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Engineering Hydrogel for Biomedical Applications

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

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 21486

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Prof. Dr. Junfeng Shi

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Guest Editor

School of Biomedical Sciences, Hunan University, Changsha 410012, China
Interests: polypeptide self-assembly; gelation and its biomedical applications
Special Issues, Collections and Topics in MDPI journals

Dr. Fei Xu

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Guest Editor

Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada
Interests: biomaterials; tissue engineering; drug delivery; biofabrication; hydrogels
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The special issue on “Engineering Hydrogel for Biomedical Applications” is dedicated to the recent development of hydrogel chemistries and properties for biomedical applications including tissue engineering, drug delivery and cell encapsulation. More than that, the advanced techniques used for hydrogel preparation will be also encouraged to discuss, such as 3D bioprinting and electrospinning to prepare structured hydrogels or techniques to fabricate microgels for drug/cell encapsulation.

Hydrogels have been widely applied for the biomedical fields given their excellent relevant physiochemical and biological properties such as hydrophilicity, biomimetic mechanics, low protein absorption, and non-toxicity. Various biomaterials, containing natural and synthetic materials, have been used to prepare multiple hydrogels through different crosslinking mechanisms. The practical use of hydrogel in biomedical applications requires development in hydrogel compositions (e.g., chemistry, crosslinking, mechanics, biological cues, degradability, etc.) and hydrogel structure (e.g., porous network, nanofibrous structure, alignment, etc.). Recently, the translation of hydrogels from lab to clinic has attracted significant attention, which accelerate the development of biofabrication of hydrogels. Techniques such as electrospinning and 3D bioprinting, have been developed to fabricate scaffolds for in vivo tissue engineering and wound healing, which shows a great potential for clinic use and commercialization.

Given it is too challenging to include all aspects of hydrogels in one issue, this special issue will focus on the engineering hydrogel chemistries and structures for biomedical applications. We look forward to the submission of new results in hydrogel research. The submission of studies relating to hydrogels for tissue engineering, cell encapsulation, drug delivery and wound healing is appreciated.

Prof. Dr. Junfeng Shi
Dr. Fei Xu
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 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hydrogel synthesis
hydrogel structure
biofabrication
tissue engineering
drug delivery
cell encapsulation
wound healing

Published Papers (10 papers)

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Research

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12 pages, 276 KiB

Open AccessArticle

Hydrogel Coating versus Calcium Sulphate Beads as a Local Antibiotic Carrier for Debridement Procedures in Acute Periprosthetic Joint Infection: A Preliminary Study

by Daniele De Meo, Paolo Martini, Maria Francesca Pennarola, Giovanni Guarascio, Marco Rivano Capparuccia, Giancarlo Iaiani, Vittorio Candela, Stefano Gumina and Ciro Villani

Gels 2023, 9(9), 758; https://doi.org/10.3390/gels9090758 - 18 Sep 2023

Viewed by 986

Abstract

Periprosthetic joint infections (PJI) are among the most difficult complications to treat in orthopaedic surgery. Debridement, antibiotics, and implant retention (DAIR) represent an efficient strategy for acute PJI, especially when resorbable local antibiotic carriers and coatings are used. The aim of this pilot study was to evaluate the difference between using antibiotic-loaded hydrogel (ALH) and calcium sulphate (CS) beads in the DAIR procedure. We analysed 16 patients who had been treated since 2018 for acute PJI, namely eight patients with knee PJI (50%), seven with hip PJI (43.7%), and one with shoulder PJI (6.2%). Nine patients were treated with the Debridement, Antibiotic Coating and Retention of the Implant (DACRI) method, while seven were treated with the Debridement, Antibiotic Pearls, Retention of the Implant (DAPRI) method. We found no significant differences between the two groups in terms of age, sex, the American Society of Anesthesiologists risk score, Charlson Comorbidity Index, localisation, days from onset to diagnosis and pathogenesis. Furthermore, no differences were found between the DACRI and DAPRI groups in terms of infection control (15 patients, 93.75% with p = 0.36) and last C-Reactive Protein values (p = 0.26), with a mean follow-up of 26.1 ± 7.7 months. Treatment for one patient affected by knee Candida albicans PJI in the DACRI group was not successful. In conclusion, DAPRI and DACRI appear to be safe and effective treatments for PJIs. This evidence will encourage the development of new clinical research into local carriers and coatings for use in acute implant-associated infections. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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13 pages, 3660 KiB

Open AccessArticle

3D Printing Type 1 Bovine Collagen Scaffolds for Tissue Engineering Applications—Physicochemical Characterization and In Vitro Evaluation

by Vasudev Vivekanand Nayak, Nick Tovar, Doha Khan, Angel Cabrera Pereira, Dindo Q. Mijares, Marcus Weck, Alejandro Durand, James E. Smay, Andrea Torroni, Paulo G. Coelho and Lukasz Witek

Gels 2023, 9(8), 637; https://doi.org/10.3390/gels9080637 - 08 Aug 2023

Cited by 2 | Viewed by 1484

Abstract

Collagen, an abundant extracellular matrix protein, has shown hemostatic, chemotactic, and cell adhesive characteristics, making it an attractive choice for the fabrication of tissue engineering scaffolds. The aim of this study was to synthesize a fibrillar colloidal gel from Type 1 bovine collagen, as well as three dimensionally (3D) print scaffolds with engineered pore architectures. 3D-printed scaffolds were also subjected to post-processing through chemical crosslinking (in N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide) and lyophilization. The scaffolds were physicochemically characterized through Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis, Differential Scanning Calorimetry, and mechanical (tensile) testing. In vitro experiments using Presto Blue and Alkaline Phosphatase assays were conducted to assess cellular viability and the scaffolds’ ability to promote cellular proliferation and differentiation. Rheological analysis indicated shear thinning capabilities in the collagen gels. Crosslinked and lyophilized 3D-printed scaffolds were thermally stable at 37 °C and did not show signs of denaturation, although crosslinking resulted in poor mechanical strength. PB and ALP assays showed no signs of cytotoxicity as a result of crosslinking. Fibrillar collagen was successfully formulated into a colloidal gel for extrusion through a direct inkjet writing printer. 3D-printed scaffolds promoted cellular attachment and proliferation, making them a promising material for customized, patient-specific tissue regenerative applications. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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27 pages, 3213 KiB

Open AccessArticle

Exploring the Impact of Alginate—PVA Ratio and the Addition of Bioactive Substances on the Performance of Hybrid Hydrogel Membranes as Potential Wound Dressings

by Diana Stan, Elena Codrici, Ana-Maria Enciu, Ewa Olewnik-Kruszkowska, Georgiana Gavril, Lavinia Liliana Ruta, Carmen Moldovan, Oana Brincoveanu, Lorena-Andreea Bocancia-Mateescu, Andreea-Cristina Mirica, Dana Stan and Cristiana Tanase

Gels 2023, 9(6), 476; https://doi.org/10.3390/gels9060476 - 09 Jun 2023

Cited by 2 | Viewed by 1944

Abstract

Healthcare professionals face an ongoing challenge in managing both acute and chronic wounds, given the potential impact on patients’ quality of life and the limited availability of expensive treatment options. Hydrogel wound dressings offer a promising solution for effective wound care due to their affordability, ease of use, and ability to incorporate bioactive substances that enhance the wound healing process. Our study aimed to develop and evaluate hybrid hydrogel membranes enriched with bioactive components such as collagen and hyaluronic acid. We utilized both natural and synthetic polymers and employed a scalable, non-toxic, and environmentally friendly production process. We conducted extensive testing, including an in vitro assessment of moisture content, moisture uptake, swelling rate, gel fraction, biodegradation, water vapor transmission rate, protein denaturation, and protein adsorption. We evaluated the biocompatibility of the hydrogel membranes through cellular assays and performed instrumental tests using scanning electron microscopy and rheological analysis. Our findings demonstrate that the biohybrid hydrogel membranes exhibit cumulative properties with a favorable swelling ratio, optimal permeation properties, and good biocompatibility, all achieved with minimal concentrations of bioactive agents. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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18 pages, 2657 KiB

Open AccessArticle

Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization

by Ghufran Ullah, Asif Nawaz, Muhammad Shahid Latif, Kifayat Ullah Shah, Saeed Ahmad, Fatima Javed, Mulham Alfatama, Siti Aisyah Abd Ghafar and Vuanghao Lim

Gels 2023, 9(1), 43; https://doi.org/10.3390/gels9010043 - 04 Jan 2023

Cited by 3 | Viewed by 2984

Abstract

Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs’ and excipients’ compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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13 pages, 2674 KiB

Open AccessArticle

Photosensitive Hydrogel-Based Embolic Agent Treatment of Wide-Necked Aneurysms: Preliminary Animal Results

by Jerry C. Ku, Yuta Dobashi, Christopher R. Pasarikovski, Joel Ramjist, Clement Hamani, Chinthaka Heyn, Konrad Walus and Victor X. D. Yang

Gels 2022, 8(12), 788; https://doi.org/10.3390/gels8120788 - 01 Dec 2022

Viewed by 1863

Abstract

Background: The endovascular treatment of cerebral aneurysms has become widespread but may still be limited by recurrence rates or complications. The discovery of novel embolic strategies may help mitigate these concerns. Methods: We formulated a Photosensitive Hydrogel Polymer (PHP) embolic agent which is low-viscosity, shear-thinning, and radio-opaque. After the filling of an aneurysm with PHP with balloon assistance, we utilized photopolymerization to induce solidification. Different methods of light delivery for photopolymerization were assessed in silicone models of aneurysms and in four acute animal trials with venous anastomosis aneurysms in pigs. Then, balloon-assisted embolization with PHP and photopolymerization was performed in three aneurysms in pigs with a one-month follow-up. Filling volume, recurrence rates, and complications were recorded. Results: The PHP was found to be suitable for the intravascular delivery and treatment of cerebral aneurysms. It was found that light delivery through the balloon catheter, as opposed to light delivery through the injection microcatheter, led to higher rates of filling in the 3D model and acute animal model for cerebral aneurysms. Using the balloon-assisted embolization and light delivery strategy, three wide-necked aneurysms were treated without complication. One-month follow-up showed no recurrence or neck remnants. Conclusions: We demonstrated a novel method of balloon-assisted photosensitive hydrogel polymer embolization and photopolymerization, leading to complete aneurysm filling with no recurrence at 1 month in three wide-necked aneurysms in pigs. This promising methodology will be investigated further with longer-term comparative animal trials. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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14 pages, 4793 KiB

Open AccessArticle

Enhanced Delivery of Insulin through Acrylamide-Modified Chitosan Containing Smart Carrier System

by Wasmia Mohammed Dahan, Faruq Mohammad, AbdelRahman O. Ezzat, Ayman M. Atta, Hissah Hamad Al-Tilasi and Hamad A. Al-Lohedan

Gels 2022, 8(11), 701; https://doi.org/10.3390/gels8110701 - 30 Oct 2022

Cited by 3 | Viewed by 1383

Abstract

The present study develops on insulin-release studies from the chitosan-amide-modified stimuli-responsive polymers formed from various fatty acids including stearic acid, oleic acid, linoleic acid, and linolenic acid. This is the continuation of an earlier reported study that investigates the insulin-release profiles of chitosan-modified fatty acid amides (without stimuli responsive polymers). Following the synthesis and characterization of many different fatty acid amides with a varying amount of unsaturation, the insulin drug loading and release effects were compared among N-isopropylacrylamide (NIPAm), a thermo-responsive polymer, and 2-acrylamide-2-methylpropane sulfonic acid (AMPS), a pH-responsive polymer-modified hydrogel that is expected to enhance environmental response and the controllability of release. Finally, drug release effects were studied to investigate the drug release mechanisms with the help of five different pharmacokinetic models including the zero-order, first-order, Higuchi, Korsmeyers–Peppas, and Hixson models. The results indicate that the Higuchi and Hixson models are valid in terms of the operation of the NIPAm and AMPS matrices during the delivery of insulin. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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15 pages, 2711 KiB

Open AccessArticle

Printing Structurally Anisotropic Biocompatible Fibrillar Hydrogel for Guided Cell Alignment

by Zhengkun Chen, Nancy Khuu, Fei Xu, Sina Kheiri, Ilya Yakavets, Faeze Rakhshani, Sofia Morozova and Eugenia Kumacheva

Gels 2022, 8(11), 685; https://doi.org/10.3390/gels8110685 - 22 Oct 2022

Cited by 7 | Viewed by 1930

Abstract

Many fibrous biological tissues exhibit structural anisotropy due to the alignment of fibers in the extracellular matrix. To study the impact of such anisotropy on cell proliferation, orientation, and mobility, it is important to recapitulate and achieve control over the structure of man-made hydrogel scaffolds for cell culture. Here, we report a chemically crosslinked fibrous hydrogel due to the reaction between aldehyde-modified cellulose nanofibers and gelatin. We explored two ways to induce structural anisotropy in this gel by extruding the hydrogel precursor through two different printheads. The cellulose nanofibers in the hydrogel ink underwent shear-induced alignment during extrusion and retained it in the chemically crosslinked hydrogel. The degree of anisotropy was controlled by the ink composition and extrusion flow rate. The structural anisotropy of the hydrogel extruded through a nozzle affected the orientation of human dermal fibroblasts that were either seeded on the hydrogel surface or encapsulated in the extruded hydrogel. The reported straightforward approach to constructing fibrillar hydrogel scaffolds with structural anisotropy can be used in studies of the biological impact of tissue anisotropy. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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18 pages, 3493 KiB

Open AccessArticle

In Vitro Evaluation of Smart and pH-Sensitive Chondroitin Sulfate/Sodium Polystyrene Sulfonate Hydrogels for Controlled Drug Delivery

by Muhammad Suhail, I-Hui Chiu, Ming-Chia Hung, Quoc Lam Vu, I-Ling Lin and Pao-Chu Wu

Gels 2022, 8(7), 406; https://doi.org/10.3390/gels8070406 - 25 Jun 2022

Cited by 7 | Viewed by 2472

Abstract

Ibuprofen is an antipyretic and analgesic drug used for the management of different inflammatory diseases, such as rheumatoid arthritis and osteoarthritis. Due to a short half-life and rapid elimination, multiple doses of ibuprofen are required in a day to maintain pharmacological action for a long duration of time. Due to multiple intakes of ibuprofen, certain severe adverse effects, such as gastric irritation, bleeding, ulcers, and abdominal pain are produced. Therefore, a system is needed which not only prolongs the release of ibuprofen but also overcomes the drug’s adverse effects. Hence, the authors have synthesized chondroitin sulfate/sodium polystyrene sulfonate–co-poly(acrylic acid) hydrogels by the free radical polymerization technique for the controlled release of ibuprofen. Sol-gel, porosity, swelling, and drug release studies were performed on the fabricated hydrogel. The pH-responsive behavior of the fabricated hydrogel was determined by both swelling and drug release studies in three different pH values, i.e., pH 1.2, 4.6, and 7.4. Maximum swelling and drug release were observed at pH 7.4, as compared to pH 4.6 and 1.2. Similarly, the structural arrangement and crosslinking of the hydrogel contents were confirmed by Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) evaluated the hard and irregular surface with a few macrospores of the developed hydrogel, which may be correlated with the strong crosslinking of polymers with monomer content. Similarly, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) demonstrated the high thermal stability of the formulated hydrogel, as compared to pure polymers. A decrease in the crystallinity of chondroitin sulfate and sodium polystyrene sulfonate after crosslinking was revealed by powder X-ray diffraction (PXRD). Thus, considering the results, we can demonstrate that a developed polymeric network of hydrogel could be used as a safe, stable, and efficient carrier for the controlled release of ibuprofen. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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15 pages, 1488 KiB

Open AccessReview

Hydrogels for Salivary Gland Tissue Engineering

by Sangeeth Pillai, Jose G. Munguia-Lopez and Simon D. Tran

Gels 2022, 8(11), 730; https://doi.org/10.3390/gels8110730 - 10 Nov 2022

Cited by 3 | Viewed by 3359

Abstract

Mimicking the complex architecture of salivary glands (SGs) outside their native niche is challenging due their multicellular and highly branched organization. However, significant progress has been made to recapitulate the gland structure and function using several in vitro and ex vivo models. Hydrogels are polymers with the potential to retain a large volume of water inside their three-dimensional structure, thus simulating extracellular matrix properties that are essential for the cell and tissue integrity. Hydrogel-based culture of SG cells has seen a tremendous success in terms of developing platforms for cell expansion, building an artificial gland, and for use in transplantation to rescue loss of SG function. Both natural and synthetic hydrogels have been used widely in SG tissue engineering applications owing to their properties that support the proliferation, reorganization, and polarization of SG epithelial cells. While recent improvements in hydrogel properties are essential to establish more sophisticated models, the emphasis should still be made towards supporting factors such as mechanotransduction and associated signaling cues. In this concise review, we discuss considerations of an ideal hydrogel-based biomaterial for SG engineering and their associated signaling pathways. We also discuss the current advances made in natural and synthetic hydrogels for SG tissue engineering applications. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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18 pages, 979 KiB

Open AccessReview

Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering

by Filipe Miguel, Frederico Barbosa, Frederico Castelo Ferreira and João Carlos Silva

Gels 2022, 8(11), 710; https://doi.org/10.3390/gels8110710 - 03 Nov 2022

Cited by 6 | Viewed by 2066

Abstract

Articular cartilage is a highly specialized tissue found in diarthrodial joints, which is crucial for healthy articular motion. Despite its importance, articular cartilage has limited regenerative capacities, and the degeneration of this tissue is a leading cause of disability worldwide, with hundreds of millions of people affected. As current treatment options for cartilage degeneration remain ineffective, tissue engineering has emerged as an exciting approach to create cartilage substitutes. In particular, hydrogels seem to be suitable candidates for this purpose due to their biocompatibility and high customizability, being able to be tailored to fit the biophysical properties of native cartilage. Furthermore, these hydrogel matrices can be combined with conductive materials in order to simulate the natural electrochemical properties of articular cartilage. In this review, we highlight the most common conductive materials combined with hydrogels and their diverse applications, and then present the current state of research on the development of electrically conductive hydrogels for cartilage tissue engineering. Finally, the main challenges and future perspectives for the application of electrically conductive hydrogels on articular cartilage repair strategies are also discussed. Full article

(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)

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