Rapid closure and hemostasis of ruptured soft tissues using a modified human tropoelastin-based sealant in preclinical models.

Abstract

Treatment of injuries to soft elastic organs is often hindered by challenging anatomical features and limitations of existing sealant materials, which may lack adequate tissue adhesion, elasticity, biocompatibility, and effective hemostatic properties. To address these clinical challenges, we developed an injectable elastic sealant formulated with methacryloyl-modified human recombinant tropoelastin (MeTro) and Laponite silicate nanoplatelets (SNs). We optimized the hydrogel formulation for mechanical properties, adhesion, biocompatibility, and hemostatic properties and used visible light for cross-linking to improve safety. MeTro/SN hydrogels had increased tissue adhesion strength and burst pressure in vitro and ex vivo compared with MeTro alone or commercial sealants. The addition of SNs to the hydrogels facilitated faster blood clotting in vitro without increasing hemolysis. Applied to incisional injuries on rat lungs or aortas, MeTro/SN had burst pressures comparable to those of native tissue and greater than those of MeTro after a 7-day in vivo application. On porcine lungs, MeTro/SN also supported effective lung sealing and burst pressure similar to native lung 14 days after injury sealing. In a rodent tail hemostasis model, MeTro/SN reduced bleeding compared with MeTro. In an injured porcine lung model, early hemostasis was better than the tested commercial sealants. The results demonstrated that MeTro/SN provided effective tissue sealing and promoted hemostasis in a time frame that minimized blood loss without causing a major inflammatory response. These findings highlight the translational potential of our engineered sealant with biomimetic mechanics, durable tissue adhesion, and rapid hemostasis as a multipronged approach for the sealing and repair of traumatic injuries to soft organs.