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Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications
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Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications

A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 11395

Special Issue Editors

Dr. Camelia Elena Iurciuc-Tincu

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Guest Editor
Department of Natural and Synthetic Polymers, “Cristofor Simioescu” Faculty of Chemical Engineering and Protection of the Environment, “Gheorghe Asachi” Technical University, 700050 Iasi, Romania
Interests: biomaterials; hydrogels; drug delivery; bioactive compounds; polymeric nanoparticles; active targeting of drugs; modification of biopolymers
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Lacramioara Ochiuz

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Guest Editor
Department of Pharmaceutical Sciences, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania
Interests: cutaneous drug delivery; oral modified drug delivery systems; matrix solid dosage forms; nanoparticles as drug delivery systems; cosmetics and dermatocosmetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue, “Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications”, analyzes the latest advancements in the design, synthesis, and application of hydrogels derived from biopolymers. These natural polymers, which include polysaccharides and proteins, are becoming increasingly important in the biomedical field. Hydrogels are three-dimensional polymeric networks that can absorb substantial quantities of water or biological fluids and are obtained by the chemical or physical cross-linking of the polymer chains. Due to their high water content, porosity, and soft texture, they simulate natural living tissue, making them a top choice among synthetic materials. Their growing popularity is attributed mainly to their biocompatibility, biodegradability, and their ability to tailor their properties for specific uses, making them a compelling choice for a wide range of applications.

Various types of hydrogels are available for biomedical applications, including pH-sensitive hydrogels, thermogels, electro-sensitive hydrogels, and light-sensitive hydrogels, which could be used in the field of drug delivery or regenerative medicine.

A multidisciplinary approach is necessary to better understand the properties of these biomaterials that are based on hydrogels and are used in biomedical applications, as well as understanding their interactions with cells and biological tissues. This approach can cover various topics such as synthesizing biopolymer-based hydrogels, hydrogel structure, interactions of macromolecules with biological tissue, properties of biomaterials used for specific biomedical applications such as drug delivery, cell carriers and entrapment, wound management, and tissue engineering. We encourage the submission of both original articles and review articles.

Dr. Camelia Elena Iurciuc-Tincu
Prof. Dr. Lacramioara Ochiuz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Gels is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hydrogels
  • biopolymer
  • sensitive hydrogels
  • functional hydrogels
  • biomaterials
  • synthetic materials
  • drug delivery
  • cell carrier
  • tissue engineering

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Related Special Issue

Published Papers (7 papers)

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Research

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24 pages, 8655 KB  
Article
Response Surface Optimization of Curcumin Oil-Loaded Dual-Crosslinked PVOH/CMC/Gellan Gum Hydrogels with Controlled Release and Anti-Inflammatory Activity
by Suthaphat Kamthai, Ratana Banjerdpongchai, Aree Deenu, Kamonwan Tachai and Patompong Khaw-on
Gels 2026, 12(2), 132; https://doi.org/10.3390/gels12020132 - 2 Feb 2026
Viewed by 624
Abstract
Wound-related inflammatory pain is a major contributor to wound healing success and requires wound-specific therapeutic platforms with minimal systemic adverse effects. This study builds a dual-crosslinked polyvinyl alcohol (PVOH)/carboxymethyl cellulose (CMC)/gellan gum hydrogel system with optimized mechanical strength and sustained anti-inflammatory drug delivery [...] Read more.
Wound-related inflammatory pain is a major contributor to wound healing success and requires wound-specific therapeutic platforms with minimal systemic adverse effects. This study builds a dual-crosslinked polyvinyl alcohol (PVOH)/carboxymethyl cellulose (CMC)/gellan gum hydrogel system with optimized mechanical strength and sustained anti-inflammatory drug delivery by developing predictive mathematical models using response surface methodology with central composite design. The effects of citric acid (5–15% w/w) and dialdehyde carboxymethyl cellulose (DCMC, 0.0125–0.0375% w/w) on mechanical properties were systematically evaluated. The optimal formulation (2.23 g low-acyl gellan gum, 1.00 g high-acyl gellan gum, 0.02% DCMC, 10.21% citric acid) achieved firmness of 1.27 ± 0.06 N, rupture strength of 24.24 ± 0.52 N, and compressive strength of 41.91 ± 0.62 kPa. Curcumin oil incorporation yielded 82% cumulative release over 360 min following Korsmeyer–Peppas kinetics (R2 = 0.9887, n = 0.8773). Cell viability exceeded 70% throughout the release period, confirming biocompatibility. The hydrogel strongly inhibited reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages (p < 0.001) and enhanced macrophage migration, increasing wound closure from 40–80% (p < 0.001). This dual-crosslinked hydrogel shows great potential for localized inflammatory pain relief. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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31 pages, 6033 KB  
Article
Synergistic and Intelligent Hydrogel for Conducting Osteoblast Proliferation: Synthesis, Characterization, and Multifunctional Properties
by Karen Michelle Guillén-Carvajal, Benjamín Valdez-Salas, Ernesto Alonso Beltrán-Partida, Jorge Salomón Salvador-Carlos, Mario Alberto Curiel-Álvarez, Jhonathan Castillo-Saenz, Daniel González-Mendoza and Nelson Cheng
Gels 2025, 11(11), 910; https://doi.org/10.3390/gels11110910 - 14 Nov 2025
Viewed by 885
Abstract
Current trends in intelligent hydrogels design for tissue engineering demand multifunctional biomaterials that respond to external stimuli, while maintaining adhesion, controlled degradation, and cytocompatibility. The present work describes the synthesis and characterization of a novel, intelligent and synergistic hydrogel for promoting osteoblastic growth [...] Read more.
Current trends in intelligent hydrogels design for tissue engineering demand multifunctional biomaterials that respond to external stimuli, while maintaining adhesion, controlled degradation, and cytocompatibility. The present work describes the synthesis and characterization of a novel, intelligent and synergistic hydrogel for promoting osteoblastic growth and regeneration. The hydrogel comprises a complex matrix blend of natural biodegradable polymers, vitamins (A, K2, D3, and E), and bioactive components such as zinc phosphate nanoparticles and manganese-doped hydroxyapatite to improve osteoblastic functionality. The hydrogel proved to have physicochemical properties for recovery and self-healing, highlighting its potential application as an auxiliary in bone rehabilitation. Key parameters such as rheological behavior, moisture content, water absorption, solubility, swelling, biodegradability, and responsiveness to temperature and pH variations were thoroughly evaluated. Furthermore, its adhesion to different surfaces and biocompatibility were confirmed. Skin contact test revealed no inflammatory, allergic, or secondary effects, indicating its safety for medical applications. Importantly, the hydrogel showed high biocompatibility with no cytotoxicity signs, favoring cell migration and highlighting its potential for applications in regenerative medicine. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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17 pages, 3324 KB  
Article
Silica Nanoparticle-Reinforced Bioactive Oxidized Alginate/Polyacrylamide–Gelatin Interpenetrating Polymer Network Composite Hydrogels
by Yanan Bu, Jiayi Liu, Jiji Fan, Xiuqiong Chen, Huiqiong Yan and Qiang Lin
Gels 2025, 11(9), 748; https://doi.org/10.3390/gels11090748 - 17 Sep 2025
Cited by 3 | Viewed by 1291
Abstract
Alginate hydrogels are promising tissue engineering biomaterials due to their biocompatibility and structural similarity to the extracellular matrix, but their poor mechanical strength, rapid degradation, and lack of bioactivity limit applications. To address this, a novel oxidized alginate/polyacrylamide/silica nanoparticle–gelatin (OA/PAAm/SiO2-GT) composite [...] Read more.
Alginate hydrogels are promising tissue engineering biomaterials due to their biocompatibility and structural similarity to the extracellular matrix, but their poor mechanical strength, rapid degradation, and lack of bioactivity limit applications. To address this, a novel oxidized alginate/polyacrylamide/silica nanoparticle–gelatin (OA/PAAm/SiO2-GT) composite hydrogel was developed using an interpenetrating polymer network (IPN) strategy, reinforced with silica nanoparticles and coated with gelatin. The influence of SiO2 content on the microstructure, mechanical properties, swelling behavior, biodegradability, biomineralization, and cytocompatibility of the composite hydrogel was systematically investigated. Experimental results revealed that SiO2 nanoparticles interacted with the polymer matrix within the composite hydrogel. With increasing content of SiO2, the porosity of the OA/PAAm/SiO2-GT composite hydrogel gradually decreased, while the mechanical properties exhibited a trend of initial enhancement followed by reduction, with maximum compressive strength at a SiO2 content of 1.0% (w/v). Moreover, the incorporation of SiO2 nanoparticles effectively modulated the swelling behavior, biodegradability, and biomineralization capacity of the composite hydrogel under in vitro conditions. Meanwhile, the OA/PAAm/SiO2-GT composite hydrogel supported favorable cell adhesion and proliferation, optimal at a SiO2 content of 0.5% (w/v). Furthermore, with increasing concentration of SiO2 nanoparticles, the intracellular alkaline phosphatase (ALP) activity progressively increased, suggesting a promotive effect of SiO2 nanoparticles on the osteogenic differentiation of MG63 cells. Therefore, the incorporation of SiO2 nanoparticles into the OA/PAAm IPN matrices provides an effective means to tailor its biological properties, rendering it great potential for biomedical applications such as tissue engineering. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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51 pages, 8996 KB  
Article
Development of an Innovative Nanosystem Based on Functionalized Albumin and Oxidized Gellan for the Synergistic Delivery of Curcumin and Temozolomide in the Treatment of Brain Cancer
by Camelia Elena Iurciuc (Tincu), Gabriela Vochița, Daniela Gherghel, Cosmin-Teodor Mihai, Silvia Vasiliu, Ștefania Racoviță, Anca Niculina Cadinoiu, Corina Lenuța Logigan, Mihaela Hamcerencu, Florin Mitu, Marcel Popa and Lăcrămioara Ochiuz
Gels 2025, 11(9), 708; https://doi.org/10.3390/gels11090708 - 3 Sep 2025
Cited by 2 | Viewed by 1597
Abstract
Treating brain cancer remains challenging due to the blood–brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin [...] Read more.
Treating brain cancer remains challenging due to the blood–brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and 1H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC50 values for co-encapsulated formulations, indicating a synergistic effect. Curcumin’s antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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11 pages, 2908 KB  
Article
On the Conditions Determining the Formation of Self-Crosslinking Chitosan Hydrogels with Carboxylic Acids
by Nils Münstermann and Oliver Weichold
Gels 2025, 11(5), 333; https://doi.org/10.3390/gels11050333 - 29 Apr 2025
Viewed by 1503
Abstract
The formation of self-crosslinking chitosan hydrogels using carboxylic acids has a number of limitations. Chitosan dissolves in oxalic, malonic, and succinic acids at a ratio of 1 amino group to 2 carboxyl groups into viscous solutions (G′ < G′′), but does not dissolve [...] Read more.
The formation of self-crosslinking chitosan hydrogels using carboxylic acids has a number of limitations. Chitosan dissolves in oxalic, malonic, and succinic acids at a ratio of 1 amino group to 2 carboxyl groups into viscous solutions (G′ < G′′), but does not dissolve with lower amounts of the acid. Mixing chitosan hydrochloride with disodium carboxylates does not afford gels, but only a coacervate in the case of disodium oxalate, which dissolves upon dialysis. In the homologous series of N-carboxyalkyl derivatives (alkyl = methyl, ethyl, propyl), all members form gels (G′ > G′′). At approx. 50% of substitution, the storage modulus increases from 40 Pa (methyl) to 30,000 Pa (propyl) indicating the increasing strength of intermolecular interactions with the increasing length of the alkyl spacer. This could indicate that a sufficiently long spacer is required to properly connect the chitosan helices. N-succinyl chitosan, where the spacer is attached to the backbone as an amide, also forms polymer gels across all degrees of N-acylation. When compared to N-carboxypropyl chitosan, the latter forms significantly stiffer gels that swell less. This indicates that one covalent bond, a sufficient length, and the conformational flexibility of the spacer are important for gelation. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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Review

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31 pages, 1677 KB  
Review
Recent Advances in Smart Stimulus-Responsive Hydrogels for Precision Drug Delivery in Tumours
by Huiling Zuo, Yuhang Jiao, Jiaxin Chen, Sen Tong, Yan Li and Wei Zhao
Gels 2026, 12(2), 98; https://doi.org/10.3390/gels12020098 - 23 Jan 2026
Cited by 1 | Viewed by 1905
Abstract
Cancer remains one of the most prominent global health concerns, posing a substantial threat to public health. Millions of people die from cancer each year, and many cancer types remain incurable at present. Conventional cancer treatments, including surgery, chemotherapy, radiotherapy, and immunotherapy, often [...] Read more.
Cancer remains one of the most prominent global health concerns, posing a substantial threat to public health. Millions of people die from cancer each year, and many cancer types remain incurable at present. Conventional cancer treatments, including surgery, chemotherapy, radiotherapy, and immunotherapy, often fail to achieve optimal clinical outcomes and are frequently associated with severe trauma and adverse effects. Consequently, there is an urgent need to develop novel therapeutic strategies to address these limitations. Hydrogels have been widely utilised as platforms for loading drugs, proteins, DNA, and stem cells in biomedical tissue repair and cancer therapy. Through modification of their physicochemical properties and functions, hydrogels can be endowed with responsiveness to multiple stimuli. In recent years, stimuli-responsive hydrogels (also known as smart-responsive hydrogels), as novel drug delivery systems, have demonstrated remarkable efficacy in cancer treatment. Stimuli-responsive hydrogels are capable of altering their mechanical properties, swelling behaviour, hydrophilicity, bioactivity, and molecular permeability in response to endogenous stimuli (including pH, ROS, and temperature) and exogenous stimuli (including light, ultrasound, and magnetic fields). This review highlights recent advances and applications of responsive hydrogels triggered by endogenous stimuli (including pH, ROS, and temperature) and exogenous stimuli (including light, ultrasound, and magnetic force) in cancer drug delivery and treatment. Finally, the current application limitations and future prospects of smart-responsive hydrogels are summarised. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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49 pages, 8174 KB  
Review
Biocompatible Stimuli-Sensitive Natural Hydrogels: Recent Advances in Biomedical Applications
by Jose M. Calderon Moreno, Mariana Chelu and Monica Popa
Gels 2025, 11(12), 993; https://doi.org/10.3390/gels11120993 - 10 Dec 2025
Cited by 12 | Viewed by 2876
Abstract
Biocompatible stimuli-sensitive hydrogels are a versatile and promising class of materials with significant potential for various biomedical applications. These ‘’smart’’ hydrogels can dynamically respond to external environmental stimuli such as pH, temperature, enzymes, or biomolecular interactions, enabling controlled drug release, tissue regeneration, wound [...] Read more.
Biocompatible stimuli-sensitive hydrogels are a versatile and promising class of materials with significant potential for various biomedical applications. These ‘’smart’’ hydrogels can dynamically respond to external environmental stimuli such as pH, temperature, enzymes, or biomolecular interactions, enabling controlled drug release, tissue regeneration, wound healing, and biosensing applications. Hydrogels derived from natural polymers, including chitosan, alginate, collagen, and hyaluronic acid, offer key advantages such as intrinsic biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Their ability to respond to environmental stimuli—including pH, temperature, redox potential, and enzymatic activity—enables control over drug release and tissue regeneration processes. This review explores the fundamental principles governing the design, properties, and mechanisms of responsiveness of natural stimuli-sensitive hydrogels. It also highlights recent advancements in their biomedical applications, discusses existing challenges, and outlines future research directions aimed at improving their functional performance and therapeutic potential for sustainable healthcare solutions. Full article
(This article belongs to the Special Issue Innovative Approaches of Biopolymer-Based Hydrogels: Development, Characterization, and Biomedical Applications)
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