Engineering a naturally derived hemostatic sealant for sealing internal organs

Abstract

Controlling bleeding from a raptured tissue, especially during the surgeries, is essentially important. Particularly for soft and dynamic internal organs where use of sutures, staples, or wires is limited, treatments with hemostatic adhesives have proven to be beneficial. However, major drawbacks with clinically used hemostats include lack of adhesion to wet tissue and poor mechanics. In view of these, herein, we engineered a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion. Mechanistically, the engineered hydrogel controlled the bleeding through its wound-sealing capability and inherent chemical activity. This mussel-inspired hemostatic adhesive hydrogel, named gelatin methacryloyl-catechol (GelMAC), contained covalently functionalized catechol and methacrylate moieties and showed excellent biocompatibility both in vitro and in vivo . Hemostatic property of GelMAC hydrogel was initially demonstrated with an in vitro blood clotting assay, which showed significantly reduced clotting time compared to the clinically used hemostat, Surgicel®. This was further assessed with an in vivo liver bleeding test in rats where GelMAC hydrogel closed the incision rapidly and initiated blood coagulation even faster than Surgicel®. The engineered GelMAC hydrogel-based seaalant with excellent hemostatic property and tissue adhesion can be utilized for controlling bleeding and sealing of soft internal organs.

Bioinspired gelatin based sticky hydrogel for diverse surfaces in burn wound care

“…The classical optimization adopted in the present research has led to the development of the GbH with a bioinspired polydomine’s sticky property 2 , 18 . The PVA hydrogels have numerous applications in the pharmaceutical and biomedical industry due to their ease of processing, biocompatibility, non-carcinogenicity, bioadhesiveness, non-toxicity and transparency nature.…”

“…Such soft wound dressing can be beneficial for treating burn wounds since the stickiness of the hydrogel is not extreme adhesive and tough. For many marketed gelatin-based sealants, tissue adhesives can be beneficial for tissue repairs 1 , 8 , 18 . Such tissue injuries call for immediate attention to restore standard organ functionality.…”

“…The blend of PVA-starch and crosslinked with GA served as a base to further incorporate the sticky property. The recent bioinspired research tends to modify the polymeric properties of hydrogels 2 , 18 . The practice of using alkali polymerized dopamine 65 to induce diverse surface sticky properties in a polyacrylamide and bis-acrylamide hydrogel system has been previously reported 4 , even though various researchers have established its carcinogenic effect 66 .…”

Engineering a highly elastic bioadhesive for sealing soft and dynamic tissues

“…To synthesis GelMAC prepolymer, gelatin (4 mg/ml) was dissolved in water at 50°C. Next, 2 mM BOP, 2 mM HOBt, 20 mM dopamine hydrochloride, and 20 mM of triethylamine were added and kept for 12 h under N 2 atmosphere 40 . Dopamine conjugated gelatin was finally precipitated with cold acetone and further reacted with methacrylic anhydride as previously described 41 .…”

“…To synthesis GelMAC prepolymer, gelatin (4 mg/ml) was dissolved in water at 50 C. Next, 2 mM BOP, 2 mM HOBt, 20 mM dopamine hydrochloride, and 20 mM of triethylamine were added and kept for 12 h under N 2 atmosphere. 40 Dopamine conjugated gelatin was finally precipitated with cold acetone and further reacted with methacrylic anhydride as previously described. 41 Briefly, dopamine-modified gelatin was dissolved in DPBS at a concentration of 10% (wt/vol) and heated to 50 C. Next, 8% (vol/vol) methacrylic anhydride was added dropwise to the solution under continuous stirring at 50 C and allowed to react for 3 h. Finally, the reaction was stopped by diluting the reaction mixture with DPBS.…”