandages. Although radical-mediated polymerizations are an attractive means for fabricating materials for use in biological applications, owing to their ability to rapidly cure without solvent at room temperature, the majority of radical-mediated polymerizations are susceptible to oxygen inhibition. In the proposed work, oxygen initiates rather than inhibits the polymerization, therefore eliciting the counter effect. We propose novel, oxygen-mediated thiol-ene polymerization systems to address the shortcomings of current approaches to in situ polymerization for medical procedures. This approach for the initiation of thiol-ene polymerization is analogous to cyanoacrylate polymerization, where liquid monomer remains stable while in its packaging but, upon application to a wound site, cures rapidly. However, unlike cyanoacrylates, the chemical and mechanical properties of thiol-ene materials are readily varied. Initially, approaches for oxygen-mediated radical generation will be developed to initiate thiol-ene polymerization. Subsequently, thiol-ene resins, utilizing these oxygen-mediated initiation schemes for biomedical adhesives and sealants, will be formulated and benchmarked against commercial materials. Finally, modeling of the polymerization will be performed to guide and optimize formulation development with respect to application constraints such as thickness and temperature rise due to polymerization. PUBLIC HEALTH RELEVANCE: This project seeks to develop thiol-ene biomedical adhesives and sealants which polymerize upon exposure to oxygen. Utilizing thiol-ene systems, which demonstrate superior mechanical properties, biocompatibility, and ability to rapidly cure at ambient conditions, is expected to greatly improve upon both the utility and efficacy of existing materials.