Latest Advances 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: 20 December 2024 | Viewed by 12272

Special Issue Editors


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Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
Interests: biomaterials; multifunctional carriers; drug delivery systems (DDS); micro- and nanoparticles; hydrogel; membranes

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
Interests: drug delivery systems (DDS); biomaterials; multifunctional carriers; micro-and nano-particles; pro-drugs
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
Interests: drug delivery systems (DDS); biomaterials; multifunctional carriers; micro- and nano-particles; pro-drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, hydrogels have received increasing attention as materials for biomedical applications because they are biocompatible and non-toxic. They consist of three-dimensional hydrophilic polymeric networks that can absorb large amounts of water or biological fluids due to the presence of hydrophilic groups, and are considered excellent candidates for biosensors, drug delivery vectors, wound healing, and vectors or cell matrices in tissue engineering. Depending on their characteristics, they can be natural or synthetic and classified as neutral or ionic hydrogels, while the network can consist of linear homopolymers, linear copolymers and block or graft copolymers. They can also be reactive to various stimuli, including heating, pH, light, and chemicals. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small molecules and macromolecular drugs. They possess modulable physical properties and the ability to protect labile drugs from degradation by controlling their release; furthermore, due to their high biodegradability, low immunogenicity, ability to be transformed into solids, semi-solids, and liquids, and due to their ease of use, they are widely used in biomedicine. This Special Issue covers all aspects concerning recent studies on the design, preparation, and performance evaluation of hydrogels for biomedical applications.

Dr. Federica Curcio
Prof. Dr. Roberta Cassano
Prof. Dr. Sonia Trombino
Guest Editors

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Keywords

  • hydrogels
  • biomedical application
  • drug delivery
  • scaffold
  • tissue engineering
  • biosensor
  • wound healing
  • stimuli responsive
  • method realization

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Published Papers (7 papers)

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Research

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22 pages, 5087 KiB  
Article
Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement
by Alexandre Porcello, Michèle Chemali, Cíntia Marques, Corinne Scaletta, Kelly Lourenço, Philippe Abdel-Sayed, Wassim Raffoul, Nathalie Hirt-Burri, Lee Ann Applegate and Alexis Laurent
Gels 2024, 10(6), 361; https://doi.org/10.3390/gels10060361 - 24 May 2024
Cited by 1 | Viewed by 1463
Abstract
Hyaluronic acid (HA) hydrogels are commonly used for facial dermal filling and for alternative medical aesthetic purposes. High diversity exists in commercial formulations, notably for the optimization of finished product stability, functionality, and performance. Polyvalent ingredients such as calcium hydroxylapatite (CaHA) or vitamin [...] Read more.
Hyaluronic acid (HA) hydrogels are commonly used for facial dermal filling and for alternative medical aesthetic purposes. High diversity exists in commercial formulations, notably for the optimization of finished product stability, functionality, and performance. Polyvalent ingredients such as calcium hydroxylapatite (CaHA) or vitamin B3 (niacinamide) are notably used as bio-stimulants to improve skin quality attributes at the administration site. The aim of the present study was to perform multi-parametric characterization of two novel cross-linked dermal filler formulas (HAR-1 “Instant Refine” and HAR-3 “Maxi Lift”) for elucidation of the various functional impacts of vitamin B3 incorporation. Therefore, the HAR products were firstly comparatively characterized in terms of in vitro rheology, cohesivity, injectability, and resistance to chemical or enzymatic degradation (exposition to H2O2, AAPH, hyaluronidases, or xanthine oxidase). Then, the HAR products were assessed for cytocompatibility and in vitro bio-stimulation attributes in a primary dermal fibroblast model. The results showed enhanced resilience of the cohesive HAR hydrogels as compared to JUVÉDERM® VOLBELLA® and VOLUMA® reference products in a controlled degradation assay panel. Furthermore, significant induction of total collagen synthesis in primary dermal fibroblast cultures was recorded for HAR-1 and HAR-3, denoting intrinsic bio-stimulatory effects comparable or superior to those of the Radiesse® and Sculptra reference products. Original results of high translational relevance were generated herein using robust and orthogonal experimental methodologies (hydrogel degradation, functional benchmarking) and study designs. Overall, the reported results confirmed the dual functionalization role of vitamin B3 in cross-linked HA dermal fillers, with a significant enhancement of hydrogel system stability attributes and the deployment of potent bio-stimulatory capacities. Full article
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29 pages, 23868 KiB  
Article
Active Media Perfusion in Bioprinted Highly Concentrated Collagen Bioink Enhances the Viability of Cell Culture and Substrate Remodeling
by Denisa Kanokova, Roman Matejka, Margit Zaloudkova, Jan Zigmond, Monika Supova and Jana Matejkova
Gels 2024, 10(5), 316; https://doi.org/10.3390/gels10050316 - 5 May 2024
Viewed by 1528
Abstract
The bioprinting of high-concentrated collagen bioinks is a promising technology for tissue engineering and regenerative medicine. Collagen is a widely used biomaterial for bioprinting because of its natural abundance in the extracellular matrix of many tissues and its biocompatibility. High-concentrated collagen hydrogels have [...] Read more.
The bioprinting of high-concentrated collagen bioinks is a promising technology for tissue engineering and regenerative medicine. Collagen is a widely used biomaterial for bioprinting because of its natural abundance in the extracellular matrix of many tissues and its biocompatibility. High-concentrated collagen hydrogels have shown great potential in tissue engineering due to their favorable mechanical and structural properties. However, achieving high cell proliferation rates within these hydrogels remains a challenge. In static cultivation, the volume of the culture medium is changed once every few days. Thus, perfect perfusion is not achieved due to the relative increase in metabolic concentration and no medium flow. Therefore, in our work, we developed a culture system in which printed collagen bioinks (collagen concentration in hydrogels of 20 and 30 mg/mL with a final concentration of 10 and 15 mg/mL in bioink) where samples flow freely in the culture medium, thus enhancing the elimination of nutrients and metabolites of cells. Cell viability, morphology, and metabolic activity (MTT tests) were analyzed on collagen hydrogels with a collagen concentration of 20 and 30 mg/mL in static culture groups without medium exchange and with active medium perfusion; the influence of pure growth culture medium and smooth muscle cells differentiation medium was next investigated. Collagen isolated from porcine skins was used; every batch was titrated to optimize the pH of the resulting collagen to minimize the difference in production batches and, therefore, the results. Active medium perfusion significantly improved cell viability and activity in the high-concentrated gel, which, to date, is the most limiting factor for using these hydrogels. In addition, based on SEM images and geometry analysis, the cells remodel collagen material to their extracellular matrix. Full article
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20 pages, 3875 KiB  
Article
Insight into CMC-PVA-fHNTs Nanocomposite Hydrogel as an Advance Carrier for Cefadroxil Monohydrate: Fabrication and Characterization/Angiogenic Potential Analysis
by Saba Zia, Shahzad Maqsood Khan, Muhammad Taqi Zahid Butt and Nafisa Gull
Gels 2024, 10(4), 235; https://doi.org/10.3390/gels10040235 - 29 Mar 2024
Cited by 2 | Viewed by 1513
Abstract
Controlled drug delivery is a key strategy aimed at reducing both the frequency of therapeutic dosages and potential systemic side effects, particularly in the case of high drug concentrations. The nanocomposite hydrogel systems presented in this study were synthesized by combining carboxymethyl cellulose, [...] Read more.
Controlled drug delivery is a key strategy aimed at reducing both the frequency of therapeutic dosages and potential systemic side effects, particularly in the case of high drug concentrations. The nanocomposite hydrogel systems presented in this study were synthesized by combining carboxymethyl cellulose, polyvinyl alcohol, and (3-aminopropyl)triethoxysilane-functionalized halloysite nanotubes (fHNTs). This hydrogel system is a potential candidate for the controlled release of cefadroxil monohydrate. These hydrogels are analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and rheological measurements. Additionally, swelling properties, porosity, hydrophilicity, drug release, and in vitro and in vivo analyses were also evaluated. The observed trends in swelling and drug release demonstrated that the outcomes are dependent on the presence of fHNTs in the hydrogel matrix. Notably, fHNTs-loaded hydrogels displayed sustained drug release patterns. This innovative approach eliminates the need for traditional encapsulation and presents promising and translatable strategies for achieving more effective drug release. Full article
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14 pages, 3664 KiB  
Article
Pluronic 123 Liquid Lyotropic Crystals for Transdermal Delivery of Caffeic Acid—Insights from Structural Studies and Drug Release
by Martina Romeo, Elisabetta Mazzotta, Francesca Lovati, Michele Porto, Cesare Oliviero Rossi and Rita Muzzalupo
Gels 2024, 10(3), 181; https://doi.org/10.3390/gels10030181 - 6 Mar 2024
Viewed by 1335
Abstract
Background: This study aims to evaluate the percutaneous permeation profiles of caffeic acid (CA) from the cubic and hexagonal liquid crystalline phases of Pluronic P123/water mixtures. Method: The resulting drug-loaded mesophases were subjected to characterisation through deuterium nuclear magnetic resonance spectroscopy and polarised [...] Read more.
Background: This study aims to evaluate the percutaneous permeation profiles of caffeic acid (CA) from the cubic and hexagonal liquid crystalline phases of Pluronic P123/water mixtures. Method: The resulting drug-loaded mesophases were subjected to characterisation through deuterium nuclear magnetic resonance spectroscopy and polarised optical microscopy observations. These analyses aimed to evaluate the structural changes that occurred in the mesophases loading with CA. Additionally, steady and dynamic rheology studies were conducted to further explore their mechanical properties and correlate them to the supramolecular structure. Finally, CA release experiments were carried out at two different temperatures to examine the behaviour of the structured systems in a physiological or hyperthermic state. Results: As the concentration of the polymer increases, an increase in the viscosity of the gel is noted; however, the addition of caffeic acid increases microstructure fluidity. It is observed that the temperature effect conforms to expectations. The increase in temperature causes a decrease in viscosity and, consequently, an increase in the rate of permeation of caffeic acid. Conclusions: The CA permeation profile from the prepared formulations is mostly dependent on the structural organisation and temperature. Cubic mesophase LLC 30/CA showed greater skin permeation with good accumulation in the skin at both tested temperatures. Full article
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21 pages, 3930 KiB  
Article
Cross-Linked Hyaluronan Derivatives in the Delivery of Phycocyanin
by Francesca Terracina, Mario Saletti, Marco Paolino, Jacopo Venditti, Germano Giuliani, Claudia Bonechi, Mariano Licciardi and Andrea Cappelli
Gels 2024, 10(2), 91; https://doi.org/10.3390/gels10020091 - 25 Jan 2024
Cited by 2 | Viewed by 1647
Abstract
An easy and viable crosslinking technology, based on the “click-chemistry” reaction copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (click-crosslinking), was applied to graft copolymers of medium molecular weight (i.e., 270 kDa) hyaluronic acid (HA) grafted with ferulic acid (FA) residues bearing clickable [...] Read more.
An easy and viable crosslinking technology, based on the “click-chemistry” reaction copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (click-crosslinking), was applied to graft copolymers of medium molecular weight (i.e., 270 kDa) hyaluronic acid (HA) grafted with ferulic acid (FA) residues bearing clickable propargyl groups, as well as caffeic acid derivatives bearing azido-terminated oligo(ethylene glycol) side chains. The obtained crosslinked materials were characterized from the point of view of their structure and aggregation liability to form hydrogels in a water environment. The most promising materials showed interesting loading capability regarding the antioxidant agent phycocyanin (PC). Two novel materials complexes (namely HA(270)-FA-TEGEC-CL-20/PC and HA(270)-FA-HEGEC-CL-20/PC) were obtained with a drug-to-material ratio of 1:2 (w/w). Zeta potential measurements of the new complexes (−1.23 mV for HA(270)-FA-TEGEC-CL-20/PC and −1.73 mV for HA(270)-FA-HEGEC-CL-20/PC) showed alterations compared to the zeta potential values of the materials on their own, suggesting the achievement of drug–material interactions. According to the in vitro dissolution studies carried out in different conditions, novel drug delivery systems (DDSs) were obtained with a variety of characteristics depending on the desired route of administration and, consequently, on the pH of the surrounding environment, thanks to the complexation of phycocyanin with these two new crosslinked materials. Both complexes showed excellent potential for providing a controlled/prolonged release of the active pharmaceutical ingredient (API). They also increased the amount of drug that reach the target location, enabling pH-dependent release. Importantly, as demonstrated by the DPPH free radical scavenging assay, the complexation process, involving freezing and freeze-drying, showed no adverse effects on the antioxidant activity of phycocyanin. This activity was preserved in the two novel materials and followed a concentration-dependent pattern similar to pure PC. Full article
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15 pages, 6650 KiB  
Article
In Situ Hydrogel Formulation for Advanced Wound Dressing: Influence of Co-Solvents and Functional Excipient on Tailored Alginate–Pectin–Chitosan Blend Gelation Kinetics, Adhesiveness, and Performance
by Chiara Amante, Giovanni Falcone, Rita P. Aquino, Paola Russo, Luigi Nicolais and Pasquale Del Gaudio
Gels 2024, 10(1), 3; https://doi.org/10.3390/gels10010003 - 20 Dec 2023
Cited by 2 | Viewed by 2144
Abstract
Chronic skin wounds affect more than 40 million patients worldwide, representing a huge problem for healthcare systems. This study elucidates the optimization of an in situ gelling polymer blend powder for biomedical applications through the use of co-solvents and functional excipients, underlining the [...] Read more.
Chronic skin wounds affect more than 40 million patients worldwide, representing a huge problem for healthcare systems. This study elucidates the optimization of an in situ gelling polymer blend powder for biomedical applications through the use of co-solvents and functional excipients, underlining the possibility of tailoring microparticulate powder properties to generate, in situ, hydrogels with advanced properties that are able to improve wound management and patient well-being. The blend was composed of alginate, pectin, and chitosan (APC). Various co-solvents (ethanol, isopropanol, and acetone), and salt excipients (sodium bicarbonate and ammonium carbonate) were used to modulate the gelation kinetics, rheology, adhesiveness, and water vapor transmission rate of the gels. The use of co-solvents significantly influenced particle size (mean diameter ranging from 2.91 to 5.05 µm), depending on the solvent removal rate. Hydrogels obtained using ethanol were able to absorb over 15 times their weight in simulated wound fluid within just 5 min, whereas when sodium bicarbonate was used, complete gelation was achieved in less than 30 s. Such improvement was related to the internal microporous network typical of the particle matrix obtained with the use of co-solvents, whereas sodium bicarbonate was able to promote the formation of allowed particles. Specific formulations demonstrated an optimal water vapor transmission rate, enhanced viscoelastic properties, gel stiffness, and adhesiveness (7.7 to 9.9 kPa), facilitating an atraumatic removal post-use with minimized risk of unintended removal. Microscopic analysis unveiled that porous inner structures were influencing fluid uptake, gel formation, and transpiration. In summary, this study provided valuable insights for optimizing tailored APC hydrogels as advanced wound dressings for chronic wounds, including vascular ulcers, pressure ulcers, and partial and full-thickness wounds, characterized by a high production of exudate. Full article
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Review

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21 pages, 4872 KiB  
Review
OnyxTMGel or Coil versus Hydrogel as Embolic Agents in Endovascular Applications: Review of the Literature and Case Series
by Paolo Perri, Giuseppe Sena, Paolo Piro, Tommaso De Bartolo, Stefania Galassi, Davide Costa and Raffaele Serra
Gels 2024, 10(5), 312; https://doi.org/10.3390/gels10050312 - 2 May 2024
Viewed by 1805
Abstract
This review focuses on the use of conventional gel or coil and “new” generation hydrogel used as an embolic agent in endovascular applications. In general, embolic agents have deep or multidistrict vascular penetration properties as they ensure complete occlusion of vessels by exploiting [...] Read more.
This review focuses on the use of conventional gel or coil and “new” generation hydrogel used as an embolic agent in endovascular applications. In general, embolic agents have deep or multidistrict vascular penetration properties as they ensure complete occlusion of vessels by exploiting the patient’s coagulation system, which recognises them as substances foreign to the body, thus triggering the coagulation cascade. This is why they are widely used in the treatment of endovascular corrections (EV repair), arteriovenous malformations (AVM), endoleaks (E), visceral aneurysms or pseudo-aneurysms, and embolisation of pre-surgical or post-surgical (iatrogenic) lesions. Conventional gels such as Onyx or coils are now commercially available, both of which are frequently used in endovascular interventional procedures, as they are minimally invasive and have numerous advantages over conventional open repair (OR) surgery. Recently, these agents have been modified and optimised to develop new embolic substances in the form of hydrogels based on alginate, chitosan, fibroin and other polymers to ensure embolisation through phase transition phenomena. The main aim of this work was to expand on the data already known in the literature concerning the application of these devices in the endovascular field, focusing on the advantages, disadvantages and safety profiles of conventional and innovative embolic agents and also through some clinical cases reported. The clinical case series concerns the correction and exclusion of endoleak type I or type II appeared after an endovascular procedure of exclusion of aneurysmal abdominal aortic (EVAR) with a coil (coil penumbra released by a LANTERN microcatheter), the exclusion of renal arterial malformation (MAV) with a coil (penumbra coil released by a LANTERN microcatheter) and the correction of endoleak through the application of Onyx 18 in the arteries where sealing by the endoprosthesis was not guaranteed. Full article
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