همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Boosting Healing Through Stabilized Fibrin Clot: Structural Bioinformatics Exploration of Collagen’s Potential as a Sustained-Release Carrier for Tranexamic Acid

نویسندگان :

Mohammad Amin Rastegar¹ Sadegh Hasannia² Elnaz Tamjid³

1- دانشگاه تربیت مدرس 2- دانشگاه تربیت مدرس 3- دانشگاه تربیت مدرس

کلمات کلیدی :

Collagen،Tranexamic acid،Sustained-release sysytem،Molecular docking،Structural bioinformatics

چکیده :

The growing demand for efficient and cost-effective strategies in biomedical research highlights the importance of computational tools in optimizing systems before transitioning to experimental settings. These tools significantly reduce the time, costs, and resources spent on trial-and-error approaches in laboratory. Drug delivery systems play a pivotal role in modern medicine, ensuring precise and controlled administration of therapeutics. Among these, sustained release systems, comprising a carrier and a cargo, demand a delicate balance of binding energies to form stable interactions while enabling controlled cleavage for release. Structural bioinformatics has emerged as an indispensable tool in this domain, offering valuable insights into molecular interactions that can guide experimental designs with unparalleled efficiency and accuracy. In this study, we utilized structural bioinformatics to investigate the feasibility of collagen as a matrix for the sustained release of tranexamic acid at a targeted injury. Collagen, a well-known biomaterial with excellent biocompatibility, is widely used in drug delivery systems for its structural stability and adaptability (Zheng and Wang, 2023). Tranexamic acid, an antifibrinolytic agent extensively used in emergency settings via intravenous administration, reduces excessive bleeding by inhibiting fibrin degradation (Colomina and Contreras, 2022). However, localizing its presence through a sustained release system could enhance therapeutic efficacy and reduce systemic side effects (Ausen and Fossmark, 2022). In our work, the localization of tranexamic acid extends beyond its hemostatic application, aiming to leverage its antifibrinolytic properties for enhancing wound healing. By stabilizing the fibrin clot, tranexamic acid prolongs clot presence, creating an ideal natural scaffold for wound repair (Richter and Ku, 2023). The fibrin clot provides a dynamic substrate that binds and releases various growth factors, induces angiogenesis, supports cellular adhesion as a provisional matrix, modulates inflammatory responses, and fulfills its essential hemostatic role (Barbosa and Martins, 2018). This multifaceted bioactivity underscores the significance of designing a sustained release system to harness these benefits. In this context, the 3D molecular structures of collagen (PDB ID: 1BKV) and tranexamic acid (converted to PDB format from SDF using OpenBabel software) were retrieved from the RCSB database (Berman and Westbrook, 2002). Following retrieval, the files underwent further preparation, including the conversion of PDB files into PDBQT format using MGLTools software. Molecular docking was performed using AutoDockTools (Morris and Huey, 2009) with the following parameters: 20 genetic algorithm runs, a maximum of 25,000,000 evaluations, and the output based on the Lamarckian Genetic Algorithm (version 4.2). Blind docking simulations were conducted to evaluate the binding affinities and clustering of docked poses. The results revealed binding energies ranging from -4.37 to -5.20 kcal/mol, with the most abundant cluster at -4.90 kcal/mol, categorized as moderate interactions (Varadwaj and Marques, 2020). These moderate interactions indicate a suitable balance for developing a sustained release system, where stable bonding ensures matrix integrity while enabling controlled release of tranexamic acid. These findings suggest that collagen exhibits a promising binding profile for sustained release applications of tranexamic acid, offering a localized delivery system that stabilizes the fibrin clot and accelerates wound healing by enhancing the natural repair process.