journal article·2026-05-11Open access

In Vitro Evaluation of Anti-Inflammatory and Antioxidant Properties of a Novel Calcium Alginate–Zinc Hemostatic Biomaterial

Tanja Lunić, Marija Rakić, Maria Sbeih, Marina Samardzic, Céline des Courtils, Biljana Božić Nedeljković

Abstract

Achieving hemostasis is crucial in neurosurgery, yet conventional methods are not always feasible, making topical hemostatic agents necessary. Current resorbable hemostatic agents allow effective hemostasis but must remain in situ to prevent rebleeding. This can provoke foreign body reactions leading to prolonged microglia-mediated neuroinflammation, which may exacerbate damage and delay recovery. It highlights the need for new hemostatic materials that can be removed after controlling bleeding while being safe for neurons and microglia. One candidate is Hemo-Ionic, a non-resorbable hemostatic compress composed of calcium alginate and zinc (Zn2+). Hemo-Ionic previously demonstrated effective in vitro and in vivo hemostasis, comparable to Surgicel and TachoSil, and pro-repair properties. In this study, Hemo-Ionic’s effect on neuronal and microglial cells was investigated in vitro. Results showed that Hemo-Ionic preserved cell viability and had an antioxidant capacity through protection from lipid peroxidation. Hemo-Ionic also reduced nitric oxide and pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) expression and release by lipopolysaccharide (LPS)-stimulated microglial cells. Finally, neuronal viability was restored when exposed to supernatants of Hemo-Ionic-treated microglia. These findings indicate that Hemo-Ionic’s safety and capacity to reduce neuroinflammation, combined with its hemostatic efficacy and non-resorbable nature, make it a promising alternative to resorbable hemostatic agents used in neurosurgery.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Hemostasis and retained surgical items · Wound Healing and Treatments · Surgical Sutures and Adhesives

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia

Laboratoires Brothier, 92000 Nanterre, France

References (55)

Show source-provided references
1. Place des agents hémostatiques locaux en neurochirurgie: Chirurgie spinale et intracrânienne
2. Topical hemostatic agents in neurosurgery, a comprehensive review: 15 years update10.1007/s10143-021-01684-1 ↗
3. Pinchuk, A., Tonchev, N., Schaufler, A., Dumitru, C.A., Stein, K.-P., Neyazi, B., Sandalcioglu, I.E., and Rashidi, A. (2025). Predictors of Postoperative Bleeding After Cranial Surgery: The Role of Perioperative and Tumor-Related Factors. Curr. Oncol., 33.10.3390/curroncol33010003 ↗
4. Utilisation des agents hémostatiques en neurochirurgie
5. Histological appearance of topical hemostatic agents and materials in neuropathology10.1093/jnen/nlaf032 ↗
6. Straits Research (2026, January 21). Hemostasis & Tissue Sealing Agents Market Size, Growth, Report to 2033: Hemostasis & Tissue Sealing Agents Market Size, Share & Trends Analysis Report by Product (Topical Hemostat, Adhesives & Tissue Sealan) and by Region (North America, Europe, APAC, Middle East and Africa, LATAM) Forecasts, 2025–2033 SRMD1997DR. Available online: https://straitsresearch.com/report/hemostasis-and-tissue-sealing-agents-market.
7. Grand View Research (2026, January 21). Hemostasis and Tissue Sealing Agents Market (2025–2030): Size, Share & Trends Analysis Report by Product (Topical Hemostat, Adhesive & Tissue Sealant), by Material (Gelatin-Based, Collagen-Based, ORC-Based), by Application, by End-Use, by Region, and Segment Forecasts 978-1-68038-597-7. Available online: https://www.grandviewresearch.com/industry-analysis/hemostasis-tissue-sealing-agents-market.
8. Delayed cerebral edema: Possible association with an inflammatory foreign body reaction10.1016/j.inat.2021.101207 ↗
9. Wound healing effect of regenerated oxidized cellulose versus fibrin sealant patch: An in vivo study10.7181/acfs.2019.00472 ↗
10. Brain-derived textiloma post glioblastoma resection and application of oxidized regenerated cellulose: A pilot, bedside-to-bench, translational study10.1111/bpa.13331 ↗
11. Microglia-mediated neuroinflammation in traumatic brain injury: A review10.1007/s11033-024-09995-4 ↗
12. Radiculopathy after lumbar discectomy due to intraspinal retained Surgicel: Clinical and magnetic resonance imaging evaluation10.1016/j.spinee.2005.12.006 ↗
13. Intracranial foreign material granulomas after cranial surgery10.1007/s00701-018-3663-0 ↗
14. Foreign Body Granuloma After Cranial Surgery: A Systematic Review of Reported Cases10.1016/j.wneu.2018.09.143 ↗
15. Hemostatic Thrombin-Gelatin Matrix-Related Intracranial Cyst Formation10.1016/j.wneu.2019.03.030 ↗
16. Two Cases of Cerebral Infarcts Caused by Topical Hemostatic Agent Embolism10.1097/PAF.0000000000000630 ↗
17. Gelatin-thrombin Hemostatic Matrix-related Cyst Formation after Cerebral Hematoma Evacuation: A Report of Two Cases10.2176/nmccrj.cr.2021-0130 ↗
18. A new hemostatic agent composed of Zn2+-enriched Ca2+ alginate activates vascular endothelial cells in vitro and promotes tissue repair in vivo
19. The blood coagulation system as a molecular machine10.1002/bies.10360 ↗
20. Calcium signaling in platelets10.1111/j.1538-7836.2009.03455.x ↗
21. A Comprehensive Review on the Hemostatic Properties of Metal-based Materials and Substances10.1007/s12011-026-04985-y ↗
22. Calcium: A potential central regulator in wound healing in the skin (version originale)10.1046/j.1524-475X.2002.10502.x ↗
23. Extracellular heavy-metal ions stimulate Ca2+ mobilization in hepatocytes10.1042/bj3390555 ↗
24. A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport10.1073/pnas.201193398 ↗
25. Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets10.1007/s11302-005-0777-7 ↗
26. Willi, P., and Chandra, P. (2015). Alginates: Wound Dressings. Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, 11 Volume Set, CRC Press. [1st ed.].
27. Zinc: An important cofactor in haemostasis and thrombosis10.1160/TH12-07-0465 ↗
28. Lisek, M., Tomczak, J., Boczek, T., and Zylinska, L. (2024). Calcium-Associated Proteins in Neuroregeneration. Biomolecules, 14.10.3390/biom14020183 ↗
29. The Impact of Zinc on Cellular Dynamics, Brain Function, and its Therapeutic Potential in Neuronal Regeneration10.1007/s12035-026-05678-2 ↗
30. Díaz-Piña, D.A., Rivera-Ramírez, N., García-López, G., Díaz, N.F., and Molina-Hernández, A. (2024). Calcium and Neural Stem Cell Proliferation. Int. J. Mol. Sci., 25.10.3390/ijms25074073 ↗
31. A review study on the effect of zinc on oxidative stress-related neurological disorders10.1016/j.jtemb.2025.127618 ↗
32. (2002). Test Methods for Primary Wound Dressings—Part 1: Aspects of Absorbency (Standard No. ISO 13726-1:2002).
33. (1992). Textiles—Test Methods for Nonwovens—Part 3: Determination of Tensile Strength and Elongation (Standard No. ISO 29073-3:1992).
34. (2007). Water quality—Determination of Selected Elements by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) (Standard No. ISO 11885:2007).
35. (2021). Biological Evaluation of Medical Devices—Part 12: Sample Preparation and Reference Materials (Standard No. ISO 10993-12:2021).
36. Antioxidant activity of extracts obtained by different isolation procedures from some aromatic herbs grown in Lithuania10.1002/(SICI)1097-0010(199805)77:1<140::AID-JSFA18>3.0.CO;2-K ↗
37. A new method for measuring antioxidant activity10.1042/bst021095s ↗
38. Antioxidant Determinations by the Use of a Stable Free Radical10.1038/1811199a0 ↗
39. Studies on Products of Browning Reaction10.5264/eiyogakuzashi.44.307 ↗
40. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays10.1016/0022-1759(83)90303-4 ↗
41. Analysis of Nitrate, Nitrite, and [15N]Nitrate in Biological Fluids10.1016/0003-2697(82)90118-X ↗
42. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal10.1155/2014/360438 ↗
43. Gandla, K., Babu, A.K., Unnisa, A., Sharma, I., Singh, L.P., Haque, M.A., Dashputre, N.L., Baig, S., Siddiqui, F.A., and Khandaker, M.U. (2023). Carotenoids: Role in Neurodegenerative Diseases Remediation. Brain Sci., 13.10.3390/brainsci13030457 ↗
44. Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children10.1007/s12028-019-00870-w ↗
45. Healing and Preventive Effects of Calcium Alginate on Carbon Tetrachloride Induced Liver Injury in Rats10.3390/md203108 ↗
46. The mechanism of the neuroprotective effect of zinc against cadmium-induced behavioral impairments in male Wister rats: Focus on tryptophan degradation pathway, oxidative-inflammatory stress, and histologic evidence10.1016/j.tox.2022.153191 ↗
47. Effect of Zinc on the Oxidative Stress Biomarkers in the Brain of Nickel-Treated Mice
48. Alterations of extracellular calcium elicit selective modes of cell death and protease activation in SH-SY5Y human neuroblastoma cells10.1046/j.1471-4159.1999.0721853.x ↗
49. In vitro effects of wound-dressings on key wound healing properties of dermal fibroblasts10.1111/exd.15098 ↗
50. Adib, Y., Serror, K., Pinzon, J.A., Duciel, L., Delagrange, M., Ducos, B., Boccara, D., Mimoun, M., Chaouat, M., and Bensussan, A. (2025). In Vitro Modulation of Macrophage Inflammatory and Pro-Repair Properties Essential for Wound Healing by Calcium and Calcium-Alginate Dressings. Cells, 14.10.3390/cells14120909 ↗
51. Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress10.1016/j.freeradbiomed.2011.08.030 ↗
52. Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells10.1016/j.jad.2019.02.041 ↗
53. Zinc-Directed Coordination Network Hydrogels for A20-Mediated Inflammation Modulation and Enhanced Axonal Regeneration in Spinal Cord Injury10.1002/adfm.202422906 ↗
54. A novel calcium alginate hydrogel formulation to enhance monocyte/macrophage anti-inflammatory activity10.1016/j.ijbiomac.2025.141251 ↗
55. Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis10.1016/j.febslet.2014.05.046 ↗