New self-assembling antimicrobial biomaterials based on spider silk.

蜘蛛丝是一种大蛋白(200-250 kDa)，具有良好的生物相容性、降解速度慢、免疫原性和致热性低等特点。丝绸具有特殊的机械性能--它比任何合成材料(包括防弹凯夫拉纤维)都更坚韧，按重量计算也比钢更坚固。不幸的是，由于蜘蛛的自相残杀和高度地域性，饲养蜘蛛是不可行的。在这个项目中，我们使用在细菌中重组表达的合成微型蜘蛛丝结构，从而消除了蜘蛛养殖的需要。此外，与蜘蛛不同，细菌能够将带有选择性活性侧链的人造氨基酸整合到丝蛋白序列中。通过这种方式，我们可以使用合成生物学来生产一个可定制的丝绸平台，以便以一种严格受控、可持续和可扩展的方法进行进一步修改。此外，重组丝可以很容易地加工成不同稳定的形态，如纤维、水凝胶、球体、胶水和易于适应其最终角色的自组装膜。本项目的目的是创造具有抗菌性能的重组蜘蛛丝基材料。我们打算使用点击化学来用抗菌分子装饰丝绸--点击化学是一系列强大的、高产的、生物相容的化学反应，可以耐受各种条件。此外，该项目还将评估抗菌丝结合物的生物活性。抗菌丝结合物在各种医疗和生物工程领域具有广泛的应用潜力。功能化的丝绸可以加工成抗感染的外科缝合线和胶水、伤口敷料和医疗器械涂层。这种定制设计的抗菌丝材料可以处理易感部位的感染，缓解与系统性过度使用抗生素、表面相关细菌生长和医院感染相关的问题。

Spider silk is a large (200-250 kDa) protein known for its excellent biocompatibility, slow degradation, and low immunogenicity and pyrogenicity. Silks exhibit exceptional mechanical properties - it is tougher than any synthetic material (including bullet-proof Kevlar) and stronger than steel on weight-per-weight basis. Unfortunately, it is not feasible to farm spiders due to their cannibalistic and highly territorial nature.In this project, we use synthetic miniature spider silk constructs that are expressed recombinantly in bacteria, therefore eliminating the need for spider farming. Additionally, unlike spiders, bacteria are able to incorporate man-made amino acids with selectively reactive side chains into the silk protein sequence. In this way, we can use synthetic biology to produce a customisable silk platform for further modification in a tightly controlled, sustainable and scalable approach. Furthermore, recombinant silk can be easily processed into different stable morphologies, such as fibres, hydrogels, spheres, glues, and self-assembling films that can be readily adapted to their final role.The aim of this project is to create recombinant spider silk-based materials with antimicrobial properties. We intend to decorate silk with antimicrobial molecules using click chemistry - a series of robust, high yielding, biocompatible chemical reactions that are tolerant to a wide range of conditions. Further, this project will assess the biological activity of the antimicrobial silk conjugates. Antimicrobial silk conjugates have an extensive potential in various medical and bioengineering applications. Functionalised silks can be processed into infection-resistant surgical sutures and glues, wound dressings, and medical device coatings. Such custom-designed antimicrobial silk materials tackle infection at the susceptible site, mitigating issues associated with systemic overuse of antibiotics, surface-associated bacterial growth, and hospital-acquired infections.