Biomimetic lung sealant to rapidly heal pulmonary air leaks, decrease recovery time, and reduce associated costs to the healthcare system,

仿生肺密封剂可快速治愈肺部漏气、缩短恢复时间并降低医疗保健系统的相关成本，

• 批准号: 10005701
• 负责人: John David O'Neill
• 金额: $ 22.41万
• 依托单位: XYLYX BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005701
• 关键词: Adhesives; Air; Alveolar; Animals; Biocompatible Materials; Biodegradation; Biomimetics; Biotechnology; Blood; Cells; Chest; Chest Tubes; Chronic; Data; Development; Drainage procedure; Elasticity; Empyema; Extracellular Matrix; Extravasation; FDA approved; Family suidae; Fistula; Formulation; Glues; Goals; Health; Health Care Costs; Healthcare Systems; Hemostatic function; Human; Immobilization; Immune response; Incidence; Infection; Inflammation; Inflammatory; Inpatients; Knowledge; Length of Stay; Lung; Lymphocyte; Mechanics; Medicine; Methods; Modeling; Modulus; Nature; Notification; Operative Surgical Procedures; Outcome; Pain; Patient-Focused Outcomes; Patients; Performance; Phase; Pneumonia; Polymers; Porosity; Postoperative Complications; Postoperative Period; Preparation; Puncture procedure; Rattus; Recovery; Resistance; Risk; Safety; Science; Small Business Innovation Research Grant; Standardization; Structure; Structure of parenchyma of lung; Surgeon; Surgical incisions; Tensile Strength; Testing; Therapeutic; Time; Tissues; Toxic effect; Trauma; Traumatic injury; Work; biomaterial compatibility; commercial application; commercialization; cost; design; disease transmission; healing; high risk; hospital readmission; improved outcome; in vitro testing; in vivo; infection risk; innovation; irritation; macrophage; mimetics; neutrophil; novel; pre-clinical; pressure; regenerative; repaired; respiratory; response; seal; technological innovation; wound; wound healing

ABSTRACT Xylyx Bio is developing an innovative biomimetic lung-derived extracellular matrix (ECM) foam sealant material that effectively seals and supports tissue healing for pulmonary air leaks after lung surgery and thoracic trauma. Pulmonary air leak is one of the most common complications after lung surgery, leading to extended chest tube drainage time, patient pain and immobilization, increased risk of infection and bronchopleural fistulae, and subsequent longer hospital stay, with higher associated healthcare costs. In the US alone, over 400,000 patients are at risk for developing pulmonary air leaks every year. Despite the high risk, incidence, and cost of post-surgical pulmonary air leaks, an effective lung sealant is not available. Several synthetic and naturally-derived materials have been tested, but none achieve the required tensile strength, elasticity, adhesive strength and burst pressure resistance for reliably sealing and healing air leaks, thus leaving a significant unmet need. This Phase I SBIR will develop, demonstrate performance, and assess biocompatibility/systemic response of a biomimetic foam sealant comprised of lung ECM that both seals and heals pulmonary air leaks, filling a known gap in therapeutic options for treating and managing air leaks. The technological innovation is the demonstrably novel, unique ‘lung-mimetic’ foam sealant features – porous (alveolar-like) structure, mechanics, and bioactivity – that enable rapid sealing and active lung tissue healing, and the proprietary methods for isolating/processing lung ECM and formulating the sealant. The long-term goal is to develop a lung-mimetic sealant that rapidly seals and heals pulmonary air leaks, leading to reduction of recovery time, postoperative complications, and healthcare costs. The Phase I hypothesis is that a lung-mimetic sealant comprised of lung tissue-derived ECM components with elastic modulus and porosity similar to those of lung tissue can effectively seal and repair air leaks, with excellent biocompatibility, appropriate biodegradation rate, and immunologic response that supports wound healing. Specific aims are to establish lung sealant formulation that results in the desired lung-mimetic features, demonstrate sealant performance in an ex-vivo swine lung model, and assess biocompatibility and systemic response to the foam sealant in a rat model. After Phase I aims are accomplished, demonstrating safety and efficacy in a large animal long-term survival model will be essential for development towards commercialization. Thus, in Phase II, we will assess sealant performance and wound healing in a chronic swine model to inform a preliminary draft of 510(k) premarket notification. Xylyx Bio will then work towards making a lung-mimetic lung sealant commercially available to surgeons in need of a reliable, effective lung sealant to reduce costs to the health care system and improve outcomes for patients recovering from lung surgery and thoracic trauma.

抽象的 Xylyx Bio正在开发创新的仿生肺细胞外基质（ECM）泡沫密封剂 有效密封并支持肺部手术后肺部空气泄漏的组织愈合的材料 胸痛。肺部泄漏是肺手术后最常见的并发症之一，导致 延长胸管排水时间，患者疼痛和固定，感染风险增加和 支气管假设瘘，随后的住院时间更长，相关的医疗费用更高。在 仅美国，每年有超过40万名患者面临肺部泄漏的风险。尽管很高 手术后肺气泄漏的风险，事件和成本，有效的肺密封剂不可用。 已经测试过几种合成和自然衍生的材料，但没有人实现所需的拉伸材料 强度，弹性，粘合强度和抗压力抗性，可靠地密封和治愈空气泄漏， I阶段I SBIR将发展，证明性能， 并评估肺ECM的仿生泡沫密封剂的生物相容性/全身反应 密封和治愈肺部空气泄漏，填补了治疗和管理的治疗选择的已知差距 空气泄漏。技术创新是明显的新颖，独特的“肺模仿”泡沫密封剂 特征 - 多孔（牙槽样）结构，力学和生物活性 - 可以快速密封和主动 肺组织愈合以及隔离/加工肺ECM并配制的专有方法 密封剂。长期目标是开发一种肺模拟密封剂，该密封剂迅速密封并治愈肺气 泄漏，导致恢复时间，术后并发症和医疗保健费用的减少。第一阶段 假设是，肺组织衍生的ECM成分积累了肺模拟密封剂 与肺组织类似的模量和孔隙率相似 生物相容性，适当的生物降解率和支持伤口愈合的免疫学反应。 具体目的是建立肺密封剂配方，从而产生所需的肺模拟特征， 在前体内猪肺模型中展示密封剂性能，并评估生物相容性和全身性 大鼠模型中对泡沫密封剂的响应。一阶段之后的目标完成后，证明了安全性和 大型动物长期生存模型的功效对于发展至关重要 商业化。在第二阶段，我们将评估密封剂性能和伤口愈合 慢性猪模型，以告知510（k）上市前通知的初步草案。 Xylyx Bio然后将工作 为了使需要可靠， 有效的肺密封剂可降低医疗保健系统的成本并改善患者的预后 从肺部手术和胸部创伤中恢复。