Development of a Polysaccharide-Based Patch for Use as a Therapeutic Lung Sealant

 描述：手术、损伤或疾病引起的肺渗漏可能导致肺萎陷，这可能立即危及生命。治疗萎陷的肺开始于将胸管紧急放置到胸膜腔中，使得积聚的空气或液体可以被排出，以便使肺重新膨胀。然而，塌陷通常发生在愈合不良的组织中。广泛的组织损伤和慢性渗漏导致大量的发病率、死亡率和相应的高医疗保健成本。为了应对这些挑战，拟议的研究将探索使用天然材料藻酸盐作为组织密封剂和治疗贴片，以有效治疗肺渗漏并帮助肺组织再生。化学改性的藻酸盐，甲基丙烯酸化藻酸盐（Alg-MA），将进一步修改，以提高粘附到肺表面，形成更好的密封。还提出使用水凝胶作为药物载体来增强伤口愈合。因此，我们申请的首要目标是确定Alg-MA水凝胶作为组合胸膜封闭剂和治疗贴剂的潜在临床功效。实验设计集中于三个目的：1）确定Alg-MA水凝胶的物理性质如何影响其密封胸膜渗漏的能力，2）确定Alg-MA水凝胶性质如何影响其动态机械稳定性和药物控释的能力，和3）评估药物洗脱Alg-MA水凝胶在体内修复受损胸膜组织的能力。Alg-MA材料将被氧化以增强组织粘附，从而改善材料的爆破压力和密封剂性能。此外，Alg-MA与类似天然材料透明质酸（HA）的混合将增强动态机械性能，以确保动态耐久性和体内防漏的寿命。为了表征水凝胶密封剂的长期使用，将定制粘附性和机械性能以增强降解性能和药物释放速率。体内啮齿动物模型将用于评价Alg-MA水凝胶作为治疗药物的耐久密封剂和载体的功效。事实上，所提出的研究的更广泛的影响是开发用于各种用途的医用密封剂，特别是在需要选择性组织粘附的情况下。

 DESCRIPTION: Lung leaks from surgery, injury or diseases may result in lung collapse, which can be immediately life threatening. Treating a collapsed lung begins with emergent placement of a chest tube into the pleural space so that the accumulated air or liquid can be evacuated in order to re-inflate the lung. However, collapse often occurs in the setting of poorly healing tissue. Extensive tissue damage and chronic leak lead to substantial morbidity, mortality, and correspondingly high health care costs. To address these challenges, the proposed research will explore the use of a natural material, alginate, for use as a tissue sealant and therapeutic patch, to effectively treat lung leaks and aid in lung tissue regeneration. Chemically modified alginate, methacrylated alginate (Alg-MA), will be further modified to enhance adhesion to the lung surface to form a better seal. The use of the hydrogel as a drug carrier is also proposed to enhance wound healing. The overarching goal of our application is thus to establish the potential clinical efficacy of Alg- MA hydrogels as combination pleural sealants and therapeutic patches. The experimental design is centered on three aims: 1) to determine how the physical properties of Alg-MA hydrogels impact their capacity to seal a pleural leak, 2) to determine how Alg-MA hydrogel properties affect their capacity for dynamic mechanical stability and controlled release of drugs, and 3) to assess the ability of drug-eluting Alg-MA hydrogels to repair damaged pleural tissue in vivo. Alg-MA materials will be oxidized to enhance tissue adhesion, thus improving the burst pressure and sealant properties of the material. In addition, blending of Alg-MA with a similar natural material, hyaluronan (HA) will enhance the dynamic mechanical properties to ensure dynamic durability and longevity of leak prevention in vivo. To characterize the long-term use of the hydrogel sealant, adhesion and mechanical properties will be tailored to enhance degradation properties and drug release rates. An in vivo rodent model will be used to evaluate the efficacy of Alg-MA hydrogels as durable sealants and carriers for therapeutic drugs. Indeed, the broader impact of the proposed research is the development of a medical sealant for various uses, especially in cases when selective tissue adhesion is desired.