Evaporative Assembly of Drug-Eluting Bioresorbable Nanocomposite Micropatterns

该奖项由材料研究部的生物材料项目授予史蒂文斯理工学院，旨在探索将药物洗脱的、可生物吸收的微图案喷墨打印到整形外科植入物表面，作为防止植入物细菌感染的新方法。感染的发生是因为少量细菌优先附着在非生物植入物表面并形成生物膜，在生物膜中细菌受到宿主防御和抗生素的保护。该项目寻求建立一种新的范例，通过这种范例，未来的种植体表面被设计成防止细菌附着和生物膜形成，同时促进它们的骨整合功能。这项研究是重要的和及时的，因为在种植过程中医院获得性细菌感染已经成为种植失败的主要模式。在喷墨打印过程中，蒸发组装机制被用来创建纳米复合微图案，该图案由分散在可生物降解的聚合物基质中的磷酸钙和抗生素纳米晶(~100 nm)组成。配制油墨是为了适应纳米复合材料的形态：1)稳定的抗生素释放，作为一种杀死接触到植入物表面的机会细菌的机制，从而防止生物膜的形成；以及2)优化磷酸钙纳米晶体的骨传导性能，以快速和直接地形成新骨。微流控共培养工具被用来投影微图案防止生物膜形成的能力，同时促进钛合金表面形成3D骨组织样结构。这个项目的结果被用来定义设计最佳感染预防和伤口愈合功能的植入物表面的标准。该项目还支持对1名博士和12名本科生进行跨学科培训，让他们在发现、合作和创业的兴奋中开发新一代预防感染的生物医学设备。该项目探索了在骨科植入物表面喷墨打印药物洗脱的、可生物吸收的微图案，作为预防植入物细菌感染的新方法。虽然我们生产骨科植入物的能力在过去几十年里有了极大的提高，但种植过程中医院获得性细菌感染已经成为植入物失败的主要模式。感染的发生是因为少量细菌优先附着在植入物表面并形成生物膜，从而保护细菌免受宿主防御和抗生素的伤害。因此，在美国，受感染的植入物必须通过手术移除，造成巨大的患者创伤和每年超过30亿美元的额外医疗负担。尽管这个感染问题很严重，但由于我们对宿主组织、细菌和生物材料之间复杂的相互作用缺乏了解，进展有限。这项研究试图通过建立一个跨越生物材料、设备感染和微流体的高度跨学科的研究前沿，为设计预防感染的植入物提供新的科学理解。作为这一新范式的一个例子，喷墨打印微图案概念为感染问题提供了一种变革性的解决方案，它消除了细菌形成的生物膜，同时促进了种植体表面快速而牢固的骨形成。该项目还支持对1名博士和12名本科生进行跨学科培训，让他们在发现、合作和创业的兴奋中开发新一代预防感染的生物医学设备。这一主题对新泽西州北部地区极其重要，该地区的生物医疗设备行业在地区、国家和全球经济中发挥着关键作用。

This award by the Biomaterials program in the Division of Materials Research to Stevens Institute of Technology is to explore the inkjet printing of drug-eluting, bioresorbable micropatterns onto the surface of orthopaedic implants, as a novel means of preventing bacterial infection of the implants. Infection occurs because a small number of bacteria adhere preferentially to abiotic implant surfaces and form biofilms, in which the bacteria are protected from host defense and antibiotics. The project seeks to establish a new paradigm by which future implant surfaces are engineered to prevent bacteria attachment and biofilm formation and, at the same time, to promote their osteointegration function. This research is important and timely, since hospital-acquired bacterial infection during implantation procedures has emerged as the dominant mode of implant failure. During inkjet printing, evaporative assembly mechanisms are used to create nanocomposite micropatterns which consist of calcium phosphate and antibiotic nanocrystals (~100 nm) dispersed in a biodegradable polymer matrix. Inks are formulated to tailor nanocomposite morphology for: 1) steady antibiotic release as a mechanism of killing opportunistic bacteria that will come in contact with implant surfaces and thus preventing biofilm formation; and 2) optimization of the osteoconductive property of calcium phosphate nanocrystals for rapid and direct new bone formation. Microfluidic co-culture tools are used to project the ability of micropatterns to prevent biofilm formation while enhancing the formation of 3D bone tissue-like structures on the titanium alloy surface. Results from this project are used to define the criteria for designing implant surfaces for optimum infection-prevention and wound-healing functions. The project also supports the interdisciplinary training of one doctoral and twelve undergraduate students with the excitement of discovery, collaboration, and entrepreneurship in developing a new generation of infection-preventing biomedical devices. This project explores the inkjet printing of drug-eluting, bioresorbable micropatterns onto the surface of orthopaedic implants, as a novel means of preventing bacterial infection of the implants. While our ability to produce orthopaedic implants has tremendously improved over past several decades, hospital-acquired bacterial infection during implantation procedures has emerged as the dominant mode of implant failure. Infection occurs because a small number of bacteria adhere preferentially to implant surfaces and form biofilms, which protect the bacteria from host defense and antibiotics. Consequently, infected implants must be surgically removed with tremendous patient trauma and additional healthcare burden of over $3B in the U.S. every year. Despite the severity of this infection problem, progress has been limited due to the lack of our understanding of the complex interplay among host tissues, bacteria, and biomaterials. This research seeks to provide a new scientific understanding for designing infection-preventing implant by establishing a highly cross-disciplinary research frontier that cuts across biomaterials, device infection, and microfluidics. The inkjet-printed micropattern concept, as an example of this new paradigm, offers a transformative solution to the infection problem by eliminating the formation of biofilm by bacteria while promoting rapid and strong bone formation on the implant surfaces. The project also supports the interdisciplinary training of one doctoral and twelve undergraduate students with the excitement of discovery, collaboration, and entrepreneurship in developing a new generation of infection-preventing biomedical devices. This theme is extremely important to the Northern New Jersey area, where the biomedical device industry plays a key role in the regional, national, and global economies.