Recent Advances in Hydrogels for Tissue Engineering Applications

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

Deadline for manuscript submissions: 28 February 2026 | Viewed by 4581

Special Issue Editors


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Guest Editor
Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, 57001 Thessaloniki, Greece
Interests: drug delivery systems; nanocarriers; vaccines; mucosal delivery; hydrogels; tissue repair
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Guest Editor
Centre for Research and Technology-Hellas, Thessaloniki, Greece
Interests: hydrogels; cell culture; tissue engineering; drug delivery systems; nanocarriers; vaccines

Special Issue Information

Dear Colleagues,

Tissue engineering (TE) is a promising strategy for tissue repair/regeneration that is based on the combination of three-dimensional (3D) solid scaffolds and/or hydrogels containing biomaterials with biomolecules and cells. Hydrogels are extremely water-swollen, three-dimensional crosslinked networks of synthetic polymers (e.g., polyacrylates, polyethylene glycol) and/or polymers of natural origin (e.g., polysaccharides, collagen, fibrin). Hydrogels exhibit many advantages over solid 3D scaffolds, such as an ability to fine-tune their physicochemical, rheological/mechanical, and biological properties (e.g., gelation kinetics, degree of swelling, stiffness, degradation kinetics) to resemble those of the extracellular matrix (ECM). Furthermore, hydrogels biofunctionalized with cell adhesion peptides and/or other bioactive molecules can increase the adhesion, proliferation, and differentiation of various types of cells (e.g., mesenchymal stem cells, fibroblasts, nerve cells, etc). Finally, hydrogels can be applied in a non-invasive manner in the form of topical injections, allowing for in situ crosslinking, and used as bioinks for 3D bioprinting.

This Special Issue is devoted to state-of-the-art research on polymer-based hydrogels for TE applications and will cover the synthesis of novel macromers, the biofunctionalization of new and/or existing biopolymers, the formation of hydrogels via different crosslinking mechanisms, and the fine-tuning of their physicochemical properties, as well as their in vitro, ex vivo, and in vivo assessment. In addition to original research papers, the Special Issue welcomes critical reviews on the recent advances in biomimetic hydrogels and the challenges that need to be surpassed to advance their clinical translation.

Dr. Olga Kammona
Dr. Evgenia Tsanaktsidou
Guest Editors

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Keywords

  • hydrogels
  • tissue engineering
  • bioink formulations
  • 3D bioprinting
  • cells
  • biomolecules
  • polymers
  • injectable
  • biomimetic
  • stimuli-responsive hydrogels

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Published Papers (3 papers)

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Research

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18 pages, 5421 KB  
Article
Elucidating the Chemistry Behind Thiol-Clickable GelAGE Hydrogels for 3D Culture Applications
by Sara Swank, Peter VanNatta and Melanie Ecker
Gels 2025, 11(11), 874; https://doi.org/10.3390/gels11110874 - 1 Nov 2025
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Abstract
Although covalently crosslinked gelatin hydrogels have been investigated for use in 3D cell culture due to inherent bioactivity and proliferation within the denatured collagen precursor, the stability of the matrix, and relatively inexpensive synthesis, current systems lack precise control over mechanical properties, including [...] Read more.
Although covalently crosslinked gelatin hydrogels have been investigated for use in 3D cell culture due to inherent bioactivity and proliferation within the denatured collagen precursor, the stability of the matrix, and relatively inexpensive synthesis, current systems lack precise control over mechanical properties, including homogeneity, stiffness, and efficient diffusion of nutrients to embedded cells. Difficulties in modifying gel matrix composition and functionalization have limited the use of covalently crosslinked gelatin hydrogels as a three-dimensional (3D) cell culture medium, lacking the ability to tailor the microenvironment for specific cell types. In addition, the currently utilized chain-growth photopolymerization mechanism for crosslinking hydrogels has a potential for side reactions between the matrix backbone and components of the cell surface, requires a high concentration of radicals for initiation, and only cures with long irradiation times, which could lead to cytotoxicity. To overcome these limitations, a superfast curing reaction mechanism, in which a thiol monomer reacts efficiently with non-homopolymerizable alkenes, is suggested. This mechanism reliably produces a well-defined matrix that does not require a high radical concentration for photoinitiation. Mechanical customization of the hydrogel is largely achievable through variation in degree of functionalization of the gelatin backbone, dependent on reaction conditions such as pH, allyl concentration, and time. This work provides a mechanistic framework for GelAGE hydrogel fabrication by elucidating the molecular mechanism of gelatin functionalization with AGE and the thiol-ene crosslinking reactions controlling network stiffness. These insights provide the foundation for engineering hydrogels that mimic the viscoelastic and structural characteristics of cartilage, enabling advanced in vitro models for osteoarthritis research. Full article
(This article belongs to the Special Issue Recent Advances in Hydrogels for Tissue Engineering Applications)
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23 pages, 3604 KB  
Article
Amphiphilic Thermoresponsive Triblock PLA-PEG-PLA and Diblock mPEG-PLA Copolymers for Controlled Deferoxamine Delivery
by Nikolaos D. Bikiaris, Ermioni Malini, Evi Christodoulou, Panagiotis A. Klonos, Apostolos Kyritsis, Apostolos Galaris and Kostas Pantopoulos
Gels 2025, 11(9), 742; https://doi.org/10.3390/gels11090742 - 15 Sep 2025
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Abstract
This study focuses on the synthesis and characterization of thermoresponsive hydrogels of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), PLA–PEG copolymers, aiming at the targeted and controlled release of deferoxamine (DFO), a clinically applied iron-chelating drug. Triblock (PLA-PEG-PLA) and diblock (mPEG-PLA) copolymers were [...] Read more.
This study focuses on the synthesis and characterization of thermoresponsive hydrogels of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), PLA–PEG copolymers, aiming at the targeted and controlled release of deferoxamine (DFO), a clinically applied iron-chelating drug. Triblock (PLA-PEG-PLA) and diblock (mPEG-PLA) copolymers were synthesized using ring-opening polymerization (ROP) with five different PEGs with molecular weights of 1000, 1500, 2000, 4000, and 6000 g/mol and two types of lactide (L-lactide and D-lactide). Emulsions of the polymers in phosphate-buffered saline (PBS) were prepared at concentrations ranging from 10% to 50% w/w to study the sol–gel transition properties of the copolymers. Amongst the synthesized copolymers, only those that demonstrated thermoresponsive sol-to-gel transitions near physiological temperature (37 °C) were selected for further analysis. Structural and molecular confirmation was performed by Nuclear Magnetic Resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR), while the molecular weights were determined via Gel Permeation Chromatography (GPC). The thermal transitions were studied by calorimetry (DSC) and crystallinity via X-ray diffraction (XRD) analysis. DFO-loaded hydrogels were prepared, and their drug release profiles were investigated under simulated physiological conditions (37 °C) for seven days using HPLC analysis. The thermoresponsive characteristics of these systems can offer a promising strategy for injectable drug delivery applications, where micelles serve as drug carriers and undergo in situ gelation, enabling controlled release. This alternative procedure may significantly improve the bioavailability of DFO and enhance patient compliance by addressing key limitations of conventional administration routes. Full article
(This article belongs to the Special Issue Recent Advances in Hydrogels for Tissue Engineering Applications)
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Review

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35 pages, 1038 KB  
Review
Hydrogels in Cardiac Surgery: Versatile Platforms for Tissue Repair, Adhesion Prevention, and Localized Therapeutics
by Seok Beom Hong, Jin-Oh Jeong and Hoon Choi
Gels 2025, 11(7), 564; https://doi.org/10.3390/gels11070564 - 21 Jul 2025
Cited by 3 | Viewed by 3086
Abstract
Hydrogels have emerged as multifunctional biomaterials in cardiac surgery, offering promising solutions for myocardial regeneration, adhesion prevention, valve engineering, and localized drug and gene delivery. Their high water content, biocompatibility, and mechanical tunability enable close emulation of the cardiac extracellular matrix, supporting cellular [...] Read more.
Hydrogels have emerged as multifunctional biomaterials in cardiac surgery, offering promising solutions for myocardial regeneration, adhesion prevention, valve engineering, and localized drug and gene delivery. Their high water content, biocompatibility, and mechanical tunability enable close emulation of the cardiac extracellular matrix, supporting cellular viability and integration under dynamic physiological conditions. In myocardial repair, injectable and patch-forming hydrogels have been shown to be effective in reducing infarct size, promoting angiogenesis, and preserving contractile function. Hydrogel coatings and films have been designed as adhesion barriers to minimize pericardial adhesions after cardiotomy and improve reoperative safety. In heart valve and patch engineering, hydrogels contribute to scaffold design by providing bio-instructive, mechanically resilient, and printable matrices that are compatible with 3D fabrication. Furthermore, hydrogels serve as localized delivery platforms for small molecules, proteins, and nucleic acids, enabling sustained or stimuli-responsive release while minimizing systemic toxicity. Despite these advances, challenges such as mechanical durability, immune compatibility, and translational scalability persist. Ongoing innovations in smart polymer chemistry, hybrid composite design, and patient-specific manufacturing are addressing these limitations. This review aims to provide an integrated perspective on the application of hydrogels in cardiac surgery. The relevant literature was identified through a narrative search of PubMed, Scopus, Web of Science, Embase, and Google Scholar. Taken together, hydrogels offer a uniquely versatile and clinically translatable platform for addressing the multifaceted challenges of cardiac surgery. Hydrogels are poised to redefine clinical strategies in cardiac surgery by enabling tailored, bioresponsive, and functionally integrated therapies. Full article
(This article belongs to the Special Issue Recent Advances in Hydrogels for Tissue Engineering Applications)
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