SBIR Phase I: Antibacterial Nanotopography for Orthopedic Fixation Devices

SBIR 第一阶段：用于骨科固定装置的抗菌纳米形貌

• 批准号: 1842823
• 负责人: Daniel Hickey
• 金额: $ 22.5万
• 依托单位: Tyber Medical, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1842823&HistoricalAwards=false
• 关键词: SBIR; Phase; Antibacterial; Nanotopography; Orthopedic

This SBIR Phase I project addresses the unacceptable incidence of orthopedic device-related infections, as well as the dangerous rise of antibiotic resistant bacteria. More than 100,000 implanted orthopedic fixation devices (pins, plates, and screws) acquire bacterial infections each year in the US, accounting for approximately $1.5 trillion in associated medical and surgical treatment costs. Furthermore, the overuse and misuse of antibiotics to treat these infections has led to a dramatic rise in antibiotic resistance, which poses a severe risk to human health. This project aims to develop and optimize a commercially viable process to impart orthopedic fixation devices with a unique surface nanotexture designed to inhibit bacterial attachment and disrupt the biofilm cycle while simultaneously stimulating robust implant integration with adjacent bone. Importantly, this treatment acts via topography alone and does not incorporate antimicrobial agents or pharmaceuticals. Due to the ubiquity and gravity of the infection epidemic, this first-of-its-kind antibacterial surface technology is expected to rapidly infiltrate the orthopedic device market and drive a dramatic market shift towards the development of products with enhanced biological activity. Ultimately, this project has the potential to alleviate significant clinical and economic burdens while stimulating technological advances in a competitive market. The proposed work aims to create an antibacterial surface nanotexture by utilizing a proprietary modified atomic deposition technique. The fabrication parameters used during this deposition process are closely linked to the resulting surface characteristics (and thus its antimicrobial efficacy). However, the link between fabrication parameters and antimicrobial efficacy is inadequately understood currently. Therefore, the proposed work employs a systematic strategy to elucidate the relationships involved and establish control over the fabrication process and resulting surface properties. The project is separated into four stages, each designed to explore the effect of a specific fabrication parameter on performance outcomes, including bacterial colonization, bone cell functions, and trends in certain surface properties that often correlate with cell-substrate interactions (e.g. surface energy, roughness, skewness, etc.). The relationships revealed through testing will be used to build a set of equations that describe how the properties of the nanotextured surface vary as a function of the fabrication parameters. This set of equations will then be used to optimize the system, enabling consistent and controllable operation of the deposition process as manufacturing specifications evolve. In addition to advancing the development of a market-changing product, the proposed research will contribute to the growing understanding of cell and bacteria responses on nanostructured surfaces in an ongoing effort to mitigate infection associated with orthopedic implants.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.

该SBIR第一阶段项目解决了骨科器械相关感染的不可接受的发生率，以及抗生素耐药细菌的危险增加。在美国，每年有超过100，000个植入的骨科固定器械（销、板和螺钉）发生细菌感染，约占相关医疗和手术治疗费用的1.5万亿美元。此外，过度使用和滥用抗生素治疗这些感染导致抗生素耐药性急剧上升，对人类健康构成严重威胁。该项目旨在开发和优化一种商业上可行的工艺，以赋予骨科固定器械独特的表面纳米纹理，旨在抑制细菌附着并破坏生物膜循环，同时刺激植入物与相邻骨的牢固整合。重要的是，这种治疗仅通过局部解剖学起作用，不包括抗微生物剂或药物。由于感染流行的普遍性和严重性，这种首创的抗菌表面技术预计将迅速渗透到骨科器械市场，并推动市场转向开发具有增强生物活性的产品。最终，该项目有可能减轻重大的临床和经济负担，同时在竞争激烈的市场中刺激技术进步。拟议的工作旨在通过利用专有的改性原子沉积技术来创建抗菌表面纳米纹理。在该沉积过程中使用的制造参数与所得表面特性（以及因此其抗微生物功效）密切相关。然而，制造参数和抗菌功效之间的联系目前还没有得到充分的理解。因此，拟议的工作采用系统的策略来阐明所涉及的关系并建立对制造过程和由此产生的表面特性的控制。该项目分为四个阶段，每个阶段旨在探索特定制造参数对性能结果的影响，包括细菌定植，骨细胞功能以及通常与细胞-基质相互作用相关的某些表面特性的趋势（例如表面能，粗糙度，偏斜度等）。通过测试揭示的关系将用于建立一组方程，描述纳米织构表面的性质如何作为制造参数的函数而变化。然后，这组方程将用于优化系统，随着制造规范的发展，使沉积过程的操作一致且可控。除了推动市场变化产品的开发外，拟议的研究将有助于不断了解纳米结构表面上的细胞和细菌反应，以持续努力减轻与骨科植入物相关的感染。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。