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Gels
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Hydrogels for Cartilage Tissue Engineering and Mechanobiology
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Hydrogels for Cartilage Tissue Engineering and Mechanobiology

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

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 5444

Special Issue Editors

Dr. Seyed Ali Elahi

E-Mail Website
Guest Editor
1. Department of Movement Sciences, Human Movement Biomechanics Research Group, KU Leuven, Tervuursevest 101—Box 1501, 3001 Leuven, Belgium
2. Department of Mechanical Engineering, KU Leuven, Celestijnenlaan 300—Box 2422, 3001 Leuven, Belgium
Interests: mechanical characterization; soft tissues; in silico modeling; inverse methods; cartilage
Dr. Rocío Castro-Viñuelas

E-Mail Website
Guest Editor
1. Department of Movement Sciences, Human Movement Biomechanics Research Group, KU Leuven, Tervuursevest 101—Box 1501, 3001 Leuven, Belgium
2. Department of Development and Regeneration, Laboratory of Tissue Homeostasis and Disease, KU Leuven, Leuven, Belgium
3. Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium
Interests: cartilage; tissue culture; osteoarthritis; mechanobiology; mechanotransduction
Dr. Veerle Bloemen

E-Mail Website
Guest Editor
1. Surface and Interface Engineered Materials (SIEM), Group T Leuven Campus, KU Leuven, Andreas Vesaliusstraat 13, 3000 Leuven, Belgium
2. Department of Materials Engineering (MTM), KU Leuven, Kasteelpark Arenberg 44—Box 2450, B-3001 Leuven, Belgium
3. Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium
4. Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium
Interests: bone; cartilage; tissue engineering; biofabrication; bioprinting; melt electrowriting; hydrogels

Special Issue Information

Dear Colleagues,

Hydrogels are increasingly recognized as a crucial material in the field of tissue engineering and mechanobiological studies, particularly for advancing cartilage regeneration. Possessing favorable properties for biomedical applications, such as biocompatibility, high water content and mechanical properties, hydrogels serve as ideal substrates for mimicking the intricate microenvironment of tissues.

In cartilage tissue engineering and mechanobiological studies, hydrogels can be used to support the growth and proliferation of chondrocytes, thanks to their flexibility and suppleness, which closely emulate the mechanical properties of native cartilage. Furthermore, engineered hydrogels can be designed to degrade at a rate synchronized with the growth of new tissue, thereby supporting the fusion of the new tissue with the body.

The ability of hydrogels to mimic natural extracellular matrix (ECM), coupled with their tunable properties, positions them as desirable candidates for creating scaffolds aimed at supporting tissue regeneration. However, challenges persist, notably in matching hydrogel degradation rates with tissue growth and enhancing mechanical properties without compromising biocompatibility and bioactivity. Nevertheless, ongoing research and development endeavors hold promise for overcoming these hurdles and further enhancing the efficacy of hydrogels in cartilage  mechanobiological research and skeletal tissue engineering applications.

Dr. Seyed Ali Elahi
Dr. Rocío Castro-Viñuelas
Dr. Veerle Bloemen
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

  • hydrogels
  • tissue engineering
  • cartilage
  • biocompatibility
  • mechanobiology
  • mechanical properties
  • scaffolds

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Published Papers (4 papers)

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Research

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18 pages, 3809 KB  
Article
Dialdehyde Starch Cross-Linked Collagen with Heparin Conjugation: Characterization and Feasibility Study for Osteochondral Tissue Repair
by Jason K. Lee, Jihye Baek, Shawn P. Grogan, Tae-Hoon Koo and Darryl D. D’Lima
Gels 2025, 11(11), 850; https://doi.org/10.3390/gels11110850 - 24 Oct 2025
Cited by 1 | Viewed by 986
Abstract
Collagen is widely used in tissue engineering due to its excellent biocompatibility; however, its limited intrinsic mechanical strength restricts its application in load-bearing environments. This study introduces dialdehyde starch (DAS) as a biocompatible macromolecular cross-linker to enhance the mechanical integrity of collagen hydrogels. [...] Read more.
Collagen is widely used in tissue engineering due to its excellent biocompatibility; however, its limited intrinsic mechanical strength restricts its application in load-bearing environments. This study introduces dialdehyde starch (DAS) as a biocompatible macromolecular cross-linker to enhance the mechanical integrity of collagen hydrogels. Collagen gels were cross-linked with DAS during neutralization under optimized conditions, resulting in a significant increase in compressive stiffness (up to ~125 kPa), thereby improving their suitability for mechanically demanding applications. Degradation studies of DAS-crosslinked collagen confirmed the long-term stability of the gel, while post-neutralization heparin incorporation improved bifunctionality, as evidenced by increased surface retention. FT-IR analysis confirmed the successful DAS cross-linking and heparin conjugation while preserving the native collagen structure. Bioactivity assays of DAS-crosslinked and heparin-conjugated collagen gel demonstrated enhanced chondrocyte migration in PDGF-BB-functionalized gels and improved cell viability, proliferation, and matrix deposition in TGF-β3-treated constructs. Preliminary ex vivo culture using a rabbit osteochondral defect model showed promising tissue integration and glycosaminoglycan accumulation. These results highlight the potential of DAS-crosslinked and heparin-conjugated collagen hydrogels as mechanically robust and biologically supportive scaffolds for osteochondral tissue engineering and regenerative medicine applications. Full article
(This article belongs to the Special Issue Hydrogels for Cartilage Tissue Engineering and Mechanobiology)
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27 pages, 4951 KB  
Article
Novel GelMA/GelMA-AEMA Hydrogel Blend with Enhanced Printability as a Carrier for iPSC-Derived Chondrocytes In Vitro
by Paulo A. Amorim, Hannah Agten, Margaux Vermeulen, Sandra Van Vlierberghe, Liesbet Geris and Veerle Bloemen
Gels 2025, 11(9), 698; https://doi.org/10.3390/gels11090698 - 2 Sep 2025
Cited by 1 | Viewed by 1703
Abstract
Cartilage tissue engineering aims to restore damaged cartilage using biomaterials, cells, and/or biological cues to support cell growth and tissue repair. Although in the past decades scientific advances have moved the field forward, their translation to a clinical setting is still hampered. One [...] Read more.
Cartilage tissue engineering aims to restore damaged cartilage using biomaterials, cells, and/or biological cues to support cell growth and tissue repair. Although in the past decades scientific advances have moved the field forward, their translation to a clinical setting is still hampered. One major hurdle to take is to reduce process variability to ensure a predictable biological outcome. Using enabling technologies such as bioprinting has shown the potential to improve process robustness. However, developing bioinks that balance printability with biological functionality remains a major challenge. This study presents the development and structure–property relationships of a novel gelatin-based hydrogel blend, GelMA/GelMA-AEMA, optimized for extrusion-based bioprinting (EBB) while maintaining the crucial biological properties of GelMA for tissue engineering applications. The novel GelMA/GelMA-AEMA blend demonstrated superior flowability and printability compared to GelMA, effectively addressing common 3D-printing defects such as filament shape inhomogeneity. A systematic rheological characterization revealed that the blend exhibits a softer, elastically dominated structure with improved compliance. The blend behaves as a yield-stress fluid with a strong shear-thinning degree, making it highly suitable for EBB. The superior flow properties of the blend are deemed to enhance bond slippage and stress-induced orientation of its more imperfect gel structure, resulting in greater macroscopic deformation and enhanced print fidelity. In addition, histological assessment of a 21-day in vitro study with iPSC-derived chondrocytes suggested that the blend is at least equally performant as GelMA in supporting matrix formation. Histological analysis shows similar matrix deposition profiles, whereas gene expression analysis and compression tests even have suggested superior characteristics for cartilage TE. This study emphasizes the central role of rheology in bioink development and provides foundations for future material development for EBB, with potential implications for cartilage tissue engineering. Full article
(This article belongs to the Special Issue Hydrogels for Cartilage Tissue Engineering and Mechanobiology)
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15 pages, 3160 KB  
Article
Annealed Polyvinyl Alcohol Hydrogels for Cartilage Replacement: Effects of Synthesis Parameters on Mechanical Properties
by Hassan Mahmoud, Christian M. Puttlitz, Benjamin C. Gadomski and Kevin M. Labus
Gels 2025, 11(8), 644; https://doi.org/10.3390/gels11080644 - 14 Aug 2025
Viewed by 1781
Abstract
The objective of this paper was to determine the interactive effects of multiple synthesis parameters on annealed PVA hydrogel properties and assess these hydrogels for the application of cartilage replacement. PVA hydrogels were synthesized at two different molecular weight ranges (89–98 kDa and [...] Read more.
The objective of this paper was to determine the interactive effects of multiple synthesis parameters on annealed PVA hydrogel properties and assess these hydrogels for the application of cartilage replacement. PVA hydrogels were synthesized at two different molecular weight ranges (89–98 kDa and 146–186 kDa), two polymer concentrations (10% PVA and 20% PVA), and four different annealing temperatures (120 °C, 135 °C, 150 °C, and 165 °C). The compressive, tensile, and wear mechanical properties were measured, and the crystalline structure of these hydrogels was assessed via differential scanning calorimetry. Hydrogels showed increasing polymer weight percent, tensile modulus, and compressive modulus with increasing annealing temperature. Depending on synthesis parameters, the hydrogels matched or exceeded the previously published compressive and tensile properties of native cartilage. Higher molecular weight PVA hydrogels (146–186 kDa) exhibited less wear, but greater friction, compared to lower molecular weight PVA (89–98 kDa). The PVA hydrogels exhibited crystallinity in the range of 53–78%, but no consistent differences in crystallinity were detected between hydrogel variants. It was concluded that the (10% PVA, 146 kDa, 165 °C) annealed PVA hydrogel demonstrated the most appropriate balance of high tensile strength and compressive compliance comparable to cartilage. Full article
(This article belongs to the Special Issue Hydrogels for Cartilage Tissue Engineering and Mechanobiology)
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Review

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24 pages, 888 KB  
Review
Challenges and Strategies in Hydrogel-Based Cartilage Regeneration
by Carola Cavallo, Emanuela Amore, Sara Carpentieri and Livia Roseti
Gels 2026, 12(5), 350; https://doi.org/10.3390/gels12050350 - 22 Apr 2026
Viewed by 204
Abstract
The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent [...] Read more.
The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients. Full article
(This article belongs to the Special Issue Hydrogels for Cartilage Tissue Engineering and Mechanobiology)
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