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Gels
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Composite Hydrogels for Biomedical Applications
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Composite Hydrogels for Biomedical Applications

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

Deadline for manuscript submissions: 25 September 2025 | Viewed by 6986

Special Issue Editors

Dr. Marta Slavkova

E-Mail Website
Guest Editor
Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria
Interests: drug delivery; hydrogels; controlled delivery; nanoparticles; lipid based drug delivery systems
Dr. Marieta Constantin

E-Mail Website
Guest Editor
"Petru Poni" Institute of Macromolecular Chemistry, Grigore Ghica Voda Alley 41A, 700487 Iasi, Romania
Interests: amphiphilic cationic polysaccharides; micro- and nanoparticles; natural and synthetic polymers-based hydrogels; composite materials; drug delivery systems

Special Issue Information

Dear Colleagues,

Hydrogels have gained significant scientific attention in tissue engineering and drug delivery processes due to their unique properties. They possess a three-dimensional cross-linked network and the ability to swell in an aqueous medium or physiological fluids. Hydrogels appear to be suitable drug delivery platforms due to their biocompatibility and adaptability. The adequate choice of polymer governs the structure and properties of the hydrogel and can thus provide stimuli responsiveness, tailoring the drug release profiles. Composite hydrogels refer to systems prepared either by a mixture of polymers or hydrogels embedding different nanocarriers. The incorporation of nanocarriers within the hydrogels offers limitless opportunities for the improvement of desired characteristics. The nanoparticles offer a number of advantageous properties, such as a high drug loading, the improvement of bioavailability for drugs with limited aqueous solubility, better targeting and cell internalization, providing stability for problematic substances, etc. Due to their versatile and tunable properties, the composite hydrogels offer the necessary conditions for potential biomedical applications, including drug administration via various routes (oral, dermal, parenteral, ocular, etc.) or other medical disorders (wound healing, chemotherapeutics, tissue engineering, etc.). Nevertheless, we lack thorough understandings of the mechanisms, interactions, and applicability of such composite hydrogel-based drug delivery systems.

Therefore, this Special Issue aims at collecting the most recent scientific progress in the development of composite hydrogels. Original research articles, comprehensive reviews, short communications, and perspectives, with topics addressing—but not limited to—the key findings and contributions on composite hydrogels, including preparation methods, characterization (in vitro and in vivo), and biomedical applications, are welcomed.

Dr. Marta Slavkova
Dr. Marieta Constantin
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 100 words) can be sent to the Editorial Office for announcement on this website.

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
  • drug delivery
  • composite hydrogels
  • gel characterization
  • biomedical application
  • wound healing
  • tissue engineering

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Published Papers (5 papers)

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Research

21 pages, 4941 KiB  
Article
Ophthalmic In Situ Nanocomposite Gel for Delivery of a Hydrophobic Antioxidant
by Marta Slavkova, Christina Voycheva, Teodora Popova, Borislav Tzankov, Diana Tzankova, Ivanka Spassova, Daniela Kovacheva, Denitsa Stefanova, Virginia Tzankova and Krassimira Yoncheva
Gels 2025, 11(2), 105; https://doi.org/10.3390/gels11020105 - 2 Feb 2025
Viewed by 754
Abstract
The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the [...] Read more.
The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the practical use. Applying a composite in situ thermoresponsive hydrogel formulation embedded with polymer nanoparticles is a potent strategy to overcome all the identified drawbacks. In the present work we prepared uniform spherical nanoparticles (296.4 ± 3.1 nm) efficiently loaded with curcumin (EE% 82.5 ± 2.3%) based on the biocompatible and biodegradable poly-(lactic-co-glycolic acid). They were thoroughly physicochemically characterized in terms of FTIR, SEM, TGA, and DLS, in vitro release following Fickian diffusion (45.62 ± 2.37%), and stability over 6 months. Their lack of cytotoxicity was demonstrated in vitro on HaCaT cell lines, and the potential for antioxidant protection was also outlined, starting from concentrations as low as 0.1 µM and reaching 41% protection at 5 µM. An in situ thermoresponsive hydrogel (17% w/v poloxamer 407 and 0.1% Carbopol) with suitable properties for ophthalmic application was optimized with respect to gelation temperature (31.40 ± 0.36 °C), gelling time (8.99 ± 0.28 s) upon tears dilution, and gel erosion (90.75 ± 4.06%). Upon curcumin-loaded nanoparticle embedding, the in situ hydrogels demonstrated appropriate pseudoplastic behavior and viscosity at 35 °C (2129 ± 24 Pa∙s), 6-fold increase in the permeation, and prolonged release over 6 h. Full article
(This article belongs to the Special Issue Composite Hydrogels for Biomedical Applications)
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21 pages, 8687 KiB  
Article
Development and Characterization of Dual-Loaded Niosomal Ion-Sensitive In Situ Gel for Ocular Delivery
by Viliana Gugleva, Rositsa Mihaylova, Katya Kamenova, Dimitrina Zheleva-Dimitrova, Denitsa Stefanova, Virginia Tzankova, Maya Margaritova Zaharieva, Hristo Najdenski, Aleksander Forys, Barbara Trzebicka, Petar D. Petrov and Denitsa Momekova
Gels 2024, 10(12), 816; https://doi.org/10.3390/gels10120816 - 11 Dec 2024
Viewed by 993
Abstract
The study investigates the development and characterization of dual-loaded niosomes incorporated into ion-sensitive in situ gel as a potential drug delivery platform for ophthalmic application. Cannabidiol (CBD) and epigallocatechin-3-gallate (EGCG) simultaneously loaded niosomes were prepared via the thin film hydration (TFH) method followed [...] Read more.
The study investigates the development and characterization of dual-loaded niosomes incorporated into ion-sensitive in situ gel as a potential drug delivery platform for ophthalmic application. Cannabidiol (CBD) and epigallocatechin-3-gallate (EGCG) simultaneously loaded niosomes were prepared via the thin film hydration (TFH) method followed by pulsatile sonication and were subjected to comprehensive physicochemical evaluation. The optimal composition was included in a gellan gum-based in situ gel, and the antimicrobial activity, in vitro toxicity in a suitable corneal epithelial model (HaCaT cell line), and antioxidant potential of the hybrid system were further assessed. Dual-loaded niosomes based on Span 60, Tween 60, and cholesterol (3.5:3.5:3 mol/mol) were characterized by appropriate size (250 nm), high entrapment efficiency values for both compounds (85% for CBD and 50% for EGCG) and sustained release profiles. The developed hybrid in situ gel exhibited suitable rheological characteristics to enhance the residence time on the ocular surface. The conducted microbiological studies reveal superior inhibition of methicillin-resistant Staphylococcus aureus (MRSA) adhesion by means of the niosomal in situ gel compared to the blank gel and untreated control. Regarding the antioxidant potential, the dual loading of CBD and EGCG in niosomes enhances their protective properties, and the inclusion of niosomes in gel form preserves these effects. The obtained outcomes indicate the developed niosomal in situ gel as a promising drug delivery platform in ophthalmology. Full article
(This article belongs to the Special Issue Composite Hydrogels for Biomedical Applications)
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19 pages, 6173 KiB  
Article
Bio-Composite Nanogels Based on Chitosan and Hyaluronic Acid for the Treatment of Lung Infections
by Francesca Della Sala, Marco Barretta, Mario di Gennaro, Rubina Paradiso, Giorgia Borriello and Assunta Borzacchiello
Gels 2024, 10(11), 709; https://doi.org/10.3390/gels10110709 - 1 Nov 2024
Viewed by 1802
Abstract
Pathogen infections constitute a serious problem in the field of lung diseases, especially in severe conditions such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Exacerbations of COPD and ARDS can be significantly influenced by bacterial infections from Pseudomonas [...] Read more.
Pathogen infections constitute a serious problem in the field of lung diseases, especially in severe conditions such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Exacerbations of COPD and ARDS can be significantly influenced by bacterial infections from Pseudomonas aeruginosa and Staphylococcus aureus, which can hasten the decline of lung function. Moreover, the abuse of high-dose antibiotics used to treat obstinate infections is contributing to the growing issue of multidrug resistance (MDR) by microorganisms. Currently, new therapeutic strategies capable of surprising and fighting pathogens with new modalities are missing. In this framework, bio-composite nanogels (NGs) based on natural polymers with intrinsic antimicrobial properties such as chitosan (CS) and hyaluronic acid (HA) have been developed for the treatment of lung infections. The DLS and TEM results showed that NGs have a spherical shape with a size smaller than 100 nm, making it possible for them to potentially reach the lung site and evade the clearance of alveolar macrophages. FTIR spectra demonstrated that only electrostatic interactions, not chemical reactions, occur between NG precursors. Rheological analysis highlighted NGs’ injectability and mucoadhesive capacity. Moreover, an MTT assay on human lung fibroblast cells for biocompatibility evaluation showed good viability up to 48 h. Finally, an antimicrobial test on P. aeruginosa and S. aureus showed an increase in antimicrobial activity as the NG concentration increases, with a reduction in bacterial growth of around 60% at 375 μg/mL. Full article
(This article belongs to the Special Issue Composite Hydrogels for Biomedical Applications)
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13 pages, 3616 KiB  
Article
Double-Network Hydrogel 3D BioPrinting Biocompatible with Fibroblast Cells for Tissue Engineering Applications
by Immacolata Greco, Hatim Machrafi and Carlo S. Iorio
Gels 2024, 10(11), 684; https://doi.org/10.3390/gels10110684 - 23 Oct 2024
Cited by 1 | Viewed by 1436
Abstract
The present study examines the formulation of a biocompatible hydrogel bioink for 3D bioprinting, integrating poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA) using a double-network approach. These materials were chosen for their synergistic qualities, with PEGDA contributing to mechanical integrity and SA [...] Read more.
The present study examines the formulation of a biocompatible hydrogel bioink for 3D bioprinting, integrating poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA) using a double-network approach. These materials were chosen for their synergistic qualities, with PEGDA contributing to mechanical integrity and SA ensuring biocompatibility. Fibroblast cells were included in the bioink and printed with a Reg4Life bioprinter employing micro-extrusion technology. The optimisation of printing parameters included needle size and flow velocities. This led to precise structure development and yielded results with a negligible deviation in printed angles and better control of line widths. The rheological characteristics of the bioink were evaluated, demonstrating appropriate viscosity and shear-thinning behaviour for efficient extrusion. The mechanical characterisation revealed an average compressive modulus of 0.38 MPa, suitable for tissue engineering applications. The printability of the bioink was further confirmed through the evaluations of morphology and diffusion rates, confirming structural integrity. Biocompatibility assessments demonstrated a high cell viability rate of 82.65% following 48 h of incubation, supporting the bioink’s suitability for facilitating cell survival. This study introduced a reliable technique for producing tissue-engineered scaffolds that exhibit outstanding mechanical characteristics and cell viability, highlighting the promise of PEGDA–SA hydrogels in bioprinting applications. Full article
(This article belongs to the Special Issue Composite Hydrogels for Biomedical Applications)
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16 pages, 2277 KiB  
Article
Innovative Approach to Accelerate Wound Healing: Synthesis and Validation of Enzymatically Cross-Linked COL–rGO Biocomposite Hydrogels
by Luisbel González, Víctor Espinoza, Mauricio Tapia, Valentina Aedo, Isleidy Ruiz, Manuel Meléndrez, Claudio Aguayo, Leonard I. Atanase and Katherina Fernández
Gels 2024, 10(7), 448; https://doi.org/10.3390/gels10070448 - 6 Jul 2024
Cited by 5 | Viewed by 1337
Abstract
In this study, an innovative conductive hybrid biomaterial was synthetized using collagen (COL) and reduced graphene oxide (rGO) in order for it to be used as a wound dressing. The hydrogels were plasticized with glycerol and enzymatically cross-linked with horseradish peroxidase (HRP). A [...] Read more.
In this study, an innovative conductive hybrid biomaterial was synthetized using collagen (COL) and reduced graphene oxide (rGO) in order for it to be used as a wound dressing. The hydrogels were plasticized with glycerol and enzymatically cross-linked with horseradish peroxidase (HRP). A successful interaction among the components was demonstrated by FTIR, XRD, and XPS. It was demonstrated that increasing the rGO concentration led to higher conductivity and negative charge density values. Moreover, rGO also improved the stability of hydrogels, which was expressed by a reduction in the biodegradation rate. Furthermore, the hydrogel’s stability against the enzymatic action of collagenase type I was also strengthened by both the enzymatic cross-linking and the polymerization of dopamine. However, their absorption capacity, reaching values of 215 g/g, indicates the high potential of the hydrogels to absorb fluids. The rise of these properties positively influenced the wound closure process, achieving an 84.5% in vitro closure rate after 48 h. These findings clearly demonstrate that these original composite biomaterials can be a viable choice for wound healing purposes. Full article
(This article belongs to the Special Issue Composite Hydrogels for Biomedical Applications)
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