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Gels
Special Issues
Innovations in Application of Biofunctional Hydrogels
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Innovations in Application of Biofunctional Hydrogels

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

Deadline for manuscript submissions: 31 October 2026 | Viewed by 12993

Editors

Dr. Yannan Liu

E-Mail Website
Guest Editor
Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an 710069, China
Interests: hydrogel; tissue engineering; flexible electronics; biomaterial; wound healing; skin
Dr. Yingchun Li

E-Mail Website
Guest Editor
Advanced Interdisciplinary Research Center for Flexible Electronics, Academy of Advanced Interdisciplinary Research, Xidian University, Xi’an 710071, China
Interests: collagen degradation; ginsenoside Rk1; inflammation; oxidative stress; skin photoaging

Special Issue Information

Dear Colleagues,

Biofunctional hydrogels have emerged as a transformative class of materials with tunable physicochemical properties and dynamic bioactivity, enabling their widespread application in diverse fields, such as biomedicine, tissue engineering, drug delivery, and soft bioelectronics. Their ability to mimic the extracellular matrix, respond to physiological stimuli, and interact intelligently with living systems makes them highly attractive for next-generation biomedical technologies. This Special Issue aims to highlight recent innovations in the design, synthesis, characterization, and application of biofunctional hydrogels. We place particular emphasis on their functional integration into complex biological environments, such as dynamic tissue interfaces, wound sites, and implantable devices. Topics of interest include, but are not limited to, smart and responsive hydrogels, bioprintable and injectable hydrogels, hydrogel-based biosensors, and systems for targeted therapy or regenerative medicine. We welcome original research articles and comprehensive reviews that showcase interdisciplinary advances, spanning materials science, bioengineering, chemistry, and medicine. By collecting cutting-edge contributions, this Special Issue seeks to deepen our understanding of structure–property–function relationships and to inspire innovative strategies for engineering advanced hydrogel-based platforms with enhanced performance, biocompatibility, and clinical potential.

Dr. Yannan Liu
Dr. Yingchun Li
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-anonymized 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
  • biofunctional
  • tissue engineering
  • biomedical applications
  • soft electronics
  • biomaterial

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Published Papers (6 papers)

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Research

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16 pages, 3422 KB  
Article
Chlorogenic Acid-Embedded Hydrogel for Visual pH Monitoring and Enhanced Antibacterial Performance
by Yufeng Li, Jia Wang, Yarong Ding, Shitong Zhang, Le Li, Xu Yang, Guishu Yang, Yannan Liu and Yingchun Li
Gels 2026, 12(6), 512; https://doi.org/10.3390/gels12060512 - 9 Jun 2026
Viewed by 610
Abstract
Bacteria-infected wounds remain a major global biomedical challenge, with persistent inflammation and the lack of real-time monitoring significantly impairing wound healing. To address the limitations of conventional dressings, which often provide single-function and static treatment, we developed a multifunctional HP@CGA hydrogel based on [...] Read more.
Bacteria-infected wounds remain a major global biomedical challenge, with persistent inflammation and the lack of real-time monitoring significantly impairing wound healing. To address the limitations of conventional dressings, which often provide single-function and static treatment, we developed a multifunctional HP@CGA hydrogel based on methacrylated hyaluronic acid (HA-MA) and polyvinyl alcohol (PVA), incorporating chlorogenic acid (CGA) and bromothymol blue (BTB). In the presence of a photoinitiator, the methacryloyl groups of HA-MA undergo UV-induced free-radical polymerization to form a covalently crosslinked network, while PVA chains interact with the HA-MA backbone through hydrogen bonding and physical entanglement, resulting in a stable interpenetrating double-network structure. This integrated “treatment + monitoring” design offers a low-cost and convenient alternative to conventional wound dressings and separate sensing systems. Material characterization and preliminary experiments demonstrated that the hydrogel enabled visual pH detection within the range of 6.0–8.0 through distinct color changes. In addition, it exhibited excellent antibacterial activity, achieving antibacterial rates of 99.9% ± 0.08% against both S. aureus and E. coli. These results demonstrate the multifunctional performance of the HP@CGA hydrogel, including bacterial inhibition, inflammation alleviation, and real-time wound pH feedback, thereby providing a favorable microenvironment for infected wound healing. This work highlights the potential of HP@CGA hydrogel for precise and intelligent wound care. Full article
(This article belongs to the Special Issue Innovations in Application of Biofunctional Hydrogels)
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12 pages, 3406 KB  
Article
A 3D Collagen–Alginate Hydrogel Model for Mechanoregulation of Autophagy in Periodontal Ligament Cells
by Xueping Kang, Bei Gao, Tong Wang, Qingbo Zhao, Shiyang Wu, Chuqi Li, Hui Zhang, Rui Zou and Yijie Wang
Gels 2026, 12(1), 91; https://doi.org/10.3390/gels12010091 - 20 Jan 2026
Viewed by 730
Abstract
Mechanical loading is a central cue in periodontal tissues, where compression of the periodontal ligament guides remodeling and orthodontic tooth movement (OTM). However, most mechanobiology studies have used two-dimensional cultures with poorly defined loading, and the role of autophagy under realistic three-dimensional compression [...] Read more.
Mechanical loading is a central cue in periodontal tissues, where compression of the periodontal ligament guides remodeling and orthodontic tooth movement (OTM). However, most mechanobiology studies have used two-dimensional cultures with poorly defined loading, and the role of autophagy under realistic three-dimensional compression remains unclear. In this study, we constructed a three-dimensional static compression model by encapsulating human periodontal ligament cells in collagen–alginate–CaSO4 hydrogels, whose swelling, degradation, and viscoelasticity approximate those of native matrix. When exposed to a controlled static compressive stress, the cells exhibited an early autophagic response with increased ATG7, Beclin1, and LC3-II/LC3-I; accumulation of LC3-positive puncta; and reduced p62 expression between 4 and 8 h. Pharmacological modulation showed that activation of AKT-mTOR signaling suppressed this response, whereas its inhibition further augmented autophagy, identifying AKT-mTOR as a negative regulator of compression-induced autophagy. Together, these findings demonstrate that moderate static compression drives AKT-mTOR-dependent autophagy in periodontal ligament cells and establish a simple hydrogel platform for quantitative studies of periodontal remodeling. Full article
(This article belongs to the Special Issue Innovations in Application of Biofunctional Hydrogels)
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Review

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47 pages, 2334 KB  
Review
Programmable Hydrogels for Surgical Interface Control: Function-Based Design, DNA-Based Molecular Modules, and Translational Evaluation
by Hyun Jung Koh, Jin-Oh Jeong and Hoon Choi
Gels 2026, 12(8), 695; https://doi.org/10.3390/gels12080695 - 4 Aug 2026
Viewed by 273
Abstract
Surgical procedures create dynamic interfaces between tissues, fluids, gases, and applied materials. Failure to control these interfaces can cause leakage, postoperative adhesion, scar tethering, poor tissue integration, maladaptive host responses, or loss of mechanical support. Hydrogels are attractive surgical materials because their hydrated [...] Read more.
Surgical procedures create dynamic interfaces between tissues, fluids, gases, and applied materials. Failure to control these interfaces can cause leakage, postoperative adhesion, scar tethering, poor tissue integration, maladaptive host responses, or loss of mechanical support. Hydrogels are attractive surgical materials because their hydrated polymer networks can be engineered for wet-tissue conformity, adhesion, transport, degradation, mechanical compatibility, and local biological activity. However, many hydrogel systems are still evaluated by polymer chemistry, stimulus type, or isolated physicochemical properties rather than by the operative function required at a defined surgical boundary. This narrative review proposes a function-based framework for designing and evaluating programmable hydrogels in surgical-interface control. Four principal functions—sealing, separation, protection, and integration/reinforcement—are linked to dominant failure modes, design priorities, endpoints, and comparator requirements. Hemostatic and other biological activities are treated as primary clinical claims or adjunct programs when they support these interface functions. Responsiveness is distinguished from clinically meaningful programmability using five operational criteria: input relevance, encoded transition, baseline and off-target stability, interface-level output, and matched-control comparison. DNA-based hydrogels are discussed as molecular modules for recognition, assembly, crosslinking, degradation, actuation, and release, mainly within mechanically robust hybrid systems. This framework emphasizes time-resolved, function-specific evaluation under procedure-relevant conditions. Full article
(This article belongs to the Special Issue Innovations in Application of Biofunctional Hydrogels)
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37 pages, 5704 KB  
Review
β-Hairpin-Based Peptide Hydrogels: The Case of MAX1
by Mariantonietta Pizzella, Valéria Gomes, Enrico Gallo, Sérgio Veloso, Célio Fernandes, Antonella Accardo and Carlo Diaferia
Gels 2026, 12(2), 100; https://doi.org/10.3390/gels12020100 - 24 Jan 2026
Cited by 1 | Viewed by 1832
Abstract
This review explores the advancements and applications of β-hairpin peptide hydrogels, starting from the paradigmatic case of MAX1 and its highly versatile analogue MAX8. MAX1 (H-VKVKVKVKVDPPTKVKVKVKV-NH2) has been identified as the first synthetic β-hairpin peptide for the preparation of [...] Read more.
This review explores the advancements and applications of β-hairpin peptide hydrogels, starting from the paradigmatic case of MAX1 and its highly versatile analogue MAX8. MAX1 (H-VKVKVKVKVDPPTKVKVKVKV-NH2) has been identified as the first synthetic β-hairpin peptide for the preparation of stimuli-responsive peptide-based hydrogels. At low ionic strength or neutral pH, MAX1 remains unfolded and soluble. However, under physiological conditions, it folds into a β-hairpin structure, then producing a self-supporting matrix within minutes. The formed gel is shear-thinning and self-healing, making it suitable for injectable therapies. To explore MAX1 molecular space and enhance its practical clinical use, the primary sequence was engineered via chemical modification, with specific single amino acid substitution and relative net charge alteration. This approach generates MAX1 analogues, differing in gelation kinetics, mechanical response and biological performances. The β-hairpin peptide hydrogels are categorized into five different groups: MAX1, MAX1 analogues, MAX8, MAX8 analogues and non-MAX peptides sequences. Collectively, the review outcomes demonstrate the use of β-hairpin peptide matrices as tunable platforms for the development of predictable and stable biomaterials for advanced tissue engineering and drug delivery applications. Full article
(This article belongs to the Special Issue Innovations in Application of Biofunctional Hydrogels)
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35 pages, 2208 KB  
Review
Recent Advances in Injectable Hydrogels for Biomedical and Aesthetic Applications: Focus on Rheological Characteristics
by Hyerin Lee, Yujin Jeong, Nayeon Lee, Inhye Lee and Jin Hyun Lee
Gels 2026, 12(1), 11; https://doi.org/10.3390/gels12010011 - 23 Dec 2025
Cited by 14 | Viewed by 4270
Abstract
Injectable hydrogels (IHs) have gained considerable interest in biomedical and aesthetic applications due to their minimally invasive delivery, selective localization, and sustained release of bioactive agents. They exhibit flowability during administration and undergo in situ gelation under physiological conditions. These behaviors are influenced [...] Read more.
Injectable hydrogels (IHs) have gained considerable interest in biomedical and aesthetic applications due to their minimally invasive delivery, selective localization, and sustained release of bioactive agents. They exhibit flowability during administration and undergo in situ gelation under physiological conditions. These behaviors are influenced by their tunable structural, physical, mechanical, and viscoelastic properties, modulating performance. Rheological parameters, including viscosity (η), storage modulus (G′), loss modulus (G″), and yield stress (τy) of IHs with time (t), shear rate (γ·), and frequency (f), explaining their shear thinning, thixotropy, viscoelasticity, and gelatin kinetics, serve as key quantitative indicators of their injectability, self-healing capability, and structural and mechanical stability. The rheological characteristics reflect molecular interactions and crosslinking mechanisms within IH networks, thereby linking formulation to provide overall performance, including injectability, biodegradability, and controlled release. This review summarizes recent advances in IHs for diverse applications, with a primary focus on their rheological properties. It also briefly addresses their composition, intermolecular interactions, and correlated function and performance. The applications discussed include hemostatic and wound dressings, tissue engineering and regenerative medicine scaffolds, drug delivery systems, reconstructive and aesthetic materials, and functional bioinks for 3D printing. Overall, this review demonstrates that rheological characterization provides an essential framework for the rational engineering of next-generation IH systems. Full article
(This article belongs to the Special Issue Innovations in Application of Biofunctional Hydrogels)
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41 pages, 2871 KB  
Review
Inflammation-Responsive Hydrogels in Perioperative Pain and Wound Management: Design Strategies and Emerging Potential
by Young Eun Moon, Jin-Oh Jeong and Hoon Choi
Gels 2025, 11(9), 691; https://doi.org/10.3390/gels11090691 - 1 Sep 2025
Cited by 18 | Viewed by 4697
Abstract
Surgical procedures trigger dynamic inflammatory responses that influence postoperative pain, wound healing, and long-term outcomes. Conventional therapies rely on the systemic delivery of anti-inflammatory and analgesic agents, which often lack spatiotemporal precision and carry significant side effects. Inflammation-responsive hydrogels offer a promising alternative [...] Read more.
Surgical procedures trigger dynamic inflammatory responses that influence postoperative pain, wound healing, and long-term outcomes. Conventional therapies rely on the systemic delivery of anti-inflammatory and analgesic agents, which often lack spatiotemporal precision and carry significant side effects. Inflammation-responsive hydrogels offer a promising alternative by enabling localized, stimulus-adaptive drug release aligned with the evolving biochemical milieu of surgical wounds. These smart biomaterials respond to endogenous triggers, such as reactive oxygen species, acidic pH, and proteolytic enzymes, allowing precise modulation of inflammation and tissue repair. This narrative review outlines the pathophysiological features of perioperative inflammation and the design principles of responsive hydrogel systems, including pH-, reactive oxygen species-, enzyme-sensitive, and multi-stimuli platforms. We evaluated the integration of key payloads, NSAIDs, corticosteroids, α2-adrenergic agonists, and biologics, highlighting their therapeutic synergy and translational relevance. Preclinical studies across soft tissue, orthopedic, thoracic, and abdominal models have demonstrated the efficacy of these systems in modulating immune responses, reducing pain, and enhancing regeneration. Despite these encouraging results, challenges remain, including trigger fidelity, surgical compatibility, and regulatory readiness. Future advances in biosensor integration, logic-based design, and artificial intelligence-guided formulation may accelerate clinical translation. Inflammation-responsive hydrogels represent a transformative strategy for precise perioperative care. Full article
(This article belongs to the Special Issue Innovations in Application of Biofunctional Hydrogels)
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