Engineering nanoparticle-polymer interactions to create instructive, tough nanocomposite hydrogels without negatively impacting self-healing behavior for bone tissue regeneration

Project Information

Nano4Bone

Grant agreement ID: 101087812

DOI

10.3030/101087812

EC signature date 23 March 2023

Start date 1 September 2023

End date 31 August 2028

Funded under

• European Research Council (ERC)

Total cost

€ 2 000 000,00

EU contribution

€ 2 000 000,00

Coordinated by

UNIVERSITEIT MAASTRICHT
Netherlands

Periodic Reporting for period 1 - Nano4Bone (Engineering nanoparticle-polymer interactions to create instructive, tough nanocomposite hydrogels without negatively impacting self-healing behavior for bone tissue regeneration)

Reporting period: 2023-09-01 to 2026-02-28

Summary of the context and overall objectives of the project

Each year, millions of people suffer from severe tissue damage or organ loss caused by injury, disease, or cancer. For many, transplantation is the only treatment option, yet donor organs and tissues are scarce. Regenerative medicine seeks to solve this problem by combining cells, biomaterials, and bioactive molecules to restore or replace damaged tissue. Among the different materials being developed, hydrogels have shown great promise because of their water-rich structure, which closely resembles natural tissue. However, most existing hydrogels are too weak and fragile to be used in demanding medical applications such as bone repair. Another key limitation is that they often cannot guide cells to rebuild functional tissue. The challenge is to create hydrogels that are both mechanically strong and biologically instructive, while keeping their ability to self-heal after damage. The Nano4Bone project addresses this challenge by developing a new generation of nanocomposite hydrogels that can repair themselves, resist mechanical stress, and actively promote tissue regeneration. The project combines expertise from chemistry, materials science, and bioengineering to design materials that can sense and respond to their biological environment. At the core of the Nano4Bone approach is the use of metal–ligand coordination bonds; dynamic chemical interactions that can be both strong and reversible. These bonds allow materials to recover from damage while maintaining toughness, making them ideal for self-healing systems. The project also uses mesoporous silica nanoparticles (MSNs) as building blocks. These nanoparticles act as structural reinforcements to strengthen the material and as carriers for therapeutic ions that stimulate bone growth or fight cancer cells. Nano4Bone focuses on optimizing these materials to bone regeneration after osteosarcoma (OS), a severe bone cancer that often requires removal of large sections of bone. Current treatments rely on chemotherapy and bone grafting, which can lead to complications, donor shortages, and poor healing. The innovative materials developed in Nano4Bone aim to eliminate remaining cancer cells and regenerate bone at the same time, offering a completely new therapeutic approach.

The project is built around three main objectives:
1. Develop nanocomposite hydrogels that combine rapid self-healing with high mechanical strength.
2. Design bioinorganic ion-loaded nanoparticles that can target cancer cells and promote bone and blood vessel formation.
3. Integrate these technologies into multifunctional materials that guide bone regeneration in advanced laboratory models.

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

Nano4Bone combines chemical design with biological testing to create adaptive and multifunctional biomaterials. The team developed a versatile polymer platform that makes it possible to study how metal–ligand coordination bonds affect material properties. By attaching different chemical groups to a polymer backbone, researchers can fine-tune how tightly the network is connected and how fast it can self-heal. This approach provides a flexible “toolbox” for designing hydrogels that are both durable and responsive, properties essential for tissue engineering applications.
In parallel, the project developed bioactive nanoparticles that provide biological instructions to surrounding cells. One of the most promising examples are selenium-doped mesoporous silica nanoparticles (Se-MSNs). Selenium is a trace element known for its anticancer and bone-promoting properties. When incorporated into MSNs, selenium can be released gradually in a controlled way, helping to combat osteosarcoma cells while supporting the activity of bone-forming stem cells. These nanoparticles can also be attached to ceramic scaffolds, allowing stable and localized release within the bone defect site. Building on this foundation, Nano4Bone is now expanding toward hybrid and combinatorial systems that integrate multiple biological signals. The team is investigating ways to combine therapeutic ions with biomolecules to promote blood vessel and bone formation. This approach aims to create smart biomaterials capable of addressing several stages of tissue healing.
To evaluate the materials under realistic biological conditions, Nano4Bone is also using a 3D osteosarcoma-on-a-chip model developed in collaboration with bioengineers. This microfluidic system mimics a bone defect affected by cancer and allows dynamic co-culture of tumor and stem cells under controlled flow. Using this platform, the researchers can observe how their materials perform in an environment that closely resembles living tissue, providing a valuable bridge between laboratory research and potential clinical 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)

Nano4Bone is expected to have a significant scientific impact. The project introduces new design rules for self-healing biomaterials, showing how dynamic metal–ligand chemistry can be used to combine strength, flexibility, and biological function in a single system. It also deepens our understanding of how therapeutic ions and nanoparticle–polymer interactions can be used to create adaptive, instructive materials for tissue regeneration.
In the future, the project’s results could help the development of innovative treatments for bone cancer and bone defects, offering materials that both eliminate tumor cells and stimulate new bone growth. Such multifunctional systems would reduce the need for repeated surgeries and donor tissue, improving patients’ recovery and quality of life. Beyond osteosarcoma, the materials and concepts developed in Nano4Bone can be applied to a wide range of regenerative medicine and biomedical fields — including cartilage repair, soft-tissue healing, organoid culture, and wound closure technologies.
At the institutional level, the ERC grant has enabled the growth of a multidisciplinary research group embedded in the newly formed Biomaterials Department, combining expertise in chemistry, materials science, and bioengineering. The project has strengthened European leadership in regenerative biomaterials and fostered collaborations with academic and clinical partners across Europe.
In summary, Nano4Bone is pioneering a new class of adaptive biomaterials that can both repair and instruct tissue — offering a step change in how regenerative materials are designed and bringing new hope for patients suffering from bone cancer and other severe tissue damage.