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Gels
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Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition)
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Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition)

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

Deadline for manuscript submissions: 30 November 2025 | Viewed by 13125

Special Issue Editors

Dr. Wen Shi

E-Mail Website
Guest Editor
Department of internal medicine, University of Nebraska Medical Center, Omaha, NE, USA
Interests: 3D bioprinting; hydrogels; tissue engineering; regenerative medicine; nanomedicine; drug conjugate; radiopharmaceuticals
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Shixuan Chen

E-Mail Website
Guest Editor
Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China
Interests: regenerative medicine; wound healing; bone regeneration; nanofiber; biofabrication
Special Issues, Collections and Topics in MDPI journals
Dr. Bo Liu

E-Mail Website
Guest Editor
Department of internal medicine, University of Nebraska Medical Center, Omaha, NE, USA
Interests: hydrogels; regenerative medicine; polymer chemistry; exosomes; cryopreservation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tissue engineering and regenerative medicine (TERM) is a rapidly developing field aiming to fully repair or regenerate damaged tissues/organs and restore their functions by combining advancements and experiences from both engineering and medicine. Hydrogels, three-dimensional water-swollen materials, have exhibited versatile features for TERM applications. In addition to common hydrogels being employed as biocompatible and minimally invasive scaffolds for loading drugs or cells, more advanced hydrogels presenting multifunctional properties play more important roles in improving treatment outcomes in TERM.

These advanced hydrogel properties include, but are not limited to, self-healing, environmental stimuli responsiveness, antibacterial, anti-inflammatory, conductivity, etc. For example, self-healing hydrogels are promising candidates for bone and cartilage tissue engineering, as their self-healing characteristics can help them better deal with load-bearing conditions in native bone and cartilage sites. Additionally, the application of anti-bacterial and anti-inflammatory hydrogels can significantly accelerate wound healing by modulating the microenvironments in chronic wounds. On the other hand, hydrogels are also an essential component of bioinks in 3D bioprinting due to being structurally similar to the extracellular matrix of human tissues. Through the adjustment of hydrogel components and mechanical properties, 3D bio-printed tissues/organs can better mimic native tissue structures and support cellular growth, differentiation, and function, thereby enhancing TERM efficacy. The purpose of this Special Issue is to summarize the progress achieved regarding advanced hydrogels within the TERM area, and encourage the discovery of new advanced hydrogels for better tissue/organ regeneration.

Dr. Wen Shi
Prof. Dr. Shixuan Chen
Dr. Bo Liu
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
  • tissue engineering
  • regenerative medicine
  • 3D bioprinting
  • multifunctional
  • disease models
  • scaffolds
  • stem cells
  • extracellular matrix

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Related Special Issue

Published Papers (5 papers)

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Research

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50 pages, 14462 KiB  
Article
Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties
by Valentina Anuța, Mihaela-Alexandra Nica, Răzvan-Mihai Prisada, Lăcrămioara Popa, Bruno Ștefan Velescu, Ioana Cristina Marinas, Diana-Madalina Gaboreanu, Mihaela Violeta Ghica, Florentina Iuliana Cocoș, Cristian Andi Nicolae and Cristina-Elena Dinu-Pîrvu
Gels 2025, 11(3), 208; https://doi.org/10.3390/gels11030208 - 15 Mar 2025
Viewed by 637
Abstract
Buccal drug delivery systems often struggle with poor drug solubility, limited adhesion, and rapid clearance, leading to suboptimal therapeutic outcomes. To address these limitations, we developed a novel hybrid eutectogel composed of xanthan gum (XTG), hyaluronic acid (HA), and a Natural Deep Eutectic [...] Read more.
Buccal drug delivery systems often struggle with poor drug solubility, limited adhesion, and rapid clearance, leading to suboptimal therapeutic outcomes. To address these limitations, we developed a novel hybrid eutectogel composed of xanthan gum (XTG), hyaluronic acid (HA), and a Natural Deep Eutectic Solvent (NADES) system (choline chloride, sorbitol, and glycerol in 2:1:1 mole ratio), incorporating 2.5% ibuprofen (IBU) as a model drug. The formulation was optimized using a face-centered central composite design to enhance the rheological, textural, and drug release properties. The optimized eutectogels exhibited shear-thinning behavior (flow behavior index, n = 0.26 ± 0.01), high mucoadhesion (adhesiveness: 2.297 ± 0.142 N·s), and sustained drug release over 24 h, governed by Higuchi kinetics (release rate: 237.34 ± 13.61 μg/cm2/min1/2). The ex vivo residence time increased substantially with NADES incorporation, reaching up to 176.7 ± 23.1 min. An in vivo anti-inflammatory evaluation showed that the eutectogel reduced λ-carrageenan-induced paw edema within 1 h and that its efficacy was sustained in the kaolin model up to 24 h (p < 0.05), achieving comparable efficacy to a commercial 5% IBU gel, despite a lower drug concentration. Additionally, the eutectogel presented a minimum inhibitory concentration for Gram-positive bacteria of 25 mg/mL, and through direct contact, it reduced microbial viability by up to 100%. Its efficacy against Bacillus cereus, Enterococcus faecium, and Klebsiella pneumoniae, combined with its significant anti-inflammatory properties, positions the NADES-based eutectogel as a promising multifunctional platform for buccal drug delivery, particularly for inflammatory conditions complicated by bacterial infections. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition))
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27 pages, 3818 KiB  
Article
In Situ Gelling Dexamethasone Oromucosal Formulation: Physical Characteristics Influencing Drug Delivery
by Daniel Krchňák, Ľudmila Balážová, Michal Hanko, Dominika Žigrayová and Miroslava Špaglová
Gels 2025, 11(1), 26; https://doi.org/10.3390/gels11010026 - 2 Jan 2025
Viewed by 1025
Abstract
The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint [...] Read more.
The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint essential oil (EO), and a third series containing EO and DEX solubilized in propylene glycol (PG). In the composition, polymers in the role of mucoadhesive agent were interchanged (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), carboxymethyl cellulose (CMC), and sodium carboxymethyl cellulose (NaCMC). Specifically, DEX was incorporated at a concentration of 0.1% (w/w) in each formulation. The influence of mint EO and DEX solubilization on the physical properties (pH measurements, rheological analysis, swelling ability, and texture analysis) and in vitro drug release was studied. Key findings revealed that HPMC-based formulation containing mint EO and PG exhibited best swelling properties (700 ± 46% after 5 h), adequate adhesiveness and in vitro drug release (34.7 ± 5.9%). Furthermore, the irritation potential assessed via the hen’s egg test on the chorioallantoic membrane (HET-CAM) demonstrated low irritancy risk. Finally, Fourier-transform infrared spectroscopy (FT-IR) showed no incompatibility between DEX and excipients. Overall, the research highlights the potential of mucoadhesive systems in improving the therapeutic efficacy of oromucosal drug delivery for managing painful oral lesions. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition))
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18 pages, 10433 KiB  
Article
Development and Evaluation of the Biological Activities of a Plain Mucoadhesive Hydrogel as a Potential Vehicle for Oral Mucosal Drug Delivery
by Ana G. Pardo-Rendón, Jorge L. Mejía-Méndez, Edgar R. López-Mena and Sergio A. Bernal-Chávez
Gels 2024, 10(9), 574; https://doi.org/10.3390/gels10090574 - 3 Sep 2024
Cited by 2 | Viewed by 2036
Abstract
This study aimed to develop HGs based on cationic guar gum (CGG), polyethylene glycol (PEG), propylene glycol (PG), and citric acid (CA) using a 2k factorial experimental design to optimize their properties. HGs were characterized through FTIR and Raman spectroscopy, scanning electron [...] Read more.
This study aimed to develop HGs based on cationic guar gum (CGG), polyethylene glycol (PEG), propylene glycol (PG), and citric acid (CA) using a 2k factorial experimental design to optimize their properties. HGs were characterized through FTIR and Raman spectroscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The biological activities of HGs were determined by evaluating their mucoadhesive capacity and antibacterial activity in vitro, whereas their toxicity was analyzed using Artemia salina nauplii as an in vivo model. Results revealed that HGs were successfully optimized for their viscosity, pH, and sensory properties, and it was observed that varying concentrations of PEG-75 did not influence them. Through SEM analyses, it was noted that increased levels of PEG-75 resulted in HGs with distinct porosity and textures, whereas FTIR and Raman spectroscopy exhibited representative peaks of the raw materials used during the synthesis process. TGA studies indicated the thermal stability of HGs, as they presented degradation patterns at 100 and 300 °C. The synthesized HGs exhibited similar mucoadhesion kinetic profiles, demonstrating a displacement factor at an equilibrium of 0.57 mm/mg at 5 min. The antibacterial activity of HGs was appraised as poor against Gram-positive and Gram-negative bacteria due to their MIC90 values (>500 μg/mL). Regarding A. salina, treatment with HGs neither decreased their viability nor induced morphological changes. The obtained results suggest the suitability of CGG/PEG HGs for oral mucosa drug delivery and expand the knowledge about their mucoadhesive capacity, antibacterial potential, and in vivo biocompatibility. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition))
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Review

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31 pages, 19426 KiB  
Review
Natural Regenerative Hydrogels for Wound Healing
by Mariana Chelu, Jose M. Calderon Moreno, Adina Magdalena Musuc and Monica Popa
Gels 2024, 10(9), 547; https://doi.org/10.3390/gels10090547 - 23 Aug 2024
Cited by 14 | Viewed by 4987
Abstract
Regenerative hydrogels from natural polymers have come forth as auspicious materials for use in regenerative medicine, with interest attributed to their intrinsic biodegradability, biocompatibility, and ability to reassemble the extracellular matrix. This review covers the latest advances in regenerative hydrogels used for wound [...] Read more.
Regenerative hydrogels from natural polymers have come forth as auspicious materials for use in regenerative medicine, with interest attributed to their intrinsic biodegradability, biocompatibility, and ability to reassemble the extracellular matrix. This review covers the latest advances in regenerative hydrogels used for wound healing, focusing on their chemical composition, cross-linking mechanisms, and functional properties. Key carbohydrate polymers, including alginate, chitosan, hyaluronic acid, and polysaccharide gums, including agarose, carrageenan, and xanthan gum, are discussed in terms of their sources, chemical structures and specific properties suitable for regenerative applications. The review further explores the categorization of hydrogels based on ionic charge, response to physiological stimuli (i.e., pH, temperature) and particularized roles in wound tissue self-healing. Various methods of cross-linking used to enhance the mechanical and biological performance of these hydrogels are also examined. By highlighting recent innovations and ongoing challenges, this article intends to give a detailed understanding of natural hydrogels and their potential to revolutionize regenerative medicine and improve patient healing outcomes. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition))
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25 pages, 1275 KiB  
Review
Advanced Hydrogels in Breast Cancer Therapy
by Xiangyu Gao, Benjamin R. Caruso and Weimin Li
Gels 2024, 10(7), 479; https://doi.org/10.3390/gels10070479 - 19 Jul 2024
Cited by 3 | Viewed by 3707
Abstract
Breast cancer is the most common malignancy among women and is the second leading cause of cancer-related death for women. Depending on the tumor grade and stage, breast cancer is primarily treated with surgery and antineoplastic therapy. Direct or indirect side effects, emotional [...] Read more.
Breast cancer is the most common malignancy among women and is the second leading cause of cancer-related death for women. Depending on the tumor grade and stage, breast cancer is primarily treated with surgery and antineoplastic therapy. Direct or indirect side effects, emotional trauma, and unpredictable outcomes accompany these traditional therapies, calling for therapies that could improve the overall treatment and recovery experiences of patients. Hydrogels, biomimetic materials with 3D network structures, have shown great promise for augmenting breast cancer therapy. Hydrogel implants can be made with adipogenic and angiogenic properties for tissue integration. 3D organoids of malignant breast tumors grown in hydrogels retain the physical and genetic characteristics of the native tumors, allowing for post-surgery recapitulation of the diseased tissues for precision medicine assessment of the responsiveness of patient-specific cancers to antineoplastic treatment. Hydrogels can also be used as carrier matrices for delivering chemotherapeutics and immunotherapeutics or as post-surgery prosthetic scaffolds. The hydrogel delivery systems could achieve localized and controlled medication release targeting the tumor site, enhancing efficacy and minimizing the adverse effects of therapeutic agents delivered by traditional procedures. This review aims to summarize the most recent advancements in hydrogel utilization for breast cancer post-surgery tissue reconstruction, tumor modeling, and therapy and discuss their limitations in clinical translation. Full article
(This article belongs to the Special Issue Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition))
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