Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents

• Published in: Scientific reports Vol. 14; no. 1; pp. 19411 - 11
• Main Authors: Casado, Carlos, Cepeda-Franco, Carmen, Pereira Arenas, Sheila, Suarez, Maria Dolores, Gómez-Bravo, Miguel Ángel, Alaminos, Miguel, Chato-Astrain, Jesús, Fernández-Muñoz, Beatriz, Campos-Cuerva, Rafael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4020/4021/288; 692/700/565/545; Animals; Body temperature; Body weight; Cryopreservation; Cryopreservation - methods; Cytotoxicity; Fibrin; Fibrin - chemistry; Fibrin hydrogel; Hematoma; Hemostasis; Hemostasis - drug effects; Hemostatic patch; Hemostatics - chemistry; Hemostatics - pharmacology; Hepatectomy; Hepatectomy - methods; Humanities and Social Sciences; Humans; Hydrogels; Hydrogels - chemistry; Liver resection; Male; multidisciplinary; Nanostructures - chemistry; Rats; Rats, Sprague-Dawley; Safety; Science; Science (multidisciplinary); Sepharose - chemistry; Surgery; TachoSil; Trehalose; Liver resection; Hemostatic patch; Trehalose; Cryopreservation; TachoSil; Fibrin hydrogel
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70456-w

Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.