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Gels
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Current Directions and Prospects of Hydrogels for Biomedical Applications
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Current Directions and Prospects of Hydrogels for Biomedical Applications

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

Deadline for manuscript submissions: 28 February 2025 | Viewed by 18986

Special Issue Editors

Dr. Zhiyuan Jia

E-Mail Website
Guest Editor
Biomed Center Innovation gGmbH, Ludwig-Thoma-Strasse 36C, 95447 Bayreuth, Germany
Interests: hydrogels; biosensors; surface modification for bioapplication
Prof. Dr. Holger Schönherr

E-Mail Website
Guest Editor
Physical Chemistry I, Department of Chemistry & Biology & Research Center of Micro and Nanochemistry and (Bio)Technology (Cμ), University of Siegen, Adolf-Reichwein-Str. 2, 57076 Siegen, Germany
Interests: hydrogel sensing materials; bacteria detection; polymer brushes; stimulus-responsive polymers; cell release surfaces; nanobubbles, nanodroplets and nanocapsules; microparticle self-assembly
Dr. Nowsheen Goonoo

E-Mail Website
Guest Editor
Biomaterials, Drug Delivery and Nanotechnology Unit, Centre for Biomedical and Biomaterials Research, University of Mauritius, MSIRI Building, 80837 Réduit, Mauritius
Interests: biomaterials; nanotechnology; regenerative medicine; polymer engineering; cell-material interactions

Special Issue Information

Dear Colleagues, 

Hydrogels are interesting biomaterials due to their high swelling capacity, which allows them to hold and release materials at tailorable rates, as well as their excellent biocompatibility with minimal inflammatory responses. Even though the term ‘hydrogel’ was first coined in 1864, it was not until 1960 that these self-supporting 3D water-swollen viscoelastic polymer networks found their first application in the biomedical field, as reported in the seminal paper co-authored by Wichterle and Lim.

Single-component hydrogel systems have shown limitations due to either poor mechanical properties or insufficient cell-recognition moieties to facilitate cell adhesion and proliferation. To improve the performance of hydrogels in the biomedical field, new synthetic and analytical methods have been used to design more advanced smart and responsive (temperature, pH, light, ultrasound, enzyme, ionic strength, electrical, magnetic, etc.) hydrogels to better suit the targeted biomedical application.

For instance, the inclusion of nanomaterials into hydrogels led to the creation of a new generation of hydrogels known as nanocomposite hydrogels. Self-healing hydrogels have been designed for their own repair, or to help in the healing of damaged tissues.

This Special Issue of Gels focuses on recent innovations related to hydrogels, and showcases state-of-the-art original articles as well as comprehensive reviews in this rapidly evolving field.

Dr. Zhiyuan Jia
Prof. Dr. Holger Schönherr
Dr. Nowsheen Goonoo
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
  • stimuli-responsive materials
  • self-healing
  • nanocomposite
  • biomedical application

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Published Papers (7 papers)

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Research

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13 pages, 1752 KiB  
Article
Customizable Hydrogel Coating of ECM-Based Microtissues for Improved Cell Retention and Tissue Integrity
by Shani Elgin, Eric Silberman, Assaf Shapira and Tal Dvir
Gels 2024, 10(8), 515; https://doi.org/10.3390/gels10080515 - 5 Aug 2024
Viewed by 1176
Abstract
Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are [...] Read more.
Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues’ protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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25 pages, 7411 KiB  
Article
Comprehensive Evaluation of Injectability Attributes in OxiFree™ Dermal Fillers: MaiLi® Product Variants and Clinical Case Reports
by Patrick Micheels, Alexandre Porcello, Thierry Bezzola, Daniel Perrenoud, Marie-Odile Christen, Lee Ann Applegate and Alexis Laurent
Gels 2024, 10(4), 276; https://doi.org/10.3390/gels10040276 - 19 Apr 2024
Viewed by 1592
Abstract
Dermal filler injectability is a critical factor for commercial product adoption by medical aesthetic professionals and for successful clinical administration. We have previously reported (in vitro and ex vivo) cross-linked hyaluronic acid (HA)-based dermal filler benchmarking in terms of manual and automated injectability [...] Read more.
Dermal filler injectability is a critical factor for commercial product adoption by medical aesthetic professionals and for successful clinical administration. We have previously reported (in vitro and ex vivo) cross-linked hyaluronic acid (HA)-based dermal filler benchmarking in terms of manual and automated injectability requirements. To further enhance the function-oriented product characterization workflows and the clinical relevance of dermal filler injectability assessments, the aim of this study was to perform in vivo evaluations. Therefore, several variants of the MaiLi® product range (OxiFree™ technology) were characterized in vitro and in vivo in terms of injectability attributes, with a focus on hydrogel system homogeneity and ease of injection. Firstly, standardized in vitro assays were performed in SimSkin® cutaneous equivalents, with variations of the clinical injector, injection site, and injection technique. Then, automated injections in SimSkin® cutaneous equivalents were comparatively performed in a texture analysis setup to obtain fine-granulometry injection force profile results. Finally, five female participants were recruited for the in vivo arm of the study (case reports), with variations of the clinical injector, injection site, and injection technique. Generally, the obtained quantitative force values and injection force profiles were critically appraised from a translational viewpoint, based on discussions around the OxiFree™ manufacturing technology and on in-use specialized clinician feedback. Overall, the present study outlined a notable level of homogeneity across the MaiLi® product range in terms of injectability attributes, as well as consistently high ease of administration by medical aesthetic clinicians. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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25 pages, 2611 KiB  
Article
Clinical Perspectives on the Injectability of Cross-Linked Hyaluronic Acid Dermal Fillers: A Standardized Methodology for Commercial Product Benchmarking with Inter-Injector Assessments
by Patrick Micheels, Alexandre Porcello, Thierry Bezzola, Daniel Perrenoud, Pierre Quinodoz, Yogeshvar Kalia, Eric Allémann, Alexis Laurent and Olivier Jordan
Gels 2024, 10(2), 101; https://doi.org/10.3390/gels10020101 - 26 Jan 2024
Cited by 7 | Viewed by 4138
Abstract
The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of lidocaine or other functional excipients, types of syringes, and injection techniques. Finished product injectability constitutes a critical quality attribute for clinical [...] Read more.
The injectability of cross-linked hyaluronic acid (HA) dermal fillers is influenced by polymer concentration, polymer cross-linking type and degree, the presence of lidocaine or other functional excipients, types of syringes, and injection techniques. Finished product injectability constitutes a critical quality attribute for clinical injectors, as it strongly influences product applicability and ease of use in aesthetic medicine. While injectable product extrusion force specifications are provided by the respective device manufacturers, the qualitative informative value of such datasets is low for injectors wishing to compare product brands and technologies from an injectability standpoint. Therefore, the present study comparatively assessed 28 cross-linked HA dermal fillers (JUVÉDERM®, Restylane®, BELOTERO®, TEOSYAL RHA®, and STYLAGE® brands) using various injectability benchmarking setups for enhanced clinical-oriented relevance. Manual product injections were performed by three specialized and experienced clinicians, whereas automatic product extrusion was performed using a Texture Analyzer instrument. The various hydrogel products were injected into ex vivo human skin and into SimSkin® cutaneous equivalents to appropriately account for injection-related counterpressure. The injectability results revealed important variability between and within product brands, with a strong influence of the local anesthetic lidocaine, HA contents, and needle gauge size. Critical appraisals of the investigated products were performed, notably from manufacturing process-based and clinical ease of application-based standpoints, centered on respective experimental injectability quality levels. Generally, it was confirmed that each HA-based dermal filler product requires specific expertise for optimal injection, mainly due to differing viscoelastic characteristics and injectability attributes. Overall, the present study set forth evidence-based and clinical-oriented rationale elements confirming the importance for injectors to work with injectable products with which they are experienced and comfortable to optimize clinical results. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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14 pages, 3042 KiB  
Article
Hydrogel-Transformable Antioxidant Poly-γ-Glutamic Acid/Polyethyleneimine Hemostatic Powder for Efficient Wound Hemostasis
by Xiang Li, Wenli Han, Gao He, Jiahao Yang, Jing Li, Hongxia Ma and Shige Wang
Gels 2024, 10(1), 68; https://doi.org/10.3390/gels10010068 - 17 Jan 2024
Cited by 6 | Viewed by 1777
Abstract
Hemostatic powder, which can absorb large amounts of water and tends to produce repeated hydration with tissue, has been clinically proven as an ideal engineering material for treating wounds and tissues. We herein designed a polypeptide-based hemostatic powder. A water-soluble polypeptide, γ-polyglutamic acid [...] Read more.
Hemostatic powder, which can absorb large amounts of water and tends to produce repeated hydration with tissue, has been clinically proven as an ideal engineering material for treating wounds and tissues. We herein designed a polypeptide-based hemostatic powder. A water-soluble polypeptide, γ-polyglutamic acid (γ-PGA), was mixed with the polyethyleneimine (PEI), N-hydroxysuccinimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide. The solution of these polymers was lyophilized to harvest the γ-PGA/PEI powder (PP hemostatic powder). When deposited on a bleeding wound, the PP hemostatic powder can quickly absorb a large amount of blood and interstitial fluid, concentrate coagulation factors, coagulate blood cells, and eventually form a stable mechanical hydrogel. The wound bleeding time of the PP hemostatic powder group was 1.8 ± 0.4 min, significantly lower than that of the commercial chitosan hemostatic powder group (2.8 ± 0.4 min). The PP hemostatic powder was endowed with antioxidant capacity by introducing protocatechuic aldehyde, which can effectively inhibit inflammation and promote wound healing. Therefore, via preparation through a facile lyophilization method, the PP hemostatic powder is expected to find a wide application prospect as a qualified hemostatic powder. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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24 pages, 12286 KiB  
Article
Temperature-Sensitive Hydrogels as Carriers for Modulated Delivery of Acetaminophen
by Snežana Ilić-Stojanović, Ljubiša Nikolić, Vesna Nikolić, Ivan Ristić, Suzana Cakić and Slobodan D. Petrović
Gels 2023, 9(9), 684; https://doi.org/10.3390/gels9090684 - 25 Aug 2023
Cited by 1 | Viewed by 1702
Abstract
The purposes of this study are the polymerization of temperature-sensitive copolymers based on N-isopropyl acrylamide and 10 mol % of 2-hydroxypropylmethacrylate, characterisations of their thermal, morphological and swelling properties, as well as the analysis of potential application in drug-delivery systems. Acetaminophen, the representative [...] Read more.
The purposes of this study are the polymerization of temperature-sensitive copolymers based on N-isopropyl acrylamide and 10 mol % of 2-hydroxypropylmethacrylate, characterisations of their thermal, morphological and swelling properties, as well as the analysis of potential application in drug-delivery systems. Acetaminophen, the representative of non-steroidal anti-inflammatory drugs, was used as a model drug in this study. It is a common pain relief drug, which is also used for fever treatment. However, oral administration comes with certain health risks, mainly the overdose and frequent administration of up to four times a day. The goal of applying temperature-sensitive hydrogel is to enable extended administration once a day, depending on the body temperature. The swelling behavior of the obtained poly(N-isopropyl acrylamide-co-2-hydroxypropylmethacrylate) (p(NIPA/HPMA)) hydrogels and their temperature-sensitivity, kinetics and order of swelling processes at 18 and 38 °C were analyzed. The thermal properties of these hydrogels were observed by the DSC method, and the obtained thermograms showed both melting and glass transitions. The drug delivery system of p(NIPA/HPMA) hydrogels with loaded acetaminophen was analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy methods. Structural analysis of FTIR spectra indicates that non-covalent intermolecular interactions of the type of hydrogen bonds were formed among functional groups of acetaminophen and side-chains of p(NIPA/HPMA) hydrogels. The surface structure of p(NIPA/HPMA) hydrogels after drug loading indicates the acetaminophen presence into the pores of the hydrogel network, and their loading efficiency was higher than 92%. Qualitative and quantitative analysis of acetaminophen, determined by the high-pressure liquid chromatography method, showed that about 90–99% of the loaded amount was released from p(NIPA/HPMA) hydrogels within 24 h. Kinetic parameters of the acetaminophen release under simulated gastrointestinal conditions were determined. Based on obtained results, the drug delivery system of temperature-sensitive p(NIPA/HPMA) hydrogels with loaded acetaminophen could be suitable for additional investigation for modulated drug administration, e.g., for extended drug administration. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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Review

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22 pages, 1763 KiB  
Review
Natural Polymeric Hydrogels Encapsulating Small Molecules for Diabetic Wound Healing
by Elena Iulia Oprita, Andreea Iosageanu and Oana Craciunescu
Gels 2023, 9(11), 867; https://doi.org/10.3390/gels9110867 - 30 Oct 2023
Cited by 4 | Viewed by 2494
Abstract
Diabetes is a condition correlated with a high number of diagnosed chronic wounds as a result of a complex pathophysiological mechanism. Diabetic chronic wounds are characterized by disorganized and longer stages, compared to normal wound healing. Natural polymer hydrogels can act as good [...] Read more.
Diabetes is a condition correlated with a high number of diagnosed chronic wounds as a result of a complex pathophysiological mechanism. Diabetic chronic wounds are characterized by disorganized and longer stages, compared to normal wound healing. Natural polymer hydrogels can act as good wound dressings due to their versatile physicochemical properties, represented mainly by high water content and good biocompatibility. Natural bioactive hydrogels are polymers loaded with bioactive compounds providing antibacterial and antioxidant properties, modulation of inflammation and adherence to wounded tissue, compared to traditional dressings, which enables promising future applications for diabetic wound healing. Natural bioactive compounds, such as polyphenols, polysaccharides and proteins have great advantages in promoting chronic wound healing in diabetes due to their antioxidant, anti-inflammatory, antimicrobial, anti-allergic and wound healing properties. The present paper aims to review the wound healing mechanisms underlining the main issues of chronic wounds and those specifically occurring in diabetes. Also, the review highlights the recent state of the art related to the effect of hydrogels enriched with natural bioactive compounds developed as biocompatible functional materials for improving diabetic-related chronic wound healing and providing novel therapeutic strategies that could prevent limb amputation and increase the quality of life in diabetic patients. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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38 pages, 412 KiB  
Review
Recent Progress in Gels for Neuropathic Pain
by Ciprian Pușcașu, Anca Zanfirescu and Simona Negreș
Gels 2023, 9(5), 417; https://doi.org/10.3390/gels9050417 - 16 May 2023
Cited by 7 | Viewed by 4897
Abstract
Neuropathic pain is a complex and debilitating condition that affects millions of people worldwide. While several treatment options are available, they often have limited efficacy and are associated with adverse effects. In recent years, gels have emerged as a promising option for the [...] Read more.
Neuropathic pain is a complex and debilitating condition that affects millions of people worldwide. While several treatment options are available, they often have limited efficacy and are associated with adverse effects. In recent years, gels have emerged as a promising option for the treatment of neuropathic pain. Inclusion of various nanocarriers, such as cubosomes and niosomes, into gels results in pharmaceutical forms with higher drug stability and increased drug penetration into tissues compared to products currently marketed for the treatment of neuropathic pain. Furthermore, these compounds usually provide sustained drug release and are biocompatible and biodegradable, which makes them a safe option for drug delivery. The purpose of this narrative review was to provide a comprehensive analysis of the current state of the field and identify potential directions for future research in the development of effective and safe gels for the treatment of neuropathic pain, ultimately improving the quality of life for patients suffering from neuropathic pain. Full article
(This article belongs to the Special Issue Current Directions and Prospects of Hydrogels for Biomedical Applications)
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