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Special Issue "Hydrogels for Tissue Engineering and Regenerative Medicine"

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

Deadline for manuscript submissions: closed (30 September 2020).

Special Issue Editor

Prof. Dr. Silvia Marchesan
E-Mail Website
Guest Editor
Università degli Studi di Trieste, Trieste, Italy
Interests: nanomaterials, hydrogels, carbon nanostructures, peptides, chirality, green methods, sustainability, supramolecular chemistry, systems chemistry, self-assembly

Special Issue Information

Dear Colleagues,

Hydrogels are optimal scaffolds to repair damaged tissues, and can serve numerous functions that span from organizing and directing cells, to delivering bioactive molecules and drugs, to simply filling space for mechanical support and ensure correct exchange of nutrients and metabolic waste. An optimal therapeutic outcome requires a fine interplay at the correct time between molecules, that will eventually translate into the restoration of physiological processes at the cell and tissue levels. This complex scenario makes regenerative medicine a highly multi-disciplinary area that still presents numerous unsolved challenges to be addressed by scientists from backgrounds as diverse as engineering and chemistry. This Special Issue aims at bringing together different voices in the field to capture the current state of the art in this stimulating area, and to outline the future direction that this exciting subject is taking. It is only with a highly collaborative spirit that it will be possible to bridge over current limitations, and to fill the gaps, for the collective success to competently repair and regenerate human bodies for a healthier future. https://www.mdpi.com/journal/molecules/special_issues/hydrogels_tissue_engineering

Prof. Dr. Silvia Marchesan
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 papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hydrogels
  • tissue engineering
  • regenerative medicine
  • drug delivery
  • polymers
  • supramolecular
  • self-assembly

Published Papers (10 papers)

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Research

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Open AccessArticle
Tripeptide Self-Assembly into Bioactive Hydrogels: Effects of Terminus Modification on Biocatalysis
Molecules 2021, 26(1), 173; https://doi.org/10.3390/molecules26010173 - 31 Dec 2020
Viewed by 780
Abstract
Bioactive hydrogels based on the self-assembly of tripeptides have attracted great interest in recent years. In particular, the search is active for sequences that are able to mimic enzymes when they are self-organized in a nanostructured hydrogel, so as to provide a smart [...] Read more.
Bioactive hydrogels based on the self-assembly of tripeptides have attracted great interest in recent years. In particular, the search is active for sequences that are able to mimic enzymes when they are self-organized in a nanostructured hydrogel, so as to provide a smart catalytic (bio)material whose activity can be switched on/off with assembly/disassembly. Within the diverse enzymes that have been targeted for mimicry, hydrolases find wide application in biomaterials, ranging from their use to convert prodrugs into active compounds to their ability to work in reverse and catalyze a plethora of reactions. We recently reported the minimalistic l-His–d-Phe–d-Phe for its ability to self-organize into thermoreversible and biocatalytic hydrogels for esterase mimicry. In this work, we analyze the effects of terminus modifications that mimic the inclusion of the tripeptide in a longer sequence. Therefore, three analogues, i.e., N-acetylated, C-amidated, or both, were synthesized, purified, characterized by several techniques, and probed for self-assembly, hydrogelation, and esterase-like biocatalysis. This work provides useful insights into how chemical modifications at the termini affect self-assembly into biocatalytic hydrogels, and these data may become useful for the future design of supramolecular catalysts for enhanced performance. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessFeature PaperArticle
The Optimization of a Novel Hydrogel—Egg White-Alginate for 2.5D Tissue Engineering of Salivary Spheroid-Like Structure
Molecules 2020, 25(23), 5751; https://doi.org/10.3390/molecules25235751 - 06 Dec 2020
Viewed by 740
Abstract
Hydrogels have been used for a variety of biomedical applications; in tissue engineering, they are commonly used as scaffolds to cultivate cells in a three-dimensional (3D) environment allowing the formation of organoids or cellular spheroids. Egg white-alginate (EWA) is a novel hydrogel which [...] Read more.
Hydrogels have been used for a variety of biomedical applications; in tissue engineering, they are commonly used as scaffolds to cultivate cells in a three-dimensional (3D) environment allowing the formation of organoids or cellular spheroids. Egg white-alginate (EWA) is a novel hydrogel which combines the advantages of both egg white and alginate; the egg white material provides extracellular matrix (ECM)-like proteins that can mimic the ECM microenvironment, while alginate can be tuned mechanically through its ionic crosslinking property to modify the scaffold’s porosity, strength, and stiffness. In this study, a frozen calcium chloride (CaCl2) disk technique to homogenously crosslink alginate and egg white hydrogel is presented for 2.5D culture of human salivary cells. Different EWA formulations were prepared and biologically evaluated as a spheroid-like structure platform. Although all five EWA hydrogels showed biocompatibility, the EWA with 1.5% alginate presented the highest cell viability, while EWA with 3% alginate promoted the formation of larger size salivary spheroid-like structures. Our EWA hydrogel has the potential to be an alternative 3D culture scaffold that can be used for studies on drug-screening, cell migration, or as an in vitro disease model. In addition, EWA can be used as a potential source for cell transplantation (i.e., using this platform as an ex vivo environment for cell expansion). The low cost of producing EWA is an added advantage. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessArticle
Numerical Simulations as Means for Tailoring Electrically Conductive Hydrogels towards Cartilage Tissue Engineering by Electrical Stimulation
Molecules 2020, 25(20), 4750; https://doi.org/10.3390/molecules25204750 - 16 Oct 2020
Viewed by 668
Abstract
Cartilage regeneration is a clinical challenge. In recent years, hydrogels have emerged as implantable scaffolds in cartilage tissue engineering. Similarly, electrical stimulation has been employed to improve matrix synthesis of cartilage cells, and thus to foster engineering and regeneration of cartilage tissue. The [...] Read more.
Cartilage regeneration is a clinical challenge. In recent years, hydrogels have emerged as implantable scaffolds in cartilage tissue engineering. Similarly, electrical stimulation has been employed to improve matrix synthesis of cartilage cells, and thus to foster engineering and regeneration of cartilage tissue. The combination of hydrogels and electrical stimulation may pave the way for new clinical treatment of cartilage lesions. To find the optimal electric properties of hydrogels, theoretical considerations and corresponding numerical simulations are needed to identify well-suited initial parameters for experimental studies. We present the theoretical analysis of a hydrogel in a frequently used electrical stimulation device for cartilage regeneration and tissue engineering. By means of equivalent circuits, finite element analysis, and uncertainty quantification, we elucidate the influence of the geometric and dielectric properties of cell-seeded hydrogels on the capacitive-coupling electrical field stimulation. Moreover, we discuss the possibility of cellular organisation inside the hydrogel due to forces generated by the external electric field. The introduced methodology is easily reusable by other researchers and allows to directly develop novel electrical stimulation study designs. Thus, this study paves the way for the design of future experimental studies using electrically conductive hydrogels and electrical stimulation for tissue engineering. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessArticle
Small Physical Cross-Linker Facilitates Hyaluronan Hydrogels
Molecules 2020, 25(18), 4166; https://doi.org/10.3390/molecules25184166 - 11 Sep 2020
Viewed by 652
Abstract
In this study, we demonstrate that small charged molecules (NH4+, GluA+, dHA+) can form physical cross-links between hyaluronan chains, facilitating polymerization reactions between synthetically introduced thiol groups (HA-DTPH). These hybrid hydrogels can be obtained under physiological [...] Read more.
In this study, we demonstrate that small charged molecules (NH4+, GluA+, dHA+) can form physical cross-links between hyaluronan chains, facilitating polymerization reactions between synthetically introduced thiol groups (HA-DTPH). These hybrid hydrogels can be obtained under physiological conditions ideally suited for 3D cell culture systems. The type and concentration of a physical crosslinker can be adjusted to precisely tune mechanical properties as well as degradability of the desired hydrogel system. We analyze the influence of hydrogen bond formation, concentration and additional ionic interactions on the polymerization reaction of HA-DTPH hydrogels and characterize the resulting hydrogels in regard to mechanical and biocompatibility aspects. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Review

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Open AccessReview
Advanced Strategies for Tissue Engineering in Regenerative Medicine: A Biofabrication and Biopolymer Perspective
Molecules 2021, 26(9), 2518; https://doi.org/10.3390/molecules26092518 - 26 Apr 2021
Viewed by 273
Abstract
Tissue engineering is known to encompass multiple aspects of science, medicine and engineering. The development of systems which are able to promote the growth of new cells and tissue components are vital in the treatment of severe tissue injury and damage. This can [...] Read more.
Tissue engineering is known to encompass multiple aspects of science, medicine and engineering. The development of systems which are able to promote the growth of new cells and tissue components are vital in the treatment of severe tissue injury and damage. This can be done through a variety of different biofabrication strategies including the use of hydrogels, 3D bioprinted scaffolds and nanotechnology. The incorporation of stem cells into these systems and the advantage of this is also discussed. Biopolymers, those which have a natural original, have been particularly advantageous in tissue engineering systems as they are often found within the extracellular matrix of the human body. The utilization of biopolymers has become increasing popular as they are biocompatible, biodegradable and do not illicit an immune response when placed into the body. Tissue engineering systems for use with the eye are also discussed. This is of particular interest as the eye is known as an immune privileged site resulting in an extremely limited ability for natural cell regeneration. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessFeature PaperReview
Supramolecular Hydrogels for Protein Delivery in Tissue Engineering
Molecules 2021, 26(4), 873; https://doi.org/10.3390/molecules26040873 - 07 Feb 2021
Cited by 1 | Viewed by 898
Abstract
Therapeutic proteins, such as growth factors (GFs), have been used in tissue engineering (TE) approaches for their ability to provide signals to cells and orchestrate the formation of functional tissue. However, to be effective and minimize off-target effects, GFs should be delivered at [...] Read more.
Therapeutic proteins, such as growth factors (GFs), have been used in tissue engineering (TE) approaches for their ability to provide signals to cells and orchestrate the formation of functional tissue. However, to be effective and minimize off-target effects, GFs should be delivered at the target site with temporal control. In addition, protein drugs are typically sensitive water soluble macromolecules with delicate structure. As such, hydrogels, containing large amounts of water, provide a compatible environment for the direct incorporation of proteins within the hydrogel network, while their release rate can be tuned by engineering the network chemistry and density. Being formed by transient crosslinks, afforded by non-covalent interactions, supramolecular hydrogels offer important advantages for protein delivery applications. This review describes various types of supramolecular hydrogels using a repertoire of diverse building blocks, their use for protein delivery and their further application in TE contexts. By reviewing the recent literature on this topic, the merits of supramolecular hydrogels are highlighted as well as their limitations, with high expectations for new advances they will provide for TE in the near future. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessReview
Natural-Based Hydrogels for Tissue Engineering Applications
Molecules 2020, 25(24), 5858; https://doi.org/10.3390/molecules25245858 - 11 Dec 2020
Cited by 1 | Viewed by 717
Abstract
In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due [...] Read more.
In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues’ extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessReview
Hydrogel Properties and Their Impact on Regenerative Medicine and Tissue Engineering
Molecules 2020, 25(24), 5795; https://doi.org/10.3390/molecules25245795 - 08 Dec 2020
Viewed by 655
Abstract
Hydrogels (HGs), as three-dimensional structures, are widely used in modern medicine, including regenerative medicine. The use of HGs in wound treatment and tissue engineering is a rapidly developing sector of medicine. The unique properties of HGs allow researchers to easily modify them to [...] Read more.
Hydrogels (HGs), as three-dimensional structures, are widely used in modern medicine, including regenerative medicine. The use of HGs in wound treatment and tissue engineering is a rapidly developing sector of medicine. The unique properties of HGs allow researchers to easily modify them to maximize their potential. Herein, we describe the physicochemical properties of HGs, which determine their subsequent applications in regenerative medicine and tissue engineering. Examples of chemical modifications of HGs and their applications are described based on the latest scientific reports. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessReview
Design of Bio-Conjugated Hydrogels for Regenerative Medicine Applications: From Polymer Scaffold to Biomolecule Choice
Molecules 2020, 25(18), 4090; https://doi.org/10.3390/molecules25184090 - 07 Sep 2020
Cited by 2 | Viewed by 1053
Abstract
Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity [...] Read more.
Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity and displaying tunable chemical and mechanical properties. A complex scenario of molecular factors and conditions have to be taken into account to ensure the correct functionality of the bio-hydrogel as a scaffold or a delivery system, including the polymer backbone and biomolecule choice, polymerization conditions, architecture and biocompatibility. In this review, we present these key factors and conditions that have to match together to ensure the correct functionality of the bio-conjugated hydrogel. We then present recent examples of bio-conjugated hydrogel systems paving the way for regenerative medicine applications. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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Open AccessReview
Tuning Surface Morphology of Fluorescent Hydrogels Using a Vortex Fluidic Device
Molecules 2020, 25(15), 3445; https://doi.org/10.3390/molecules25153445 - 29 Jul 2020
Cited by 1 | Viewed by 713
Abstract
In recent decades, microfluidic techniques have been extensively used to advance hydrogel design and control the architectural features on the micro- and nanoscale. The major challenges with the microfluidic approach are clogging and limited architectural features: notably, the creation of the sphere, core-shell, [...] Read more.
In recent decades, microfluidic techniques have been extensively used to advance hydrogel design and control the architectural features on the micro- and nanoscale. The major challenges with the microfluidic approach are clogging and limited architectural features: notably, the creation of the sphere, core-shell, and fibers. Implementation of batch production is almost impossible with the relatively lengthy time of production, which is another disadvantage. This minireview aims to introduce a new microfluidic platform, a vortex fluidic device (VFD), for one-step fabrication of hydrogels with different architectural features and properties. The application of a VFD in the fabrication of physically crosslinked hydrogels with different surface morphologies, the creation of fluorescent hydrogels with excellent photostability and fluorescence properties, and tuning of the structure–property relationship in hydrogels are discussed. We conceive, on the basis of this minireview, that future studies will provide new opportunities to develop hydrogel nanocomposites with superior properties for different biomedical and engineering applications. Full article
(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)
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