Skip to main content
Log in

Hemostatic sponge based on easily prepared crosslinked gelatin and sodium alginate for wound healing

  • Materials for life sciences
  • Published:
Journal of Materials Science Aims and scope Submit manuscript

Abstract

Traumatic hemorrhagic shock is an important factor leading to human death; thus, it is very important to develop new hemostatic materials for first aid during traumatic events. In this study, a novel composite hemostatic sponge scaffold (GE/SA) was prepared by Ca2+ crosslinking and freeze-drying using gelatin and sodium alginate. GE, GE/SA1 (1:1), GE/SA2 (1:2), GE/SA3 (1:3), GE/SA4 (1:4) and commercial hemostatic sponge control samples were used to perform hemostasis experiments using a rat liver trauma model and a femoral artery trauma model. In addition, wound healing experiments were conducted using a rat dorsal full-layer skin defect model. Hemostasis time and blood loss values in the GE/SA3 group (liver hemorrhage model: 227.35 ± 3.22 mg, 77.83 ± 4.31 s; femoral artery bleeding model: 494.17 ± 48.66 mg, 76.50 ± 3.94 s) were significantly better than those in the other experimental groups and were similar to those in the commercial sponge group. In addition, in vitro experiments showed that SA promoted the adhesion and aggregation of platelets and red blood cells, which could further enhance hemostasis by activating the clotting process. The results showed that the optimal ratio of gelatin to sodium alginate was 1:3, which provided a theoretical basis for the subsequent construction of a drug delivery system. The gelatin sodium alginate sponge scaffold prepared in this study not only overcame the limitations of simple gelatin hemostatic sponges (such as decreased mechanical properties and poor hemostatic effects after water absorption) but also had excellent properties, such as good biocompatibility, low toxicity, high cost performance and good wound healing. Moreover, this scaffold had wide potential for clinical application.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Data availability

All data that support the findings of this study are included within the article (and any supplementary files).

References

  1. Zhang X, Yao D, Zhao W, Zhang R, Yu B, Ma G, Li Y, Hao D, Xu FJ (2021) Engineering platelet-rich plasma based dual-network hydrogel as a bioactive wound dressing with potential clinical translational value. Adv Funct Mater 31:2009258

    Article  CAS  Google Scholar 

  2. Zheng C, Zeng Q, Pimpi S, Wu W, Han K, Dong K, Lu T (2020) Research status and development potential of composite hemostatic materials. J Mater Chem B 8:5395–5410

    Article  CAS  PubMed  Google Scholar 

  3. Pan Z, Ye H, Wu D (2021) Recent advances on polymeric hydrogels as wound dressings. Apl Bioeng 5:11504

    Article  CAS  Google Scholar 

  4. Guo Y, Wang M, Liu Q, Liu G, Wang S, Li J (2023) Recent advances in the medical applications of hemostatic materials. Theranostics 13:161–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Du J, Wang J, Xu T, Yao H, Yu L, Huang D (2023) hemostasis strategies and recent advances in nanomaterials for hemostasis. Molecules 28(13):5264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Guo Y, Cheng N, Sun H, Hou J, Zhang Y, Wang D, Zhang W, Chen Z (2023) Advances in the development and optimization strategies of the hemostatic biomaterials. Front Bioeng Biotech 10:1062676

    Article  Google Scholar 

  7. Nepal A, Tran H, Nguyen NT, Ta HT (2023) Advances in haemostatic sponges: Characteristics and the underlying mechanisms for rapid haemostasis. Bioact Mater 27:231–256

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Djagny VB, Wang Z, Xu S (2001) Gelatin: a valuable protein for food and pharmaceutical industries: review. Crit Rev Food Sci 41:481–492

    Article  CAS  Google Scholar 

  9. Fan L, Yang H, Yang J, Peng M, Hu J (2016) Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings. Carbohyd Polym 146:427–434

    Article  CAS  Google Scholar 

  10. Leonhardt EE, Kang N, Hamad MA, Wooley KL, Elsabahy M (2019) Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan. Nat Commun 10:1–9

    Article  CAS  Google Scholar 

  11. Chen K, Pan H, Yan Z, Li Y, Ji D, Yun K, Su Y, Liu D, Pan W (2021) A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence. Int J Biol Macromol 182:1339–1350

    Article  CAS  PubMed  Google Scholar 

  12. Wang QQ, Liu Y, Zhang CJ, Zhang C, Zhu P (2019) Alginate/gelatin blended hydrogel fibers cross-linked by Ca(2+) and oxidized starch: Preparation and properties. Mat Sci Eng C-Mater 99:1469–1476

    Article  CAS  Google Scholar 

  13. Varaprasad K, Jayaramudu T, Kanikireddy V, Toro C, Sadiku ER (2020) Alginate-based composite materials for wound dressing application: a mini review. Carbohyd Polym 236:116025

    Article  CAS  Google Scholar 

  14. Pawar SN, Edgar KJ (2012) Alginate derivatization: a review of chemistry, properties and applications. Biomaterials 33:3279–3305

    Article  CAS  PubMed  Google Scholar 

  15. Yuguchi Y, Hasegawa A, Padol AM, Draget KI, Stokke BT (2016) Local structure of Ca(2+) induced hydrogels of alginate-oligoguluronate blends determined by small-angle-X-ray scattering. Carbohyd Polym 152:532–540

    Article  CAS  Google Scholar 

  16. Zhou R, Shi XY, Bi DC, Fang WS, Wei GB, Xu X (2015) Alginate-derived oligosaccharide inhibits neuroinflammation and promotes microglial phagocytosis of beta-amyloid. Mar Drugs 13:5828–5846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang M, Zhao X (2020) Alginate hydrogel dressings for advanced wound management. Int J Biol Macromol 162:1414–1428

    Article  CAS  PubMed  Google Scholar 

  18. Kim JO, Park JK, Kim JH, Jin SG, Yong CS, Li DX, Choi JY, Woo JS, Yoo BK, Lyoo WS (2008) Development of polyvinyl alcohol–sodium alginate gel-matrix-based wound dressing system containing nitrofurazone. Int J Pharmaceut 359:79–86

    Article  CAS  Google Scholar 

  19. Zhang M, Qiao X, Han W, Jiang T, Liu F, Zhao X (2021) Alginate-chitosan oligosaccharide-ZnO composite hydrogel for accelerating wound healing. Carbohyd Polym 266:118100

    Article  CAS  Google Scholar 

  20. Arslan AK, Aydoğdu A, Tolunay T, Basat Ç, Bircan R, Demirbilek M (2023) The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis. J Biomed Mater Res Part B: Appl Biomater 111(6):1299–1308

    Article  CAS  Google Scholar 

  21. Li M, Li H, Li X, Zhu H, Xu Z, Liu L, Ma J, Zhang M (2017) A bioinspired alginate-gum arabic hydrogel with micro-/nanoscale structures for controlled drug release in chronic wound healing. Acs Appl Mater Inter 9:22160–22175

    Article  CAS  Google Scholar 

  22. Zakerikhoob M, Abbasi S, Yousefi G, Mokhtari M, Noorbakhsh MS (2021) Curcumin-incorporated crosslinked sodium alginate-g-poly (N-isopropyl acrylamide) thermo-responsive hydrogel as an in-situ forming injectable dressing for wound healing: In vitro characterization and in vivo evaluation. Carbohyd Polym 271:118434

    Article  CAS  Google Scholar 

  23. Cleetus CM, Alvarez Primo F, Fregoso G, Lalitha Raveendran N, Noveron JC, Spencer CT, Ramana CV, Joddar B (2020) Alginate hydrogels with embedded ZnO nanoparticles for wound healing therapy. Int J Nanomed 15:5097–5111

    Article  CAS  Google Scholar 

  24. Wang M, Chen L, Zhang Z (2021) Potential applications of alginate oligosaccharides for biomedicine–A mini review. Carbohyd Polym 271:118408

    Article  CAS  Google Scholar 

  25. Che C, Liu L, Wang X, Zhang X, Luan S, Yin J, Li X, Shi H (2020) Surface-adaptive and on-demand antibacterial sponge for synergistic rapid hemostasis and wound disinfection. Acs Biomater Sci Eng 6:1776–1786

    Article  CAS  PubMed  Google Scholar 

  26. Zhang X, Dai K, Liu C, Hu H, Luo F, Qi Q, Yang F (2021) Berberine-coated biomimetic composite microspheres for simultaneously hemostatic and antibacterial performance. Polymers 13(3):360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kruk K, Winnicka K (2022) Alginates combined with natural polymers as valuable drug delivery platforms. Mar Drugs 21(1):11

    Article  PubMed  PubMed Central  Google Scholar 

  28. Song Y, Li S, Chen H, Han X, Duns GJ, Dessie W, Tang W, Tan Y, Qin Z, Luo X (2023) Kaolin-loaded carboxymethyl chitosan/sodium alginate composite sponges for rapid hemostasis. Int J Biol Macromol 233:123532

    Article  CAS  PubMed  Google Scholar 

  29. Song X, Liu H, Li Z, Li B, Hou H (2022) Preparation and properties of medical compound hemostasis dressing from Pacific cod skin, South China. Fish Sci 18:66–73

    Google Scholar 

  30. Chiara O, Cimbanassi S, Bellanova G, Chiarugi M, Mingoli A, Olivero G, Ribaldi S, Tugnoli G, Basilico S, Bindi F, Briani L, Renzi F, Chirletti P, Di Grezia G, Martino A, Marzaioli R, Noschese G, Portolani N, Ruscelli P, Zago M, Sgardello S, Stagnitti F, Miniello S (2018) A systematic review on the use of topical hemostats in trauma and emergency surgery. BMC SURG 18:68

    Article  PubMed  PubMed Central  Google Scholar 

  31. Li S, Fan M, Deng S, Tao N (2022) Characterization and application in packaging grease of gelatin–sodium alginate edible films cross-linked by pullulan. Polymers 14(15):3199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hickman DA, Pawlowski CL, Sekhon UD, Marks J, Gupta AS (2018) Biomaterials and advanced technologies for hemostatic management of bleeding. Adv Mater 30(4):1700859

    Article  Google Scholar 

  33. Zou CY, Li QJ, Hu JJ, Song YT, Zhang QY, Nie R, Li-Ling J, Xie HQ (2022) Design of biopolymer-based hemostatic material: starting from molecular structures and forms. Mater Today Bio 17:100468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhou X, Sun J, Wo K, Wei H, Lei H, Zhang J, Lu X, Mei F, Tang Q, Wang Y, Luo Z, Fan L, Chu Y, Chen L (2022) nHA-loaded gelatin/alginate hydrogel with combined physical and bioactive features for maxillofacial bone repair. Carbohyd Polym 298:120127

    Article  CAS  Google Scholar 

  35. Hajiali H, Shahgasempour S, Naimi-Jamal MR, Peirovi H (2011) Electrospun PGA/gelatin nanofibrous scaffolds and their potential application in vascular tissue engineering. Int J Nanomed 6:2133–2141

    Article  CAS  Google Scholar 

  36. Li P, Dou X, Feng C, Schonherr H (2018) Enhanced cell adhesion on a bio-inspired hierarchically structured polyester modified with gelatin-methacrylate. Biomater Sci-UK 6:785–792

    Article  CAS  Google Scholar 

  37. Qiao Y, Liu X, Zhou X, Zhang H, Zhang W, Xiao W, Pan G, Cui W, Santos HA, Shi Q (2020) Gelatin templated polypeptide co-cross-linked hydrogel for bone regeneration. Adv Healthc Mater 9:1901239

    Article  CAS  Google Scholar 

  38. Fischer M, Gebhard F, Hammer T, Zurek C, Meurer G, Marquardt C, Hoefer D (2017) Microbial alginate dressings show improved binding capacity for pathophysiological factors in chronic wounds compared to commercial alginate dressings of marine origin. J Biomater Appl 31:1267–1276

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors would like to express their high appreciation for the financial support received from the National Key R&D Program of China (2022YFC3006200), Natural Science Foundation of China (81901251, 82003992, 82002471), Beijing Natural Science Foundation (7232185) and Peking University People’s Hospital Scientific Research Development Funds (RDJP2023-17, RDJP2023-29, RDX2023-10).

Author information

Authors and Affiliations

Authors

Contributions

JZ: Conceptualization, Methodology, Software, Investigation, Writing— original draft. ML: Investigation, Writing—review & editing. YH: Formal analysis, Methodology, Investigation, Writing- review & editing. CL: Conceptualization, Methodology, Investigation, Writing—review & editing. JC: Conceptualization, Methodology, Investigation, Writing-review & editing. BC: Conceptualization, Methodology, Investigation, Writing-review & editing. CW: Conceptualization, Project administration, Supervision, Writing—review & editing. WG: Conceptualization, Project administration, Supervision, Writing— review & editing. TW: Conceptualization, Project administration, Supervision, Writing—review & editing. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Chuanlin Wang, Wei Guo or Tianbing Wang.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethicl approval

All experimental steps in this research were ethically approved by the Animal Ethics Committee of Peking University People’s Hospital (Approval No: 2021PHE067).

Additional information

Handling Editor: David Ju.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, J., Li, M., Hui, Y. et al. Hemostatic sponge based on easily prepared crosslinked gelatin and sodium alginate for wound healing. J Mater Sci 59, 8408–8426 (2024). https://doi.org/10.1007/s10853-024-09539-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10853-024-09539-y

Navigation