Authors
Lipatov V.A., Obedkov E.G., Ludwig L., Obedkova N.Ju., Nedosekin R.A., Denisov A.A., Andreev P.Ju.
Kursk State Medical University, Kursk
Abstract
Parenchymatous organ injuries affected highly vascularized organs such as liver, spleen or kidneys, become a major challenge in surgical practice, mainly because of tendency to life-threatening bleeding, complex tissue architecture and susceptibility to infections. Using biological polymers as hemostatic agents is important both for stopping bleeding and improving tissue regeneration. Medicines based on such substances are in high demand, they integrated into military medicine, civilian emergency care, surgical interventions and treatment of chronic wounds. Cross-linked chitosan-collagen systems have become a breakthrough solution for hemostasis in parenchymatous organ injuries. In this article we will demonstrate the latest innovations based on interaction of biological polymers such as chitosan and collagen. We will uncover modern processes of their production, purification and transformation, present a full analysis of pharmacodynamic and pharmacokinetic differences between hydrogel and spongy collagen-chitosan systems, compare the preclinical data and clinical studies to understand the use of a specific medical form.
Keywords: hydrogel; chitosan; collagen; bleeding; hemostasis; damage to parenchymatous organs.
References
1. Gao X, Jin Y, Zhang G. Impact of Various Hemostasis Methods on Ovarian Reserve Function in Laparoscopic Cystectomy for Ovarian Endometriomas. Altern Ther Health Med. 2024; 30(8): 312-319.
2. Briete L, Towers W, Bone R, et al. Perioperative anticoagulation management. Crit. Care Nurs. 2022; 45: 119-131. doi: 10.1097/cnq.0000000000000395.
3. Dang NC, Ardehali A, Bruckner BA, et al. Prospective, Multicenter, Randomized, Controlled Trial Evaluating the Performance of a Novel Combination Powder vs. Hemostatic Matrix in Cardiothoracic Operations. J. Card. Surg. 2020; 35: 313-319. doi: 10.1111/jocs.14376.
4. Han W, Wang S. Advances in Hemostatic Hydrogels That Can Adhere to Wet Surfaces. Gels. 2022; 9: 2. doi: 10.3390/gels9010002.
5. Moldovan H, Antoniac I, Gheorghiță D, et al. Biomaterials as Haemostatic Agents in Cardiovascular Surgery: Review of Current Situation and Future Trends. Polymers. 2022; 14: 1189. doi: 10.3390/polym 14061189.
6. Sung YK, Lee DR, Chung DJ. Advances in the development of hemostatic biomaterials for medical application. Biomater Res 2021; 25: 37. doi: 10.1186/s40824-021-00239-1.
7. Barros N, Chen Y, Hosseini V, et al. Recent developments in mussel-inspired materials for biomedical applications. Biomater. Sci. 2021; 9: 6653-6672. doi: 10.1039/d1bm01126j.
8. Biranje S, Madiwale P, Adivarekar R. Nanoscale Chitosan-Based Hemostasis Membrane. J Clin Haematol. 2020; 1(3): 85-89.
9. Huang Y, Feng L, Zhang Y, et al. Hemostasis mechanism and applications of N-alkylated chitosan sponge. Polym. Adv. Technol. 2017; 28: 1107-1114. doi: 10.1002/pat.4003.
10. Biranje S, Madiwale P, Patankar V, et al. Cytotoxicity and hemostatic activity of chitosan/carrageenan composite wound healing dressing for traumatic hemorrhage. Carbohydr. Polym. 2020; 239: 116106. doi: 10. 1016/j.carbpol.2020.116106.
11. Hossein O, Renae LW, Erma JG. Advancements and Challenges in Self-Healing Hydrogels for Wound Care. Gels. 2024; 10(4): 241. doi: 10.3390/ gels10040241.
12. Gheorghiță D, Moldovan H, Robu A, et al. Chitosan-Based Biomaterials for Hemostatic Applications: A Review of Recent Advances. Int J Mol Sci. 2023; 24(13): 10540. doi: 10.3390/ijms241310540.
13. Hu Z, Zhang DY, Lu ST, et al. Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Mar Drugs. 2018; 16(8): 273. doi: 10.3390/md16080273.
14. Azmana M, Mahmood S, Hilles R, et al. A review on chitosan and chitosan-based bionanocomposites: Promising material for combatting global issues and its applications. Int. J. Biol. Macromol. 2021; 185: 832-848. doi: 10.1016/j.ijbiomac.2021.07.023.
15. Ardean C, Davidescu C, Neme S, et al. Factors influencing the antibacterial activity of chitosan and chitosan modified by functionalization. Int. J. Mol. Sci. 2021; 22: 7449. doi: 10.3390/ijms22147449.
16. Che X, Zhao T, Hu J, et al. Application of Chitosan-Based Hydrogel in Promoting Wound Healing: A Review. Polymers (Basel). 2024; 16(3): 344. doi: 10.3390/polym16030344.
17. Pablos JL, Lozano D, Manzano M, et al. Regenerative medicine: Hydrogels and mesoporous silica nanoparticles. Materials Today Bio. 2024; 29: 101342. doi: 10.1016/j.mtbio.2024.101342.
18. Spahn D, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care 2019; 23: 98. doi: 10.1186/s13054-019- 2347-3.
19. Minervini G, Franco R, Marrapodi M, et al. The effectiveness of chitosan as a hemostatic in dentistry in patients with antiplatelet/anticoagulant therapy: systematic review with meta-analysis. BMC Oral Health. 2024; 24: 70. doi: 10.1186/s12903-023-03568-w.
20. Khan M, Mujahid M. A review on recent advances in chitosan based composite for hemostatic dressings. International Journal of Biological Macromolecules. 2019; 1(124): 138-147.
21. Hongyan W, Lin S, Zhongxu Z, et al. Fructose-Modified Chitosan/Gelatin 3D Composite Sponge for Enhanced Rapid Hemostasis. Biomacromolecules. 2025; 26(2): 1283-1293.
22. Lijun L, Rui J, Lei Y, et al. Hemostasis Strategies and Recent Advances in Hydrogels for Managing Uncontrolled Hemorrhage. ACS Applied Bio Materials. 2025; 8(1): 42-61.
23. Sajjad F, William A, Mark F, et al. External Bleeding and Advanced Biomacromolecules for Hemostasis. Biomacromolecules 2024; 25(11): 6936-6966. doi: 10.1021/acs.biomac.4c00952.
24. Xiaoyan S, Siyuan Y, Junxia D, et al. An Organic–Inorganic Hybrid Hydrogel Based on Chitosan for Effective Hemostasis. ACS Applied Polymer Materials. 2024; 6(14): 8523-8534. doi: 10.1021/acsapm.4c01278.
25. Yan Z, Rongzhan F, Chenhui Z, et al. Preparation of recombinant type I collagen (PF-I-80) and its functional characterization and biomedical applications in wound healing. International Journal of Biological Macromolecules. 2024; 282: 136679. doi: 10.1016/j.ijbiomac.2024.136679.
26. Lipatov VA, Lazarenko SV, Severinov DA, et al. Evaluation of the Hemostatic Activity of Multicomponent Polymer Sponge Implants in An In Vitro Experiment. Zhurnal im. N.V. Sklifosovskogo Neotlozhnaja medicinskaja pomoshh’. 2024; 13(2): 241-246. (In Russ.)
27. Cao J, Xiao L, Shi X. Injectable drug-loaded polysaccharide hybrid hydrogels for hemostasis. RSC Adv. 2019; 9: 36858-36866. doi: 10.1039/c9ra07116d.
28. Biranje S, Madiwale P, Patankar V, et al. Hemostasis and antinecrotic activity of wound-healing dressing containing chitosan nanoparticles. International Journal оf Biological Macromolecules. 2019; 1(121): 936-946.
29. Pan Y, Wang X, He Q, et al. Efficacy and safety of gastroscopic hemostasis in the treatment of acute gastric hemorrhage: A meta-analysis. World J Gastrointest Oncol. 2023; 15(11): 1988-1997. doi: 10.4251/wjgo.v15.i11.1988.
30. Shah A, Palmer AJR, Klein AA. Strategies to Minimize Intraoperative Blood Loss during Major Surgery. Br. J. Surg. 2020; 107: 26-38. doi: 10.1002/bjs.11393.
31. Xiao Y, Xiaoqin S, Luqi P, et al. Double-network structure sponge with enhanced mechanical properties, procoagulant potential, and 3D printability for acute hemorrhage. Chemical Engineering Journal. 2024; 487: 150608. 10. 1016/j.cej.2024.150608.
32. Hu S, Bi S, Yan D, et al. Preparation of composite hydroxybutyl chitosan sponge and its role in promoting wound healing. Carbohydr. Res. 2018; 184: 154-163. doi: 10.1016/j.carbpol.2017.12.033.
33. Wei W, Ma Y, Yao X, et al. Advanced hydrogels for the repair of cartilage defects and regeneration. Bioact Mater. 2020; 6(4): 998-1011. doi: 10.1016/j.bioactmat.2020.09.030.
34. Malik A, Rehman F. Hemostatic strategies for uncontrolled bleeding: A comprehensive update. J. Biomed. Mater. Res. Part B Appl. Biomater. 2021; 109: 1465-1477.
35. Moeinzadeh S, Park Y, Lin, S, et al. In-situ stable injectable collagen-based hydrogels for cell and growth factor delivery. Materialia. 2020; 15: 100954.
36. Ding C, Tian M, Feng R, et al. Novel Self-Healing Hydrogel with Injectable, pH-Responsive, Strain-Sensitive, Promoting Wound-Healing, and Hemostatic Properties Based on Collagen and Chitosan. ACS Biomater Sci Eng. 2020; 6(7): 3855-3867. doi: 10.1021/acsbiomaterials.0c00588.
37. Gabriel O, Sorinel M, Florin A, et al. Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review. International Journal of Molecular Sciences. 2024; 25(7): 3849. doi: 10.3390/ijms25073849.
38. Xianghao Z, Yao X, Xiaoping C, et al. Engineering collagen-based biomaterials for cardiovascular medicine. Collagen and Leathe. 2024; 6(1): 33. doi: 10.1186/s42825-024-00174-6.
39. Aiqin L, Bin M, Shiyao H, et al. Chitosan-based injectable hydrogel with multifunction for wound healing: A critical review. Carbohydrate Polymers. 2024; 333: 121952. doi: 10.1016/j. carbpol.2024.121952.
40. Shuangqing W, Yanhong L, Xusheng W, et al. Modulating macrophage phenotype for accelerated wound healing with chlorogenic acid-loaded nanocomposite hydrogel. Journal of Controlled Release. 2024; 369: 420-443. doi: 10.1016/j.jconrel.2024.03.054.
41. Anna F, Marziye G, Hamidreza M, et al. Thermoresponsive in situ forming and self-healing double- network hydrogels as injectable dressings for silymarin/levofloxacin delivery for treatment of third-degree burn wounds. Carbohydrate Polymers. 2024; 331: 121856. doi: 10.1016/j.carbpol.2024.121856.
42. Wang X, Song R, Johnson M, et al. An Injectable Chitosan-Based Self-Healable Hydrogel System as an Antibacterial Wound Dressing. Materials (Basel). 2021; 14(20): 5956. doi: 10.3390/ma14205956.


