Hydrogels in Pharmaceutical and Biomedical Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 38843

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Laboratory for the Conception and Application of Bioactive Molecules, Faculty of Pharmacy, University of Strasbourg, 67400 Illkirch-Graffenstaden, France
Interests: microencapsulation; nanoemulsions; biopharmacy; formulation; pharmaceutical engineering
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Special Issue Information

Dear Colleague,

The applications of hydrogels are growing, as is the interest they arouse. Their exceptional physicochemical characteristics allow them to be applied in pharmaceutical and biomedicalsettings, particularly in the administration of drugs (in micro- or nanospheres, or micro- or nanocapsules, using oral or transdermal dosage forms, treatment of cutaneous burns, contact lenses, etc.). They are also found in the treatment of skin burns and commonly used for a wide range of applications in experimental medicine, such as clinical trials. These applications include tissue engineering and regenerative medicine, diagnostics, cell immobilization, separation of biomolecules or cells, and the use of barrier materials to regulate biological adhesions.

Bioinspired hydrogels and biomimetics are important lines of research which could lead to the production of bio-based materials, for example, inspired by the film-filamentous mucus of hagfish. Other important research concerns the 3D printing of "hydrogel skeletons" on which to grow or hook biological muscle fibers and may soon be axons.

This Special Issue dedicated to hydrogels aims to take stock of the latest innovations in the field of hydrogels as well by their chemical aspects (polymerization, crosslinking, supramolecular state), physical (types of interactions, thermodynamics, particular viscosity, mechanics, amorphous structures or crystalline), by their biological applications such as their reactivity to environmental stimuli (pH, ionic strength, temperature, electromagnetic radiation) or their interest in the development of new drug delivery devices or medical devices.

Prof. Dr. Thierry Vandamme
Guest Editor

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Keywords

  • hydrogels
  • bioinspired hydrogels
  • biomaterials
  • drug delivery

Published Papers (17 papers)

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15 pages, 4463 KiB  
Article
Wound Dressings Based on Sodium Alginate–Polyvinyl Alcohol–Moringa oleifera Extracts
by Samir Kamel, Sawsan Dacrory, Peter Hesemann, Nadir Bettache, Lamiaa M. A. Ali, Lou Postel, Engy M. Akl and Mohamed El-Sakhawy
Pharmaceutics 2023, 15(4), 1270; https://doi.org/10.3390/pharmaceutics15041270 - 18 Apr 2023
Cited by 6 | Viewed by 1395
Abstract
Biopolymers have significant pharmaceutical applications, and their blending has favorable characteristics for their pharmaceutical properties compared to the sole components. In this work, sodium alginate (SA) as a marine biopolymer was blended with poly(vinyl) alcohol (PVA) to form SA/PVA scaffolds through the freeze–thawing [...] Read more.
Biopolymers have significant pharmaceutical applications, and their blending has favorable characteristics for their pharmaceutical properties compared to the sole components. In this work, sodium alginate (SA) as a marine biopolymer was blended with poly(vinyl) alcohol (PVA) to form SA/PVA scaffolds through the freeze–thawing technique. Additionally, polyphenolic compounds in Moringa oleifera leaves were extracted by different solvents, and it was found that extracts with 80% methanol had the highest antioxidant activity. Different concentrations (0.0–2.5%) of this extract were successfully immobilized in SA/PVA scaffolds during preparation. The characterization of the scaffolds was carried out via FT-IR, XRD, TG, and SEM. The pure and Moringa oleifera extract immobilized SA/PVA scaffolds (MOE/SA/PVA) showed high biocompatibility with human fibroblasts. Further, they showed excellent in vitro and in vivo wound healing capacity, with the best effect noted for the scaffold with high extract content (2.5%). Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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13 pages, 3463 KiB  
Article
Sustained and Targeted Delivery of Self-Assembled Doxorubicin Nonapeptides Using pH-Responsive Hydrogels for Osteosarcoma Chemotherapy
by Jie Zhu, Rui Gao, Zhongshi Wang, Zhiming Cheng, Zhonghua Xu, Zaiyang Liu, Yiqun Wu, Min Wang and Yuan Zhang
Pharmaceutics 2023, 15(2), 668; https://doi.org/10.3390/pharmaceutics15020668 - 16 Feb 2023
Cited by 3 | Viewed by 1325
Abstract
While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted [...] Read more.
While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted drug delivery system to control drug release and alleviate side effects. In this study, a pH-responsive nonapeptide hydrogel was designed and fabricated for the tumor-targeted drug delivery of doxorubicin (DOX). Using a solid-phase synthesis method, a nonapeptide named P1 peptide that is structurally akin to surfactant-like peptides (SLPs) due to its hydrophobic tail and hydrophilic head was synthesized. The physicochemical properties of the P1 hydrogel were characterized via encapsulation capacity, transmission electron microscopy (TEM), circular dichroism (CD), zeta potential, rheological analysis, and drug release studies. We also used in vitro and in vivo experiments to investigate the cytocompatibility and tumor inhibitory efficacy of the drug-loaded peptide hydrogel. The P1 peptide could self-assemble into biodegradable hydrogels under neutral conditions, and the prepared drug-loaded hydrogels exhibited good injectability and biocompatibility. The in vitro drug release studies showed that DOX-P1 hydrogels had high sensitivity to acidic conditions (pH 5.8 versus 7.4, up to 3.6-fold). Furthermore, the in vivo experiments demonstrated that the DOX-P1 hydrogel could not only amplify the therapeutic effect but also increase DOX accumulation at the tumor site. Our study proposes a promising approach to designing a pH-responsive hydrogel with controlled doxorubicin-release action based on self-assembled nonapeptides for targeted chemotherapy. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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19 pages, 13267 KiB  
Article
Silk Fibroin Bioink for 3D Printing in Tissue Regeneration: Controlled Release of MSC extracellular Vesicles
by Elia Bari, Giulia Maria Di Gravina, Franca Scocozza, Sara Perteghella, Benedetta Frongia, Sara Tengattini, Lorena Segale, Maria Luisa Torre and Michele Conti
Pharmaceutics 2023, 15(2), 383; https://doi.org/10.3390/pharmaceutics15020383 - 22 Jan 2023
Cited by 7 | Viewed by 2902
Abstract
Sodium alginate (SA)-based hydrogels are often employed as bioink for three-dimensional (3D) scaffold bioprinting. They offer a suitable environment for cell proliferation and differentiation during tissue regeneration and also control the release of growth factors and mesenchymal stem cell secretome, which is useful [...] Read more.
Sodium alginate (SA)-based hydrogels are often employed as bioink for three-dimensional (3D) scaffold bioprinting. They offer a suitable environment for cell proliferation and differentiation during tissue regeneration and also control the release of growth factors and mesenchymal stem cell secretome, which is useful for scaffold biointegration. However, such hydrogels show poor mechanical properties, fast-release kinetics, and low biological performance, hampering their successful clinical application. In this work, silk fibroin (SF), a protein with excellent biomechanical properties frequently used for controlled drug release, was blended with SA to obtain improved bioink and scaffold properties. Firstly, we produced a printable SA solution containing SF capable of the conformational change from Silk I (random coil) to Silk II (β-sheet): this transition is a fundamental condition to improve the scaffold’s mechanical properties. Then, the SA-SF blends’ printability and shape fidelity were demonstrated, and mechanical characterization of the printed hydrogels was performed: SF significantly increased compressive elastic modulus, while no influence on tensile response was detected. Finally, the release profile of Lyosecretome—a freeze-dried formulation of MSC-secretome containing extracellular vesicles (EV)—from scaffolds was determined: SF not only dramatically slowed the EV release rate, but also modified the kinetics and mechanism release with respect to the baseline of SA hydrogel. Overall, these results lay the foundation for the development of SA-SF bioinks with modulable mechanical and EV-release properties, and their application in 3D scaffold printing. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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23 pages, 11337 KiB  
Article
GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids
by Nathalie Bock, Farzaneh Forouz, Luke Hipwood, Julien Clegg, Penny Jeffery, Madeline Gough, Tirsa van Wyngaard, Christopher Pyke, Mark N. Adams, Laura J. Bray, Laura Croft, Erik W. Thompson, Thomas Kryza and Christoph Meinert
Pharmaceutics 2023, 15(1), 261; https://doi.org/10.3390/pharmaceutics15010261 - 12 Jan 2023
Cited by 15 | Viewed by 4333
Abstract
3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. [...] Read more.
3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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16 pages, 1620 KiB  
Article
Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils
by Ana Isabel Barbosa, Sofia A. Costa Lima, Ibraheem Yousef and Salette Reis
Pharmaceutics 2023, 15(1), 190; https://doi.org/10.3390/pharmaceutics15010190 - 05 Jan 2023
Cited by 6 | Viewed by 1926
Abstract
Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. Essential oils have been widely used in skin, not only for their remarkable biological properties, but also [...] Read more.
Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids’ fluidization and less lateral packing, characterized by a band at 1468 cm−1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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12 pages, 3696 KiB  
Article
Development of Gelatin-Coated Hydrogel Microspheres for Novel Bioink Design: A Crosslinker Study
by Joshua Zieman, Megan Cohan, Yale Wang, Alexa De La Sancha, Muskan Kanungo, Ryan Azzouz, Rebekah Smith, Keagan Schmidt, Subha Kumpaty, Junhong Chen and Wujie Zhang
Pharmaceutics 2023, 15(1), 90; https://doi.org/10.3390/pharmaceutics15010090 - 27 Dec 2022
Cited by 4 | Viewed by 2277
Abstract
The development of vascularized tissue is a substantial challenge within the field of tissue engineering and regenerative medicine. Studies have shown that positively-charged microspheres exhibit dual-functions: (1) facilitation of vascularization and (2) controlled release of bioactive compounds. In this study, gelatin-coated microspheres were [...] Read more.
The development of vascularized tissue is a substantial challenge within the field of tissue engineering and regenerative medicine. Studies have shown that positively-charged microspheres exhibit dual-functions: (1) facilitation of vascularization and (2) controlled release of bioactive compounds. In this study, gelatin-coated microspheres were produced and processed with either EDC or transglutaminase, two crosslinkers. The results indicated that the processing stages did not significantly impact the size of the microspheres. EDC and transglutaminase had different effects on surface morphology and microsphere stability in a simulated colonic environment. Incorporation of EGM and TGM into bioink did not negatively impact bioprintability (as indicated by density and kinematic viscosity), and the microspheres had a uniform distribution within the scaffold. These microspheres show great potential for tissue engineering applications. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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31 pages, 5185 KiB  
Article
3D Porous Collagen Matrices—A Reservoir for In Vitro Simultaneous Release of Tannic Acid and Chlorhexidine
by Lavinia Brăzdaru, Teodora Staicu, Mădălina Georgiana Albu Kaya, Ciprian Chelaru, Corneliu Ghica, Viorel Cîrcu, Minodora Leca, Mihaela Violeta Ghica and Marin Micutz
Pharmaceutics 2023, 15(1), 76; https://doi.org/10.3390/pharmaceutics15010076 - 26 Dec 2022
Cited by 3 | Viewed by 1523
Abstract
The treatment of wounds occurring accidentally or as a result of chronic diseases most frequently requires the use of appropriate dressings, mainly to ensure tissue regeneration/healing, at the same time as treating or preventing potential bacterial infections or superinfections. Collagen type I-based scaffolds [...] Read more.
The treatment of wounds occurring accidentally or as a result of chronic diseases most frequently requires the use of appropriate dressings, mainly to ensure tissue regeneration/healing, at the same time as treating or preventing potential bacterial infections or superinfections. Collagen type I-based scaffolds in tandem with adequate antimicrobials can successfully fulfill these requirements. In this work, starting from the corresponding hydrogels, we prepared a series of freeze-dried atelocollagen type I-based matrices loaded with tannic acid (TA) and chlorhexidine digluconate (CHDG) as active agents with a broad spectrum of antimicrobial activity and also as crosslinkers for the collagen network. The primary aim of this study was to design an original and reliable algorithm to in vitro monitor and kinetically analyze the simultaneous release of TA and CHDG from the porous matrices into an aqueous solution of phosphate-buffered saline (PBS, pH 7.4, 37 °C) containing micellar carriers of a cationic surfactant (hexadecyltrimethylammonium bromide, HTAB) as a release environment that roughly mimics human extracellular fluids in living tissues. Around this central idea, a comprehensive investigation of the lyophilized matrices (morpho-structural characterization through FT-IR spectroscopy, scanning electron microscopy, swelling behavior, resistance against the collagenolytic action of collagenase type I) was carried out. The kinetic treatment of the release data displayed a preponderance of non-Fickian–Case II diffusion behavior, which led to a general anomalous transport mechanism for both TA and CHDG, irrespective of their concentrations. This is equivalent to saying that the release regime is not governed only by the gradient concentration of the releasing components inside and outside the matrix (like in ideal Fickian diffusion), but also, to a large extent, by the relaxation phenomena of the collagen network (determined, in turn, by its crosslinking degree induced by TA and CHDG) and the dynamic capacity of the HTAB micelles to solubilize the two antimicrobials. By controlling the degree of physical crosslinking of collagen with a proper content of TA and CHDG loaded in the matrix, a tunable, sustainable release profile can be obtained. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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22 pages, 4822 KiB  
Article
Enzymatic Crosslinked Hydrogels of Gelatin and Poly (Vinyl Alcohol) Loaded with Probiotic Bacteria as Oral Delivery System
by Aldo F. Corona-Escalera, Ernesto Tinajero-Díaz, Rudy A. García-Reyes, Gabriel Luna-Bárcenas, Ali Seyfoddin, José Daniel Padilla-de la Rosa, Marisela González-Ávila and Zaira Y. García-Carvajal
Pharmaceutics 2022, 14(12), 2759; https://doi.org/10.3390/pharmaceutics14122759 - 09 Dec 2022
Cited by 2 | Viewed by 2208
Abstract
Probiotic bacteria are widely used to prepare pharmaceutical products and functional foods because they promote and sustain health. Nonetheless, probiotic viability is prone to decrease under gastrointestinal conditions. In this investigation, Lactiplantibacillus plantarum spp. CM-CNRG TB98 was entrapped in a gelatin–poly (vinyl alcohol) [...] Read more.
Probiotic bacteria are widely used to prepare pharmaceutical products and functional foods because they promote and sustain health. Nonetheless, probiotic viability is prone to decrease under gastrointestinal conditions. In this investigation, Lactiplantibacillus plantarum spp. CM-CNRG TB98 was entrapped in a gelatin–poly (vinyl alcohol) (Gel–PVA) hydrogel which was prepared by a “green” route using microbial transglutaminase (mTGase), which acts as a crosslinking agent. The hydrogel was fully characterized and its ability to entrap and protect L. plantarum from the lyophilization process and under simulated gastric and intestine conditions was explored. The Gel–PVA hydrogel showed a high probiotic loading efficiency (>90%) and survivability from the lyophilization process (91%) of the total bacteria entrapped. Under gastric conditions, no disintegration of the hydrogel was observed, keeping L. plantarum protected with a survival rate of >94%. While in the intestinal fluid the hydrogel is completely dissolved, helping to release probiotics. A Gel–PVA hydrogel is suitable for a probiotic oral administration system due to its physicochemical properties, lack of cytotoxicity, and the protection it offers L. plantarum under gastric conditions. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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14 pages, 3041 KiB  
Article
Thrombin and Factor Xa Hydrolysis of Chromogenic Substrates in the Presence of Sulfated Derivatives of Galactomannan and Galactoglucomannan Natural Gels
by Natalia N. Drozd, Svetlana A. Kuznetsova, Yuriy N. Malyar, Aleksandr S. Kazachenko, Valentina S. Borovkova and Yarosvala D. Berezhnaya
Pharmaceutics 2022, 14(12), 2678; https://doi.org/10.3390/pharmaceutics14122678 - 01 Dec 2022
Cited by 1 | Viewed by 1605
Abstract
Polysaccharides are important structural components of all plant species. Gel-like polysaccharides have found wide application in various fields, including medicine, construction, and the food industry. In the present work, galactomannan and galactoglucomannan gel-like polysaccharides were modified with sulfate groups and their anticoagulant activity [...] Read more.
Polysaccharides are important structural components of all plant species. Gel-like polysaccharides have found wide application in various fields, including medicine, construction, and the food industry. In the present work, galactomannan and galactoglucomannan gel-like polysaccharides were modified with sulfate groups and their anticoagulant activity was studied. Sulfation with chlorosulfonic acid in pyridine and with sulfamic acid in pyridine and a sulfamic acid–urea deep eutectic solvent were used as synthesis routes. The resulting gel-like polysaccharide sulfates were studied by elemental analysis, Fourier-transform infrared spectroscopy, and gel permeation chromatography. It was established that the anticoagulant effect of sulfated galactoglucomannan (SGGM) and galactomannan (SGM-1 and SGM-2) is related to an independent antithrombin-independent decrease in the amidolytic activity of thrombin and factor Xa. It is shown that the inhibitory activity of SGGM and SGM-2 against the collagen-induced platelet aggregation can be an additional factor in selecting compounds that are most promising for modifying polymer surfaces to ensure resistance to blood clotting. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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17 pages, 5675 KiB  
Article
Influence of Cedar Essential Oil on Physical and Biological Properties of Hemostatic, Antibacterial, and Antioxidant Polyvinyl Alcohol/Cedar Oil/Kaolin Composite Hydrogels
by Tamer M. Tamer, Maysa M. Sabet, Zahrah A. H. Alhalili, Ahmed M. Ismail, Mohamed S. Mohy-Eldin and Mohamed A. Hassan
Pharmaceutics 2022, 14(12), 2649; https://doi.org/10.3390/pharmaceutics14122649 - 29 Nov 2022
Cited by 17 | Viewed by 2361
Abstract
Polyvinyl alcohol (PVA) is a safe and biodegradable polymer. Given the unique physical and chemical properties of PVA, we physically cross-linked PVA with kaolin (K) and cedar essential oil (Ced) using the freeze-thawing approach to fabricate PVA/Ced/K sponge hydrogels as hemostatic, antibacterial, and [...] Read more.
Polyvinyl alcohol (PVA) is a safe and biodegradable polymer. Given the unique physical and chemical properties of PVA, we physically cross-linked PVA with kaolin (K) and cedar essential oil (Ced) using the freeze-thawing approach to fabricate PVA/Ced/K sponge hydrogels as hemostatic, antibacterial, and antioxidant wound healing materials. The physicochemical characteristics of PVA/Ced/K hydrogels, including water swelling profiles and gel fractions, were surveyed. Additionally, the functional groups of hydrogels were explored by Fourier transform infrared spectroscopy (FTIR), while their microstructures were studied using scanning electron microscopy (SEM). Furthermore, the thermal features of the hydrogels were probed by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Evidently, alterations in cedar concentrations resulted in significant variations in size, water uptake profiles, and hydrolytic degradation of the hydrogels. The incorporation of cedar into the PVA/K endowed the hydrogels with significantly improved antibacterial competency against Bacillus cereus (B. cereus) and Escherichia coli (E. coli). Moreover, PVA/Ced/K exhibited high scavenging capacities toward ABTS•+ and DPPH free radicals. Beyond that, PVA/Ced/K hydrogels demonstrated hemocompatibility and fast blood clotting performance in addition to biocompatibility toward fibroblasts. These findings accentuate the prospective implementation of PVA/Ced/K composite hydrogel as a wound dressing. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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13 pages, 5499 KiB  
Article
Immunomodulatory PEG-CRGD Hydrogels Promote Chondrogenic Differentiation of PBMSCs
by Meng Yang, Rong-Hui Deng, Fu-Zhen Yuan, Ji-Ying Zhang, Zi-Ning Zhang, You-Rong Chen and Jia-Kuo Yu
Pharmaceutics 2022, 14(12), 2622; https://doi.org/10.3390/pharmaceutics14122622 - 28 Nov 2022
Cited by 5 | Viewed by 1307
Abstract
Cartilage damage is a common injury. Currently, tissue engineering scaffolds with composite seed cells have emerged as a promising approach for cartilage repair. Polyethylene glycol (PEG) hydrogels are attractive tissue engineering scaffold materials as they have high water absorption capacity as well as [...] Read more.
Cartilage damage is a common injury. Currently, tissue engineering scaffolds with composite seed cells have emerged as a promising approach for cartilage repair. Polyethylene glycol (PEG) hydrogels are attractive tissue engineering scaffold materials as they have high water absorption capacity as well as nontoxic and nutrient transport properties. However, PEG is fundamentally bio-inert and lacks intrinsic cell adhesion capability, which is critical for the maintenance of cell function. Cell adhesion peptides are usually added to improve the cell adhesion capability of PEG-based hydrogels. The suitable cell adhesion peptide can not only improve cell adhesion capability, but also promote chondrogenesis and regulate the immune microenvironment. To improve the interactions between cells and PEG hydrogels, we designed cysteine-arginine-glycine-aspartic acid (CRGD), a cell adhesion peptide covalently cross-linked with PEG hydrogels by a Michael addition reaction, and explored the tissue-engineering hydrogels with immunomodulatory effects and promoted chondrogenic differentiation of mesenchymal stem cells (MSCs). The results indicated that CRGD improved the interaction between peripheral blood mesenchymal stem cells (PBMSCs) and PEG hydrogels. PEG hydrogels modified with 1 mM CRGD had the optimal capacity to promote chondrogenic differentiation, and CRGD could induce macrophage polarization towards the M2 phenotype to promote tissue regeneration and repair. PEG-CRGD hydrogels combined with PBMSCs have the potential to be suitable scaffolds for cartilage tissue engineering. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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20 pages, 2491 KiB  
Article
Multi-Crosslinked Strong and Elastic Bioglass/Chitosan-Cysteine Hydrogels with Controlled Quercetin Delivery for Bone Tissue Engineering
by Qing Min, Ronghua Tan, Yuchen Zhang, Congcong Wang, Ying Wan and Jing Li
Pharmaceutics 2022, 14(10), 2048; https://doi.org/10.3390/pharmaceutics14102048 - 26 Sep 2022
Cited by 5 | Viewed by 1656
Abstract
Chitosan-cysteine (CH-CY) conjugate with an optimal content of thiol groups was synthesized and combined with amino-functionalized mesoporous bioglass (ABG) nanoparticles (NPs) with radially-porous architecture to build multi-crosslinked ABG/CH-CY composite hydrogels. Besides the network formed by self-crosslinking of thiol groups in CY-derived side chains, [...] Read more.
Chitosan-cysteine (CH-CY) conjugate with an optimal content of thiol groups was synthesized and combined with amino-functionalized mesoporous bioglass (ABG) nanoparticles (NPs) with radially-porous architecture to build multi-crosslinked ABG/CH-CY composite hydrogels. Besides the network formed by self-crosslinking of thiol groups in CY-derived side chains, difunctionalized PEG (DF-P) crosslinkers with varying lengths of PEG segments were used to crosslink amino groups on CH-CY or ABG NPs to form other networks in the composite gels. Quercetin (Que) was loaded into ABG NPs before these NPs were incorporated into the hydrogel, intending to achieve sustainable and controllable Que release from so-built ABG/CH-CY gels. The lengths of PEG segments in DF-P were found to impose remarkable impacts on the strength or elasticity of multi-crosslinked ABG/CH-CY hydrogels. Some ABG/CH-CY hydrogels had their elastic modulus of around 8.2 kPa or higher along with yielding strains higher than 70%, specifying their mechanically strong and elastic characteristics. In addition, these gels showed the ability to release Que and Si or Ca ions in controllable ways for various durations. The optimally achieved ABG/CH-CY hydrogels were injectable and also able to support the growth of seeded MC3T3-E1 cells as well as the specific matrix deposition. The obtained results suggest that these ABG/CH-CY gels have promising potential for bone repair and regeneration. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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17 pages, 4657 KiB  
Article
Alginate/Chitosan-Based Hydrogel Film Containing α-Mangostin for Recurrent Aphthous Stomatitis Therapy in Rats
by Tiana Milanda, Faradila Ratu Cindana Mo’o, Ahmed Fouad Abdelwahab Mohammed, Khaled M. Elamin, Gofarana Wilar, Ine Suharyani and Nasrul Wathoni
Pharmaceutics 2022, 14(8), 1709; https://doi.org/10.3390/pharmaceutics14081709 - 16 Aug 2022
Cited by 4 | Viewed by 2287
Abstract
Recurrent aphthous stomatitis (RAS) is a prevalent clinical disorder that causes mouth ulcers. Furthermore, corticosteroid treatment has been widely utilized for RAS therapy; however, it has side effects on the oral mucosa that limit its application. This study aimed to develop a novel [...] Read more.
Recurrent aphthous stomatitis (RAS) is a prevalent clinical disorder that causes mouth ulcers. Furthermore, corticosteroid treatment has been widely utilized for RAS therapy; however, it has side effects on the oral mucosa that limit its application. This study aimed to develop a novel RAS therapy with the natural ingredient α-mangostin, delivered by alginate and chitosan polymers-based hydrogel film (α-M Alg/Chi-HF). To prepare α-M Alg/Chi-HF, the solvent evaporation and casting methods were used, then characterized by using SEM, FTIR, and XRD. Based on the characterization studies, the α-M in α-M/EtOH Alg/Chi-HF with ethanol (EtOH) was found to be more homogenous compared to α-M in Alg/Chi-HF with distilled water (H2O) as a casting solvent. The in vitro viability study using NIH3T3 cells showed 100% viability of α-M Alg/Chi-HF (EtOH) and Alg/Chi-HF after 24 h incubation, indicating well tolerability of these hydrogel films. Interestingly, the in vivo studies using male white rats (Rattus norvegicus Berkenhout) proved that α-M/EtOH Alg/Chi-HF with a recovery of 81.47 ± 0.09% in seven days significantly more effective RAS therapy compared to control. These results suggest that α-M/EtOH Alg/Chi-HF has the potential as an alternative for RAS therapy. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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19 pages, 3009 KiB  
Article
Microgels Formed by Spontaneous Click Chemistries Utilizing Microfluidic Flow Focusing for Cargo Release in Response to Endogenous or Exogenous Stimuli
by Paige J. LeValley, Amanda L. Parsons, Bryan P. Sutherland, Kristi L. Kiick, John S. Oakey and April M. Kloxin
Pharmaceutics 2022, 14(5), 1062; https://doi.org/10.3390/pharmaceutics14051062 - 15 May 2022
Cited by 2 | Viewed by 2570
Abstract
Protein therapeutics have become increasingly popular for the treatment of a variety of diseases owing to their specificity to targets of interest. However, challenges associated with them have limited their use for a range of ailments, including the limited options available for local [...] Read more.
Protein therapeutics have become increasingly popular for the treatment of a variety of diseases owing to their specificity to targets of interest. However, challenges associated with them have limited their use for a range of ailments, including the limited options available for local controlled delivery. To address this challenge, degradable hydrogel microparticles, or microgels, loaded with model biocargoes were created with tunable release profiles or triggered burst release using chemistries responsive to endogenous or exogeneous stimuli, respectively. Specifically, microfluidic flow-focusing was utilized to form homogenous microgels with different spontaneous click chemistries that afforded degradation either in response to redox environments for sustained cargo release or light for on-demand cargo release. The resulting microgels were an appropriate size to remain localized within tissues upon injection and were easily passed through a needle relevant for injection, providing means for localized delivery. Release of a model biopolymer was observed over the course of several weeks for redox-responsive formulations or triggered for immediate release from the light-responsive formulation. Overall, we demonstrate the ability of microgels to be formulated with different materials chemistries to achieve various therapeutic release modalities, providing new tools for creation of more complex protein release profiles to improve therapeutic regimens. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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24 pages, 9247 KiB  
Article
Click-Chemistry Cross-Linking of Hyaluronan Graft Copolymers
by Mario Saletti, Marco Paolino, Lavinia Ballerini, Germano Giuliani, Gemma Leone, Stefania Lamponi, Marco Andreassi, Claudia Bonechi, Alessandro Donati, Daniele Piovani, Alberto Giacometti Schieroni, Agnese Magnani and Andrea Cappelli
Pharmaceutics 2022, 14(5), 1041; https://doi.org/10.3390/pharmaceutics14051041 - 11 May 2022
Cited by 5 | Viewed by 2161
Abstract
An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking [...] Read more.
An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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Review

Jump to: Research

24 pages, 4773 KiB  
Review
Nanomaterials-Incorporated Chemically Modified Gelatin Methacryloyl-Based Biomedical Composites: A Novel Approach for Bone Tissue Engineering
by Abigail Herrera-Ruiz, Benjamín Betancourt Tovar, Rubén Gutiérrez García, María Fernanda Leal Tamez and Narsimha Mamidi
Pharmaceutics 2022, 14(12), 2645; https://doi.org/10.3390/pharmaceutics14122645 - 29 Nov 2022
Cited by 15 | Viewed by 2791
Abstract
Gelatin methacryloyl (GelMA)-based composites are evolving three-dimensional (3D) networking hydrophilic protein composite scaffolds with high water content. These protein composites have been devoted to biomedical applications due to their unique abilities, such as flexibility, soft structure, versatility, stimuli-responsiveness, biocompatibility, biodegradability, and others. They [...] Read more.
Gelatin methacryloyl (GelMA)-based composites are evolving three-dimensional (3D) networking hydrophilic protein composite scaffolds with high water content. These protein composites have been devoted to biomedical applications due to their unique abilities, such as flexibility, soft structure, versatility, stimuli-responsiveness, biocompatibility, biodegradability, and others. They resemble the native extracellular matrix (ECM) thanks to their remarkable cell-adhesion and matrix-metalloproteinase (MMP)-responsive amino acid motifs. These favorable properties promote cells to proliferate and inflate within GelMA-protein scaffolds. The performance of GelMA composites has been enriched using cell-amenable components, including peptides and proteins with a high affinity to harmonize cellular activities and tissue morphologies. Due to their inimitable merits, GelMA systems have been used in various fields such as drug delivery, biosensor, the food industry, biomedical, and other health sectors. The current knowledge and the role of GelMA scaffolds in bone tissue engineering are limited. The rational design and development of novel nanomaterials-incorporated GelMA-based composites with unique physicochemical and biological advantages would be used to regulate cellular functionality and bone regeneration. Substantial challenges remain. This review focuses on recent progress in mitigating those disputes. The study opens with a brief introduction to bone tissue engineering and GelMA-based composites, followed by their potential applications in bone tissue engineering. The future perspectives and current challenges of GelMA composites are demonstrated. This review would guide the researchers to design and fabricate more efficient multifunctional GelMA-based composites with improved characteristics for their practical applications in bone tissue engineering and biomedical segments. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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25 pages, 2571 KiB  
Review
3D Bioprinting Using Hydrogels: Cell Inks and Tissue Engineering Applications
by Annika C. Dell, Grayson Wagner, Jason Own and John P. Geibel
Pharmaceutics 2022, 14(12), 2596; https://doi.org/10.3390/pharmaceutics14122596 - 24 Nov 2022
Cited by 10 | Viewed by 2395
Abstract
3D bioprinting is transforming tissue engineering in medicine by providing novel methods that are precise and highly customizable to create biological tissues. The selection of a “cell ink”, a printable formulation, is an integral part of adapting 3D bioprinting processes to allow for [...] Read more.
3D bioprinting is transforming tissue engineering in medicine by providing novel methods that are precise and highly customizable to create biological tissues. The selection of a “cell ink”, a printable formulation, is an integral part of adapting 3D bioprinting processes to allow for process optimization and customization related to the target tissue. Bioprinting hydrogels allows for tailorable material, physical, chemical, and biological properties of the cell ink and is suited for biomedical applications. Hydrogel-based cell ink formulations are a promising option for the variety of techniques with which bioprinting can be achieved. In this review, we will examine some of the current hydrogel-based cell inks used in bioprinting, as well as their use in current and proposed future bioprinting methods. We will highlight some of the biological applications and discuss the development of new hydrogels and methods that can incorporate the completed print into the tissue or organ of interest. Full article
(This article belongs to the Special Issue Hydrogels in Pharmaceutical and Biomedical Applications)
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