For surgical wounds to be properly closed, the sealant material used must effectively seal on wet, slippery tissue surfaces that vary in shape and may involve tissue movement, such as an expanding lung, or have crumbly textures. The application and effectiveness of the sealant must also occur within a suitable timeframe for surgical procedures. Traditional methods such as suturing and stapling can be ineffective and time-consuming, leading to increased blood loss. Fibrin-based bioadhesive sealants are expensive, exhibit insufficient adhesion, and are susceptible to viral transmission. Although commercial gelatin-based wound dressings offer biocompatibility, low cost, and hemostatic effectiveness, they lack adhesive strength due to inherent brittleness. Previous efforts to improve adhesion through functionalization with catechol, a naturally occurring compound that can provide adhesive capabilities when bound to gelatin, have been made. However, the limited number of binding sites on the gelatin results in a low level of adhesion achievable through catechol functionalization.

Scientists from the Terasaki Institute for Biomedical Innovation (TIBI, Los Angeles, CA, USA) have utilized innovative chemistry to create an injectable biomaterial that has considerably enhanced adhesive strength, stretchability, and toughness. This hydrogel, based on gelatin and modified chemically, has numerous appealing features, including fast gelation at room temperature and customizable levels of adhesion. This specially designed biomaterial is ideal as a surgical wound sealant due to its injectability and controllable adhesion, as well as its superior ability to stick to a range of tissue and organ surfaces.

The researchers utilized caffeic acid (CA), a naturally occurring compound found in coffee and olive oil, to enhance the tissue adhesion properties of gelatin. To achieve this, they first oxidized CA to create CA oligomers (CAO), which consist of a small number of repeating catechol units. By coupling these CA derivatives with gelatin, they were able to significantly improve the chemical binding of catechol groups and enhance their adhesive capabilities. As a result, the engineered bioadhesive sealant exhibits superior adhesive strength, stretchability, toughness, and injectability, and can rapidly gel at the wound site, while maintaining stable adhesion under physiological conditions.

In addition, the sealants were engineered to exhibit selective tissue adhesion. This is crucial for effective sealing, as there must be strong bonding between the sealant and tissue at the interface, while avoiding adhesion on the opposite face of the sealant that is exposed to bodily fluids. Validation tests conducted on wet collagen sheets, as well as burst pressure experiments to assess the limits of adhesive strength, confirmed the efficacy of the new sealant and contradicted previous reports suggesting adverse effects of oxidative chemistry.

The newly developed sealant was put to the test on pig lung, heart, and bladder wounds in laboratory experiments. Results showed that the sealant's adhesive strength was significantly greater than that of commercial gelatin-based sealants. Even after being scraped and twisted experimentally, the sealant remained firmly affixed to the tissue surface. The biocompatibility of the sealant was also confirmed through testing. The sealant exhibited drug loading and drug release capabilities and demonstrated potential for promoting antioxidant effects that can aid in wound healing. This versatile technique can be applied to other biomaterials to impart strong adhesion.

“Our team has utilized manipulative and strategic chemistry to significantly improve adhesive strength and versatility in biomaterials,” said Ali Khademhosseini, TIBI’s Director and CEO. “This creates exciting possibilities for more effective surgical wound management in the clinic.” 

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