Bio-based Hydrogels by Click Chemistry for Cartilage Tissue Engineering

Project Information

ClickBioGel

Grant agreement ID: 101105270

DOI

10.3030/101105270

Project closed

EC signature date 20 July 2023

Start date 1 July 2024

End date 30 June 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 188 590,08

Coordinated by

POLITECNICO DI TORINO
Italy

Periodic Reporting for period 1 - ClickBioGel (Bio-based Hydrogels by Click Chemistry for Cartilage Tissue Engineering)

Reporting period: 2024-07-01 to 2026-06-30

Summary of the context and overall objectives of the project

Modern healthcare increasingly relies on advanced biomaterials that can support tissue repair and regeneration while reducing the need for invasive treatments. Hydrogels, which are water-rich polymeric materials that closely resemble the natural extracellular matrix of living tissues, have emerged as promising candidates for applications such as wound healing, drug delivery, and tissue engineering. In particular, cartilage regeneration remains a major clinical challenge because cartilage has a very limited capacity for self-repair, often leading to chronic pain, reduced mobility, and an increased risk of osteoarthritis. However, many currently available hydrogels suffer from limited mechanical stability, insufficient control over their physical and biological properties, or crosslinking methods that may compromise biocompatibility and hinder clinical translation. At the same time, there is a growing demand for sustainable biomaterials derived from renewable natural resources that support both advances in healthcare and the European transition towards a circular bioeconomy.
ClickBioGel addresses these challenges by developing bio-based hydrogels using highly efficient click chemistry reactions which will enable the formation of precisely controlled polymer networks under mild and cell-friendly conditions. By functionalizing naturally derived polymers and optimizing their crosslinking chemistry, ClickBioGel allows the fabrication of multi-component hydrogels with improved mechanical performance, stability, and biological functionality. The project aims to create biomaterials that better mimic the native tissue environment and provide suitable support for cell growth and tissue regeneration, with a particular focus on cartilage tissue engineering.
Beyond the scientific objectives, ClickBioGel aims to strengthen European excellence in biomaterials research by integrating expertise in polymer chemistry, materials science, and biomedical engineering. The project's outcomes contribute to the development of safer, more sustainable, and more effective biomaterials for regenerative medicine and have the potential to support future therapies for cartilage repair and other tissue engineering applications. More broadly, the project aligns with European priorities by advancing sustainable healthcare technologies, promoting innovation in bio-based materials, and contributing to improved quality of life for patients with degenerative tissue disorders.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

ClickBioGel carried out a comprehensive programme of research to develop advanced bio-based hydrogels for cartilage repair using efficient and biocompatible click chemistry strategies. Naturally derived polymers were chemically modified with reactive functional groups including methacrylate, thiol, furan and maleimide which were then combined to fabricate multi-component hydrogel networks with precisely controlled structures and tunable properties. The project successfully established optimized methodologies for the functionalization of natural polymers and developed bio-based hydrogel networks using three different chemical crosslinking routes, including UV-curing and click reactions, for cartilage tissue engineering applications.
WP1. Gelatin/alginate/ĸ-carrageenan hydrogels were successfully developed through crosslinking via thiol-ene reaction. The obtained hydrogels were characterized to evaluate their swelling capacity, morphology, degradation profile, rheological properties and mechanical properties for supporting cartilage repair.
WP2. Gelatin/alginate/ĸ-carrageenan hydrogels were successfully prepared through crosslinking via UV-curing. The developed hydrogels were characterized to evaluate their swelling capacity, morphology, degradation profile, rheological properties and mechanical properties for supporting cartilage repair.
WP3. Gelatin/alginate/chitosan hydrogels were successfully fabricated through crosslinking via Diels-Alder reaction. The developed hydrogels were characterized to evaluate their swelling capacity, morphology, degradation profile, rheological properties and mechanical properties for supporting cartilage repair. These hydrogels also displayed injectability.
WP4. Biological evaluation of the hydrogels described in WP1-3 was analyzed. All hydrogels displayed high cell viability and cell proliferation towards chondrocyte cells.
The knowledge generated through this work advances the understanding of bio-based hydrogel design and provides a strong scientific foundation for the future development of biomaterials for cartilage repair and other tissue regeneration applications.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

ClickBioGel advances the state of the art by demonstrating how click chemistry can be combined with naturally derived polymers to create multi-component bio-based hydrogels with precisely controlled properties for cartilage repair. The developed materials enabled efficient crosslinking under mild conditions while offering tunable mechanical performance, controlled degradation, and excellent biocompatibility. The project also established optimized strategies for polymer functionalization and hydrogel fabrication, providing new design principles for the development of advanced biomaterials for regenerative medicine.
The results contributed to a better understanding of the relationship between polymer chemistry, hydrogel network architecture, and biological performance, supporting the rational design of materials that more closely mimic the native extracellular matrix of cartilage. ClickBioGel was successful in developing bio-based hydrogel materials using three different chemical crosslinking routes for tissue engineering applications. The hydrogels displayed morphological, mechanical, physicochemical and biological properties suitable for cartilage tissue regeneration applications. These advances provide a versatile platform that can also be adapted for a wide range of regenerative medicine applications beyond cartilage repair.
The project lays the scientific foundation for future translation towards clinical and industrial applications. Further work is needed to evaluate the long-term safety and efficacy of the developed hydrogels in relevant preclinical models, optimize scalable and cost-effective manufacturing processes, and establish robust sterilization and quality control procedures. Overall, the project has generated valuable scientific knowledge and innovative biomaterial design strategies that have the potential to accelerate the development of next-generation hydrogel-based therapies for cartilage repair and other regenerative medicine applications.