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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.

SUBMITTER: Baghdasarian S

PROVIDER: S-EPMC8741525 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Commercially available surgical sealants for internal use either lack sufficient adhesion or produce cytotoxicity. This work describes a surgical sealant based on a polymer blend of poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) that increases wet tissue adherence by incorporation of nano-to-microscale silica particles, without significantly affecting cell viability, biodegradation rate, or local inflammation. In functional studies, PLGA/PEG/silica composite sealants produce intestinal burst pressures that are comparable to cyanoacrylate glue (160?mmHg), ?2 times greater than the non-composite sealant (59?mmHg), and ?3 times greater than fibrin glue (49?mmHg). The addition of silica to PLGA/PEG is compatible with a sprayable in situ deposition method called solution blow spinning and decreases coagulation time in vitro and in vivo. These improvements are biocompatible and cause minimal additional inflammation, demonstrating the potential of a simple composite design to increase adhesion to wet tissue through physical, noncovalent mechanisms and enable use in procedures requiring simultaneous occlusion and hemostasis. STATEMENT OF SIGNIFICANCE: Incorporating silica particles increases the tissue adhesion of a polymer blend surgical sealant. The particles enable interfacial physical bonding with tissue and enhance the flexibility of the bulk of the sealant, without significantly affecting cytotoxicity, inflammation, or biodegradation. These studies also demonstrate how silica particles decrease blood coagulation time. This surgical sealant improves upon conventional devices because it can be easily deposited with accuracy directly onto the surgical site as a solid polymer fiber mat. The deposition method, solution blow spinning, allows for high loading in the composite fibers, which are sprayed from a polymer blend solution containing suspended silica particles. These findings could easily be translated to other implantable or wearable devices due to the versatility of silica particles.

Project description:The combination of multiple physiological (swelling, porosity, mechanical, and biodegradation) and biological (cell/tissue-adhesive, cell proliferation, and hemostatic) properties on a single hydrogel has great potential for skin tissue engineering. Adhesive hydrogels based on polydopamine (PDA) have become the most popular in the biomedical field; however, integrating multiple properties on a single adhesive hydrogel remains a challenge. Here, inspired by the chemistry of mussels, we developed PDA-sodium alginate-polyacrylamide (PDA-SA-PAM)-based hydrogels with multiple physiological and biological properties for skin tissue engineering applications. The hydrogels were prepared by alkali-induced polymerization of DA followed by complexation with SA in PAM networks. The chemical composition of the hydrogels was characterized by X-ray photoelectron spectroscopy. PDA-SA complexed chains were homogeneously dispersed in the PAM network and exhibited good elasticity and excellent mechanical properties, such as a compressive stress of 0.24 MPa at a compression strain of 70% for 0.4PDA-SA-PAM. The adhesive hydrogel also maintained a highly interconnected porous structure (?94% porosity) along with PDA microfibrils. The hydrogel possesses outstanding swelling and biodegradability properties. Owing to the presence of the PDA-SA complex in the PAM network, the hydrogels show good adhesion to various substrates (plastic, skin, glass, computer screens, and leaves); for example, the adhesive strength of the 0.4PDA-SA-PAM to porcine skin was 24.5 kPa. The adhesive component of the PDA-SA chains in the PAM network significantly improves the cell proliferation, cell attachment, cell spreading, and functional expression of human skin fibroblasts (CCD-986sk) and keratinocytes. Moreover, the PDA chains exhibited good hemostatic properties, resulting in rapid blood coagulation. Considering their excellent cell affinity, and rapid blood coagulation ability, these mussel-inspired hydrogels have substantial potential for skin tissue engineering applications.

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Engineering a naturally derived hemostatic sealant for sealing internal organs.

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