Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation

Silina, Ekaterina Vladimirovna; Manturova, Natalia Evgenievna; Sevastianov, Victor Ivanovich; Perova, Nadezhda Victorovna; Gladchenko, Mikhail Petrovich; Kryukov, Alexey Anatolievich; Ivanov, Aleksandr Victorovich; Dudka, Victor Tarasovich; Prazdnova, Evgeniya Valerievna; Emelyantsev, Sergey Alexandrovich; Kozhukhova, Evgenia Igorevna; Parfenov, Vladimir Anatolievich; Ivanov, Alexander Vladimirovich; Popov, Mikhail Alexandrovich; Stupin, Victor Alexandrovich

doi:10.3390/biomedicines13112623

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation

by

Ekaterina Vladimirovna Silina

^1,*

,

Natalia Evgenievna Manturova

²,

Victor Ivanovich Sevastianov

³

,

Nadezhda Victorovna Perova

³,

Mikhail Petrovich Gladchenko

⁴,

Alexey Anatolievich Kryukov

⁴

,

Aleksandr Victorovich Ivanov

⁴

,

Victor Tarasovich Dudka

⁴,

Evgeniya Valerievna Prazdnova

⁵

,

Sergey Alexandrovich Emelyantsev

⁵

,

Evgenia Igorevna Kozhukhova

⁶,

Vladimir Anatolievich Parfenov

¹,

Alexander Vladimirovich Ivanov

⁷

,

Mikhail Alexandrovich Popov

⁷

and

Victor Alexandrovich Stupin

²

¹

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia

²

Pirogov Russian National Research Medical University, Moscow 117997, Russia

³

Institute of Biomedical Research and Technology, Moscow 123557, Russia

⁴

Kursk State Medical University, Kursk 305041, Russia

⁵

Southern Federal University, Rostov-on-Don 344090, Russia

⁶

National Research Center “Kurchatov Institute”, Moscow 123182, Russia

⁷

Institute of General Pathology and Pathophysiology, Moscow 125315, Russia

^*

Author to whom correspondence should be addressed.

Biomedicines 2025, 13(11), 2623; https://doi.org/10.3390/biomedicines13112623 (registering DOI)

Submission received: 27 August 2025 / Revised: 2 October 2025 / Accepted: 14 October 2025 / Published: 26 October 2025

(This article belongs to the Special Issue Medicinal Chemistry in Drug Design and Discovery, 2nd Edition)

Download Versions Notes

Abstract

Background: Effective regenerative therapeutics for acute and chronic wounds remain a critical unmet need in biomedicine. Objectives: This study aimed to develop novel collagen–cerium oxide nanoparticle hydrogels designed to enhance cellular metabolism, proliferation, and antioxidant/antimutagenic activity, accelerating wound regeneration in vivo. Methods: Collagen–nanocerium composites were synthesized by combining a collagen extract with cerium oxide nanoparticles at defined concentrations. In vitro assays using human fibroblasts identified two formulations that enhanced proliferation and metabolic activity by 42–50%. FTIR spectroscopy confirmed chemical interactions within the composite matrix. Toxicity, antioxidant, and antigenotoxic effects were evaluated using Escherichia coli MG1655 lux-biosensors to assess their general toxicity, antioxidant and pro-oxidant activities, and antigenotoxic and promutagenic effects. In vivo efficacy was tested in Wistar rats with full-thickness skin wounds. Treated groups were compared to untreated controls and Dexpanthenol-treated positive controls. On days 3, 7, and 14, healing was assessed clinically, histologically, and morphometrically. Results: Biosensor analysis demonstrated non-toxicity and antigenotoxic activity of the nanocomposites, reduced DNA damage by up to 45%, providing 31–49% protection against H₂O₂ and 15–23% against O₂⁻ radicals. The animal study results demonstrated significantly accelerated healing with both nanocomposites versus control and comparison groups, evidenced by improved tissue regeneration, reduced inflammation, and increased fibroblast infiltration. Conclusions: The developed hydrogels exhibit promising pharmacological profiles, including antioxidant, antimutagenic, anti-inflammatory, and pro-regenerative effects validated across in vitro and in vivo models.

Keywords: collagen; hydrogel; cerium oxide; nanoparticles; composites; nanocerium; biosensor; wound healing; fibroblasts; leukocytes; rats; antioxidants; regenerative drug

Share and Cite

MDPI and ACS Style

Silina, E.V.; Manturova, N.E.; Sevastianov, V.I.; Perova, N.V.; Gladchenko, M.P.; Kryukov, A.A.; Ivanov, A.V.; Dudka, V.T.; Prazdnova, E.V.; Emelyantsev, S.A.; et al. Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation. Biomedicines 2025, 13, 2623. https://doi.org/10.3390/biomedicines13112623

AMA Style

Silina EV, Manturova NE, Sevastianov VI, Perova NV, Gladchenko MP, Kryukov AA, Ivanov AV, Dudka VT, Prazdnova EV, Emelyantsev SA, et al. Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation. Biomedicines. 2025; 13(11):2623. https://doi.org/10.3390/biomedicines13112623

Chicago/Turabian Style

Silina, Ekaterina Vladimirovna, Natalia Evgenievna Manturova, Victor Ivanovich Sevastianov, Nadezhda Victorovna Perova, Mikhail Petrovich Gladchenko, Alexey Anatolievich Kryukov, Aleksandr Victorovich Ivanov, Victor Tarasovich Dudka, Evgeniya Valerievna Prazdnova, Sergey Alexandrovich Emelyantsev, and et al. 2025. "Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation" Biomedicines 13, no. 11: 2623. https://doi.org/10.3390/biomedicines13112623

APA Style

Silina, E. V., Manturova, N. E., Sevastianov, V. I., Perova, N. V., Gladchenko, M. P., Kryukov, A. A., Ivanov, A. V., Dudka, V. T., Prazdnova, E. V., Emelyantsev, S. A., Kozhukhova, E. I., Parfenov, V. A., Ivanov, A. V., Popov, M. A., & Stupin, V. A. (2025). Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation. Biomedicines, 13(11), 2623. https://doi.org/10.3390/biomedicines13112623

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Development of a Collagen–Cerium Oxide Nanohydrogel for Wound Healing: In Vitro and In Vivo Evaluation

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI