Dermal Integration Sleeve to Reduce Exit Site Infections.

描述（由申请人提供）：本项目的长期目标是开发可大大改善组织整合和密封经皮器械皮肤出口部位的套囊。改进的密封恢复了天然皮肤屏障，可以消除细菌感染的主要途径。在第一阶段，我们打算从猪模型的早期工作中构建，该模型显示炎症减少和真皮组织整合良好，其中工程多孔生物材料是该提议的核心，并开发更广泛和定量的结果，以支持最终的临床试验。 导管和其他经皮器械用于多种治疗情况，通常需要很长时间。感染是一个永远存在的问题;每年发生数十万例感染，仅在美国，死亡率就超过30，000例。这些感染中有很大一部分是通过皮肤屏障破裂发生的，这提供了一条沿着器械外表面的微生物迁移路径。目前解决该问题的方法依赖于从装置表面或从皮下施加的套囊释放抗微生物剂。这些减少了短期感染，但不提供任何密封来恢复天然皮肤屏障以获得长期有效性。对引发“超级细菌”菌株的药剂的长期使用、医疗保险和其他机构减少医院感染的压力不断增加以及设备使用的增加（特别是老年患者）的担忧，使得改进方法至关重要。估计每次感染的成本为25 - 5万美元，目前的情况代表美国医疗保健每年的成本为60亿美元。球模板血管再生（星星）三维支架是工程生物材料与严格控制孔径（~35微米）。以前的工作表明，当形成和应用出口部位袖口，这些支架强烈整合与真皮组织和控制表皮舌permigration。所得界面在经皮器械和周围组织之间形成紧密密封，并解决出口部位脆弱性的根本原因-造袋术、移位和微创伤。星星效应主要是由于孔径大小和很大程度上独立于材料或表面化学。这允许使用公认的生物相容性基质材料，提供更容易的商业化途径。 公共卫生相关性：经皮医疗器械的使用与感染的重大风险相关。细菌的主要途径是由非愈合皮肤出口部位提供的。目前解决这一问题的办法只能在短期内有效，不能解决根本原因。多孔生物材料和使用这些材料形成器械套囊的方法的新发展将整合和密封出口部位，从而有可能降低感染率。

DESCRIPTION (provided by applicant): The longer-term objective of this project is to develop cuffs that will greatly improve tissue integration and sealing to percutaneous devices at their skin exit sites. Improved sealing restores the natural skin barrier and can remove a major path for bacterial infection. In Phase I we intend to build from earlier work in a porcine model showing reduced inflammation and well-integrated dermal tissue with the engineered porous biomaterial central to this proposal and to develop more extensive and quantitative results in support of eventual clinical testing. Catheters and other percutaneous devices are used in multiple treatment situations, often over long time periods. Infections are an ever present issue; some hundreds of thousands occur each year with a mortality rate exceeding 30,000 patients in the US alone. A significant fraction of these infections occur via the skin barrier breach, providing a microbial migration path along the device outer surface. Present approaches to this issue rely on releasing antimicrobial agents from the device surface or from subcutaneously applied cuffs. These reduce short term infections but do not provide any seal to restore the natural skin barrier for longer term effectiveness. Concern over extended use of agents provoking "superbug" strains, rising pressure from Medicare and others to reduce nosocomial infections, and increasing device use, especially with older patients, make improved approaches essential. With an estimated cost per infection of $25 - $50k, the present situation represents a $6B annual cost to US healthcare. Sphere Templated Angiogenic Regeneration (STAR) 3D scaffolds are engineered biomaterials with tightly controlled pore sizing (~35¿m). Previous work has shown that when formed and applied as exit site cuffs; these scaffolds strongly integrate with dermal tissue and control epidermal tongue permigration. The resulting interface forms a tight seal between the percutaneous device and the surrounding tissue and addresses the root causes of exit site vulnerability - marsupialization, permigration, and microtrauma. The STAR effects are primarily due to pore sizing and largely independent of material or surface chemistry. This allows recognized biocompatible substrate materials to be used, providing an easier commercialization path. PUBLIC HEALTH RELEVANCE: Use of percutaneous medical devices is associated with a significant risk of infection. A major pathway for bacteria is provided by non healing skin exit sites. Present approaches to this problem are only short term effective and do not address the root causes. New developments in porous biomaterials and methods of using these to form device cuffs that will integrate and seal the exit site offer potential for reduced infection rates.