AP26198829 «Development of innovative hemostatic materials with sustained coagulant release»

Relevance

Modern medicine faces significant challenges in achieving effective bleeding control, especially in emergency situations and complex surgical procedures. Current hemostatic materials, such as sponges, often lack extended action and cannot regulate coagulant release, limiting their effectiveness. Addressing this need requires an innovative approach that combines the biocompatibility of the material with controlled release of active components. The primary goal of this project is to develop a biocompatible sponge with controlled release of thrombin and fibrinogen two essential components in the blood coagulation process. This solution aims to enhance bleeding control by providing both immediate action and sustained effectiveness. Our method will involve encapsulating thrombin and fibrinogen in PLGA (poly(lactic-co-glycolic acid)), a strategy that will ensure stability and gradual release, opening new possibilities for more effective hemostatic agents. The project will proceed in phases, beginning with the development of a microencapsulation method that shields thrombin and fibrinogen in a PLGA coating for sustained release. Next, a biocompatible sponge based on chitosan and gelatin will be created, integrating the microcapsules. Special attention will be given to forming a porous structure through lyophilization to enhance the sponge’s adsorption and mechanical properties. Finally, preclinical in vitro and in vivo trials will be conducted to evaluate the sponge’s biocompatibility, efficacy, and safety. The project is expected to result in an innovative medical product: a sponge with controlled release of thrombin and fibrinogen, providing rapid action and long-term effect. The sponge will be beneficial in emergency and routine surgeries, reducing risks from blood loss and improving clinical outcomes. This project will also support the scientific and technological advancement of the Republic of Kazakhstan, contributing to progress in chemistry, biotechnology, biomedicine, and pharmaceutical technology. Strengthening interdisciplinary connections across these fields will create new opportunities for scientific organizations and universities in Kazakhstan, enhancing their global competitiveness. With strong commercialization potential, the project’s outcomes are well-positioned for practical application in healthcare. Upon successful preclinical trials, the developed material can advance to clinical testing, paving the way for commercialization and integration into healthcare settings. This solution will help reduce risks related to blood loss and postoperative complications in cases of severe trauma and surgical procedures. In the long term, this project will contribute significantly to advancing medicine, science, and the economy of Kazakhstan, improving quality of life for its population.

Objective

To develop and investigate a biocompatible hemostatic sponge equipped with a controlled release system for thrombin and fibrinogen, designed to ensure effective and sustained bleeding control across various clinical applications.

Expected results

This project is focused on developing a biocompatible hemostatic sponge composed of chitosan and gelatin, encapsulated with thrombin and fibrinogen, to provide effective and prolonged bleeding control. The project’s primary result will be a sponge with controlled coagulant release, ensuring sustained efficacy and suitability for various bleeding types, including complex wound surfaces. In the second year (2026), an infrared spectrometer will be acquired to enable detailed analysis of the sponge’s physicochemical properties, including material composition, functional groups, and thermal stability. This phase will also include in vitro testing, followed by in vivo preclinical trials to assess biocompatibility and hemostatic effectiveness. Upon successful completion, the project will not only deliver an innovative solution for bleeding control but will also lay the groundwork for future biomaterials research in Kazakhstan. The expected outcomes promise a significant socio-economic impact by raising healthcare standards, improving patient quality of life, and reducing costs associated with treatment and patient care.

Project leader

PhD, Associate Professor Z.S. Akhmetkarimova.

H-index: 4; Scopus ID: 55308246100; ORCID ID: 0000-0002-9782-5521.

Research team members

Master of Biology T.N. Krivoruchko H-index 1; Scopus ID: 57196455275; ORCID ID: 0009-0000-2159-0773

Master of Biotechnology A.M. Zhulikeeva H-index 2; Scopus ID: 57414883300; WoS ID: CJX-0466-2022

 Veterinary Doctor N.V. Dashevskaya.

Publications and intellectual property related to the project

Atepileva А., Ogay V., etc. & Akhmetkarimovа Zh. (2024). Exploring the Antibacterial and Regenerative Properties of a Two-Stage Alginate Wound Dressing in a Rat Model of Purulent Wounds. Biomedicines, 12(9):2122. doi.org/10.3390/biomedicines12092122 CiteScore 2023 – 5.2; Quartile – Q1; Percentile – 85. (Pharmacology and Pharmacy).

Akhmetkarimova Z.S., Kudaibergen G.K.,Kaukabaeva G.K.,Abeldenov S.K., Rysbek A.B. (2023). Thiol-Ene Click Synthesis of Alginate Hydrogels Loaded with Silver Nanoparticles and Cefepime. Eurasian Journal of Chemistry, 110(2), 59-68. doi:10.31489/2959-0663/2-23-14. CiteScore 2022 – 0.5; Quartile – Q4

Toktarov T., Saginov B., Raimagambetov Y., Akhmetkarimova Z, Kudaibergen G,Eskendirova, S, …& Ogay, V. (2022). Heparin-Conjugated Fibrin Hydrogel with Chondroinductive Growth Factors and Human Synovium-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage Defects: Evaluation of Clinical Safety. International Journal of Biomedicine, 12(4), 539-547. doi:10.21103/Article12(4) _OA3. CiteScore 2022 – 0.5; Quartile – Q4

Kudaibergen, G., Akhmetkarimova, Z., Yildirim, E., & Baidarbekov, M. (2023). Thiol-ene clickable gelatin–hyaluronic acid cryogels. Journal of Materials Science, 1-11. doi:10.1007/s10853-023-08693-z. CiteScore 2022 – 7.7; Quartile – Q1; Percentile – 83 (Polymers and Plastics).

Sarsenova, M., Raimagambetov, Y., Issabekova, A., Karzhauov, M., Kudaibergen, G., Akhmetkarimova, Z., … & Ogay, V. (2022). Regeneration of Osteochondral Defects by Combined Delivery of Synovium-Derived Mesenchymal Stem Cells, TGF-β1 and BMP-4 in Heparin-Conjugated Fibrin Hydrogel. Polymers, 14(24), 5343. doi:10.3390/polym14245343. CiteScore 2022 – 6.6; Quartile – Q1; Percentile – 76 (Polymers and Plastics).

Atepileva А., Ogay V., etc. & Akhmetkarimovа Zh.(2024). Exploring the Antibacterial and Regenerative Properties of a Two-Stage Alginate Wound Dressing in a Rat Model of Purulent Wounds. Biomedicines, 12(9):2122. doi.org/10.3390/biomedicines12092122 CiteScore 2023 – 5.2; Quartile – Q1; Percentile – 85. (Pharmacology and Pharmacy).

Achieved results

A biocompatible polymer sponge based on chitosan and gelatin was developed during the study. The PLGA-based polymer matrix and microcapsules were successfully produced using the double-emulsion method, resulting in a stable porous structure with uniform distribution of polymer domains. During material formation, interpolymer interactions including hydrogen bonding and electrostatic contacts were established, enhancing the stability and mechanical integrity of the sponge. The chemical composition and structural characteristics of the obtained material were confirmed by a set of analytical techniques. FT-IR spectroscopy revealed characteristic absorption bands of C=O and C-O functional groups, indicating the presence of PLGA and the polysaccharide component. 1H and 13C NMR spectra confirmed the formation of the polymer matrix and the uniformity of its chemical structure. Scanning electron microscopy demonstrated a well-developed porous morphology suitable for biomedical applications.