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Hydrogel-Based Scaffolds with a Focus on Medical Use
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Hydrogel-Based Scaffolds with a Focus on Medical Use

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

Deadline for manuscript submissions: closed (10 September 2023) | Viewed by 26638

Special Issue Editors

Dr. Federica Re

E-Mail Website
Guest Editor
Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
Interests: stem cell transplantation; stem cell biology; regenerative medicine; formation of tissues and organs; mesenchymal and hematopoietic stem cells (MSCs and HSCs)
Special Issues, Collections and Topics in MDPI journals
Dr. Elisa Borsani

E-Mail Website
Guest Editor
Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
Interests: morphology and functional imaging of cells; neuroanatomy and neurophysiology; gene therapy; cell therapy; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of scaffolds with optimal characteristics is more readily achievable in polymeric scaffolds. In particular, there is currently a great research interest in hydrogel-based scaffolds. 

Hydrogel-based scaffolds have recently emerged as the most promising substrates for cell cultures to generate well-defined 3D biofabricated tissue, attracting significant research attention for their potential in medical applications.

These scaffolds act as bioactive substrate and structural supports, providing topographical and chemical stimuli for cell spreading, proliferation and differentiation in vivo. Among the specific scaffold characteristics, a high porosity and interconnectivity to facilitate scaffold/cell interactions, nutrient and oxygen infiltration and vascularization aim to obtain specific cellular responses. Scaffolds have sufficient mechanical properties to temporarily substitute the missing tissue and to permit essential physiological functions.

This Special Issue is dedicated to the design and development of advanced polymeric scaffolds and their applications for bone/cartilage/skin regeneration in vitro and in vivo.

Dr. Federica Re
Dr. Elisa Borsani
Guest Editors

Manuscript Submission Information

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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 2100 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-based scaffolds
  • resorbable scaffolds
  • synthesis of biomaterials
  • mesenchymal stromal cells
  • bioengineered models
  • bone regeneration
  • cartilage regeneration
  • skin regeneration

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Related Special Issue

Published Papers (9 papers)

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Research

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14 pages, 3887 KiB  
Article
Citric Acid Loaded Hydrogel-Coated Stent for Dissolving Pancreatic Duct Calculi
by Jing Li, Yanwei Lv, Zheng Chen, Jiulong Zhao and Shige Wang
Gels 2024, 10(2), 125; https://doi.org/10.3390/gels10020125 - 3 Feb 2024
Cited by 11 | Viewed by 2068
Abstract
In recent years, the incidence of chronic pancreatitis has increased significantly. Pancreatic calculi obstruct the pancreatic duct and induce abdominal pain in the patients. Pancreatic duct stenting is the major treatment option for chronic pancreatitis with calculi. In this study, a new kind [...] Read more.
In recent years, the incidence of chronic pancreatitis has increased significantly. Pancreatic calculi obstruct the pancreatic duct and induce abdominal pain in the patients. Pancreatic duct stenting is the major treatment option for chronic pancreatitis with calculi. In this study, a new kind of drug-eluting stent, a pancreatic stent coated by methacrylated gelatin (GelMA) hydrogel loaded with citric acid (CA), was designed for the interventional treatment of pancreatic duct calculi. The CA loading capacity reached up to 0.7 g CA/g hydrogel-coated stent. The GelMA hydrogel coating has higher mechanical strength and lower swelling performance after loading with CA. The in vitro experiments of stents exhibited good performance in CA sustained release and the calculi can be dissolved in almost 3 days. The stents also showed good blood compatibility and cell compatibility. This research has important clinical value in the treatment of chronic pancreatitis with pancreatic calculi. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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22 pages, 8745 KiB  
Article
Hydrocolloids of Egg White and Gelatin as a Platform for Hydrogel-Based Tissue Engineering
by Karinna Georgiana Pele, Hippolyte Amaveda, Mario Mora, Carlos Marcuello, Anabel Lostao, Pilar Alamán-Díez, Salvador Pérez-Huertas, María Ángeles Pérez, José Manuel García-Aznar and Elena García-Gareta
Gels 2023, 9(6), 505; https://doi.org/10.3390/gels9060505 - 20 Jun 2023
Cited by 13 | Viewed by 3420
Abstract
Innovative materials are needed to produce scaffolds for various tissue engineering and regenerative medicine (TERM) applications, including tissue models. Materials derived from natural sources that offer low production costs, easy availability, and high bioactivity are highly preferred. Chicken egg white (EW) is an [...] Read more.
Innovative materials are needed to produce scaffolds for various tissue engineering and regenerative medicine (TERM) applications, including tissue models. Materials derived from natural sources that offer low production costs, easy availability, and high bioactivity are highly preferred. Chicken egg white (EW) is an overlooked protein-based material. Whilst its combination with the biopolymer gelatin has been investigated in the food technology industry, mixed hydrocolloids of EW and gelatin have not been reported in TERM. This paper investigates these hydrocolloids as a suitable platform for hydrogel-based tissue engineering, including 2D coating films, miniaturized 3D hydrogels in microfluidic devices, and 3D hydrogel scaffolds. Rheological assessment of the hydrocolloid solutions suggested that temperature and EW concentration can be used to fine-tune the viscosity of the ensuing gels. Fabricated thin 2D hydrocolloid films presented globular nano-topography and in vitro cell work showed that the mixed hydrocolloids had increased cell growth compared with EW films. Results showed that hydrocolloids of EW and gelatin can be used for creating a 3D hydrogel environment for cell studies inside microfluidic devices. Finally, 3D hydrogel scaffolds were fabricated by sequential temperature-dependent gelation followed by chemical cross-linking of the polymeric network of the hydrogel for added mechanical strength and stability. These 3D hydrogel scaffolds displayed pores, lamellae, globular nano-topography, tunable mechanical properties, high affinity for water, and cell proliferation and penetration properties. In conclusion, the large range of properties and characteristics of these materials provide a strong potential for a large variety of TERM applications, including cancer models, organoid growth, compatibility with bioprinting, or implantable devices. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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9 pages, 1829 KiB  
Article
New Paradigm in Diabetic Foot Ulcer Grafting Techniques Using 3D-Bioprinted Autologous Minimally Manipulated Homologous Adipose Tissue (3D-AMHAT) with Fibrin Gel Acting as a Biodegradable Scaffold
by Mohd Yazid Bajuri, Jeehee Kim, Yeongseo Yu and Muhammad Shazwan Shahul Hameed
Gels 2023, 9(1), 66; https://doi.org/10.3390/gels9010066 - 13 Jan 2023
Cited by 8 | Viewed by 5195
Abstract
Adipose tissue is an abundant source of extracellular substances that support the tissue repair process. This pilot study was carried out to determine the efficacy of 3D-bioprinted autologous adipose tissue grafts on diabetic foot ulcers (DFUs), with fibrin gel used to stabilise the [...] Read more.
Adipose tissue is an abundant source of extracellular substances that support the tissue repair process. This pilot study was carried out to determine the efficacy of 3D-bioprinted autologous adipose tissue grafts on diabetic foot ulcers (DFUs), with fibrin gel used to stabilise the graft. This was a single-arm pilot study in a tertiary hospital that provides diabetic wound care services. A total of 10 patients with a DFU were enrolled, and the primary endpoint was complete healing within 12 weeks. The secondary endpoints were wound size reduction, time to healing, and adverse events. Seven out of ten patients showed complete healing of their DFU within 12 weeks (at 2, 4, 5, 10, and 12 weeks, respectively). The wound size reduction rate was significantly and progressively reduced over time. According to our data, autologous adipose tissue grafting using a 3D bioprinter, with the addition of fibrin gel that acts as a scaffold, promotes wound healing with high-quality skin reconstruction. Throughout this study period, no adverse events were observed. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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11 pages, 6200 KiB  
Article
PEG Reinforced Scaffold Promotes Uniform Distribution of Human MSC-Created Cartilage Matrix
by Kanyakorn Riewruja, Alyssa M. Aguglia, Sophie Hines, Meagan J. Makarcyzk, Sittisak Honsawek and Hang Lin
Gels 2022, 8(12), 794; https://doi.org/10.3390/gels8120794 - 3 Dec 2022
Cited by 4 | Viewed by 1779
Abstract
Previously, we used a gelatin/hyaluronic acid (GH)-based scaffold to induce chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC). The results showed that hBMSCs underwent robust chondrogenesis and facilitated in vivo cartilage regeneration. However, it was noticed that the GH scaffolds display [...] Read more.
Previously, we used a gelatin/hyaluronic acid (GH)-based scaffold to induce chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC). The results showed that hBMSCs underwent robust chondrogenesis and facilitated in vivo cartilage regeneration. However, it was noticed that the GH scaffolds display a compressive modulus that is markedly lower than native cartilage. In this study, we aimed to enhance the mechanical strength of GH scaffolds without significantly impairing their chondrosupportive property. Specifically, polyethylene glycol diacrylate (PEGDA) and photoinitiators were infiltrated into pre-formed hBMSC-laden GH scaffolds and then photo-crosslinked. Results showed that infiltration of PEG at the beginning of chondrogenesis significantly increased the deposition of glycosaminoglycans (GAGs) in the central area of the scaffold. To explore the mechanism, we compared the cell migration and proliferation in the margin and central areas of GH and PEG-infiltrated GH scaffolds (GH+PEG). Limited cell migration was noticed in both groups, but more proliferating cells were observed in GH than in GH+PEG. Lastly, the in vitro repairing study with bovine cartilage explants showed that PEG- impregnated scaffolds integrated well with host tissues. These results indicate that PEG-GH hybrid scaffolds, created through infiltrating PEG into pre-formed GH scaffolds, display good integration capacity and represent a new tool for the repair of chondral injury. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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13 pages, 4382 KiB  
Article
Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel
by Elena Gabusi, Enrico Lenzi, Cristina Manferdini, Paolo Dolzani, Marta Columbaro, Yasmin Saleh and Gina Lisignoli
Gels 2022, 8(12), 766; https://doi.org/10.3390/gels8120766 - 24 Nov 2022
Cited by 4 | Viewed by 2623
Abstract
Autophagy is a cellular process that contributes to the maintenance of cell homeostasis through the activation of a specific path, by providing the necessary factors in stressful and physiological situations. Autophagy plays a specific role in chondrocyte differentiation; therefore, we aimed to analyze [...] Read more.
Autophagy is a cellular process that contributes to the maintenance of cell homeostasis through the activation of a specific path, by providing the necessary factors in stressful and physiological situations. Autophagy plays a specific role in chondrocyte differentiation; therefore, we aimed to analyze this process in adipose-derived mesenchymal stromal cells (ASCs) laden in three-dimensional (3D) hydrogel. We analyzed chondrogenic and autophagic markers using molecular biology, immunohistochemistry, and electron microscopy. We demonstrated that ASCs embedded in 3D hydrogel showed an increase expression of typical autophagic markers Beclin 1, LC3, and p62, associated with clear evidence of autophagic vacuoles in the cytoplasm. During ASCs chondrogenic differentiation, we showed that autophagic markers declined their expression and autophagic vesicles were rare, while typical chondrogenic markers collagen type 2, and aggrecan were significantly increased. In line with developmental animal models of cartilage, our data showed that in a 3D hydrogel, ASCs increased their autophagic features. This path is the fundamental prerequisite for the initial phase of differentiation that contributes to fueling the cells with energy and factors necessary for chondrogenic differentiation. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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14 pages, 1807 KiB  
Article
An Investigation of the Sol-Gel Transition of Chitosan Lactate and Chitosan Chloride Solutions via Rheological and NMR Studies
by Katarzyna Pieklarz, Jacek Jenczyk, Zofia Modrzejewska, Piotr Owczarz and Stefan Jurga
Gels 2022, 8(10), 670; https://doi.org/10.3390/gels8100670 - 19 Oct 2022
Cited by 6 | Viewed by 2491
Abstract
In recent years, intensive research has been carried out on the use of hydrogels obtained from natural polymers, mainly chitosan. These products are increasingly replacing solutions based on synthetic materials in medicine. This publication presents the results of studies on the sol-gel transition [...] Read more.
In recent years, intensive research has been carried out on the use of hydrogels obtained from natural polymers, mainly chitosan. These products are increasingly replacing solutions based on synthetic materials in medicine. This publication presents the results of studies on the sol-gel transition of chitosan solutions as the base material for the preparation of thermosensitive hydrogels for potential applications in tissue engineering. The measurements were carried out for systems consisting of chitosan lactate and chitosan chloride solutions using β-glycerol phosphate disodium salt pentahydrate and uridine 5′-monophosphate disodium salt as the cross-linking agents. The sol-gel transition point of the solutions was determined based on the rheological measurements in the cone-plate configuration of the rotational rheometer and experiments performed using the method of nuclear magnetic resonance. The obtained results showed a significant influence of the cross-linking agent on the course of the sol-gel transition of chitosan salt solutions, and the systems that consisted of chitosan lactate seemed to be especially interesting for biomedical applications. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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Review

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49 pages, 1040 KiB  
Review
A Review of Metal Nanoparticles Embedded in Hydrogel Scaffolds for Wound Healing In Vivo
by Sara Sheikh-Oleslami, Brendan Tao, Jonathan D’Souza, Fahad Butt, Hareshan Suntharalingam, Lucas Rempel and Nafise Amiri
Gels 2023, 9(7), 591; https://doi.org/10.3390/gels9070591 - 22 Jul 2023
Cited by 3 | Viewed by 2351
Abstract
An evolving field, nanotechnology has made its mark in the fields of nanoscience, nanoparticles, nanomaterials, and nanomedicine. Specifically, metal nanoparticles have garnered attention for their diverse use and applicability to dressings for wound healing due to their antimicrobial properties. Given their convenient integration [...] Read more.
An evolving field, nanotechnology has made its mark in the fields of nanoscience, nanoparticles, nanomaterials, and nanomedicine. Specifically, metal nanoparticles have garnered attention for their diverse use and applicability to dressings for wound healing due to their antimicrobial properties. Given their convenient integration into wound dressings, there has been increasing focus dedicated to investigating the physical, mechanical, and biological characteristics of these nanoparticles as well as their incorporation into biocomposite materials, such as hydrogel scaffolds for use in lieu of antibiotics as well as to accelerate and ameliorate healing. Though rigorously tested and applied in both medical and non-medical applications, further investigations have not been carried out to bring metal nanoparticle–hydrogel composites into clinical practice. In this review, we provide an up-to-date, comprehensive review of advancements in the field, with emphasis on implications on wound healing in in vivo experiments. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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15 pages, 701 KiB  
Review
Bone Regeneration Using Mesenchymal Stromal Cells and Biocompatible Scaffolds: A Concise Review of the Current Clinical Trials
by Federica Re, Elisa Borsani, Rita Rezzani, Luciana Sartore and Domenico Russo
Gels 2023, 9(5), 389; https://doi.org/10.3390/gels9050389 - 8 May 2023
Cited by 14 | Viewed by 2634
Abstract
Bone regenerative medicine is a clinical approach combining live osteoblast progenitors, such as mesenchymal stromal cells (MSCs), with a biocompatible scaffold that can integrate into host bone tissue and restore its structural integrity. Over the last few years, many tissue engineering strategies have [...] Read more.
Bone regenerative medicine is a clinical approach combining live osteoblast progenitors, such as mesenchymal stromal cells (MSCs), with a biocompatible scaffold that can integrate into host bone tissue and restore its structural integrity. Over the last few years, many tissue engineering strategies have been developed and thoroughly investigated; however, limited approaches have been translated to clinical application. Consequently, the development and clinical validation of regenerative approaches remain a centerpiece of investigational efforts towards the clinical translation of advanced bioengineered scaffolds. The aim of this review was to identify the latest clinical trials related to the use of scaffolds with or without MSCs to regenerate bone defects. A revision of the literature was performed in PubMed, Embase, and Clinicaltrials.gov from 2018 up to 2023. Nine clinical trials were analyzed according to the inclusion criteria: six presented in the literature and three reported in Clinicaltrials.gov. Data were extracted covering background trial information. Six of the clinical trials added cells to scaffolds, while three used scaffolds alone. The majority of scaffolds were composed of calcium phosphate ceramic alone, such as β-tricalcium phosphate (TCP) (two clinical trials), biphasic calcium phosphate bioceramic granules (three clinical trials), and anorganic bovine bone (two clinical trials), while bone marrow was the primary source of the MSCs (five clinical trials). The MSC expansion was performed in GMP facilities, using human platelet lysate (PL) as a supplement without osteogenic factors. Only one trial reported minor adverse events. Overall, these findings highlight the importance and efficacy of cell–scaffold constructs in regenerative medicine under different conditions. Despite the encouraging clinical results obtained, further studies are needed to assess their clinical efficacy in treating bone diseases to optimize their application. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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16 pages, 1635 KiB  
Review
Progress in Composite Hydrogels and Scaffolds Enriched with Icariin for Osteochondral Defect Healing
by Elena Iulia Oprita, Andreea Iosageanu and Oana Craciunescu
Gels 2022, 8(10), 648; https://doi.org/10.3390/gels8100648 - 12 Oct 2022
Cited by 7 | Viewed by 2789
Abstract
Osteochondral structure reconstruction by tissue engineering, a challenge in regenerative medicine, requires a scaffold that ensures both articular cartilage and subchondral bone remodeling. Functional hydrogels and scaffolds present a strategy for the controlled delivery of signaling molecules (growth factors and therapeutic drugs) and [...] Read more.
Osteochondral structure reconstruction by tissue engineering, a challenge in regenerative medicine, requires a scaffold that ensures both articular cartilage and subchondral bone remodeling. Functional hydrogels and scaffolds present a strategy for the controlled delivery of signaling molecules (growth factors and therapeutic drugs) and are considered a promising therapeutic approach. Icariin is a pharmacologically-active small molecule of prenylated flavonol glycoside and the main bioactive flavonoid isolated from Epimedium spp. The in vitro and in vivo testing of icariin showed chondrogenic and ostseoinductive effects, comparable to bone morphogenetic proteins, and suggested its use as an alternative to growth factors, representing a low-cost, promising approach for osteochondral regeneration. This paper reviews the complex structure of the osteochondral tissue, underlining the main aspects of osteochondral defects and those specifically occurring in osteoarthritis. The significance of icariin’s structure and the extraction methods were emphasized. Studies revealing the valuable chondrogenic and osteogenic effects of icariin for osteochondral restoration were also reviewed. The review highlighted th recent state-of-the-art related to hydrogels and scaffolds enriched with icariin developed as biocompatible materials for osteochondral regeneration strategies. Full article
(This article belongs to the Special Issue Hydrogel-Based Scaffolds with a Focus on Medical Use)
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