Advances in Hydrogel Scaffolding of Stem Cells

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Pharmaceutical Processes".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 26591

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Guest Editor
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
Interests: stem cell therapy; cell transplantation; in vivo imaging; neuro-regeneration
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Special Issue Information

We are currently witnessing an exciting phase in biomedical engineering with the ever-growing amalgamation of material chemistry and stem cell biology to better model human physiological systems and to propel stem cell-mediated mitigation of tissue degeneration and organ failure. While in vitro modeling via cell encapsulation in synthetic matrices has helped us understand stem cell development, the latest advances in 3D and 4D bioprinting have driven progress in the design of mini-organs and functional tissues in diverse architectures and compositions as never before. Steady advances in the hydrogel scaffolding of stem cells have, in turn, led to the improvement of both in vitro modeling and the design of in vivo tissue repair paradigms of the heart/skin/nerve/kidney/liver/cartilage tissues owing to distinct advantages in enabling the creation of biomimetic environments with tunable chemistry, architecture, and mechanics.

A thorough understanding of stem cell microenvironments and systematic tuning of material chemistry, mechanics, and immune reactivity is crucial in the design of safe and efficient stem cell therapies. Examples for such improvements range from chemical modification of hydrogels to facilitate cell adhesion to improving hydrogel rheological properties for smooth injection of stem cells. The rational design of biomimetic hydrogels also calls for thorough considerations and novel insights in immune modulation, reactivity, and biocompatibility. 

For this Special Issue entitled “Advances in Hydrogel Scaffolding of Stem Cells”, we aim to curate novel advances in the rational development of hydrogel scaffolds to address several longstanding challenges in tissue regeneration. We cordially invite novel reports and topics encompassing (but not limited to) the following areas:  

  • (Bio)chemical synthesis of hydrogel formulations with novel chemistry and rheology for cell scaffolding
  • Design of injectable, shear-thinning hydro-/micro-/nanogels for stem cell delivery
  • Advanced biofabrication techniques for in vitro modeling of degenerative diseases/microenvironments using stem cells, embryonic cells, or induced-pluripotent (iPS) cells
  • 3D and 4D bioprinting of cell-laden hydrogels and bio-inks for in vitro investigations and as prefabricated bioscaffold constructs for preclinical testing
  • Cell-laden hydrogels for tissue repair with controlled biodegradation, immune modulation, and cell migration
  • Hydrogel-assisted 3D organoid formation for drug testing and disease modeling

Dr. Shreyas Kuddannaya
Guest Editor

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Keywords

  • hydrogels
  • stem cells
  • transplantation
  • 3D printing
  • organoids
  • functionalization
  • cell therapy
  • tissue regeneration

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Published Papers (7 papers)

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Editorial

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3 pages, 149 KiB  
Editorial
Special Issue on ‘Advances in Hydrogel Scaffolding of Stem Cells’
by Shreyas Kuddannaya
Processes 2023, 11(10), 2863; https://doi.org/10.3390/pr11102863 - 28 Sep 2023
Viewed by 671
Abstract
We are currently in the midst of an exciting phase in the field of biomedical engineering, where the convergence of material chemistry and cell biology is opening up new avenues for understanding human physiological systems and advancing stem-cell-based approaches to mitigate tissue degeneration [...] Read more.
We are currently in the midst of an exciting phase in the field of biomedical engineering, where the convergence of material chemistry and cell biology is opening up new avenues for understanding human physiological systems and advancing stem-cell-based approaches to mitigate tissue degeneration and organ failure [...] Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)

Research

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21 pages, 6231 KiB  
Article
Physical and Mechanical Characterization of Fibrin-Based Bioprinted Constructs Containing Drug-Releasing Microspheres for Neural Tissue Engineering Applications
by Ruchi Sharma, Rebecca Kirsch, Karolina Papera Valente, Milena Restan Perez and Stephanie Michelle Willerth
Processes 2021, 9(7), 1205; https://doi.org/10.3390/pr9071205 - 13 Jul 2021
Cited by 24 | Viewed by 6128
Abstract
Three-dimensional bioprinting can fabricate precisely controlled 3D tissue constructs. This process uses bioinks—specially tailored materials that support the survival of incorporated cells—to produce tissue constructs. The properties of bioinks, such as stiffness and porosity, should mimic those found in desired tissues to support [...] Read more.
Three-dimensional bioprinting can fabricate precisely controlled 3D tissue constructs. This process uses bioinks—specially tailored materials that support the survival of incorporated cells—to produce tissue constructs. The properties of bioinks, such as stiffness and porosity, should mimic those found in desired tissues to support specialized cell types. Previous studies by our group validated soft substrates for neuronal cultures using neural cells derived from human-induced pluripotent stem cells (hiPSCs). It is important to confirm that these bioprinted tissues possess mechanical properties similar to native neural tissues. Here, we assessed the physical and mechanical properties of bioprinted constructs generated from our novel microsphere containing bioink. We measured the elastic moduli of bioprinted constructs with and without microspheres using a modified Hertz model. The storage and loss modulus, viscosity, and shear rates were also measured. Physical properties such as microstructure, porosity, swelling, and biodegradability were also analyzed. Our results showed that the elastic modulus of constructs with microspheres was 1032 ± 59.7 Pascal (Pa), and without microspheres was 728 ± 47.6 Pa. Mechanical strength and printability were significantly enhanced with the addition of microspheres. Thus, incorporating microspheres provides mechanical reinforcement, which indicates their suitability for future applications in neural tissue engineering. Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)
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16 pages, 2137 KiB  
Article
Gene Expression of Mouse Hippocampal Stem Cells Grown in a Galactose-Derived Molecular Gel Compared to In Vivo and Neurospheres
by Keziban Korkmaz Bayram, Juliette Fitremann, Arslan Bayram, Zeynep Yılmaz, Ecmel Mehmetbeyoğlu, Yusuf Özkul and Minoo Rassoulzadegan
Processes 2021, 9(4), 716; https://doi.org/10.3390/pr9040716 - 18 Apr 2021
Cited by 3 | Viewed by 3156
Abstract
Background: N-heptyl-D-galactonamide (GalC7) is a small synthetic carbohydrate derivative that forms a biocompatible supramolecular hydrogel. In this study, the objective was to analyze more in-depth how neural cells differentiate in contact with GalC7. Method: Direct (ex vivo) cells of the fresh hippocampus and [...] Read more.
Background: N-heptyl-D-galactonamide (GalC7) is a small synthetic carbohydrate derivative that forms a biocompatible supramolecular hydrogel. In this study, the objective was to analyze more in-depth how neural cells differentiate in contact with GalC7. Method: Direct (ex vivo) cells of the fresh hippocampus and culture (In vitro) of the primary cells were investigated. In vitro, investigation performed under three conditions: on culture in neurospheres for 19 days, on culture in GalC7 gel for 7 days, and on culture in both neurospheres and GalC7 gel. Total RNA was isolated with TRIzol from each group, Sox8, Sox9, Sox10, Dcx, and Neurod1 expression levels were measured by qPCR. Result: Sox8 and Sox10, oligodendrocyte markers, and Sox9, an astrocyte marker, were expressed at a much higher level after 7 days of culture in GalC7 hydrogel compared to all other conditions. Dcx, a marker of neurogenesis, and Neurod1, a marker of neuronal differentiation, were expressed at better levels in the GalC7 gel culture compared to the neurosphere. Conclusions: These results show that the GalC7 hydrogel brings different and interesting conditions for inducing the differentiation and maturation of neural progenitor cells compared with polymer-based scaffolds or cell-only conditions. The differences observed open new perspectives in tissue engineering, induction, and transcript analysis. Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)
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10 pages, 2947 KiB  
Article
Hydroxy-tyrosol as a Free Radical Scavenging Molecule in Polymeric Hydrogels Subjected to Gamma-Ray Irradiation
by Mauro Fiorini, Veronica Crognaletti, Omar Sabry, Lorenzo Scalise and Paolo Fattori
Processes 2021, 9(3), 433; https://doi.org/10.3390/pr9030433 - 27 Feb 2021
Cited by 2 | Viewed by 2272
Abstract
Biomedical engineering is employing hydrogels with increasingly exciting possibilities for the treatment and regeneration of pathologically altered, degenerated, or traumatized tissues. Still, the sterilization processes may undesirably change the chemical and physical properties of hydrogels through cross-linking reactions. This work aims to characterize [...] Read more.
Biomedical engineering is employing hydrogels with increasingly exciting possibilities for the treatment and regeneration of pathologically altered, degenerated, or traumatized tissues. Still, the sterilization processes may undesirably change the chemical and physical properties of hydrogels through cross-linking reactions. This work aims to characterize a new method of producing polyethylene oxide (PEO) hydrogels exploiting hydroxy-tyrosol (HT), an anti-oxidant molecule derived from olive leaf and olive oil, as a free radical scavenger to either prevent or limit gamma-ray-induced cross-linking. For this purpose, we produced hydrogels with PEO with two different buffer solutions (phosphate and citrate), varying HT concentration. We analyzed hydrogel preparations before and after gamma-ray irradiation, assessing the viscosity through rheological analysis and the chemical changes through IR analysis. We performed high-performance liquid chromatography (HPLC) analysis to measure residual HT in hydrogels after irradiation. The obtained results show that radiation-induced cross-linking and increase in viscosity of PEO hydrogels can be prevented by tailoring the concentration of HT as a free radical scavenging agent. Irradiation only consumes small amounts of HT; its presence in polymeric hydrogels can significantly impact biomedical applications by its anti-oxidant and anti-microbial activities. Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)
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Review

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15 pages, 1747 KiB  
Review
The Potential of Fibroblast Transdifferentiation to Neuron Using Hydrogels
by Fahsai Kantawong
Processes 2021, 9(4), 632; https://doi.org/10.3390/pr9040632 - 4 Apr 2021
Cited by 1 | Viewed by 2669
Abstract
Currently there is a big drive to generate neurons from differentiated cells which would be of great benefit for regenerative medicine, tissue engineering and drug screening. Most studies used transcription factors, epigenetic reprogramming and/or chromatin remodeling drugs which might reflect incomplete reprogramming or [...] Read more.
Currently there is a big drive to generate neurons from differentiated cells which would be of great benefit for regenerative medicine, tissue engineering and drug screening. Most studies used transcription factors, epigenetic reprogramming and/or chromatin remodeling drugs which might reflect incomplete reprogramming or progressive deregulation of the new program. In this review, we present a potential different method for cellular reprogramming/transdifferentiation to potentially enhance regeneration of neurons. We focus on the use of biomaterials, specifically hydrogels, to act as non-invasive tools to direct transdifferentiation, and we draw parallel with existing transcriptional and epigenetic methods. Hydrogels are attractive materials because the properties of hydrogels can be modified, and various natural and synthetic substances can be employed. Incorporation of extracellular matrix (ECM) substances and composite materials allows mechanical properties and degradation rate to be controlled. Moreover, hydrogels in combinations with other physical and mechanical stimuli such as electric current, shear stress and tensile force will be mentioned in this review. Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)
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19 pages, 1381 KiB  
Review
Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro
by Ghmkin Hassan, Said M. Afify, Shiro Kitano, Akimasa Seno, Hiroko Ishii, Yucheng Shang, Michiya Matsusaki and Masaharu Seno
Processes 2021, 9(1), 45; https://doi.org/10.3390/pr9010045 - 28 Dec 2020
Cited by 11 | Viewed by 6495
Abstract
Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists [...] Read more.
Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists in cancer biology. However, there are many complicated obstacles in the mimicking the microenvironment of CSCs even with current advanced technology. In this context, novel biomaterials have widely been assessed as in vitro platforms for their ability to mimic cancer microenvironment. These efforts should be successful to identify and characterize various CSCs specific in each type of cancer. Therefore, extracellular matrix scaffolds made of biomaterial will modulate the interactions and facilitate the investigation of CSC associated with biological phenomena simplifying the complexity of the microenvironment. In this review, we summarize latest advances in biomaterial scaffolds, which are exploited to mimic CSC microenvironment, and their chemical and biological requirements with discussion. The discussion includes the possible effects on both cells in tumors and microenvironment to propose what the critical factors are in controlling the CSC microenvironment focusing the future investigation. Our insights on their availability in drug screening will also follow the discussion. Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)
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23 pages, 1217 KiB  
Review
Ad-Dressing Stem Cells: Hydrogels for Encapsulation
by Leonidas Kandilogiannakis, Eirini Filidou, George Kolios and Vasilis Paspaliaris
Processes 2021, 9(1), 11; https://doi.org/10.3390/pr9010011 - 23 Dec 2020
Cited by 8 | Viewed by 3835
Abstract
Regenerative medicine is a novel scientific field that employs the use of stem cells as cell-based therapy for the regeneration and functional restoration of damaged tissues and organs. Stem cells bear characteristics such as the capacity for self-renewal and differentiation towards specific lineages [...] Read more.
Regenerative medicine is a novel scientific field that employs the use of stem cells as cell-based therapy for the regeneration and functional restoration of damaged tissues and organs. Stem cells bear characteristics such as the capacity for self-renewal and differentiation towards specific lineages and, therefore, serve as a backup reservoir in case of tissue injuries. Therapeutically, they can be autologously or allogeneically transplanted for tissue regeneration; however, allogeneic stem cell transplantation can provoke host immune responses leading to a host-versus-transplant reaction. A probable solution to this problem is stem cell encapsulation, a technique that utilizes various biomaterials for the creation of a semi-permeable membrane that encases the stem cells. Stem cell encapsulation can be accomplished by employing a great variety of natural and/or synthetic hydrogels and offers many benefits in regenerative medicine, including protection from the host’s immune system and mechanical stress, improved cell viability, proliferation and differentiation, cryopreservation and controlled and continuous delivery of the stem-cell-secreted therapeutic agents. Here, in this review, we report and discuss almost all natural and synthetic hydrogels used in stem cell encapsulation, along with the benefits that these materials, alone or in combination, could offer to cell therapy through functional cell encapsulation. Full article
(This article belongs to the Special Issue Advances in Hydrogel Scaffolding of Stem Cells)
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