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

摘要 Xylyx Bio正在开发一种创新的仿生肺源性细胞外基质（ECM）泡沫密封剂 有效密封和支持肺部手术后肺部漏气的组织愈合的材料， 胸部创伤肺漏气是肺部手术后最常见的并发症之一，导致 胸管引流时间延长，患者疼痛和固定，感染风险增加， 支气管胸膜瘘，随后住院时间更长，相关医疗费用更高。在 仅在美国，每年就有超过40万患者面临肺漏气的风险。尽管高 手术后肺漏气的风险、发生率和成本，有效的肺密封剂不可用。 已经测试了几种合成和天然来源的材料，但没有一种达到所需的拉伸强度。 强度、弹性、粘合强度和抗爆裂压力，用于可靠地密封和修复漏气， 因此留下了大量未满足的需求。第一阶段SBIR将开发、演示性能， 并评估由肺ECM组成的仿生泡沫密封剂的生物相容性/全身反应， 密封和治愈肺漏气，填补了治疗和管理肺漏气的治疗选择的已知空白， 漏气。技术创新是显而易见的新颖，独特的'肺模拟'泡沫密封剂 特征-多孔（肺泡状）结构、力学和生物活性-可实现快速密封和活性 肺组织愈合，以及用于分离/处理肺ECM和配制 密封剂长期目标是开发一种能快速封闭和治愈肺部气体的仿肺封闭剂 泄漏，从而减少恢复时间、术后并发症和医疗费用。I期 假设是由肺组织衍生的ECM组分组成的肺模拟密封剂具有弹性， 与肺组织相似的模量和孔隙率可以有效地密封和修复漏气， 生物相容性、适当的生物降解速率和支持伤口愈合的免疫应答。 具体目标是建立肺密封剂配方，产生所需的肺模拟特征， 在离体猪肺模型中证明密封剂性能，并评估生物相容性和全身性 在大鼠模型中对泡沫密封剂的反应。在第一阶段目标完成后，证明安全性和 在大型动物长期存活模型中的有效性对于开发 商业化因此，在第二阶段，我们将评估密封剂的性能和伤口愈合， 慢性猪模型，以告知510（k）上市前通知的初步草案。Xylyx Bio将在 致力于制造一种商业上可用于外科医生的肺模拟肺密封剂， 有效的肺密封剂，以降低医疗保健系统的成本并改善患者的结局 从肺部手术和胸部创伤中恢复过来

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.