Engineering a Highly Adhesive and Hemostatic Sealant for Soft Tissues
The existing surgical adhesives and sealants lack strong adherence to the biological tissues in the wet environment. In addition, demonstrating both inherently high adhesion and hemostatic functionalities in one product, is a scarce characteristic of the developed biomaterials. Moreover, to eliminate the physical and mechanical mismatches with native tissues, high tuning ability is desirable but limited in the current products. As a result, the current solutions fail to either close the wound, or maintain a sufficient sealing ability during wound healing. In this work, a novel and efficient synthetic technique was successfully developed to chemically conjugate catechol motifs to the gelatin backbone. The resulting gelatin-catechol compound was then chemically functionalized with methacryloyl groups to form a highly adhesive and photocrosslinkable sealant, named gelatin methacryloyl-catechol (GelMAC). A two-step crosslinking approach was employed to form the double-networked, and highly tunable GelMAC hydrogel system. First, different concentrations of Fe3+ ions (0, 1, 2.5, 5 and 10 �M) were introduced to the 20 %(w/v) GelMAC prepolymer solution. This step was followed by a second crosslinking mechanism utilizing visible light photopolymerization. GelMAC hydrogel with 2.5 �M Fe3+ ion concentration (GelMAC-Fe) was found to have lower elastic and compressive moduli but demonstrated comparable extensibility to Gelatin-methacryloyl (GelMA) hydrogel incorporating the same Fe3+ ion concentration (GelMA-Fe). Moreover, the wound closure test with porcine skin showed a 1.5-fold higher adhesive strength for GelMAC-Fe compared to GelMA-Fe hydrogels. To study the hemostatic efficacy of GelMAC-Fe hydrogel, the time lapse of blood coagulation across experimental groups was studied in vitro. While the negative control group (untreated blood) formed a blood clot after 16 min, GelMAC hydrogels decreased the clotting time significantly to 9 min. These results were also in close agreement with those obtained for the commercially available hemostatic material, SURGICEL�. Finally, the results of the in vivo liver bleeding model showed that GelMAC-Fe hydrogel was able to rapidly crosslink the incision site and stop the bleeding faster compared to other hydrogels. GelMAC-Fe hydrogel exhibited superior adhesion strength while offering significant hemostatic ability owing to the presence of ferric ions (Fe3+) and the dopamine molecule. This novel, highly biocompatible, tunable, adhesive, and hemostatic sealant can therefore be utilized as an effective solution for controlling bleeding and sealing of soft internal organs such as the lung, heart and blood vessels.