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Hydrogel for Tissue Engineering and Biomedical Therapeutics
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Hydrogel for Tissue Engineering and Biomedical Therapeutics

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

Deadline for manuscript submissions: 31 July 2025 | Viewed by 11533

Special Issue Editor

Dr. Hyun Jong Lee

E-Mail Website
Guest Editor
Department of Chemical and Biological Engineering, Gachon University, Seongnam-si, Gyeonggi-do 13120, Republic of Korea
Interests: hydrogel; tissue engineering; drug delivery system; mechanobiology; stem cell fate control; hyaluronic acid hydrogel; click chemistry; electrospinning; three-dimensional cell culture
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Welcome to the Special Issue ‘Hydrogels for Tissue Engineering and Biomedical Therapeutics’, a platform dedicated to exploring the transformative potential of hydrogels in tissue engineering and biomedical therapeutics. This Special Issue aims to highlight the latest trends and breakthroughs in hydrogel research and promote a deeper understanding of their design, fabrication, and use. Hydrogels have shown exceptional promise in mimicking the cellular microenvironment for tissue regeneration and engineering. Their biocompatibility and tunable properties make them ideal candidates for targeted drug delivery, enabling more effective and less invasive therapeutic interventions.

We invite researchers and experts from various disciplines to contribute their insights to this Special Issue. From innovative synthesis methods and advanced characterization techniques to novel applications, we aim to provide a comprehensive overview of this rapidly evolving field. By bringing together diverse perspectives, this Special Issue will serve as a compass to guide the future directions of hydrogel-based research and ultimately shape the landscape of tissue engineering and biomedical therapies.

Dr. Hyun Jong Lee
Guest Editor

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

  • hydrogel
  • tissue engineering
  • biomedical therapeutics
  • biomimetic scaffolds
  • drug delivery
  • regenerative medicine
  • cell-material interactions

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Published Papers (7 papers)

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Research

18 pages, 2485 KiB  
Article
Evaluation of Carboxymethyl Chitosan–Genipin Hydrogels as Reservoir Systems for Suramin Delivery in Epithelial Tissues
by David Encinas-Basurto, Victor H. Ruiz, Rick G. Schnellmann and Heidi M. Mansour
Gels 2025, 11(5), 312; https://doi.org/10.3390/gels11050312 - 23 Apr 2025
Viewed by 201
Abstract
Hydrogels (HDs) offer a promising platform for localized and sustained drug delivery. In this study, carboxymethyl chitosan (CMC)—based hydrogels were crosslinked with genipin and evaluated for the controlled release and tissue retention of suramin, a polyanionic drug with anti-inflammatory and antifibrotic properties. The [...] Read more.
Hydrogels (HDs) offer a promising platform for localized and sustained drug delivery. In this study, carboxymethyl chitosan (CMC)—based hydrogels were crosslinked with genipin and evaluated for the controlled release and tissue retention of suramin, a polyanionic drug with anti-inflammatory and antifibrotic properties. The influence of crosslinking density (1%, 3%, and 5%) on drug release, permeation kinetics, and retention was investigated using in vitro synthetic membranes and reconstructed human epithelial tissue models. The 1% genipin HD exhibited the highest cumulative release and drug retention (48.8 ± 6.8 μg/cm2 in synthetic membranes; 24.06 ± 7.33 μg/cm2 in epithelial models), along with a sustained release profile governed by first-order and Fickian diffusion kinetics. Notably, the 1% crosslinked formulation also demonstrated enhanced transmembrane flux (>140 μg/cm2/h after six hours), suggesting that lower crosslinking density favors both diffusional mobility and depot functionality. In contrast, free suramin solution displayed limited tissue interaction and minimal permeation, highlighting the role of the hydrogel matrix in regulating local bioavailability. These findings demonstrate that CMC–genipin HD can closely modulate drug delivery kinetics through crosslinking density, offering a biocompatible strategy for localized treatment of ulcerated epithelial conditions such as oral mucositis or chronic wounds. Diffusion models included a synthetic multilayer membrane (Strat-M®) and a reconstructed human epidermis (EpiDerm™) to simulate skin-like barrier properties. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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20 pages, 6417 KiB  
Article
Polydeoxynucleotide-Loaded Visible Light Photo-Crosslinked Gelatin Methacrylate Hydrogel: Approach to Accelerating Cartilage Regeneration
by Sunjae Park, Youngjun Son, Jonggyu Park, Soyoon Lee, Na-Hyeon Kim, Se-Na Jang, Tae-Woong Kang, Jeong-Eun Song and Gilson Khang
Gels 2025, 11(1), 42; https://doi.org/10.3390/gels11010042 - 7 Jan 2025
Cited by 2 | Viewed by 902
Abstract
Articular cartilage faces challenges in self-repair due to the lack of blood vessels and limited chondrocyte concentration. Polydeoxyribonucleotide (PDRN) shows promise for promoting chondrocyte growth and cartilage regeneration, but its delivery has been limited to injections. Continuous PDRN delivery is crucial for effective [...] Read more.
Articular cartilage faces challenges in self-repair due to the lack of blood vessels and limited chondrocyte concentration. Polydeoxyribonucleotide (PDRN) shows promise for promoting chondrocyte growth and cartilage regeneration, but its delivery has been limited to injections. Continuous PDRN delivery is crucial for effective cartilage regeneration. This study explores using gelatin methacrylate (gelMA) hydrogel, crosslinked with visible light and riboflavin 5′-phosphate sodium (RF) as a photoinitiator, for sustained PDRN release. GelMA hydrogel’s synthesis was confirmed through spectrophotometric techniques, demonstrating successful methacrylate group incorporation. PDRN-loaded gelMA hydrogels displayed varying pore sizes, swelling ratios, degradation rates, and mechanical properties based on gelMA concentration. They showed sustained PDRN release and biocompatibility, with the 14% gelMA-PDRN composition performing best. Glycosaminoglycan (GAG) activity was higher in PDRN-loaded hydrogels, indicating a positive effect on cartilage formation. RT-PCR analysis revealed increased expression of cartilage-specific genes (COL2, SOX9, AGG) in gelMA-PDRN. Histological assessments in a rabbit cartilage defect model demonstrated superior regenerative effects of gelMA-PDRN hydrogels. This study highlights the potential of gelMA-PDRN hydrogels in cartilage tissue engineering, providing a promising approach for effective cartilage regeneration. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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28 pages, 5217 KiB  
Article
Rapid Multi-Well Evaluation of Assorted Materials for Hydrogel-Assisted Giant Unilamellar Vesicle Production: Empowering Bottom-Up Synthetic Biology
by Cherng-Wen Darren Tan, Magdalena Schöller and Eva-Kathrin Ehmoser
Gels 2025, 11(1), 29; https://doi.org/10.3390/gels11010029 - 2 Jan 2025
Viewed by 822
Abstract
Giant unilamellar vesicles (GUVs) are versatile cell models in biomedical and environmental research. Of the various GUV production methods, hydrogel-assisted GUV production is most easily implemented in a typical biological laboratory. To date, agarose, polyvinyl alcohol, cross-linked dextran-PEG, polyacrylamide, and starch hydrogels have [...] Read more.
Giant unilamellar vesicles (GUVs) are versatile cell models in biomedical and environmental research. Of the various GUV production methods, hydrogel-assisted GUV production is most easily implemented in a typical biological laboratory. To date, agarose, polyvinyl alcohol, cross-linked dextran-PEG, polyacrylamide, and starch hydrogels have been used to produce GUVs. Some leach and contaminate the GUVs, while others require handling toxic material or specialised chemistry, thus limiting their use by novices. Alternative hydrogel materials could address these issues or even offer novel advantages. To facilitate discovery, we replaced the manual spreading of reagents with controlled drop-casting in glass Petri dishes and polystyrene multi-well plates, allowing us to rapidly screen up to 96 GUV-production formulations simultaneously. Exploiting this, we rapidly evaluated assorted biomedical hydrogels, including PEG-DA, cross-linked hyaluronic acid, Matrigel, and cross-linked DNA. All of these alternatives successfully produced GUVs. In the process, we also developed a treatment for recycling agarose and polyvinyl alcohol hydrogels for GUV production, and successfully encapsulated porcine liver esterase (PLE-GUVs). PLE-GUVs offer a novel method of GUV labelling and tracing, which emulates the calcein-AM staining behaviour of cells. Our results highlight the utility of our protocol for potentiating substrate material discovery, as well as protocol and product development. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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15 pages, 3295 KiB  
Article
Electrostatic Gelatin Nanoparticles for Biotherapeutic Delivery
by Connor Tobo, Avantika Jain, Madhushika Elabada Gamage, Paul Jelliss and Koyal Garg
Gels 2024, 10(12), 757; https://doi.org/10.3390/gels10120757 - 23 Nov 2024
Viewed by 1299
Abstract
Biological agents such as extracellular vesicles (EVs) and growth factors, when administered in vivo, often face rapid clearance, limiting their therapeutic potential. To address this challenge and enhance their efficacy, we propose the electrostatic conjugation and sequestration of these agents into gelatin-based biomaterials. [...] Read more.
Biological agents such as extracellular vesicles (EVs) and growth factors, when administered in vivo, often face rapid clearance, limiting their therapeutic potential. To address this challenge and enhance their efficacy, we propose the electrostatic conjugation and sequestration of these agents into gelatin-based biomaterials. In this study, gelatin nanoparticles (GNPs) were synthesized via the nanoprecipitation method, with adjustments to the pH of the gelatin solution (4.0 or 10.0) to introduce either a positive or negative charge to the nanoparticles. The GNPs were characterized using dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM) imaging. Both positively and negatively charged GNPs were confirmed to be endotoxin-free and non-cytotoxic. Mesenchymal stem cell (MSC)-derived EVs exhibited characteristic surface markers and a notable negative charge. Zeta potential measurements validated the electrostatic conjugation of MSC-EVs with positively charged GNPs. Utilizing a transwell culture system, we evaluated the impact of EV-GNP conjugates encapsulated within a gelatin hydrogel on macrophage secretory activity. The results demonstrated the bioactivity of EV-GNP conjugates and their synergistic effect on macrophage secretome over five days of culture. In summary, these findings demonstrate the efficacy of electrostatically coupled biotherapeutics with biomaterials for tissue regeneration applications. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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23 pages, 4207 KiB  
Article
Streamlining Skin Regeneration: A Ready-To-Use Silk Bilayer Wound Dressing
by Anabela Veiga, Inês V. Silva, Juliana R. Dias, Nuno M. Alves, Ana L. Oliveira and Viviana P. Ribeiro
Gels 2024, 10(7), 439; https://doi.org/10.3390/gels10070439 - 30 Jun 2024
Cited by 1 | Viewed by 2000
Abstract
Silk proteins have been highlighted in the past decade for tissue engineering (TE) and skin regeneration due to their biocompatibility, biodegradability, and exceptional mechanical properties. While silk fibroin (SF) has high structural and mechanical stability with high potential as an external protective layer, [...] Read more.
Silk proteins have been highlighted in the past decade for tissue engineering (TE) and skin regeneration due to their biocompatibility, biodegradability, and exceptional mechanical properties. While silk fibroin (SF) has high structural and mechanical stability with high potential as an external protective layer, traditionally discarded sericin (SS) has shown great potential as a natural-based hydrogel, promoting cell–cell interactions, making it an ideal material for direct wound contact. In this context, the present study proposes a new wound dressing approach by developing an SS/SF bilayer construct for full-thickness exudative wounds. The processing methodology implemented included an innovation element and the cryopreservation of the SS intrinsic secondary structure, followed by rehydration to produce a hydrogel layer, which was integrated with a salt-leached SF scaffold to produce a bilayer structure. In addition, a sterilization protocol was developed using supercritical technology (sCO2) to allow an industrial scale-up. The resulting bilayer material presented high porosity (>85%) and interconnectivity while promoting cell adhesion, proliferation, and infiltration of human dermal fibroblasts (HDFs). SS and SF exhibit distinct secondary structures, pore sizes, and swelling properties, opening new possibilities for dual-phased systems that accommodate the different needs of a wound during the healing process. The innovative SS hydrogel layer highlights the transformative potential of the proposed bilayer system for biomedical therapeutics and TE, offering insights into novel wound dressing fabrication. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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17 pages, 5735 KiB  
Article
Coated Microneedle System for Delivery of Clotrimazole in Deep-Skin Mycoses
by Barbara Jadach, Agata Nowak, Jolanta Długaszewska, Oliwia Kordyl, Irena Budnik and Tomasz Osmałek
Gels 2024, 10(4), 264; https://doi.org/10.3390/gels10040264 - 15 Apr 2024
Cited by 7 | Viewed by 3093
Abstract
Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. [...] Read more.
Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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16 pages, 6536 KiB  
Article
Investigating the Impact of Mechanical Properties and Cell-Collagen Interaction on NIH3T3 Function: A Comparative Study on Different Substrates and Culture Environments
by A Yeon Cho and Hyun Jong Lee
Gels 2023, 9(12), 922; https://doi.org/10.3390/gels9120922 - 22 Nov 2023
Cited by 3 | Viewed by 2313
Abstract
This study investigates the intricate dynamics of matrix stiffness, substrate composition, and cell–cell interactions and elucidates their cumulative effects on fibroblast behavior in different culture contexts. Three primary substrate types were examined: non-coated, collagen-coated, and collagen hydrogel, within both two-dimensional (2D) monolayer and [...] Read more.
This study investigates the intricate dynamics of matrix stiffness, substrate composition, and cell–cell interactions and elucidates their cumulative effects on fibroblast behavior in different culture contexts. Three primary substrate types were examined: non-coated, collagen-coated, and collagen hydrogel, within both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid cultures. The research provides several key insights. First, 3D spheroid culture, which promotes robust cell–cell interactions, emerges as a critical factor in maintaining fibroblast functionality. Second, substrate stiffness significantly influences results, with the soft collagen hydrogel showing superior support for fibroblast function. Notably, fibroblasts cultured on collagen hydrogel in 2D exhibit comparable functionality to those in 3D, highlighting the importance of substrate mechanical properties. Third, surface composition, as exemplified by collagen coating, showed a limited effect compared to the other factors studied. These findings provide a basis for innovative applications in regenerative medicine, tissue engineering, and drug testing models, and offer valuable insights into harnessing the potential of fibroblasts and advancing biomedical sciences. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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