Collagen-Based Hydrogels

A special issue of Gels (ISSN 2310-2861).

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 29370

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Guest Editor
Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA
Interests: bioprinting; biofabrication; tissue/organ engineering; disease modeling
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Dear Colleagues,

Collagen is the most abundant protein in the body. Collagen-based hydrogels and hybrids thereof have been extensively used in tissue/organ engineering and drug discovery in past decades. Applications in tissue/organ engineering include vascular grafts, bone and cartilage substitutes, corneal tissue, skin, and dental pulp. In drug discovery, collagen-based hydrogels were used as platforms for cancer research and in the modeling of other diseases in vitro. Advances in biomanufacturing methods such as 3D/4D bioprinting and biofabrication have attracted attention regarding the development of collagen-based hydrogels as bioinks suitable to these technologies. Intelligent, stimuli-responsive, and reversibly crosslinkable collagen-based hydrogels with self-healing properties were recently used as injectable hydrogels for drug-delivery and regenerative medicine, as bioinks for biomanufacturing and tissue engineering, and as in vitro models to study mechanobiological details at the cell–biomaterial interface. This Special Issue on ‘’Collagen-Based Hydrogels’’ invites the submission of original research, opinions, and review articles on topics including the use of collagen-based hydrogels in in vitro, in situ, and in vivo studies in the fields of tissue/organ engineering, disease modeling, and drug discovery.

Dr. Daniela Duarte Campos
Guest Editor

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Keywords

  • Collagen hydrogel
  • Responsive hydrogel
  • Hybrid hydrogel
  • Tissue/organ engineering
  • Disease modeling
  • Drug discovery
  • Bioprinting
  • Biofabrication
  • In vitro/in situ/in vivo

Related Special Issue

Published Papers (6 papers)

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Research

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11 pages, 5963 KiB  
Communication
Monitoring the Degradation of Collagen Hydrogels by Collagenase Clostridium histolyticum
by Hon Wei Ng, Yi Zhang, Rafea Naffa and Sujay Prabakar
Gels 2020, 6(4), 46; https://0-doi-org.brum.beds.ac.uk/10.3390/gels6040046 - 27 Nov 2020
Cited by 18 | Viewed by 5397
Abstract
Collagen-based hydrogels are investigated extensively in tissue engineering for their tunable physiochemical properties, biocompatibility and biodegradability. However, the effect of the integrity of the collagen triple helical structure on biodegradability is yet to be studied. In this study, we monitored the degradation of [...] Read more.
Collagen-based hydrogels are investigated extensively in tissue engineering for their tunable physiochemical properties, biocompatibility and biodegradability. However, the effect of the integrity of the collagen triple helical structure on biodegradability is yet to be studied. In this study, we monitored the degradation of intact collagen (C-coll) and hydrolyzed collagen (D-coll) hydrogels in collagenase Clostridium histolyticum to understand their degradation process. Our results show that when peptides are present on the surface of the fibrils of D-coll hydrogels, cleavage of amide bonds occur at a much higher rate. The fibrillar structure of D-coll hydrogel results in a more pronounced breakdown of the gel network and dissolution of collagen peptides. The results from this work will improve the understanding of enzymatic degradation and the resulting bioabsorption of collagen materials used in drug delivery systems and scaffolds. Full article
(This article belongs to the Special Issue Collagen-Based Hydrogels)
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12 pages, 1141 KiB  
Article
Long-Term Cryostorage of Mesenchymal Stem Cell-Containing Hybrid Hydrogel Scaffolds Based on Fibrin and Collagen
by Marfa N. Egorikhina, Yulia P. Rubtsova and Diana Ya. Aleynik
Gels 2020, 6(4), 44; https://0-doi-org.brum.beds.ac.uk/10.3390/gels6040044 - 25 Nov 2020
Cited by 5 | Viewed by 2545
Abstract
The most difficult issue when using tissue engineering products is enabling the ability to store them without losing their restorative capacity. The numbers and viability of mesenchymal stem cells encapsulated in a hydrogel scaffold after cryostorage at −80 °C (by using, individually, two [...] Read more.
The most difficult issue when using tissue engineering products is enabling the ability to store them without losing their restorative capacity. The numbers and viability of mesenchymal stem cells encapsulated in a hydrogel scaffold after cryostorage at −80 °C (by using, individually, two kinds of cryoprotectors—Bambanker and 10% DMSO (Dimethyl sulfoxide) solution) for 3, 6, 9, and 12 months were determined, with subsequent assessment of cell proliferation after 96 h. The analysis of the cellular component was performed using fluorescence microscopy and the two fluorochromes—Hoechst 3334 and NucGreenTM Dead 488. The experimental protocol ensured the preservation of cells in the scaffold structure, retaining both high viability and proliferative activity during storage for 3 months. Longer storage of scaffolds led to their significant changes. Therefore, after 6 months, the proliferative activity of cells decreased. Cryostorage of scaffolds for 9 months led to a decrease in cells’ viability and proliferative activity. As a result of cryostorage of scaffolds for 12 months, a decrease in viability and proliferative activity of cells was observed, as well as pronounced changes in the structure of the hydrogel. The described scaffold cryostorage protocol could become the basis for the development of storage protocols for such tissue engineering products, and for helping to extend the possibilities of their clinical use while accelerating their commercialization. Full article
(This article belongs to the Special Issue Collagen-Based Hydrogels)
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9 pages, 2616 KiB  
Article
Characterization of Zinc Oxide Nanoparticle Cross-Linked Collagen Hydrogels
by Yosra Agban, Odunayo O. Mugisho, Sachin S. Thakur and Ilva D. Rupenthal
Gels 2020, 6(4), 37; https://0-doi-org.brum.beds.ac.uk/10.3390/gels6040037 - 22 Oct 2020
Cited by 5 | Viewed by 2837
Abstract
Collagen is the most abundant protein in mammals and possesses high biocompatibility and low antigenicity. These biological properties render it one of the most useful biomaterials for medical applications. This study investigated the mechanical and physical characteristics of collagen hydrogels cross-linked with different [...] Read more.
Collagen is the most abundant protein in mammals and possesses high biocompatibility and low antigenicity. These biological properties render it one of the most useful biomaterials for medical applications. This study investigated the mechanical and physical characteristics of collagen hydrogels cross-linked with different ratios of polyvinylpyrrolidone capped zinc oxide nanoparticles (ZPVP). Fourier transform infrared spectroscopy indicated molecular interactions between collagen fibers and ZPVP. Texture analysis revealed a significant increase in gel hardness, adhesiveness, and viscosity after cross-linking with ZPVP. Rheological measurements showed that as the ratio of ZPVP increased, stronger hydrogels were formed which in turn resulted in more sustained release of the model drug, dexamethasone sodium phosphate. We can therefore conclude that the mechanical properties of collagen hydrogels can be modified by controlling the ratio of ZPVP used for cross-linking, offering the potential to develop biocompatible sustained release drug delivery systems. Full article
(This article belongs to the Special Issue Collagen-Based Hydrogels)
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17 pages, 2440 KiB  
Article
Matrix Remodeling and Hyaluronan Production by Myofibroblasts and Cancer-Associated Fibroblasts in 3D Collagen Matrices
by Jiranuwat Sapudom, Claudia Damaris Müller, Khiet-Tam Nguyen, Steve Martin, Ulf Anderegg and Tilo Pompe
Gels 2020, 6(4), 33; https://0-doi-org.brum.beds.ac.uk/10.3390/gels6040033 - 30 Sep 2020
Cited by 23 | Viewed by 5111
Abstract
The tumor microenvironment is a key modulator in cancer progression and has become a novel target in cancer therapy. An increase in hyaluronan (HA) accumulation and metabolism can be found in advancing tumor progression and are often associated with aggressive malignancy, drug resistance [...] Read more.
The tumor microenvironment is a key modulator in cancer progression and has become a novel target in cancer therapy. An increase in hyaluronan (HA) accumulation and metabolism can be found in advancing tumor progression and are often associated with aggressive malignancy, drug resistance and poor prognosis. Wound-healing related myofibroblasts or activated cancer-associated fibroblasts (CAF) are assumed to be the major sources of HA. Both cell types are capable to synthesize new matrix components as well as reorganize the extracellular matrix. However, to which extent myofibroblasts and CAF perform these actions are still unclear. In this work, we investigated the matrix remodeling and HA production potential in normal human dermal fibroblasts (NHFB) and CAF in the absence and presence of transforming growth factor beta -1 (TGF-β1), with TGF-β1 being a major factor of regulating fibroblast differentiation. Three-dimensional (3D) collagen matrix was utilized to mimic the extracellular matrix of the tumor microenvironment. We found that CAF appeared to response insensitively towards TGF-β1 in terms of cell proliferation and matrix remodeling when compared to NHFB. In regards of HA production, we found that both cell types were capable to produce matrix bound HA, rather than a soluble counterpart, in response to TGF-β1. However, activated CAF demonstrated higher HA production when compared to myofibroblasts. The average molecular weight of produced HA was found in the range of 480 kDa for both cells. By analyzing gene expression of HA metabolizing enzymes, namely hyaluronan synthase (HAS1-3) and hyaluronidase (HYAL1-3) isoforms, we found expression of specific isoforms in dependence of TGF-β1 present in both cells. In addition, HAS2 and HYAL1 are highly expressed in CAF, which might contribute to a higher production and degradation of HA in CAF matrix. Overall, our results suggested a distinct behavior of NHFB and CAF in 3D collagen matrices in the presence of TGF-β1 in terms of matrix remodeling and HA production pointing to a specific impact on tumor modulation. Full article
(This article belongs to the Special Issue Collagen-Based Hydrogels)
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16 pages, 4151 KiB  
Article
Characterization of Tissue Engineered Endothelial Cell Networks in Composite Collagen-Agarose Hydrogels
by Houda Ichanti, Sanja Sladic, Stefan Kalies, Axel Haverich, Birgit Andrée and Andres Hilfiker
Gels 2020, 6(3), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/gels6030027 - 03 Sep 2020
Cited by 13 | Viewed by 4723
Abstract
Scaffolds constitute an important element in vascularized tissues and are therefore investigated for providing the desired mechanical stability and enabling vasculogenesis and angiogenesis. In this study, supplementation of hydrogels containing either MatrigelTM and rat tail collagen I (MatrigelTM/rCOL) or human [...] Read more.
Scaffolds constitute an important element in vascularized tissues and are therefore investigated for providing the desired mechanical stability and enabling vasculogenesis and angiogenesis. In this study, supplementation of hydrogels containing either MatrigelTM and rat tail collagen I (MatrigelTM/rCOL) or human collagen (hCOL) with SeaPlaqueTM agarose were analyzed with regard to construct thickness and formation and characteristics of endothelial cell (EC) networks compared to constructs without agarose. Additionally, the effect of increased rCOL content in MatrigelTM/rCOL constructs was studied. An increase of rCOL content from 1 mg/mL to 3 mg/mL resulted in an increase of construct thickness by approximately 160%. The high rCOL content, however, impaired the formation of an EC network. The supplementation of MatrigelTM/rCOL with agarose increased the thickness of the hydrogel construct by approximately 100% while supporting the formation of a stable EC network. The use of hCOL/agarose composite hydrogels led to a slight increase in the thickness of the 3D hydrogel construct and supported the formation of a multi-layered EC network compared to control constructs. Our findings suggest that agarose/collagen-based composite hydrogels are promising candidates for tissue engineering of vascularized constructs as cell viability is maintained and the formation of a stable and multi-layered EC network is supported. Full article
(This article belongs to the Special Issue Collagen-Based Hydrogels)
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Review

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21 pages, 7958 KiB  
Review
Type I Collagen-Fibrin Mixed Hydrogels: Preparation, Properties and Biomedical Applications
by Thibaud Coradin, Kun Wang, Thalie Law and Léa Trichet
Gels 2020, 6(4), 36; https://0-doi-org.brum.beds.ac.uk/10.3390/gels6040036 - 20 Oct 2020
Cited by 30 | Viewed by 7620
Abstract
Type I collagen and fibrin are two essential proteins in tissue regeneration and have been widely used for the design of biomaterials. While they both form hydrogels via fibrillogenesis, they have distinct biochemical features, structural properties and biological functions which make their combination [...] Read more.
Type I collagen and fibrin are two essential proteins in tissue regeneration and have been widely used for the design of biomaterials. While they both form hydrogels via fibrillogenesis, they have distinct biochemical features, structural properties and biological functions which make their combination of high interest. A number of protocols to obtain such mixed gels have been described in the literature that differ in the sequence of mixing/addition of the various reagents. Experimental and modelling studies have suggested that such co-gels consist of an interpenetrated structure where the two proteins networks have local interactions only. Evidences have been accumulated that immobilized cells respond not only to the overall structure of the co-gels but can also exhibit responses specific to each of the proteins. Among the many biomedical applications of such type I collagen-fibrin mixed gels, those requiring the co-culture of two cell types with distinct affinity for these proteins, such as vascularization of tissue engineering constructs, appear particularly promising. Full article
(This article belongs to the Special Issue Collagen-Based Hydrogels)
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