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Peer-reviewedCC BY 4.0Polymers

Ficin-Loaded Quaternized Chitosan Hydrogels: A Functional Biobased Platform for Enhanced Hemostasis

5 affiliations
  1. 1Biophysics and Biotechnology Department, Voronezh State University, 1 Universitetskaya Square, Voronezh 394018, Russia
  2. 2Institute for Advanced Studies, Sevastopol State University, 33 Universitetskaya Street, Sevastopol 299053, Russia
  3. 3Biology Department, Nikolay Nikolaevich Burdenko Voronezh State Medical University, 10 Studencheskaya Street, Voronezh 394036, Russia
  4. 4Laboratory of Structure and Dynamics of Biomolecular Systems, Institute of Cell Biophysics of the Russian Academy of Sciences, 3 Institutskaya Street, Pushchino 142290, Russia
  5. 5Kazan Institute of Biochemistry and Biophysics, Federal Research Center “Kazan Scientific Center of the Russian Academy of Sciences”, 2/31 Lobachevsky Street, Kazan 420111, Russia

Abstract

Biopolymer-based hydrogels are promising platforms for hemostatic applications, yet most chitosan-based materials rely on passive plug formation rather than activation of the natural coagulation cascade. This study aimed to develop hemostatic hydrogels based on quaternized chitosan that activate the coagulation cascade through immobilized ficin. N-(2-Hydroxypropyl)-3-trimethylammonium chitosan (HTCC) with varying degrees of quaternization was synthesized and crosslinked with 1,4-butanediol diglycidyl ether to obtain Cross-HTCC hydrogels. The hydrogels were characterized by FTIR spectroscopy, ζ-potential measurements, and swelling tests. Ficin was immobilized by adsorption, and the effects of pH, contact time, and protein content on immobilization efficiency and proteolytic activity were examined. Ficin release and whole-blood coagulation were also assessed. The hydrogels exhibited ζ-potential values above 30 mV and swelling ratios of up to 28.9-fold. Ficin immobilization was optimal at pH 7.4, with maximum sorption reached after ~180 min. Ficin interacted with heterogeneous sorption sites through hydrogen bonding, electrostatic, and hydrophobic interactions, as confirmed by isotherm fitting, FTIR analysis, and molecular dynamics simulations. The immobilized enzyme was released within 24 h and significantly accelerated blood clotting compared with ficin-free hydrogels. These findings demonstrate that ficin-loaded Cross-HTCC hydrogels combine efficient enzyme loading with enhanced hemostatic performance and hold promise as multifunctional hemostatic materials.

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BibTeX
@article{lavlinskaya2026ficinloaded,
  title = {{Ficin-Loaded Quaternized Chitosan Hydrogels: A Functional Biobased Platform for Enhanced Hemostasis}},
  author = {Maria S. Lavlinskaya and Andrey V. Sorokin and Yulia A. Redko and Victoria A. Koroleva and Maxim S. Kondratyev and Yuriy F. Zuev and Marina G. Holyavka and Valeriy G. Artyukhov},
  journal = {Polymers},
  year = {2026},
  month = oct,
  doi = {10.3390/polym18212679},
  url = {https://www.mdpi.com/2073-4360/18/21/2679},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Ficin-Loaded Quaternized Chitosan Hydrogels: A Functional Biobased Platform for Enhanced Hemostasis
AU  - Maria S. Lavlinskaya
AU  - Andrey V. Sorokin
AU  - Yulia A. Redko
AU  - Victoria A. Koroleva
AU  - Maxim S. Kondratyev
AU  - Yuriy F. Zuev
AU  - Marina G. Holyavka
AU  - Valeriy G. Artyukhov
PY  - 2026
DA  - 2026/10/28
JO  - Polymers
DO  - 10.3390/polym18212679
UR  - https://www.mdpi.com/2073-4360/18/21/2679
AB  - Biopolymer-based hydrogels are promising platforms for hemostatic applications, yet most chitosan-based materials rely on passive plug formation rather than activation of the natural coagulation cascade. This study aimed to develop hemostatic hydrogels based on quaternized chitosan that activate the coagulation cascade through immobilized ficin. N-(2-Hydroxypropyl)-3-trimethylammonium chitosan (HTCC) with varying degrees of quaternization was synthesized and crosslinked with 1,4-butanediol diglycidyl ether to obtain Cross-HTCC hydrogels. The hydrogels were characterized by FTIR spectroscopy, ζ-potential measurements, and swelling tests. Ficin was immobilized by adsorption, and the effects of pH, contact time, and protein content on immobilization efficiency and proteolytic activity were examined. Ficin release and whole-blood coagulation were also assessed. The hydrogels exhibited ζ-potential values above 30 mV and swelling ratios of up to 28.9-fold. Ficin immobilization was optimal at pH 7.4, with maximum sorption reached after ~180 min. Ficin interacted with heterogeneous sorption sites through hydrogen bonding, electrostatic, and hydrophobic interactions, as confirmed by isotherm fitting, FTIR analysis, and molecular dynamics simulations. The immobilized enzyme was released within 24 h and significantly accelerated blood clotting compared with ficin-free hydrogels. These findings demonstrate that ficin-loaded Cross-HTCC hydrogels combine efficient enzyme loading with enhanced hemostatic performance and hold promise as multifunctional hemostatic materials.
SN  - 2073-4360
ER  -