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Hydrogel for Tissue Regeneration

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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 (31 August 2024) | Viewed by 23569

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Special Issue Editor

Dr. Dongrim Seol

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Guest Editor

Department of Orthopedics and Rehabilitation, College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Interests: hydrogel; tissue regeneration; osteoarthritis; exosome; intervertebral disc degeneration; arthrofibrosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hydrogels have most commonly been used as a scaffold for tissue regeneration due to their potential to stimulate the construction of an extracellular matrix via a distinct 3-Dimentional structure and to deliver drugs, stem/progenitor cells, and extracellular vesicles/exosomes. The Special Issue, “Hydrogel for Tissue Regeneration”, aims to collect high-quality research and review articles in all the fields of gel materials, with a focus on application of tissue regeneration and engineering. Since the aim of this issue is to illustrate selected works and frontier research in hydrogel materials science, we encourage materials scientists, chemists, or clinical investigators to contribute papers reflecting the latest progress in their research fields. As Guest Editors, we would kindly invite you to contribute a research paper or a review on any topic related to this thread, including but not limited to:

New development and characterization of hydrogels;
Tissue regeneration/engineering;
Delivery of stem/progenitor cells, drugs, RNA, DNA, gene, and extracellular vesicles/exosomes;
3D printing, electrospinning, and molding-based injectable gels.

Dr. Dongrim Seol
Guest Editor

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.

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Keywords

hydrogel
tissue regeneration/engineering
stem/progenitor cells
drugs
RNA
DNA
gene
extracellular vesicles/exosomes
3D printing
electrospinning
molding-based injectable gels

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Published Papers (10 papers)

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Research

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16 pages, 5782 KiB

Open AccessArticle

Vancomycin-Loaded Silk Fibroin/Calcium Phosphate/Methylcellulose-Based In Situ Thermosensitive Hydrogel: A Potential Function for Bone Regeneration

by Premchirakorn Phewchan, Artit Laoruengthana, Pratthana Chomchalao, Supaporn Lamlertthon and Waree Tiyaboonchai

Gels 2024, 10(11), 695; https://doi.org/10.3390/gels10110695 - 25 Oct 2024

Viewed by 575

Abstract

This study explores the efficacy of a vancomycin-loaded silk fibroin/calcium phosphate/methylcellulose-based in situ thermosensitive hydrogel (VM-SF/CaP/MC) in promoting the osteogenic differentiation of preosteoblast cells. Three VM-SF/CaP/MC formulations with varying low (L) and high (H) concentrations of silk fibroin (SF) and calcium phosphate (CaP) were prepared: VM-HSF/LCaP/MC, VM-LSF/HCaP/MC, and VM-HSF/HCaP/MC. These hydrogels significantly enhanced MC3T3-E1 cell migration and proliferation in a dose- and time-dependent manner, achieving complete cell migration within 48 h. In addition, they significantly promoted alkaline phosphatase activity, collagen content, and mineralization in MC3T3-E1 cells, indicating their potential for osteogenesis. Among the hydrogel formulations, the VM-HSF/HCaP/MC hydrogel, with high SF and CaP content, demonstrated superior potential in promoting the osteogenic differentiation of MC3T3-E1 cells. It exhibited the highest ALP activity (11.13 ± 0.91 U/mg protein) over 14 days, along with increased collagen content (54.00 ± 1.71 µg/mg protein) and mineralization (15.79 ± 1.48 mM) over 35 days. Therefore, this formulation showed a promising candidate for clinical application in localized bone regeneration, particularly in treating osteomyelitis. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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22 pages, 7021 KiB

Open AccessEditor’s ChoiceArticle

Impact of Fibrin Gel Architecture on Hepatocyte Growth Factor Release and Its Role in Modulating Cell Behavior for Tissue Regeneration

by Svenja Wein, Shannon Anna Jung, Miriam Aischa Al Enezy-Ulbrich, Luca Reicher, Stephan Rütten, Mark Kühnel, Danny Jonigk, Wilhelm Jahnen-Dechent, Andrij Pich and Sabine Neuss

Gels 2024, 10(6), 402; https://doi.org/10.3390/gels10060402 - 16 Jun 2024

Viewed by 1065

Abstract

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of Hepatocyte Growth Factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF’s regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF’s long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold–cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF’s bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche, thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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27 pages, 2869 KiB

Open AccessArticle

Powdered Cross-Linked Gelatin Methacryloyl as an Injectable Hydrogel for Adipose Tissue Engineering

by Tess De Maeseneer, Lana Van Damme, Merve Kübra Aktan, Annabel Braem, Paula Moldenaers, Sandra Van Vlierberghe and Ruth Cardinaels

Gels 2024, 10(3), 167; https://doi.org/10.3390/gels10030167 - 26 Feb 2024

Cited by 2 | Viewed by 1966

Abstract

The tissue engineering field is currently advancing towards minimally invasive procedures to reconstruct soft tissue defects. In this regard, injectable hydrogels are viewed as excellent scaffold candidates to support and promote the growth of encapsulated cells. Cross-linked gelatin methacryloyl (GelMA) gels have received substantial attention due to their extracellular matrix-mimicking properties. In particular, GelMA microgels were recently identified as interesting scaffold materials since the pores in between the microgel particles allow good cell movement and nutrient diffusion. The current work reports on a novel microgel preparation procedure in which a bulk GelMA hydrogel is ground into powder particles. These particles can be easily transformed into a microgel by swelling them in a suitable solvent. The rheological properties of the microgel are independent of the particle size and remain stable at body temperature, with only a minor reversible reduction in elastic modulus correlated to the unfolding of physical cross-links at elevated temperatures. Salts reduce the elastic modulus of the microgel network due to a deswelling of the particles, in addition to triple helix denaturation. The microgels are suited for clinical use, as proven by their excellent cytocompatibility. The latter is confirmed by the superior proliferation of encapsulated adipose tissue-derived stem cells in the microgel compared to the bulk hydrogel. Moreover, microgels made from the smallest particles are easily injected through a 20G needle, allowing a minimally invasive delivery. Hence, the current work reveals that powdered cross-linked GelMA is an excellent candidate to serve as an injectable hydrogel for adipose tissue engineering. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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16 pages, 4523 KiB

Open AccessArticle

Optimizing PCL/PLGA Scaffold Biocompatibility Using Gelatin from Bovine, Porcine, and Fish Origin

by Mina Ghafouri Azar, Lucie Wiesnerova, Jana Dvorakova, Petra Chocholata, Omid Moztarzadeh, Jiri Dejmek and Vaclav Babuska

Gels 2023, 9(11), 900; https://doi.org/10.3390/gels9110900 - 14 Nov 2023

Viewed by 1903

Abstract

This research introduces a novel approach by incorporating various types of gelatins, including bovine, porcine, and fish skin, into polycaprolactone and poly (lactic-co-glycolic acid) using a solvent casting method. The films are evaluated for morphology, mechanical properties, thermal stability, biodegradability, hemocompatibility, cell adhesion, proliferation, and cytotoxicity. The results show that the incorporation of gelatins into the films alters their mechanical properties, with a decrease in tensile strength but an increase in elongation at break. This indicates that the films become more flexible with the addition of gelatin. Gelatin incorporation has a limited effect on the thermal stability of the films. The composites with the gelatin show higher biodegradability with the highest weight loss in the case of fish gelatin. The films exhibit high hemocompatibility with minimal hemolysis observed. The gelatin has a dynamic effect on cell behavior and promotes long-term cell proliferation. In addition, all composite films reveal exceptionally low levels of cytotoxicity. The combination of the evaluated parameters shows the appropriate level of biocompatibility for gelatin-based samples. These findings provide valuable insights for future studies involving gelatin incorporation in tissue engineering applications. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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13 pages, 2915 KiB

Open AccessArticle

Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair

by Jianuo Zheng, Yunping Wang, Yuwen Wang, Ruiping Duan and Lingrong Liu

Gels 2023, 9(9), 742; https://doi.org/10.3390/gels9090742 - 13 Sep 2023

Cited by 8 | Viewed by 1803

Abstract

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSC_S and have the potential to be used as injectable hydrogels for bone defect treatment. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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22 pages, 1317 KiB

Open AccessArticle

Tau-Marin Mucoadhesive Gel for Prevention and Treatment of Gum Diseases

by Giuseppe Giannini, Irene Ragusa, Giulia Nerina Nardone, Sara Soldi, Marina Elli, Piera Valenti and Luigi Rosa

Gels 2023, 9(8), 607; https://doi.org/10.3390/gels9080607 - 27 Jul 2023

Viewed by 2189

Abstract

An innovative and stable probiotic-containing mucoadhesive gel (AL0020), integrated with botanical extracts, has been developed to rebalance the dysbiosis associated with periodontal diseases. Tau-Marin gel, prepared with anhydrous ingredients to prevent the replication of bacteria and ensure good stability over time, was tested against some pathogenic bacteria, belonging to the so-called “red complex”, recognized as the most important pathogens in plaque specimens, adherent to the epithelial lining of periodontal pockets. This lipogel was tested in vitro, in a physiological solution (PS) and in a simulated saliva (SS), for up to 8 h, to monitor its ability to release probiotics over time. Probiotics were enumerated through two different techniques, Lacto-Counter Assay (LCA) and Colony Forming Unit (CFU). A detailed physico-chemical profile of AL0020 and its in vitro efficacy in protecting activity against pathogenic bacteria as well as soothing or irritative effect on gingival epithelium were reported. Moreover, a clinical-dermatological trial on 20 volunteers using the product once a day for 30 days was also performed, where the efficacy of the gel in the control of gum disorders was observed. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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Review

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50 pages, 9695 KiB

Open AccessEditor’s ChoiceReview

Evolution of Hybrid Hydrogels: Next-Generation Biomaterials for Drug Delivery and Tissue Engineering

by Md Mohosin Rana and Hector De la Hoz Siegler

Gels 2024, 10(4), 216; https://doi.org/10.3390/gels10040216 - 22 Mar 2024

Cited by 18 | Viewed by 4642

Abstract

Hydrogels, being hydrophilic polymer networks capable of absorbing and retaining aqueous fluids, hold significant promise in biomedical applications owing to their high water content, permeability, and structural similarity to the extracellular matrix. Recent chemical advancements have bolstered their versatility, facilitating the integration of the molecules guiding cellular activities and enabling their controlled activation under time constraints. However, conventional synthetic hydrogels suffer from inherent weaknesses such as heterogeneity and network imperfections, which adversely affect their mechanical properties, diffusion rates, and biological activity. In response to these challenges, hybrid hydrogels have emerged, aiming to enhance their strength, drug release efficiency, and therapeutic effectiveness. These hybrid hydrogels, featuring improved formulations, are tailored for controlled drug release and tissue regeneration across both soft and hard tissues. The scientific community has increasingly recognized the versatile characteristics of hybrid hydrogels, particularly in the biomedical sector. This comprehensive review delves into recent advancements in hybrid hydrogel systems, covering the diverse types, modification strategies, and the integration of nano/microstructures. The discussion includes innovative fabrication techniques such as click reactions, 3D printing, and photopatterning alongside the elucidation of the release mechanisms of bioactive molecules. By addressing challenges, the review underscores diverse biomedical applications and envisages a promising future for hybrid hydrogels across various domains in the biomedical field. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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17 pages, 2180 KiB

Open AccessReview

Hydrogels for Cardio and Vascular Tissue Repair and Regeneration

by Ilenia Motta, Michelina Soccio, Giulia Guidotti, Nadia Lotti and Gianandrea Pasquinelli

Gels 2024, 10(3), 196; https://doi.org/10.3390/gels10030196 - 13 Mar 2024

Cited by 1 | Viewed by 2072

Abstract

Cardiovascular disease (CVD), the leading cause of death globally, affects the heart and arteries with a variety of clinical manifestations, the most dramatic of which are myocardial infarction (MI), abdominal aortic aneurysm (AAA), and intracranial aneurysm (IA) rupture. In MI, necrosis of the myocardium, scar formation, and loss of cardiomyocytes result from insufficient blood supply due to coronary artery occlusion. Beyond stenosis, the arteries that are structurally and functionally connected to the cardiac tissue can undergo pathological dilation, i.e., aneurysmal dilation, with high risk of rupture. Aneurysms of the intracranial arteries (IAs) are more commonly seen in young adults, whereas those of the abdominal aorta (AAA) are predominantly seen in the elderly. IAs, unpredictably, can undergo rupture and cause life-threatening hemorrhage, while AAAs can result in rupture, internal bleeding and high mortality rate. In this clinical context, hydrogels, three-dimensional networks of water-seizing polymers, have emerged as promising biomaterials for cardiovascular tissue repair or protection due to their biocompatibility, tunable properties, and ability to encapsulate and release bioactive molecules. This review provides an overview of the current state of research on the use of hydrogels as an innovative platform to promote cardiovascular-specific tissue repair in MI and functional recovery or protection in aneurysmal dilation. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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38 pages, 5898 KiB

Open AccessEditor’s ChoiceReview

Emerging Advances in Microfluidic Hydrogel Droplets for Tissue Engineering and STEM Cell Mechanobiology

by Mohamad Orabi and Joe F. Lo

Gels 2023, 9(10), 790; https://doi.org/10.3390/gels9100790 - 1 Oct 2023

Cited by 5 | Viewed by 3862

Abstract

Hydrogel droplets are biodegradable and biocompatible materials with promising applications in tissue engineering, cell encapsulation, and clinical treatments. They represent a well-controlled microstructure to bridge the spatial divide between two-dimensional cell cultures and three-dimensional tissues, toward the recreation of entire organs. The applications of hydrogel droplets in regenerative medicine require a thorough understanding of microfluidic techniques, the biocompatibility of hydrogel materials, and droplet production and manipulation mechanisms. Although hydrogel droplets were well studied, several emerging advances promise to extend current applications to tissue engineering and beyond. Hydrogel droplets can be designed with high surface-to-volume ratios and a variety of matrix microstructures. Microfluidics provides precise control of the flow patterns required for droplet generation, leading to tight distributions of particle size, shape, matrix, and mechanical properties in the resultant microparticles. This review focuses on recent advances in microfluidic hydrogel droplet generation. First, the theoretical principles of microfluidics, materials used in fabrication, and new 3D fabrication techniques were discussed. Then, the hydrogels used in droplet generation and their cell and tissue engineering applications were reviewed. Finally, droplet generation mechanisms were addressed, such as droplet production, droplet manipulation, and surfactants used to prevent coalescence. Lastly, we propose that microfluidic hydrogel droplets can enable novel shear-related tissue engineering and regeneration studies. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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18 pages, 1792 KiB

Open AccessReview

From Free Tissue Transfer to Hydrogels: A Brief Review of the Application of the Periosteum in Bone Regeneration

by Hai Xin, Eva Tomaskovic-Crook, D S Abdullah Al Maruf, Kai Cheng, James Wykes, Timothy G. H. Manzie, Steven G. Wise, Jeremy M. Crook and Jonathan R. Clark

Gels 2023, 9(9), 768; https://doi.org/10.3390/gels9090768 - 21 Sep 2023

Cited by 5 | Viewed by 2377

Abstract

The periosteum is a thin layer of connective tissue covering bone. It is an essential component for bone development and fracture healing. There has been considerable research exploring the application of the periosteum in bone regeneration since the 19th century. An increasing number of studies are focusing on periosteal progenitor cells found within the periosteum and the use of hydrogels as scaffold materials for periosteum engineering and guided bone development. Here, we provide an overview of the research investigating the use of the periosteum for bone repair, with consideration given to the anatomy and function of the periosteum, the importance of the cambium layer, the culture of periosteal progenitor cells, periosteum-induced ossification, periosteal perfusion, periosteum engineering, scaffold vascularization, and hydrogel-based synthetic periostea. Full article

(This article belongs to the Special Issue Hydrogel for Tissue Regeneration)

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