The Bleeding Edge: A Narrative Review of Bioengineered Hemostats and Resuscitative Strategies from Point-of-Injury to the Operating Room

Fahad Mohammed Al-Thafir; Mohammed Abdullah Alskhabrah; Mohammed Razqan Matar Almutairi; Mohammed Fahad Bin Zayid; Sultan Ghusayn Aldawsari; Mohammed Mahdi Mufarrah Al-Kubra; Mohammed Abdullah Al Suliman; Mishal Rashid Al Juma; Nasser Saeed Alwuhayyid; Zakaria Mohammed Al Muhaymid; Bader Ridha Alnakhli; Hamad Abdullah Al Faisal

doi:10.64483/202412516

Fahad Mohammed Al-Thafir ⁽¹⁾ , Mohammed Abdullah Alskhabrah ⁽¹⁾ , Mohammed Razqan Matar Almutairi ⁽²⁾ , Mohammed Fahad Bin Zayid ⁽²⁾ , Sultan Ghusayn Aldawsari ⁽¹⁾ , Mohammed Mahdi Mufarrah Al-Kubra ⁽¹⁾ , Mohammed Abdullah Al Suliman ⁽¹⁾ , Mishal Rashid Al Juma ⁽³⁾ , Nasser Saeed Alwuhayyid ⁽³⁾ , Zakaria Mohammed Al Muhaymid ⁽¹⁾ , Bader Ridha Alnakhli ⁽⁴⁾ , Hamad Abdullah Al Faisal ⁽⁵⁾

(1) Al-Aflaj Hospital, Ministry of Health, Saudi Arabia,

(2) King Saud University, Saudi Arabia,

(3) Al-Aflaj General Hospital, Ministry of Health, Saudi Arabia,

(4) Imam Abdulrahman bin Faisal Hospital – Riyadh, Ministry of Health, Saudi Arabia,

(5) Tamir General Hospital – Ministry of Health, Saudi Arabia

https://doi.org/10.64483/202412516

Issue
Vol. 1 No. 2 (2024)

Submitted
January 14, 2026

Published
December 31, 2024

Keywords:

Hemostatic Agent, Trauma Resuscitation, Biomaterials, Damage Control Surgery, Pre-Hospital Care

PDF

Abstract

Background: Uncontrolled hemorrhage remains the leading cause of preventable death in trauma and surgery. The management of severe bleeding is a continuum, spanning the pre-hospital environment, emergency department resuscitation, and definitive surgical control. This review examines the integrated use of hemostatic agents across this timeline, focusing on the engineering principles behind current and future solutions. Aim: This review aims to critically synthesize the evolution, application, and future trajectory of hemostatic agents, from commercially available point-of-injury dressings to emerging bioengineered technologies, analyzing their integration into a cohesive resuscitative strategy from the field to the operating room. Methods: A narrative synthesis was conducted using literature from 2010-2024 sourced from PubMed, EMBASE, Web of Science, and major biomedical engineering journals. Results: Significant disparities exist between the simplified hemostatic needs of pre-hospital care and the complex coagulopathy management in surgery. While kaolin and chitosan-based agents dominate tactical settings, their utility in major vascular or parenchymal surgery is limited. Next-generation bioengineered solutions—including self-propelling foams, injectable hydrogels, and platelet-mimicking polymers—show remarkable pre-clinical promise for bridging this gap by offering active, targeted hemostasis, but face substantial translational hurdles in stability, deployment, and cost. Conclusion: The future of hemorrhage control lies in the development of intelligent, staged hemostatic strategies employing bioengineered materials that function effectively across the care continuum. Success requires close collaboration between materials scientists, EMS providers, and surgeons to meet the divergent yet connected challenges of point-of-injury stabilization and definitive surgical repair.

Full text article

Generated from XML file

References

1. Achneck, H. E., Sileshi, B., Jamiolkowski, R. M., Albala, D. M., Shapiro, M. L., & Lawson, J. H. (2010). A comprehensive review of topical hemostatic agents: efficacy and recommendations for use. Annals of surgery, 251(2), 217-228. DOI: 10.1097/SLA.0b013e3181c3bcca

2. Arnaud, F., Tomori, T., Carr, W., McKeague, A., Teranishi, K., Prusaczyk, K., & McCarron, R. (2008). Exothermic reaction in zeolite hemostatic dressings: QuikClot ACS and ACS+®. Annals of biomedical engineering, 36(10), 1708-1713. https://doi.org/10.1007/s10439-008-9543-7

3. Bennett, B. L. (2017). Bleeding control using hemostatic dressings: lessons learned. Wilderness & environmental medicine, 28(2_suppl), S39-S49. https://doi.org/10.1016/j.wem.2016.12.005

4. Bonanno, F. G. (2022). Management of hemorrhagic shock: physiology approach, timing and strategies. Journal of clinical medicine, 12(1), 260. https://doi.org/10.3390/jcm12010260

5. Butler Jr, F. K., Holcomb, J. B., Shackelford, S. A., Barbabella, S., Bailey, J. A., Baker, J. B., ... & Weber, M. A. (2018). Advanced Resuscitative Care in Tactical Combat Casualty Care: TCCC Guidelines Change 18-01: 14 October 2018. Journal of special operations medicine: a peer reviewed journal for SOF medical professionals, 18(4), 37-55. https://doi.org/10.55460/yjb8-zc0y

6. Cau, M. F., Ali-Mohamad, N., Baylis, J. R., Zenova, V., Khavari, A., Peng, N., ... & Kastrup, C. J. (2022). Percutaneous delivery of self-propelling hemostatic powder for managing non-compressible abdominal hemorrhage: a proof-of-concept study in swine. Injury, 53(5), 1603-1609. https://doi.org/10.1016/j.injury.2022.01.024

7. Chen, Y., Wang, X., Tao, S., Wang, Q., Ma, P. Q., Li, Z. B., ... & Li, D. W. (2023). Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties. Military Medical Research, 10(1), 37. https://doi.org/10.1186/s40779-023-00473-9

8. Dong, R., Zhang, H., & Guo, B. (2022). Emerging hemostatic materials for non-compressible hemorrhage control. National Science Review, 9(11), nwac162. https://doi.org/10.1093/nsr/nwac162

9. Eastridge, B. J., Mabry, R. L., Seguin, P., Cantrell, J., Tops, T., Uribe, P., ... & Holcomb, J. B. (2013). Death on the battlefield (2001Y2011): Implications for the future of combat casualty care: Corrigendum. J Trauma Acute Care Surg, 74(2), 705l706. DOI: 10.1097/01.ta.0000427154.40585.58

10. Granville-Chapman, J., Jacobs, N., & Midwinter, M. J. (2011). Pre-hospital haemostatic dressings: a systematic review. Injury, 42(5), 447-459. https://doi.org/10.1016/j.injury.2010.09.037

11. Hickman, D. A., Pawlowski, C. L., Sekhon, U. D., Marks, J., & Gupta, A. S. (2018). Biomaterials and advanced technologies for hemostatic management of bleeding. Advanced materials, 30(4), 1700859. https://doi.org/10.1002/adma.201700859

12. Holcomb, J. B., Tilley, B. C., Baraniuk, S., Fox, E. E., Wade, C. E., Podbielski, J. M., ... & PROPPR Study Group. (2015). Transfusion of plasma, platelets, and red blood cells in a 1: 1: 1 vs a 1: 1: 2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. Jama, 313(5), 471-482. doi:10.1001/jama.2015.12

13. Jiang, S., Liu, S., Lau, S., & Li, J. (2022). Hemostatic biomaterials to halt non-compressible hemorrhage. Journal of Materials Chemistry B, 10(37), 7239-7259. https://doi.org/10.1039/D2TB00546H

14. Kauvar, D. S., Dubick, M. A., Walters, T. J., & Kragh Jr, J. F. (2018). Systematic review of prehospital tourniquet use in civilian limb trauma. Journal of trauma and acute care surgery, 84(5), 819-825. DOI: 10.1097/TA.0000000000001826

15. Li, X., Duan, L., Kong, M., Wen, X., Guan, F., & Ma, S. (2022). Applications and mechanisms of stimuli-responsive hydrogels in traumatic brain injury. Gels, 8(8), 482. https://doi.org/10.3390/gels8080482

16. Luc, N. F., Rohner, N., Girish, A., Didar Singh Sekhon, U., Neal, M. D., & Sen Gupta, A. (2022). Bioinspired artificial platelets: past, present and future. Platelets, 33(1), 35-47. https://doi.org/10.1080/09537104.2021.1967916

17. Nandi, S., & Brown, A. C. (2016). Platelet-mimetic strategies for modulating the wound environment and inflammatory responses. Experimental Biology and Medicine, 241(10), 1138-1148. https://doi.org/10.1177/1535370216647126

18. Pourshahrestani, S., Zeimaran, E., Kadri, N. A., Mutlu, N., & Boccaccini, A. R. (2020). Polymeric hydrogel systems as emerging biomaterial platforms to enable hemostasis and wound healing. Advanced healthcare materials, 9(20), 2000905. https://doi.org/10.1002/adhm.202000905

19. Pusateri, A. E., Malloy, W. W., Sauer, D., Benov, A., Corley, J. B., Rambharose, S., ... & Weiskopf, R. B. (2022). Use of dried plasma in prehospital and austere environments. Anesthesiology, 136(2), 327-335. DOI: 10.1097/ALN.0000000000004089

20. Pusateri, A. E., Moore, E. E., Moore, H. B., Le, T. D., Guyette, F. X., Chapman, M. P., ... & Sperry, J. L. (2020). Association of prehospital plasma transfusion with survival in trauma patients with hemorrhagic shock when transport times are longer than 20 minutes: a post hoc analysis of the PAMPer and COMBAT clinical trials. JAMA surgery, 155(2), e195085-e195085. doi:10.1001/jamasurg.2019.5085

21. Qasim, Z., Butler, F. K., Holcomb, J. B., Kotora, J. G., Eastridge, B. J., Brohi, K., ... & Duchesne, J. (2022). Selective prehospital advanced resuscitative care–developing a strategy to prevent prehospital deaths from noncompressible torso hemorrhage. Shock, 57(1), 7-14. DOI: 10.1097/SHK.0000000000001816

22. Satterly, S., Nelson, D., Zwintscher, N., Oguntoye, M., Causey, W., Theis, B., ... & Rush Jr, R. M. (2013). Hemostasis in a noncompressible hemorrhage model: an end-user evaluation of hemostatic agents in a proximal arterial injury. Journal of surgical education, 70(2), 206-211. https://doi.org/10.1016/j.jsurg.2012.11.001

23. Schonauer, C., Mastantuoni, C., Somma, T., De Falco, R., Cappabianca, P., & Tessitore, E. (2022). Topical hemostatic agents in neurosurgery, a comprehensive review: 15 years update. Neurosurgical Review, 45(2), 1217-1232. https://doi.org/10.1007/s10143-021-01684-1

24. Shander, A., Hofmann, A., Ozawa, S., Theusinger, O. M., Gombotz, H., & Spahn, D. R. (2010). Activity‐based costs of blood transfusions in surgical patients at four hospitals. Transfusion, 50(4), 753-765. https://doi.org/10.1111/j.1537-2995.2009.02518.x

25. Spotnitz, W. D. (2014). Fibrin sealant: the only approved hemostat, sealant, and adhesive—a laboratory and clinical perspective. International scholarly research notices, 2014(1), 203943. https://doi.org/10.1155/2014/203943

26. Tan, L., Li, M., Chen, H., Zhang, Y., Liu, Y., Chen, M., ... & Hu, Y. (2023). Dynamic hydrogel with environment-adaptive autonomous wound-compressing ability enables rapid hemostasis and inflammation amelioration for hemorrhagic wound healing. Nano Today, 52, 101962. https://doi.org/10.1016/j.nantod.2023.101962

27. Wedmore, I., McManus, J. G., Pusateri, A. E., & Holcomb, J. B. (2006). A special report on the chitosan-based hemostatic dressing: experience in current combat operations. Journal of Trauma and Acute Care Surgery, 60(3), 655-658. DOI: 10.1097/01.ta.0000199392.91772.44

28. Yang, L., Patel, K. D., Rathnam, C., Thangam, R., Hou, Y., Kang, H., & Lee, K. B. (2022). Harnessing the therapeutic potential of extracellular vesicles for biomedical applications using multifunctional magnetic nanomaterials. Small, 18(13), 2104783. https://doi.org/10.1002/smll.202104783

29. Yoon, U., Bartoszko, J., Bezinover, D., Biancofiore, G., Forkin, K. T., Rahman, S., ... & Tinguely, P. (2022). Intraoperative transfusion management, antifibrinolytic therapy, coagulation monitoring and the impact on short‐term outcomes after liver transplantation—a systematic review of the literature and expert panel recommendations. Clinical Transplantation, 36(10), e14637. https://doi.org/10.1111/ctr.14637

30. Zhang, X., Koo, S., Kim, J. H., Huang, X., Kong, N., Zhang, L., ... & Kim, J. S. (2021). Nanoscale materials-based platforms for the treatment of bone-related diseases. Matter, 4(9), 2727-2764. https://doi.org/10.1016/j.matt.2021.05.019

31. Zhu, B., Cheng, W., Zhao, K., Hu, Z., Zhou, F., Zhou, M., ... & Ding, Z. (2023). Multifunctional composite dressings based on Bletilla striata polysaccharide and zeolite for rapid hemostatic and accelerated wound healing. Journal of Materials Science, 58(12), 5427-5443. https://doi.org/10.1007/s10853-023-08306-9