Sealants are useful as agents that can prevent the leakage of gas or nonclotting fluids from damaged tissues and of blood from the vascular system following injury or repair. Various formulations for sealants have been developed and applied clinically, but problems still remain in terms of biocompatibility issues, long crosslinking times and low adhesive properties. Herein, to address these issues, we report a methacrylated silk fibroin sealant (Sil-MAS) with rapidly crosslinkable, highly adhesive and biocompatible properties and demonstrate its versatility as a medical glue. The excellent physical properties of Sil-MAS are revealed via in vitro mechanical tests and ex vivo aorta pressure tests. In addition, in in vivo biological tests on the skin, liver, and blood vessels of rats, Sil-MAS showed a superb hemostatic and adhesive ability, with high biocompatibility. Specifically, Sil-MAS strongly contributed to faster wound healing than commercially available materials. Furthermore, we showed a successful proof of concept that Sil-MAS could serve as an ideal photocuring laparoscopic medical glue in a laceration rabbit model of liver and stomach serosa using a homemade endoscopic device. These findings on the applicability of rapidly photocurable silk fibroin indicate that Sil-MAS is a suitable material to supplant existing sealants, adhesives, or hemostatic agents.
Hemostasis plays an essential role in all surgical procedures. Uncontrolled hemorrhage is the primary cause of death during surgeries, and effective blood loss control can significantly reduce mortality. For modern surgeons to select the right agent at the right time, they must understand the mechanisms of action, the effectiveness, and the possible adverse effects of each agent. Over the past decade, various hemostatic agents have grown intensely. These agents vary from absorbable topical hemostats, including collagen, gelatins, microfibrillar, and regenerated oxidized cellulose, to biologically active topical hemostats such as thrombin, biological adhesives, and other combined agents. Commercially available products have since expanded to include topical hemostats, surgical sealants, and adhesives. Silk is a natural protein consisting of fibroin and sericin. Silk fibroin (SF), derived from silkworm Bombyx mori, is a fibrous protein that has been used mostly in fashion textiles and surgical sutures. Additionally, SF has been widely applied as a potential biomaterial in several biomedical and biotechnological fields. Furthermore, SF has been employed as a hemostatic agent in several studies. In this review, we summarize the several morphologic forms of SF and the latest technological advances on the use of SF-based hemostatic agents.
Among various bioreactors used in the field of tissue engineering and regenerative medicine, a magnetic bioreactor is more capable of providing steady force to the cells while avoiding direct manipulation of the materials. However, most of them are complex and difficult to fabricate, with drawbacks in terms of consistency and biocompatibility. In this study, a magnetic bioreactor system and a magnetic hydrogel were manufactured by single-stage three-dimensional (3D) printing with digital light processing (DLP) technique for differentiation of myoblast cells. The hydrogel was composed of a magnetic part containing iron oxide and glycidyl-methacrylated silk fibroin, and a cellular part printed by adding mouse myoblast cell (C2C12) to gelatin glycidyl methacrylate, that was placed in the magnetic bioreactor system to stimulate the cells in the hydrogel. The composite hydrogel was steadily printed by a one-stage layering technique using a DLP printer. The magnetic bioreactor offered mechanical stretching of the cells in the hydrogel in 3D ways, so that the cellular differentiation could be executed in three dimensions just like the human environment. Cell viability, as well as gene expression using quantitative reverse transcription-polymerase chain reaction, were assessed after magneto-mechanical stimulation of the myoblast cell-embedded hydrogel in the magnetic bioreactor system. Comparison with the control group revealed that the magnetic bioreactor system accelerated differentiation of mouse myoblast cells in the hydrogel and increased myotube diameter and length in vitro . The DLP-printed magnetic bioreactor and the hydrogel were simply manufactured and easy-to-use, providing an efficient environment for applying noninvasive mechanical force via FDA-approved silk fibroin and iron oxide biocomposite hydrogel, to stimulate cells without any evidence of cytotoxicity, demonstrating the potential for application in muscle tissue engineering.