Cold Sintering Process for Fabrication of Biodegradable Drug-Eluting Ceramics

Project Information

DrugCer

Grant agreement ID: 101063841

DOI

10.3030/101063841

Project closed

EC signature date 9 August 2022

Start date 1 August 2023

End date 31 July 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 189 687,36

Coordinated by

FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
Germany

Periodic Reporting for period 1 - DrugCer (Cold Sintering Process for Fabrication of Biodegradable Drug-Eluting Ceramics)

Reporting period: 2023-08-01 to 2025-07-31

Summary of the context and overall objectives of the project

The project DrugCer – Cold Sintering Process for the Fabrication of Biodegradable Drug-Eluting Ceramics aimed to develop a sustainable manufacturing route for bioceramics with controlled drug release and bone-like mechanical performance. Conventional sintering requires temperatures above 1000 °C, which limits the integration of drugs, polymers, and metals. The Cold Sintering Process (CSP) overcomes this barrier by enabling densification of materials at near-room temperatures under high pressure. This approach reduces energy use and CO2 emissions while opening new opportunities for multifunctional biomedical materials.
The project focused on creating biodegradable ceramic–polymer composites that can release therapeutic agents and provide strength comparable to that of compact bone. Beyond developing drug-eluting bioceramics, a new concept for bioceramics with embedded metallic lines was proposed. Such functional bioceramics hold potential for bone-integrated sensors and neural interfaces. These materials could bridge the gap between hard implants and flexible electronics, contributing to future human–machine interfaces.
The project addressed EU strategic priorities by reducing the environmental footprint of ceramic manufacturing (European Green Deal), promoting technological innovation in the health and materials sectors (An Economy that Works for People), and supporting medical technologies that improve the quality of life (European Way of Life).

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

The project developed and optimized Cold Sintering Process (CSP) routes for hydroxyapatite–gelatin (HAp–gelatin) composites. The process preserved the flake-like nanostructure of hydroxyapatite and yielded materials with strength and ductility similar to those of bone. Bioceramic–polymer composites loaded with 1 wt% of the antibiotic vancomycin showed a compressive strength of approximately 186 MPa, comparable to the 200 MPa strength of natural bone, and a ductile fracture behavior.
The mechanisms of densification and drug release were studied through a short research stay at the G.E.R.N. Center for Tissue Replacement, Regeneration, and Neogenesis at the University of Freiburg. Drug-release kinetics were quantified using high-performance liquid chromatography (HPLC), revealing a Case II transport mechanism consistent with controlled diffusion. These results represent the first demonstration of drug-release modeling for cold-sintered ceramic–polymer composites.
In parallel, new work packages were implemented to explore bioceramic–metal co-sintering. Metallic lines were inkjet-printed and successfully embedded into ceramic matrices using cold sintering, establishing a stable metal–ceramic interface formed at room temperature. This technology allows the fabrication of functional bioceramics capable of electrical transmission and stimulation, expanding the scope of CSP toward active biomedical implants.
Scientific results from the project were published (Open Ceramics, Journal of the European Ceramic Society, Fraunhofer Annual Report 2024/25) and presented at international conferences (World Biomaterials Congress 2024, Israel Materials Engineering Conference 2025, Conference of European Ceramics Society 2025).

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)

The project demonstrated that cold sintering enables the co-processing of ceramics, polymers, and metals in a single step, unachievable by conventional high-temperature sintering. These possibilities open new pathways for biohybrid materials that combine mechanical strength, drug release, biodegradability, and electrical functionality.
Key results of the project include:
• Dense, bone-like hydroxyapatite–gelatin composites that mimic bone in composition and microstructure;
• Dense, drug-eluting bioceramics and an identified model for drug-release kinetics from the developed materials;
• A concept for bioceramics with embedded metallization with potential for bone-integrated electrodes and sensors.
The results provide a foundation for further development of cold-sintered hybrid implants, conductive bone implants, and drug-delivery devices. The technology is currently at TRL 2–4 (proof of concept to early validation). Engagement with medical and industrial partners during project implementation led to follow-up grant applications (M-ERA.Net 2024, BMBF MaterialVital 2025) and ongoing collaborations with universities and startups in Germany, Denmark, Israel, and the Netherlands. Continued research and cooperation with industrial and medical partners are necessary for advancing the technology toward higher TRLs.