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Gels
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Synthesis, Characterization and Applications of Collagen-Based Gels
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Synthesis, Characterization and Applications of Collagen-Based Gels

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

Deadline for manuscript submissions: 20 May 2026 | Viewed by 25239

Special Issue Editors

Dr. Andreea-Mariana Negrescu

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
Interests: biomaterials; biocompatibility; tissue engineering; regenerative medicine; cell biology; biomedical materials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Anişoara Cîmpean

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
Interests: biomedical materials; cell biomaterial interactions; biocompatibility; tissue engineering; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Due to their distinctive characteristics, namely their biocompatibility, accessibility, affordability, and programmable properties, biopolymers are employed in a multitude of fields, including pharmaceutical and biomedical research, as well as cosmetics and food. Being the most abundant protein in mammals, with a triple-helix structure and an innately biocompatible, biomimetic, biodegradable, and haemostatic nature, collagen became one of the most commonly used biopolymers. Moreover, owing to the remarkable capacity of its fibers to self-assemble via non-covalent bonds and form in situ gels, collagen has been exploited in a plethora of applications, such tissue engineering, drug delivery systems, skin care, etc. The advantage of collagen-based gels is that they can be readily manipulated, and their mechanical and physical properties can be enhanced by chemical cross-linkers. However, sometimes, collagen-based gels face some limitations in the form of a weak mechanical strength and lack of elasticity. In light of these considerations, the field of collagen-based gels represents an ongoing area of research that requires a more comprehensive understanding of the technologies involved in their synthesis, gel formulations, and emerging applications. Thus, with this Special Issue, we aim to gather researchers who are interested in the field of collagen-based gels, from both a theoretical and applicative perspective. In particular, we welcome submissions presenting new insights into their fabrication, optimization parameters, drug loading and release mechanisms, the formulation and manufacturing aspects of novel collagen-based gels, and their innovative applications, with an emphasis on their biomedical use.

Dr. Andreea-Mariana Negrescu
Prof. Dr. Anişoara Cîmpean
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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

  • collagen-based gels
  • soft materials
  • mechanical properties
  • functional applications
  • tissue engineering
  • regenerative medicine
  • drug delivery

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Published Papers (5 papers)

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Research

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14 pages, 5040 KB  
Article
Being a Target for Glycation by Methylglyoxal Contributes to Therapeutic Efficacy of Injectable Collagen Hydrogels Post-Myocardial Infarction
by Xixi Guo, Ramis Ileri, Marc Ruel, Emilio I. Alarcon and Erik J. Suuronen
Gels 2026, 12(1), 18; https://doi.org/10.3390/gels12010018 - 24 Dec 2025
Viewed by 341
Abstract
Despite the advances in medical therapies for treating myocardial infarction (MI), morbidity and mortality rates remain high. Following MI, increased methylglyoxal (MG) production leads to the accumulation of advanced glycation end-products (AGEs), which contribute to adverse remodeling and to the deterioration of cardiac [...] Read more.
Despite the advances in medical therapies for treating myocardial infarction (MI), morbidity and mortality rates remain high. Following MI, increased methylglyoxal (MG) production leads to the accumulation of advanced glycation end-products (AGEs), which contribute to adverse remodeling and to the deterioration of cardiac function. We previously reported that an injectable collagen type I hydrogel improves the repair and function of mouse hearts post-MI. Notably, we observed that the injected hydrogel was a target for MG-AGE glycation, and that there were less MG-modified proteins in the myocardium. In this study, we further evaluated this protective mechanism by pre-glycating the hydrogels and assessing their therapeutic efficacy for treating MI. In vitro experiments showed that the viability of macrophages was reduced when cultured with the glycated hydrogel in the presence of MG. In vivo, female C57BL/6 mice were randomly assigned to receive intramyocardial injections of one of three treatments: phosphate-buffered saline, normal collagen hydrogel, or MG-glycated hydrogel. After 28 days, echocardiography was performed to evaluate cardiac function, and hearts were harvested for immunohistochemistry. Our results showed that the MG-glycated hydrogel had a reduced treatment effect (greater scar size, fewer wound-healing macrophages, less viable myocardium and decreased cardiac function) compared to mice that received the normal collagen hydrogel. In summary, this study demonstrates that the ability of the collagen hydrogel to act as a target for glycation and remove MG from the environment contributes to its therapeutic effect in treating the post-MI heart. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Applications of Collagen-Based Gels)
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13 pages, 1290 KB  
Article
Development and Characterization of Hollow-Shell Collagen Microcapsules for Three-Dimensional Cell Culture
by Yusuke Chiwata, Shigehisa Aoki, Takehisa Sakumoto and Takayuki Narita
Gels 2026, 12(1), 15; https://doi.org/10.3390/gels12010015 - 24 Dec 2025
Viewed by 291
Abstract
Three-dimensional (3D) cell culture systems require biocompatible carriers that provide both structural support and efficient mass transport. Conventional alginate-based encapsulation systems suffer from poor molecular diffusion, lack of cell adhesion motifs, and structural instability under physiological conditions. Here, we report the first development [...] Read more.
Three-dimensional (3D) cell culture systems require biocompatible carriers that provide both structural support and efficient mass transport. Conventional alginate-based encapsulation systems suffer from poor molecular diffusion, lack of cell adhesion motifs, and structural instability under physiological conditions. Here, we report the first development of hollow-shell collagen microcapsules (CMCs) fabricated via a gelatin sacrificial template approach that overcomes these critical limitations. The hollow architecture combined with collagen’s intrinsic bioactivity achieved 2.5-fold enhancement in molecular permeability compared to conventional alginate beads, while maintaining structural integrity for 14 days versus 3-day collapse of alginate controls. NIH 3T3 fibroblasts encapsulated within CMCs demonstrated superior proliferation and formed tissue-like multilayered structures with extensive extracellular matrix deposition. This platform represents a significant advance in 3D cell culture technology, providing a biologically functional microenvironment with enhanced mass transport properties for applications in tissue engineering and regenerative medicine. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Applications of Collagen-Based Gels)
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32 pages, 11077 KB  
Article
Gelatin/Cerium-Doped Bioactive Glass Composites for Enhancing Cellular Functions of Human Mesenchymal Stem Cells (hBMSCs)
by Andrey Iodchik, Gigliola Lusvardi, Alfonso Zambon, Poh Soo Lee, Hans-Peter Wiesmann, Anne Bernhardt and Vera Hintze
Gels 2025, 11(6), 425; https://doi.org/10.3390/gels11060425 - 1 Jun 2025
Cited by 2 | Viewed by 16078
Abstract
Delayed or non-healing of bone defects in an aging, multi-morbid population is still a medical challenge. Current replacement materials, like autografts, are limited. Thus, artificial substitutes from biodegradable polymers and bioactive glasses (BGs) are promising alternatives. Here, novel cerium-doped mesoporous BG microparticles (Ce-MBGs) [...] Read more.
Delayed or non-healing of bone defects in an aging, multi-morbid population is still a medical challenge. Current replacement materials, like autografts, are limited. Thus, artificial substitutes from biodegradable polymers and bioactive glasses (BGs) are promising alternatives. Here, novel cerium-doped mesoporous BG microparticles (Ce-MBGs) with different cerium content were included in photocrosslinkable, methacrylated gelatin (GelMA) for promoting cellular functions of human mesenchymal stem cells (hBMSCs). The composites were studied for intrinsic morphology and Ce-MBGs distribution by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). They were gravimetrically analyzed for swelling and stability, compressive modulus via Microsquisher® and bioactivity by Fluitest® calcium assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), also determining silicon and cerium ion release. Finally, seeding, proliferation, and differentiation of hBMSCs was investigated. Ce-MBGs were evenly distributed within composites. The latter displayed a concentration-dependent but cerium-independent decrease in swelling, while mechanical properties were comparable. A MBG type-dependent bioactivity was shown, while an enhanced osteogenic differentiation of hBMSCs was achieved for Ce-MBG-composites and related to different ion release profiles. These findings show their strong potential in promoting bone regeneration. Still, future work is required, e.g., analyzing the expression of osteogenic genes, providing further evidence for the composites’ osteogenic effect. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Applications of Collagen-Based Gels)
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23 pages, 6412 KB  
Article
Influence of Cell Seeding Density and Material Stiffness on Chondrogenesis of Human Stem Cells Within Soft Hydrogels, Without the Use of Exogenous Growth Factors
by Arianna De Mori, Nadide Aydin, Giada Lostia, Alessia Manca, Gordon Blunn and Marta Roldo
Gels 2025, 11(3), 213; https://doi.org/10.3390/gels11030213 - 18 Mar 2025
Cited by 2 | Viewed by 2690
Abstract
Mesenchymal stem cells (MSCs) can differentiate into chondrocytes provided with the appropriate environmental cues. In this study, we loaded human adipose-derived stem cells (hAdMSCs) into collagen/alginate hydrogels, which have been shown to induce chondrogenesis in ovine bone marrow stem cells without the use [...] Read more.
Mesenchymal stem cells (MSCs) can differentiate into chondrocytes provided with the appropriate environmental cues. In this study, we loaded human adipose-derived stem cells (hAdMSCs) into collagen/alginate hydrogels, which have been shown to induce chondrogenesis in ovine bone marrow stem cells without the use of any exogenous chondrogenic growth factors. We examined the influence of hydrogel stiffness (5.75 and 6.85 kPa) and cell seeding density (1, 2, 4, and 16 × 106 cells/mL) on the chondrogenic induction of hAdMSCs, without exogenous differentiation growth factors. Over time, the behaviour of the hAdMSCs in the scaffolds was investigated by analysing the amount of DNA; their morphology; their cell viability; the expression of chondrogenic genes (RT-qPCR); and the deposition of collagen I, collagen II, and aggrecan. The results showed that all scaffolds supported the acquisition of a rounded morphology and the formation of cell aggregates, which were larger with higher cell seeding densities. Furthermore, the cells were viable within the hydrogels throughout the experiment, indicating that high cell density did not have a detrimental effect on viability. All the conditions supported the upregulation of chondrogenic genes (SOX9, COL2A1, SOX5, and ACAN). By comparison, only the highest cell seeding density (16 × 106 cells/mL) promoted a superior extracellular matrix deposition composed of collagen II and aggrecan with limited production of collagen I. These molecules were deposited in the pericellular space. Furthermore, no histological difference was noted between the two stiffnesses. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Applications of Collagen-Based Gels)
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Review

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37 pages, 2784 KB  
Review
A Recent Insight into Research Pertaining to Collagen-Based Hydrogels as Dressings for Chronic Skin Wounds
by Andreea Mariana Negrescu and Anisoara Cimpean
Gels 2025, 11(7), 527; https://doi.org/10.3390/gels11070527 - 8 Jul 2025
Cited by 4 | Viewed by 5251
Abstract
Affecting millions of individuals each year, chronic wounds place a substantial strain on both the healthcare system and healthcare providers, becoming a global health issue that requires a rapid and efficient solution. Unlike acute wounds that heal naturally without any external intervention, chronic [...] Read more.
Affecting millions of individuals each year, chronic wounds place a substantial strain on both the healthcare system and healthcare providers, becoming a global health issue that requires a rapid and efficient solution. Unlike acute wounds that heal naturally without any external intervention, chronic wounds necessitate proper medical treatment in order to promote the wound-healing process and avoid any arising complications. However, the traditional therapeutic strategies are often limited when it comes to treating chronic wounds, which is why new approaches that facilitate the timely and effective healing of skin have been explored. Due to their unique properties, collagen-based hydrogels have been widely investigated as potential candidates for the management of chronic skin wounds, owing to their good biocompatibility, high water retention capacity, which provides a moist microenvironment, and capacity to promote cell adhesion, proliferation, migration, and differentiation for optimal tissue repair. In this context, the current paper discusses the recent advancements in collagen-based hydrogels as wound dressings, thus highlighting their potential as a future therapeutic approach for skin chronic wound care. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Applications of Collagen-Based Gels)
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