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Gels
Special Issues
Hydrogels: Properties and Application in Biomedicine
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Hydrogels: Properties and Application in Biomedicine

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

Deadline for manuscript submissions: 20 July 2026 | Viewed by 4194

Special Issue Editors

Dr. Martina Lenzuni

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Guest Editor
Institute of Electronics, Computer and Telecommunication Engineering (IEIIT)—National Research Council of Italy (CNR), 16163 Genoa, Italy
Interests: biomaterials; nanotechnology; tissue regeneration; EMF for health; cell–material interactions; stimuli-responsive materials; computational material science; hydrogel
Special Issues, Collections and Topics in MDPI journals
Dr. Salvatore Gallo

E-Mail Website
Guest Editor
Department of Physics “Aldo Pontremoli”, University of Milan, 20133 Milan, Italy
Interests: applied physics; medical physics; dosimetry; material sciences
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hydrogels represent a rapidly evolving class of biomaterials that combine structural versatility with high biocompatibility. Their ability to absorb and retain large amounts of water, mimic the extracellular matrix, and be functionalized with biological or synthetic cues makes them highly attractive for applications in tissue engineering, regenerative medicine, wound healing, drug delivery, and biosensing. The past decade has witnessed remarkable progress in the development of smart hydrogels, including injectable and stimuli-responsive systems, which can interact dynamically with biological environments or be activated by external triggers.

This Special Issue aims to gather cutting-edge research and comprehensive reviews that address both fundamental aspects and translational potential of hydrogels in biomedicine. By bringing together experimental, theoretical, and computational perspectives, we intend to foster interdisciplinary dialogue and highlight innovative strategies for clinical translation.

In this Special Issue, we welcome original research articles and reviews that cover, but are not limited to, the following topics:

  • Design and synthesis of novel hydrogels for tissue engineering applications;
  • Smart hydrogels for controlled drug delivery in regenerative medicine;
  • Stimuli-responsive hydrogels activated by ultrasound, electromagnetic fields, or other external factors;
  • Hydrogels in 3D bioprinting and scaffold development;
  • Injectable hydrogels for regenerative therapies;
  • Mechanistic studies of hydrogel degradation and bio-resorption;
  • Application of hydrogels in wound healing and skin regeneration;
  • Hydrogel-based microenvironments for stem cell differentiation and tissue regeneration;
  • Computational modelling and simulation of hydrogel behaviour in biological environments.

Dr. Martina Lenzuni
Dr. Salvatore Gallo
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
  • biomedical applications
  • stimuli-responsive materials
  • tissue engineering
  • computational modelling

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Published Papers (6 papers)

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Research

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17 pages, 4244 KB  
Article
Ejection Behavior of Commercial Hydrogels with Potential Use for Biomedical Applications via In Situ Bioprinting
by Sirje Liukko, Katarina Dimic-Misic, Milica Marceta Kaninski and Michael Gasik
Gels 2026, 12(5), 401; https://doi.org/10.3390/gels12050401 - 6 May 2026
Viewed by 365
Abstract
For personalized treatments, including soft tissues repair, the use of in situ bioprinting is of increased interest. Many soft tissues, such as sphincters, have poorly known mechanical properties and a complex structure, with limited options for a medical practitioner to assess where the [...] Read more.
For personalized treatments, including soft tissues repair, the use of in situ bioprinting is of increased interest. Many soft tissues, such as sphincters, have poorly known mechanical properties and a complex structure, with limited options for a medical practitioner to assess where the injections should be made and how much should be injected. The rate of injection and its variation have a direct implication on pain sensation for patients, but post-injection efficacy largely depends on the ability of the hydrogel to adapt to local loads and displacements, keeping the 3D structure compliant to the surrounding tissues. Such a method is known as ‘in situ bioprinting’. There are, however, limited data regarding hydrogels’ functionalities for such applications, and many commercial hydrogels, as medical devices, are used off-label. This study aims to introduce an innovative, robust, and reliable approach for evaluating the ejection-related mechanical properties of various commercial hydrogels. The ejectability of six clinically approved hydrogels was assessed through their rheological properties, characterized by measuring apparent viscosity using a mechanical testing device in a novel setup combined with the dynamic syringe pump analysis (for a pre-set constant ejection rate). It was shown that a well-established power-law approximation offers a straightforward, less computationally intensive approach than more complex models that attempt to account for viscosity, shear rate, and wall slip. It assesses hydrogel performance within an actual system, including the syringe and nozzle, rather than just characterizing the material in isolation, thus making it particularly valuable for predicting how gels will behave under real conditions. This method can be adapted for specific clinical bioprinting applications, including sphincter repair, lipoatrophy correction, or deep dermal/transdermal targets, optimizing speed, flow rate, and applied force. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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29 pages, 4674 KB  
Article
3D-Printed Mucoadhesive Hydrogel Buccal Films Based on HPMC and Carbopol Bioinks Incorporating Cyclodextrin–Cannabinoid Complexes and Terpenes
by Anushree Nagaraj and Ali Seyfoddin
Gels 2026, 12(5), 386; https://doi.org/10.3390/gels12050386 - 1 May 2026
Viewed by 675
Abstract
Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based [...] Read more.
Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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17 pages, 21488 KB  
Article
Cellular Crosstalk Within Magnetically Functionalised Hydrogel-Composite Scaffolds for Enhanced Vascularisation and Bone Repair
by Jingyi Xue, Neelam Gurav and Sanjukta Deb
Gels 2026, 12(4), 315; https://doi.org/10.3390/gels12040315 - 7 Apr 2026
Viewed by 585
Abstract
Repairing maxillofacial bone defects remains a major clinical challenge due to inadequate vascularisation and poor integration with host tissue. While bioactive scaffolds have shown promise in supporting osteogenesis and angiogenesis, achieving robust and synchronised dual regenerative outcomes is still elusive. This study presents [...] Read more.
Repairing maxillofacial bone defects remains a major clinical challenge due to inadequate vascularisation and poor integration with host tissue. While bioactive scaffolds have shown promise in supporting osteogenesis and angiogenesis, achieving robust and synchronised dual regenerative outcomes is still elusive. This study presents a multifunctional, cell-free magnetic hydrogel platform designed to biomimetically coordinate osteogenic and angiogenic processes for effective maxillofacial bone regeneration. The composite poly(vinyl alcohol)-vaterite (PVA-Vat) hydrogel scaffold incorporates tuneable magnetic nanoparticles (MNPs) composed of single-domain superparamagnetic iron oxide (Fe3O4). By harnessing magneto-mechanical cues to orchestrate bilateral communication between human bone mesenchymal stem cells and endothelial cells, this platform provides a deeper mechanistic understanding of coupled tissue regeneration and delivers superior dual-regenerative performance for maxillofacial bone repair. Under magnetic stimulation, a coculture system demonstrated strong osteogenesis-angiogenesis coupling mediated by reciprocal VEGFA-BMP2 signalling. This reciprocal crosstalk was evidenced by a synergistic amplification of VEGFA and BMP2 expression in coculture compared to monocultures, where MNP-stimulated osteoprogenitors secreted VEGFA to drive endothelial capillary-like network formation, while endothelial cells reciprocally enhanced endogenous BMP2 levels to accelerate osteoblastic mineralisation. These findings establish MNP-integrated hydrogels as a cell-free, multifunctional platform capable of synchronising dual regenerative pathways, offering a biomimetic strategy to overcome vascularisation and integration barriers in maxillofacial bone repair. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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25 pages, 5358 KB  
Article
Engineering Thermoresponsive In Situ Gels Incorporating Nutraceutical-Laden Nanostructured Lipid Carriers for Controlled Periodontal Drug Release
by Rabia Ashfaq, Anita Kovács, Szilvia Berkó, Gábor Katona, Rita Ambrus, Tamás Ferenc Polgár, Mária Szécsényi, Katalin Burián and Mária Budai-Szűcs
Gels 2026, 12(4), 268; https://doi.org/10.3390/gels12040268 - 24 Mar 2026
Viewed by 637
Abstract
Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers [...] Read more.
Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5–15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol–gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer–Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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18 pages, 3767 KB  
Article
Formulation and 3D Printing of Collagen/Chitosan Inks: Tailoring the Scaffold Properties
by Teresa Carranza, Mireia Andonegui, Raquel Hernáez, Ana Aiastui, Yi Zhang, Koro de la Caba and Pedro Guerrero
Gels 2026, 12(3), 261; https://doi.org/10.3390/gels12030261 - 21 Mar 2026
Viewed by 684
Abstract
The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and [...] Read more.
The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and suitability for cartilage tissue engineering. Rheological analyses revealed that all samples exhibited shear-thinning behavior and solid-like viscoelasticity, with the formulation of an 80:20 COL/CHI ratio (20CHI) demonstrating optimal filament formation and dimensional stability. Physicochemical analyses confirmed the preservation of the collagen triple helix and the formation of hydrogen bonding between chitosan and collagen. 20CHI scaffolds showed swelling capacity and high cohesiveness. In vitro studies confirmed the cytocompatibility of the scaffolds with murine fibroblasts and the ability of the scaffolds to promote adhesion, proliferation, and extracellular matrix production of both chondrocytes and adipogenic mesenchymal stem cells (aMSCs). Quantification of sulfated glycosaminoglycan (sGAG) indicated sustained matrix deposition over 28 days, particularly by chondrocytes. These findings demonstrate that 20CHI hydrogel is a promising candidate for 3D printing of biomimetic scaffolds for cartilage regeneration. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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Review

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23 pages, 3918 KB  
Review
Scoping Review of the Biomedical Investigations of Cellulose Nanocrystal-Based Hydrogels: A Critical Analysis of Current Evidence, Research Gaps and Future Perspectives
by Dinuki M. Seneviratne, Eliza J. Whiteside, Louisa C. E. Windus, Paulomi (Polly) Burey, Raelene Ward and Pratheep K. Annamalai
Gels 2026, 12(3), 207; https://doi.org/10.3390/gels12030207 - 28 Feb 2026
Cited by 1 | Viewed by 718
Abstract
Hydrogel-based products are used in many areas of biomedicine and healthcare. Recently, the incorporation of cellulose nanocrystals (CNC), a renewable and functional nanomaterial, into hydrogels has enhanced their functionality, particularly by imparting mechanical strength and structural integrity. This scoping review aims to appraise [...] Read more.
Hydrogel-based products are used in many areas of biomedicine and healthcare. Recently, the incorporation of cellulose nanocrystals (CNC), a renewable and functional nanomaterial, into hydrogels has enhanced their functionality, particularly by imparting mechanical strength and structural integrity. This scoping review aims to appraise the types of biomedical models and assays that have been utilised to investigate the effects of CNC incorporation into hydrogels in tissue engineering, wound healing, medical implantation and drug delivery applications, and reports on the rationale for including these models and assays. A structured literature search was undertaken in major scientific databases (PubMed Central, PubMed, BioMed Central, ScienceDirect, Wiley and EBSCOhost), focusing on identifying primary research published between 2016 and 2024. From this process, fifteen studies providing biomedical analyses met the inclusion criteria. Most of these investigations employed in vitro cell-line models (n = 12), with a smaller number utilising in vivo experimental systems (n = 5). Across the included studies, CNC incorporation typically yielded measurable performance gains: reported compressive or storage modulus improvements of 20–40% over hydrogel-only controls, consistently high cell viability (>85%) across multiple human and murine cell types for up to 21 days, and sustained drug release profiles (days–weeks) in stent and antitumour contexts. Where quantified, functional outcomes in vivo included preserved graft volume (autologous fat grafts) and reduced intimal hyperplasia signals in vascular graft models. Critical gaps included heterogeneous CNC sources and surface chemistries, inconsistent reporting of CNC concentration and hydrogel formulation parameters, the limited duration and scope of biocompatibility testing, and minimal alignment with standard evaluation protocols, constraining reproducibility and cross-study comparability. To date, there are no human clinical trials of CNC-hydrogels. Translational readiness will require standardised ISO-compliant biocompatibility evaluations. Large-animal studies under relevant mechanical and physiological conditions, and rigorous long-term degradation and immunogenicity assessments to de-risk progression to human trials. We recommend standardised CNC sources and surface functionalisation reporting, concentration (wt%) ranges, hydrogel rheological characterisation (G′, G″, swelling), and consistent biological endpoints (viability, differentiation, inflammation panels) to enable robust meta-analyses and translational benchmarking. Distinct from prior nanocellulose reviews that emphasise material synthesis and properties, this analysis centres on the biomedical models and assays applied to CNC-incorporated hydrogels, identifying the methodological convergence and divergence that directly impact translational pathways. Full article
(This article belongs to the Special Issue Hydrogels: Properties and Application in Biomedicine)
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