Snake venom-based first-aid gel could soon save your life

Significance 

Snake venom is a complex mixture of proteins, enzymes, and other bioactive molecules that are produced by venomous snakes for the purpose of immobilizing and/or killing their prey. Understanding the specific components of different types of venom is important for developing effective therapeutic agents. Indeed, snake venoms have been shown to have some medical benefits. For instance, some snake venoms contain proteins and peptides that can act as painkillers and therefore has the potential to treat chronic pain. Other venom peptides can lower blood pressure by relaxing blood vessels, which can be useful for treating hypertension.

Uncontrolled bleeding, or hemorrhage, is a serious medical emergency that can result in significant morbidity and mortality if not promptly and effectively treated. When blood is lost faster than it can be replaced, the body may go into shock, which can cause organ failure and even death. Uncontrolled bleeding can be caused by a variety of factors, including trauma, surgical complications, and certain medical conditions. In some cases, bleeding may be so severe that it cannot be stopped by conventional means such as pressure or sutures. Existing hemostatic agents act either upstream in the clotting cascade or nonspecifically as tissue glues. Due to their mode of action, these agents are highly prone to failure. The commonly available antifibrinolytic agents like tranexamic acid and aprotinin have been used to solve this problem with minimal success. Another major limitation of these hemostatic agents is that they require a functioning clotting system to control bleeding and do not have antifibrinolytic agent to counter fibrinolysis by plasmin.

To this note, PhD candidate Ramanathan Yegappan, Dr. Jan Lauko, PhD candidate Zhao Wang, Emeritus Professor Martin Lavin, Dr. Amanda Kijas and Professor Alan Rowan from The University of Queensland developed a novel wound sealant comprising two recombinants snake venom proteins: procoagulant ecarin and an antifibrinolytic textilinin. Specifically, a synthetic thermoresponsive hydrogel scaffold was engineered to facilitate the delivery of these recombinant venom proteins to target wound sites. Their work is currently published in the peer-reviewed journal, Advanced Healthcare Materials.

The research team showed that ecarin and textilinin were responsible for rapidly initiating blood clotting and preventing blood clot breakdown, respectively. The authors tested the snake venom hydrogel in vitro using human platelet poor plasma and whole blood tests and showed rapid initiation of clotting and effective inhibition of clot breakdown. Moreover, when they conducted animal studies using a mouse tail amputation model, they demonstrated its immunocompatibility and its ability to rapidly control coagulopathic bleeding. This new class of hemostatic agents could form rapid and stable blood clots even in the presence of blood thinners with no performance degradation.

The venom hydrogels formed stable clot within 60 seconds compared to eight minutes associated with endogenous clotting. The addition of the synthetic polyisocyanopeptide polymer did not affect the clot initiation time but did show some protection of blood clot breakdown in a hypofibrinolytic mimic condition. The snake venom hydrogel could reduce bleed volume from 48% to 12% with excellent immunocompatibility. According to the authors the main advantages of this innovative thermoreversible hydrogel scaffold are its biocompatibility and easy application to irregular wounds and subsequent easy removal. It was worth noting that under heavy bleeding, this hydrogel would require a gauze over dressing to retain its localized condition to achieve adhesion.

In summary, this is the first study to successfully demonstrate the application of two recombinant snake venom proteins as a rapid hemostatic agent for uncontrolled bleeding. The employed thermoresponsive hydrogel functionalization strategy established a technology pipeline for delivering the potent bioactive components to target sites. In a statement to Advances in Engineering, Professor Alan Rowan explained that the presented new approach would contribute to developing the next generation of bleeding control products, exploring alternative delivery scaffolds to meet both clinical needs and function in the extreme austere conditions, such as faced by Military casualties.

About the author

Ramanathan Yegappan completed his Bachelor of Technology (B.Tech) in Genetic Engineering from SRM Institute of Science and Technology, India in 2015 and completed his bachelor’s dissertation in Texas A&M University, US where he developed protein-functionalised hydrogel microparticles for tissue engineering, drug delivery and biosensing applications. He was also a visiting researcher in University of South Australia, Adelaide in 2015-2016. His passion to understand material interface with biology at nano- scale motivated him to complete his Master of Technology (M.Tech) in Nanomedical Sciences from Amrita Centre for Nanosciences and Molecular Medicine, India in 2018 where he was a recipient of scholarship funded by Nanomission, Department of Science and Technology, Government of India. In 2019, he started his PhD in Australian Institute for Bioengineering and Nanotechnology at the University of Queensland under the supervision of Prof. Alan Rowan, Dr. Amanda Kijas and Dr. Jan Lauko.

About the author

Jan received his PhD from the group of Alan Rowan in Nijmegen, the Netherlands, where he was focusing on the design of extended-conjugation supramolecular graphene constructs using click chemistry and macrocyclic sensor probes for mechanistic studies of epoxidation reactions. In 2012 he joined a Dutch Biomedical start-up company NovioSense BV as CTO where he developed the coating and sensor elements as well as the integration of electronics and medical device design for the NovioSense sensor platform. After 4 years at NovioSense, he decided to take up a new challenge and join Prof. Rowan at the University of Queensland to aid him in establishing his new research group and oversee the chemistry and materials science aspects of the development of tailored biomimetic hydrogels.

About the author

Zhao Wang received his Bachelor of Dental Science (BDSc) and Master of Dental Surgery (MDS) degrees from Nanjing Medical University, China in 2013 and 2016, respectively. He obtained Dentist Qualification Certificate in 2013 and registered as a practitioner. His master’s degree focused on multiple genetics and therapeutics in Head and Neck Squamous Cell Carcinoma (HNSCC) supervised by Prof Yunong Wu. He started his PhD in Australian Institute for Bioengineering and Nanotechnology (AIBN) at the University of Queensland supervised by Prof Alan Rowan, Dr Amanda Kijas, and Dr Jan Lauko.

About the author

The major focus of Professor Lavin’s research has been on the importance of DNA damage response in minimising genetic instability and cancer. He has also stablished an international reputation for my work on the human genetic disorder ataxia-telangiectasia. Professor Lavin’s research interests included cancer genetics; neurodegenerative disease; early detection of prostate cancer and evaluation of snake venom proteins with therapeutic potential.

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About the author

Dr Amanda Wraith Kijas is a passionate research scientist working at the interface between material science and biological responses. With a focus on understanding the biophysical drivers of biological responses that synergistically function with the well-known biochemical cues, for application to unmet medical needs. With a major focus on modulating wound healing outcomes through biophysical mediated approaches. Projects range from engineering new biomaterials, to dissecting biophysical modulators underlying biological responses, to more translational projects such as tissue regeneration and the development of innovative new venom driven bleeding control products.

About the author

Professor Alan Rowan is performing his research at the interface of chemistry and biology with seminal and pioneering work on processive catalysis and functional self-assembly. His latest scientific achievement has been the development of the first truly biomimetic hydrogel which mimics the mechanic and functional properties of the extracellular membrane. This recent discovery has further established Professor Rowan as a truly innovative scientist, working toward understanding at the molecular level the functional of hierarchical materials and catalysis. Professor Rowan has published nearly 300 hundred peer-reviewed articles and books (h-index 68), including 18 Science and Nature-family papers, that were cited more than 17,000 times (Google Scholar). His research has also led to several patents, with a variety of commercial applications. He has had the pleasure of supervising more than 55 PhD students who have received their doctoral degree. Professor Rowan is currently an ARC Laureate Fellow, a Fellow of the Australian Academy of Science, Chair of the Scientific Advisory Board for the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and board member of: The UQ Confucius Institute; The Dow Centre for Sustainability; and of UQ Senior Management group.

Reference

Yegappan, R., Lauko, J., Wang, Z., Lavin, M. F., Kijas, A. W., & Rowan, A. E. (2022). Snake Venom Hydrogels as a rapid hemostatic agent for uncontrolled bleeding. Advanced Healthcare Materials, 11(15), 2200574.

Go To Advanced Healthcare Materials

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