Polymer Grafted Implant Surfaces with Biofilm Sensitizing Ability

描述(申请人提供)：生物膜中的细菌表现出独特的生理特征，与浮游培养的表型有很大不同。与生物膜相关的医院感染和疾病目前是美国第四大死亡原因，仅次于心脏病、癌症和中风。无论使用什么抗生物膜方法，成功率仍然有限，植入的设备上仍会形成生物膜。在大多数情况下，生物被膜引起的感染只能通过移除植入物的高成本和不受欢迎的程序来治愈。细菌生物膜最重要的特征之一是对抗菌剂和宿主免疫系统的攻击具有抵抗力。生活在生物膜中的细菌对抗生素的抗药性比浮游细菌高出1000倍。我们建议从一个新的方向来对抗生物膜，通过直接处理附着的细菌和形成生物膜来辐射生物膜相关感染。我们计划构建新型的聚合物接枝表面，通过破坏生物膜的结构，增加生物膜的通透性，阻止生物膜的成熟，使附着的细菌或形成的生物膜敏化宿主免疫系统的攻击和抗生素治疗。该领域R15项目包括三个主要目标：特定目标#1，创建对生物被膜形成具有期望敏感性的各种聚合物接枝表面；特定目标#2，研究在体外创建的聚合物接枝表面上生物膜的形成动力学和抗生素敏感性；特定目标#3，研究聚合物接枝表面的生物膜敏化机制。这项研究首次尝试将抗生物膜活性直接集成到材料中来开发生物膜敏化表面，这一研究具有重大的智力优势。对pH-聚合物接枝表面生物膜敏化机理的研究将丰富我们的知识，促进我们的研究打赢生物膜之战。此外，这笔R15拨款对于研究人员和他的合作者继续在史蒂文斯理工学院的教学和研究活动非常重要。 细菌可以附着在植入装置的表面，并在患者体内生长成菌群(称为生物膜)。与普通细菌不同，生物膜很难通过普通的抗生素治疗而被杀死，因此植入设备相关的感染和疾病目前是美国第四大死亡原因，仅次于心脏病、癌症和中风。这项研究的目标是开发新型的设备表面，以防止生物膜的形成和植入相关的感染和疾病。

DESCRIPTION (provided by applicant): Bacteria in biofilm show unique physiological characteristics that are much different from planktonic cultured phenotypes. Biofilm associated nosocomial (hospital acquired) infection and disease is currently the fourth leading cause of death in the United States, behind only heart disease, cancer and stroke . Regardless what anti-biofilm methods are used, the success rates are still limited and biofilm will nevertheless form on implanted devices. In most cases, biofilm-induced infections can only be cured by a high cost and undesirable procedure through the removal of the implants. One of the most important features of bacterial biofilms is their resistance to antimicrobial agents and the host immune system attacks. Bacteria living in biofilms can exhibit up to 1000 time greater resistance to antibiotics than planktonic bacteria. We propose to fight against biofilm from a new direction by directly dealing with attached bacteria and formed biofilm to eradiate biofilm associated infection. We plan to construct novel polymer grafted surface which can sensitize attached bacteria or formed biofilm to host immune system attack and antibiotic treatment through disrupting biofilm architecture, increasing biofilm permeability, and blocking biofilm maturation. Three broad objectives are included in this AREA R15 project: Specific aim #1, create various polymer grafted surfaces with desired sensitivity to biofilm formation; Specific aim #2, study the formation dynamics and antibiotic sensitivity of biofilm on created polymer-grafted surfaces in vitro; Specific aim #3, study biofilm sensitizing mechanisms of polymer-grafted surfaces. This research holds significant intellectual merits for its first attempt of integrating the anti-biofilm activity directly into materials to develop biofilm sensitizing surfaces. Study of the biofilm sensitizing mechanism on pH-polymer grafted surfaces will enrich our knowledge and promote the research to win our battle with biofilms. In addition, this R15 grant is important for the investigator and his collaborators to continue their teaching and research activities at Stevens Tech. Bacteria can attach the surface of implant device and grow into bacteria clusters (called biofilm) in the patients' bodies. Unlike common bacteria, biofilm can hardly be killed by ordinary antibiotic treatment and thus implant device associated infection and disease is currently the fourth leading cause of death in the United States, behind only heart disease, cancer and stroke. The goal of this research is to develop new types of device surfaces to prevent biofilm formation and implantation association infections and diseases.