Oxygen-Mediated Initiation of Thiol-ene Adhesives and Sealants

描述（由申请人提供）：已经出现了几种组织粘合剂和密封剂的材料和方法；然而，仍需要大量的研究关注，以充分发挥材料的潜力，这些材料可以以液体形式应用于伤口部位并在原位固化，从而减轻缝合或绷带的需要。虽然自由基介导的聚合是一种有吸引力的制造生物材料的方法，因为它们能够在室温下无溶剂快速固化，但大多数自由基介导的聚合容易受到氧抑制。在提议的工作中，氧引发而不是抑制聚合，因此引发反效应。我们提出了新的，氧介导的硫醇烯聚合系统，以解决目前的医疗程序原位聚合方法的缺点。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后，迅速固化。然而，与氰基丙烯酸酯不同，巯基材料的化学和机械性能很容易变化。最初，氧介导自由基生成的方法将被开发，以引发巯基聚合。随后，利用这些氧介导引发方案用于生物医学粘合剂和密封剂的巯基树脂将被配制并以商业材料为基准。最后，将进行聚合建模，以指导和优化配方开发，并考虑到应用约束，如聚合引起的厚度和温升。

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.