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Gels
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Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition)
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Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition)

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

Deadline for manuscript submissions: closed (20 December 2025) | Viewed by 8016

Special Issue Editors

Dr. Federica Re

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Guest Editor
Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
Interests: stem cell transplantation; stem cell biology; regenerative medicine; formation of tissues and organs; mesenchymal and hematopoietic stem cells (MSCs and HSCs); hydrogel
Special Issues, Collections and Topics in MDPI journals
Dr. Elisa Borsani

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Guest Editor
Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
Interests: morphology and functional imaging of cells; neuroanatomy and neurophysiology; gene therapy; cell therapy; regenerative medicine; hydrogel
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of scaffolds with optimal characteristics is more readily achievable in polymeric scaffolds. Currently, there is huge research interest in hydrogel-based scaffolds. 

Hydrogel-based scaffolds have recently emerged as the most promising substrates for cell cultures to generate well-defined 3D biofabricated tissue, attracting significant research attention for their potential in medical applications.

These scaffolds act as bioactive substrates and structural supports, providing topographical and chemical stimuli for cell spreading, proliferation, and differentiation in vivo. Among the specific scaffold characteristics, high porosity and interconnectivity facilitate scaffold–cell interactions, while nutrient and oxygen infiltration and vascularization aim to obtain specific cellular responses. Scaffolds have sufficient mechanical properties to temporarily substitute the missing tissue and permit essential physiological functions.

This Special Issue is dedicated to the design and development of advanced polymeric scaffolds and their applications for bone/cartilage/skin regeneration in vitro and in vivo.

Dr. Federica Re
Dr. Elisa Borsani
Guest Editors

Manuscript Submission Information

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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-based scaffolds
  • resorbable scaffolds
  • synthesis of biomaterials
  • mesenchymal stromal cells
  • bioengineered models
  • bone regeneration
  • cartilage regeneration
  • skin regeneration

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Published Papers (8 papers)

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Research

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28 pages, 10428 KB  
Article
Biomedical Interpenetrated Hydrogels Fabricated via Quaternary Ammonium Chitosan and Dopamine-Conjugated Gelatin Integrated with Genipin and Epigallocatechin Gallate
by Ling Wang, Shuxin Hu, Zheng Wei, Peng Ding, Yaling Deng, Yanting Han, Yanfang Sun, Guohua Jiang and Lei Nie
Gels 2026, 12(1), 67; https://doi.org/10.3390/gels12010067 - 11 Jan 2026
Viewed by 234
Abstract
Multifunctional hydrogels with an interpenetrated network structure have shown great potential for biomedical and tissue-regeneration applications. In this work, the biomedical hydrogel was fabricated with an interpenetrated network based on dopamine grafted gelatin (DA-Gel), and genipin crosslinked quaternary ammonium chitosan (QCS), incorporating epigallocatechin [...] Read more.
Multifunctional hydrogels with an interpenetrated network structure have shown great potential for biomedical and tissue-regeneration applications. In this work, the biomedical hydrogel was fabricated with an interpenetrated network based on dopamine grafted gelatin (DA-Gel), and genipin crosslinked quaternary ammonium chitosan (QCS), incorporating epigallocatechin gallate (EGCG). The EDC/NHS and Schiff-base bond connections occurred in the hydrogels, as confirmed by Fourier-transform infrared (FT-IR) analysis. The properties of the fabricated hydrogels, including microstructure, degradation rate, adhesive strength, mechanical strength, and rheological behavior, can be regulated by adjusting the DA-Gel/QCS ratio or by using different crosslinking approaches. In addition, the fabricated hydrogels exhibited self-healing properties and strong adhesion to various materials and organs. Furthermore, the hydrogels performed good antibacterial activity against the typical bacteria, Escherichia coli and Staphylococcus aureus. EGCG encapsulated hydrogels displayed excellent antioxidant activities and good hemocompatibility. The hydrogels also demonstrated excellent cytocompatibility and good cell migration ability. The above results provide a facile approach to fabricate the biomedical hydrogels with a regulated network structure and multifunctional characteristics with potential in biomedical applications. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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18 pages, 2865 KB  
Article
A Novel Thermosensitive Curcumin-Loaded Hydrogel That Modulates Macrophage M1/M2 Polarization for Osteoarthritis Therapy
by Yuanyuan Zhou, Shengsheng Li, Zitong Huang, Zhongjia Yu, Hang Liu, Wanshan Wu, Qiao Xu, Keyun Chen and Jun Huang
Gels 2026, 12(1), 7; https://doi.org/10.3390/gels12010007 - 21 Dec 2025
Viewed by 462
Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation, and pain, for which conventional systemic therapies often lack sustained efficacy. Therefore, localized delivery platforms that provide both sustained release and therapeutic activity are urgently needed. We developed a thermosensitive injectable [...] Read more.
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation, and pain, for which conventional systemic therapies often lack sustained efficacy. Therefore, localized delivery platforms that provide both sustained release and therapeutic activity are urgently needed. We developed a thermosensitive injectable hydrogel—hydroxybutyl chitosan (HBC)—that transitions from a sol to a gel at physiological temperature (37 °C). Curcumin, a natural anti-inflammatory compound with poor bioavailability, was loaded to create a composite hydrogel system (Cur@HBC). HBC exhibited excellent injectability, stability, and biocompatibility. Cur@HBC enabled sustained release of curcumin and significantly attenuated OA progression in vivo, as evidenced by reduced cartilage degradation, decreased expression of MMP13 and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), improved Collagen II retention, and recovery of cartilage function. Mechanistically, curcumin inhibited chondrocyte apoptosis and promoted macrophage polarization toward the M2 phenotype. This study presents a dual-functional hydrogel platform that combines thermosensitive mechanical support with sustained anti-inflammatory drug delivery. The injectable Cur@HBC hydrogel shows great promise as a localized OA therapy, with the potential to improve joint function. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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20 pages, 4584 KB  
Article
Three-Dimensional-Bioprinted Embedded-Based Cerebral Organoids: An Alternative Approach for Mini-Brain In Vitro Modeling Beyond Conventional Generation Methods
by Rosalba Monica Ferraro, Paola Serena Ginestra, Miriam Seiti, Mattia Bugatti, Gabriele Benini, Luana Ottelli, William Vermi, Pietro Luigi Poliani, Elisabetta Ceretti and Silvia Giliani
Gels 2025, 11(4), 284; https://doi.org/10.3390/gels11040284 - 11 Apr 2025
Cited by 1 | Viewed by 3363
Abstract
Cerebral organoids (cORGs) obtained from induced pluripotent stem cells (iPSCs) have become significant instruments for investigating human neurophysiology, with the possibility of simulating diseases and enhancing drug discovery. The current approaches require a strict process of manual inclusion in animal-derived matrix Matrigel® [...] Read more.
Cerebral organoids (cORGs) obtained from induced pluripotent stem cells (iPSCs) have become significant instruments for investigating human neurophysiology, with the possibility of simulating diseases and enhancing drug discovery. The current approaches require a strict process of manual inclusion in animal-derived matrix Matrigel® and are challenged by unpredictability, operators’ skill and expertise, elevated costs, and restricted scalability, impeding their extensive applicability and translational potential. In this study, we present a novel method to generate brain organoids that address these limitations. Our approach does not require a manual, operator-dependent embedding. Instead, it employs a chemically defined hydrogel in which the Matrigel® is diluted in a solution enriched with sodium alginate (SA) and sodium carboxymethylcellulose (CMC) and used as a bioink to print neural embryoid bodies (nEBs). Immunohistochemical, immunofluorescence, and gene expression analyses confirmed that SA-CMC-Matrigel® hydrogel can sustain the generation of iPSC-derived cortical cORGs as the conventional Matrigel®-based approach does. By day 40 of differentiation, hydrogel-based 3D-bioprinted cORGs showed heterogeneous and consistent masses, with a cytoarchitecture resembling an early-stage developmental fetal brain composed of neural progenitor cells PAX6+/Ki67+ organized into tubular structures, and densely packed cell somas with extensive neurites SYP+, suggestive of cortical tissue-like neuronal layer formation. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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Review

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29 pages, 811 KB  
Review
Smart Composite Hydrogels for Monitoring and Managing Chronic Wounds
by Jun Zhu, Yibin Huang, Junbo Tong, Antong Li and Bin Chu
Gels 2026, 12(2), 120; https://doi.org/10.3390/gels12020120 - 29 Jan 2026
Abstract
The precise management of chronic wounds poses a global medical challenge, owing to their complex and dynamically shifting pathological microenvironment, coupled with their inherent difficulty in healing. Traditional dressings, which lack capabilities for real-time monitoring and active intervention, fall short of meeting modern [...] Read more.
The precise management of chronic wounds poses a global medical challenge, owing to their complex and dynamically shifting pathological microenvironment, coupled with their inherent difficulty in healing. Traditional dressings, which lack capabilities for real-time monitoring and active intervention, fall short of meeting modern clinical needs. Composite hydrogels offer a novel solution to this problem. By integrating functional fillers within biocompatible hydrogel matrices, they form intelligent materials capable of sensing key wound parameters. This review systematically outlines the composite systems and material classification of such hydrogels designed for the intelligent monitoring of chronic wounds. It subsequently details the construction of multimodal monitoring systems and their applications across different types of chronic wounds., Finally, future development direction are discussed, aiming to advance the implementation of next generation, personalized intelligent wound management systems. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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27 pages, 980 KB  
Review
Rational Design of Mechanically Optimized Hydrogels for Bone Tissue Engineering: A Review
by Shengao Qin, Han Yuan, Zhaochen Shan, Jiaqi Wang and Wen Pan
Gels 2026, 12(1), 71; https://doi.org/10.3390/gels12010071 - 13 Jan 2026
Viewed by 194
Abstract
Bone tissue engineering, as an important branch of regenerative medicine, integrates multidisciplinary knowledge from cell biology, materials science, and biomechanics, aiming to develop novel biomaterials and technologies for functional repair and regeneration of bone tissue. Hydrogels are among the most commonly used scaffold [...] Read more.
Bone tissue engineering, as an important branch of regenerative medicine, integrates multidisciplinary knowledge from cell biology, materials science, and biomechanics, aiming to develop novel biomaterials and technologies for functional repair and regeneration of bone tissue. Hydrogels are among the most commonly used scaffold materials; however, conventional hydrogels exhibit significant limitations in physical properties such as strength, tensile strength, toughness, and fatigue resistance, which severely restrict their application in load-bearing bone defect repair. As a result, the development of high-strength hydrogels has become a research hotspot in the field of bone tissue engineering. This paper systematically reviews the latest research progress in this area: First, it delves into the physicochemical characteristics of high-strength hydrogels at the molecular level, focusing on core features such as their crosslinking network structure, dynamic bonding mechanisms, and energy dissipation principles. Next, it categorically summarizes novel high-strength hydrogel systems and different types of biomimetic hydrogels developed based on various reinforcement strategies. Furthermore, it provides a detailed evaluation of the application effects of these advanced materials in specific anatomical sites, including cranial reconstruction, femoral repair, alveolar bone regeneration, and articular cartilage repair. This review aims to provide systematic theoretical guidance and technical references for the basic research and clinical translation of high-strength hydrogels in bone tissue engineering, promoting the effective translation of this field from laboratory research to clinical application. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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23 pages, 2568 KB  
Review
Ultra-Short Peptide Hydrogels as 3D Bioprinting Materials
by Davina In, Androulla N. Miliotou, Panoraia I. Siafaka and Yiannis Sarigiannis
Gels 2026, 12(1), 49; https://doi.org/10.3390/gels12010049 - 2 Jan 2026
Viewed by 716
Abstract
Ultra-short peptides (USPs; ≤7–8 amino acids) emerge as minimal self-assembling building blocks for hydrogel-based biomaterials. Their intrinsic biocompatibility, straightforward synthesis, and ease of tunability make them particularly attractive candidates for potential use in bioprinting. This review provides an overview of the properties of [...] Read more.
Ultra-short peptides (USPs; ≤7–8 amino acids) emerge as minimal self-assembling building blocks for hydrogel-based biomaterials. Their intrinsic biocompatibility, straightforward synthesis, and ease of tunability make them particularly attractive candidates for potential use in bioprinting. This review provides an overview of the properties of USPs along with their applications in three-dimensional (3D) bioprinting. We first discuss how peptide sequence, terminal and side-chain modifications, and environmental triggers govern USPs’ self-assembly into nanofibers and 3D networks and how these supramolecular features translate into key rheological properties such as shear-thinning, rapid gelation, and mechanical tunability. We then survey reported applications in tissue engineering, wound healing, and organotypic models, as well as emerging ultra-short peptide-based systems for drug delivery, biosensing, and imaging, highlighting examples where printed constructs support cell viability, differentiation, and matrix deposition. Attention is given to hybrid and multi-material formulations in which USPs provide bioactivity while complementary components contribute structural robustness or additional functionality. Finally, this review outlines the main challenges that currently limit widespread adoption, including achieving high print fidelity with cytocompatible crosslinking, controlling batch-to-batch variability, and addressing the scalability, cost, and sustainability of peptide manufacturing. We conclude by discussing future opportunities such as AI-assisted peptide design, adaptive and multi-material bioprinting workflows, and greener synthetic routes, which together may accelerate the translation of ultra-short peptide-based bioinks from proof-of-concept studies to clinically and industrially relevant platforms. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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33 pages, 5540 KB  
Review
Silk Fibroin-Derived Smart Living Hydrogels for Regenerative Medicine and Organoid Engineering: Bioactive, Adaptive, and Clinically Translatable Platforms
by Asim Mushtaq, Khai Ly Do, Abdul Wahab, Muhammad Yousaf, Abdul Rahman, Hamid Hussain, Muhammad Ali, Pingfan Du and Miao Su
Gels 2025, 11(11), 908; https://doi.org/10.3390/gels11110908 - 13 Nov 2025
Cited by 1 | Viewed by 1629
Abstract
Silk fibroin (SF) has evolved from a traditional biopolymer to a leading regenerative medicine material. Its combination of mechanical strength, biocompatibility, tunable degradation, and molecular adaptability makes SF a unique matrix that is both bioactive and intelligent. Advances in hydrogel engineering have transformed [...] Read more.
Silk fibroin (SF) has evolved from a traditional biopolymer to a leading regenerative medicine material. Its combination of mechanical strength, biocompatibility, tunable degradation, and molecular adaptability makes SF a unique matrix that is both bioactive and intelligent. Advances in hydrogel engineering have transformed SF from a passive scaffold into a smart, living hydrogel. These systems can instruct cell fate, sense microenvironmental signals, and deliver therapeutic signals as needed. By incorporating stem cells, progenitors, or engineered immune and microbial populations, SF hydrogels now serve as synthetic niches for organoid maturation and as adaptive implants for tissue regeneration. These platforms replicate extracellular matrix complexity and evolve with tissue, showing self-healing, shape-memory, and stimuli-responsive properties. Such features are redefining biomaterial–cell interactions. SF hydrogels are used for wound healing, musculoskeletal repair, neural and cardiac patches, and developing scalable organoid models for disease and drug research. Challenges remain in maintaining long-term cell viability, achieving clinical scalability, and meeting regulatory standards. This review explores how advances in SF engineering, synthetic biology, and organoid science are enabling SF-based smart living hydrogels in bridging the gap between research and clinical use. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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48 pages, 3153 KB  
Review
Laser-Based Fabrication of Hydrogel Scaffolds for Medicine: From Principles to Clinical Applications
by Dan Stefan Manoliu, Cristian Zagar, Irina Negut and Anita Ioana Visan
Gels 2025, 11(10), 811; https://doi.org/10.3390/gels11100811 - 9 Oct 2025
Cited by 1 | Viewed by 954
Abstract
Hydrogel scaffolds have emerged as pivotal materials in regenerative medicine due to their biocompatibility, tunable mechanical properties, and ability to mimic the extracellular matrix. However, conventional fabrication techniques often lack the precision required to create complex architectures, limiting their effectiveness in tissue engineering. [...] Read more.
Hydrogel scaffolds have emerged as pivotal materials in regenerative medicine due to their biocompatibility, tunable mechanical properties, and ability to mimic the extracellular matrix. However, conventional fabrication techniques often lack the precision required to create complex architectures, limiting their effectiveness in tissue engineering. This review explores advanced laser-based fabrication methods, such as two-photon polymerization, laser-induced forward transfer, selective laser sintering/melting, and laser direct writing, which offer unparalleled resolution and control over scaffold geometry. These techniques enable the production of intricate 3D structures tailored to specific clinical needs, from vascular networks to patient-specific implants. We analyze the principles, advantages, and limitations of each method, highlighting their biomedical applications and the challenges of scalability, material compatibility, and cost. By bridging the gap between laboratory research and clinical implementation, laser-based technologies hold significant promise for advancing personalized medicine and tissue regeneration. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use (3rd Edition))
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