Development of nature-inspired hemostatic materials and its applications

Abstract

Adhesives play important roles in industrial fields such as electronics, architectures, energy plantation, and others. However, adhesives used for medical purpose are rather under-developed compared with those used in industry and consumer products. One key property required for medical adhesives is to maintain their adhesiveness in the presence of body fluid. Moreover, hemostasis of unexpected bleeding frequently occurred in surgical procedures that causes early death by trauma or infectious complications is a challenging issue. Although hemostatic materials are being extensively developed, arresting perioperative bleeding of patients with medical, surgical, or combined factor-related bleeding problems is a difficult task. The first part (Chapter 2), we report an entirely new class of medical adhesives called TAPE

this is produced by intermolecular hydrogen bonding between a well-known polyphenol compound, tannic acid, and poly(ethylene glycol). The preparation method of TAPE is extremely easy, forming a few liters at once by just the simple mixing of the two compounds without any further chemical synthetic procedures. TAPE shows a 250% increase in adhesion strength compared with fibrin glue, and the adhesion is well maintained in aqueous environments. It is demonstrated that TAPE is an effective hemostatic material and a biodegradable patch for detecting gastroesophageal reflux disease in vivo. Widespread use of TAPE is anticipated in various medical and pharmaceutical applications such as mucoadhesives, drug depots, and others, because of its scalability, adhesion, and facile preparation. The second part (Chapter 3, 4), we show a novel design principle of hemostats for delayed hemostasis by instantly forming blood protein barriers. We unexpectedly observe that chitosan-catechol spontaneously formed porous membranes in blood plasma and then, blood protein barriers are formed by interactions of chitosan-catechol and blood proteins. Through this mechanism of barrier formation on hemorrhaging sites, chitosan-catechol materials arrest the bleeding rapidly. We carried out to determine the hemostatic efficacy of chitosan-catechol hemostatic material in normal rat model and heparinized swine model. A study on thromboelastography of actual clinical cases also imply that successful hemostasis caused by complexation of chitosan-catechol and blood proteins. Our results demonstrate that these chitosan-catechol hemostatic materials robustly arrest the bleeding for all patients regardless of their medical history and safely use in surgical procedures.