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Biomedical Hydrogels: Synthesis, Design and Applications
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Biomedical Hydrogels: Synthesis, Design and Applications

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Applied Chemistry".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 26515

Special Issue Editors

Prof. Dr. Li-Ming Zhang

E-Mail Website
Guest Editor
Material Science and Engineering School, Sun Yat-sen (Zhongshan) University, Guangzhou 510275, China
Interests: hydrogels; preparation; characterization; applications
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Tze-Wen Chung

E-Mail Website
Guest Editor
Department of Biomedical Engineering, National Yang-Ming University, Taipei 11221, Taiwan
Interests: biomaterials; hydrogels; surface modifications; tissue engineering; functional nanoparticles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural, synthetic, and composite hydrogels have received great attentions for wide biomedical applications. The advances have been achieved in both physically or chemically crosslinked hydrogels. In physically crosslinked hydrogels, the interactions between polymers chains in amphiphilic block and graft copolymers are established by ionic or hydrophobic interactions. In chemically crosslinked hydrogels, the covalent bonds are formed between polymer chains. The crosslinks hydrogels can be generated by radical polymerization, chemical reaction of complementary groups and enzymes. To explore novel biomedical functions, composite hydrogels were widely designed and developed. In this special issue, we will discuss and review recent progress in synthesis, design and applications of varying types of biomedical hydrogels for drug delivery, cell encapsulation, tissue engineering and varying aspects of biomedical applications including self-healing properties.

Prof. Dr. Li Ming Zhang
Prof. Dr. Tze-Wen Chung
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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
  • Drug delivery
  • Cell encapsulation
  • Tissue engineering
  • Biomedical applications

Related Special Issue

Published Papers (7 papers)

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Research

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25 pages, 6383 KiB  
Article
Gallic Acid-Loaded Sodium Alginate-Based (Polyvinyl Alcohol-Co-Acrylic Acid) Hydrogel Membranes for Cutaneous Wound Healing: Synthesis and Characterization
by Abid Naeem, Chengqun Yu, Weifeng Zhu, Xuanbin Chen, Xuan Wu, Lihua Chen, Zhenzhong Zang and Yongmei Guan
Molecules 2022, 27(23), 8397; https://doi.org/10.3390/molecules27238397 - 1 Dec 2022
Cited by 11 | Viewed by 3066
Abstract
Traditional wound dressings often cannot treat wounds caused by bacterial infections or other wound types that are insensitive to these wound treatments. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. The purpose of this study was to develop [...] Read more.
Traditional wound dressings often cannot treat wounds caused by bacterial infections or other wound types that are insensitive to these wound treatments. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. The purpose of this study was to develop a hydrogel membrane comprised of sodium alginate, polyvinyl alcohol, acrylic acid, and gallic acid for treating skin wounds. The newly developed membranes were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), sol-gel fraction, porosity, mechanical strength, swelling, drug release and data modelling, polymeric network parameters, biodegradation, and antioxidation (DPPH and ABTS) and antimicrobial activity against Gram-positive and negative bacteria. The results revealed that hydrogel membranes were crosslinked successfully and had excellent thermal stability, high drug loading, greater mechanical strength, and exhibited excellent biodegradation. Additionally, the swelling ability and the porosity of the surface facilitated a controlled release of the encapsulated drug (gallic acid), with 70.34% release observed at pH 1.2, 70.10% at pH 5.5 (normal skin pH), and 86.24% at pH 7.4 (wounds pH) in 48 h. The gallic acid-loaded hydrogel membranes showed a greater area of inhibition against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli bacteria as well as demonstrated excellent antioxidant properties. Based on Franz cell analyses, the permeation flux of the drug from optimized formulations through mice skin was 92 (pH 5.5) and 110 (pH 7.4) μg/cm2·h−1. Moreover, hydrogel membranes retained significant amounts of drug in the skin for 24 h, such as 2371 (pH 5.5) and 3300 µg/cm2 (pH 7.4). Acute dermal irritation tests in rats showed that hydrogel membranes were nonirritating. Hydrogel membranes containing gallic acid could be an effective option for improving wound healing and could result in faster wound healing. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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19 pages, 3436 KiB  
Article
Carboxymethyl Chitosan and Gelatin Hydrogel Scaffolds Incorporated with Conductive PEDOT Nanoparticles for Improved Neural Stem Cell Proliferation and Neuronal Differentiation
by Shui Guan, Yangbin Wang, Feng Xie, Shuping Wang, Weiping Xu, Jianqiang Xu and Changkai Sun
Molecules 2022, 27(23), 8326; https://doi.org/10.3390/molecules27238326 - 29 Nov 2022
Cited by 9 | Viewed by 1864
Abstract
Tissue engineering scaffolds provide biological and physiochemical cures to guide tissue recovery, and electrical signals through the electroactive materials possess tremendous potential to modulate the cell fate. In this study, a novel electroactive hydrogel scaffold was fabricated by assembling poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles on [...] Read more.
Tissue engineering scaffolds provide biological and physiochemical cures to guide tissue recovery, and electrical signals through the electroactive materials possess tremendous potential to modulate the cell fate. In this study, a novel electroactive hydrogel scaffold was fabricated by assembling poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles on a carboxymethyl chitosan/gelatin (CMCS/Gel) composite hydrogel surface via in situ chemical polymerization. The chemical structure, morphology, conductivity, porosity, swelling rate, in vitro biodegradation, and mechanical properties of the prepared hydrogel samples were characterized. The adhesion, proliferation, and differentiation of neural stem cells (NSCs) on conductive hydrogels were investigated. The CMCS/Gel-PEDOT hydrogels exhibited high porosity, excellent water absorption, improved thermal stability, and adequate biodegradability. Importantly, the mechanical properties of the prepared hydrogels were similar to those of brain tissue, with electrical conductivity up to (1.52 ± 0.15) × 10−3 S/cm. Compared to the CMCS/Gel hydrogel, the incorporation of PEDOT nanoparticles significantly improved the adhesion of NSCs, and supported long-term cell growth and proliferation in a three-dimensional (3D) microenvironment. In addition, under the differentiation condition, the conductive hydrogel also significantly enhanced neuronal differentiation with the up-regulation of β-tubulin III expression. These results suggest that CMCS/Gel-PEDOT hydrogels may be an attractive conductive substrate for further studies on neural tissue repair and regeneration. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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17 pages, 3300 KiB  
Article
In Situ Swelling Formulation of Glycerol-Monooleate-Derived Lyotropic Liquid Crystals Proposed for Local Vaginal Application
by Martine Tarsitano, Antonia Mancuso, Maria Chiara Cristiano, Donatella Paolino and Massimo Fresta
Molecules 2022, 27(19), 6295; https://doi.org/10.3390/molecules27196295 - 23 Sep 2022
Cited by 5 | Viewed by 1546
Abstract
Hydrogels have been extensively investigated to identify innovative formulations that can fulfill all the necessary purposes to improve local vaginal therapy through the mucosa. Herein, we propose in situ-forming lyotropic liquid crystals (LLCs) derived from a cheap and GRAS (generally recognized as safe) [...] Read more.
Hydrogels have been extensively investigated to identify innovative formulations that can fulfill all the necessary purposes to improve local vaginal therapy through the mucosa. Herein, we propose in situ-forming lyotropic liquid crystals (LLCs) derived from a cheap and GRAS (generally recognized as safe) ingredient as an intravaginal delivery system. The system consists of a precursor solution loaded with sertaconazole nitrate as a model drug, which is able to easily swell in a stable three-dimensional structure by absorbing simulated vaginal fluid. Under polarized light microscopy the precursor solution and the formed phase of LLCs showed the typical textures belonging to anisotropic and an isotropic mesophases, respectively. A deep rheological investigation by Kinexus® Pro proved the stability and strength of the cubic phase, as well as its potential in mucoadhesion. In vitro degradation studies showed a slow matrix erosion, consistent with data obtained from lipophilic drug release studies in simulated vaginal fluid. Therefore, the suggested cubic phase based on lyotropic liquid crystals could represent a valid proposal as a vaginal drug delivery system due to its characteristics of resistance, adhesion and the possibility of providing a slow and controlled release of drugs directly at the administration site. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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21 pages, 493 KiB  
Article
Swelling of Thermo-Responsive Gels in Aqueous Solutions of Salts: A Predictive Model
by A. D. Drozdov and J. deClaville Christiansen
Molecules 2022, 27(16), 5177; https://doi.org/10.3390/molecules27165177 - 14 Aug 2022
Viewed by 1023
Abstract
The equilibrium degree of swelling of thermo-responsive (TR) gels is strongly affected by the presence of ions in an aqueous solution. This phenomenon plays an important role in (i) the synthesis of multi-stimuli-responsive gels for soft robotics, where extraordinary strength and toughness are [...] Read more.
The equilibrium degree of swelling of thermo-responsive (TR) gels is strongly affected by the presence of ions in an aqueous solution. This phenomenon plays an important role in (i) the synthesis of multi-stimuli-responsive gels for soft robotics, where extraordinary strength and toughness are reached by soaking of a gel in solutions of multivalent ions, and (ii) the preparation of hybrid gels with interpenetrating networks formed by covalently cross-linked synthetic chains and ionically cross-linked biopolymer chains. A model is developed for equilibrium swelling of a TR gel in aqueous solutions of salts at various temperatures T below and above the critical temperature at which collapse of the gel occurs. An advantage of the model is that it involves a a small (compared with conventional relations) number of material constants and allows the critical temperature to be determined explicitly. Its ability (i) to describe equilibrium swelling diagrams on poly(N-isopropylacrylamide) gels in aqueous solutions of mono- and multivalent salts and (ii) to predict the influence of volume fraction of salt on the critical temperature is confirmed by comparison of observations with results of numerical simulation. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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11 pages, 52976 KiB  
Article
Synthesis of Fibrin-Type I Collagen Biomaterials via an Acidic Gel
by Kun Wang, Marie Camman, Gervaise Mosser, Bernard Haye, Léa Trichet and Thibaud Coradin
Molecules 2022, 27(7), 2099; https://doi.org/10.3390/molecules27072099 - 24 Mar 2022
Cited by 1 | Viewed by 2466
Abstract
Fibrin-Type I collagen composite gels have been widely studied as biomaterials, in which both networks are usually formed simultaneously at a neutral pH. Here, we describe a new protocol in which mixed concentrated solutions of collagen and fibrinogen were first incubated at acidic [...] Read more.
Fibrin-Type I collagen composite gels have been widely studied as biomaterials, in which both networks are usually formed simultaneously at a neutral pH. Here, we describe a new protocol in which mixed concentrated solutions of collagen and fibrinogen were first incubated at acidic pH to induce fibrinogen gel formation, followed by a pH change to neutral inducing collagen fiber formation. Thrombin was then added to form fibrin-collagen networks. Using this protocol, mixed gels containing 20 mg.mL−1 fibrin and up to 10 mg.mL−1 collagen could be prepared. Macroscopic observations evidenced that increasing the content of collagen increases the turbidity of the gels and decreases their shrinkage during the fibrinogen-to-fibrin conversion. The presence of collagen had a minor influence on the rheological properties of the gels. Electron microscopy allowed for observation of collagen fibers within the fibrin network. 2D cultures of C2C12 myoblasts on mixed gels revealed that the presence of collagen favors proliferation and local alignment of the cells. However, it interferes with cell differentiation and myotube formation, suggesting that further control of in-gel collagen self-assembly is required to elaborate fully functional biomaterials. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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Review

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23 pages, 6757 KiB  
Review
Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects
by Peng Fan, Yanbo Zeng, Dionisio Zaldivar-Silva, Lissette Agüero and Shige Wang
Molecules 2023, 28(3), 1473; https://doi.org/10.3390/molecules28031473 - 3 Feb 2023
Cited by 39 | Viewed by 4634
Abstract
The design of new hemostatic materials to mitigate uncontrolled bleeding in emergencies is challenging. Chitosan-based hemostatic hydrogels have frequently been used for hemostasis due to their unique biocompatibility, tunable mechanical properties, injectability, and ease of handling. Moreover, chitosan (CS) absorbs red blood cells [...] Read more.
The design of new hemostatic materials to mitigate uncontrolled bleeding in emergencies is challenging. Chitosan-based hemostatic hydrogels have frequently been used for hemostasis due to their unique biocompatibility, tunable mechanical properties, injectability, and ease of handling. Moreover, chitosan (CS) absorbs red blood cells and activates platelets to promote hemostasis. Benefiting from these desired properties, the hemostatic application of CS hydrogels is attracting ever-increasing research attention. This paper reviews the recent research progress of CS-based hemostatic hydrogels and their advantageous characteristics compared to traditional hemostatic materials. The effects of the hemostatic mechanism, effects of deacetylation degree, relative molecular mass, and chemical modification on the hemostatic performance of CS hydrogels are summarized. Meanwhile, some typical applications of CS hydrogels are introduced to provide references for the preparation of efficient hemostatic hydrogels. Finally, the future perspectives of CS-based hemostatic hydrogels are presented. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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29 pages, 2118 KiB  
Review
Hydrogels: Properties and Applications in Biomedicine
by Tzu-Chuan Ho, Chin-Chuan Chang, Hung-Pin Chan, Tze-Wen Chung, Chih-Wen Shu, Kuo-Pin Chuang, Tsai-Hui Duh, Ming-Hui Yang and Yu-Chang Tyan
Molecules 2022, 27(9), 2902; https://doi.org/10.3390/molecules27092902 - 2 May 2022
Cited by 149 | Viewed by 10358
Abstract
Hydrogels are crosslinked polymer chains with three-dimensional (3D) network structures, which can absorb relatively large amounts of fluid. Because of the high water content, soft structure, and porosity of hydrogels, they closely resemble living tissues. Research in recent years shows that hydrogels have [...] Read more.
Hydrogels are crosslinked polymer chains with three-dimensional (3D) network structures, which can absorb relatively large amounts of fluid. Because of the high water content, soft structure, and porosity of hydrogels, they closely resemble living tissues. Research in recent years shows that hydrogels have been applied in various fields, such as agriculture, biomaterials, the food industry, drug delivery, tissue engineering, and regenerative medicine. Along with the underlying technology improvements of hydrogel development, hydrogels can be expected to be applied in more fields. Although not all hydrogels have good biodegradability and biocompatibility, such as synthetic hydrogels (polyvinyl alcohol, polyacrylamide, polyethylene glycol hydrogels, etc.), their biodegradability and biocompatibility can be adjusted by modification of their functional group or incorporation of natural polymers. Hence, scientists are still interested in the biomedical applications of hydrogels due to their creative adjustability for different uses. In this review, we first introduce the basic information of hydrogels, such as structure, classification, and synthesis. Then, we further describe the recent applications of hydrogels in 3D cell cultures, drug delivery, wound dressing, and tissue engineering. Full article
(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis, Design and Applications)
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