Smart 4D biodegradable metallic shape-shifting implants for dynamic tissue restoration

Project Information

BIOMET4D

Grant agreement ID: 101047008

DOI

10.3030/101047008

EC signature date 24 March 2022

Start date 1 July 2022

End date 31 December 2026

Funded under

• The European Innovation Council (EIC)

Total cost

€ 4 039 541,25

EU contribution

€ 4 039 541,25

Coordinated by

FUNDACION IMDEA MATERIALES
Spain

Periodic Reporting for period 2 - BIOMET4D (Smart 4D biodegradable metallic shape-shifting implants for dynamic tissue restoration)

Reporting period: 2023-07-01 to 2024-12-31

Summary of the context and overall objectives of the project

Reconstructive surgeries frequently require multiple, often complex, procedures at high social and economic costs. A shape-morphing implant that can be implanted using less invasive procedures and that then undergoes predesigned shape changes, leading to tissue expansion and allowing for complete degradation coupled with tissue regeneration, is a radically new treatment concept. The BIOMET4D project aims to create a new generation of shape-shifting and load-bearing implants for dynamic tissue restoration and to introduce a revolutionary paradigm in how actuators can be implemented in biomedicine. The scientific and technological objectives of the project aim to develop and demonstrate new shape-morphing metamaterials, 4D smart metallic actuators, advanced multi-domain optimization tools, and finally proof-of-concept for two potential clinical applications. Technologically, this vision goes beyond existing paradigms because of the step-by-step actuation mechanisms, enabled through the additive manufacturing of multi-material degradable metallic structures, that are targeted for an order of magnitude improvement compared to the state-of-the-art. In the biomedical field, the futuristic long-term vision of this breakthrough technology is to dynamically regenerate entire tissues, and proof-of-concept will be demonstrated within the BIOMET4D project for craniosynostosis treatment and skin expansion. On the one hand, craniosynostosis is characterized by the premature fusion of the sutures in the skull and can lead to increased intracranial pressure, permanent brain injury, and deformation of the facial bones. It affects approximately one in every 2000 live births, and the current main treatment option is an invasive surgery. On the other hand, skin expansion is usually required during the reconstruction of large and disfiguring defects or malformations and allows for plastic reconstruction with neighboring skin of similar color, texture, sensation, thickness, and hair-bearing capability. Current skin expanders (essentially implanted rubber balloons) are inflated with weekly saline injections via a port, requiring regular outpatient visits with painful punctures and a risk of expander infection. In both cases, the potential impact of BIOMET4D’s technology on patients’ quality of life and healthcare costs is huge, by moving towards less invasive treatment options and reduced costs and time associated with follow-up care. Overall, the BIOMET4D project brings together an interdisciplinary team and approach to achieve this long-term vision and will likely have high social and economic impact as well as provide a new line of research for applications of smart metamaterials in medicine and engineering.

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 scientific activities of the BIOMET4D project have been organized into six main areas, and the main achievements for each are summarized here.
1. Principles of shape morphing: New shape-morphing actuators and principles based on multi-material structures and mechanical metamaterials have been conceived, designed, and experimentally demonstrated.
2. 3D printing of biodegradable metals: The project has identified reproducible processing parameters for the laser powder bed fusion (LPBF) processing of the biodegradable metals magnesium (Mg) and zinc (Zn) as well as for the LPBF processing of Mg and Zn into multi-material specimens.
3. Characterization and testing: Parameters, such as the composition and quality of the starting powders, the orientation of samples relative to print direction, and the specific post-processing of the samples, have been identified that influence the printed samples’ material and mechanical properties, including the degradation/corrosion behavior. The composition and processing methods have also been shown to influence the cytocompatibility of the samples, with results influencing choices for moving forward for pre-clinical evaluation.
4. Computational modeling: First, an enhanced phenomenological model for surface-based localized corrosion of Mg alloys was developed that extended existing approaches to more accurately capture spatial and temporal features of localized corrosion. Second, a physically-based model has been implemented to simulate the corrosion of bioabsorbable metals in environments that resemble biological fluids. Third, a topology optimization framework for lattice-based structures was developed.
5. Proof-of-concept for skin expansion: Animal ethical dossiers are being prepared to test the preliminary skin expander devices in relevant in vivo models as well as ex vivo in a bioreactor setup.
6. Proof-of-concept for craniosynostosis therapy: Animal ethical dossiers for rodent studies to be used in evaluation of the biocompatibility of the developed materials have been submitted to the relevant authorities and approved. In preliminary work, immune panels to allow the analysis of many physiological peripheral immune cellular subsets from a minimal amount of whole blood were defined.

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 BIOMET4D project has produced several scientific results that are beyond the state of the art during its first and second reporting periods. This has covered three main areas: multi-material shape-morphing actuators, laser powder bed fusion processing (LPBF) processing of the biodegradable metals magnesium (Mg) and zinc (Zn), and computational models related to the corrosion of Mg alloys. In particular, new shape-morphing actuators based on multi-material structures have been conceived, designed, and experimentally demonstrated, which has resulted in a patent application. Further, the project has identified reproducible processing parameters for LPBF of Mg and Zn alloys, as well as the combination of Mg and Zn in the same printed specimens. We have shown that parameters, such as the composition and quality of the starting powders, the orientation of samples relative to print direction, and the specific post-processing of the samples, influence the printed samples’ material and mechanical properties, including the degradation behavior and, therefore, their cytocompatibility. Finally, two computational models – an enhanced phenomenological model for surface-based localized corrosion of Mg alloys to more accurately capture spatial and temporal features of localized corrosion and a physically-based model to simulate the corrosion of bioabsorbable metals in environments that resemble biological fluids – have been developed and published in scientific journals. During the remainder of the project, we expect to achieve impactful results related to the development of 4D smart metallic actuators, advanced multi-domain optimization tools, and finally proof-of-concept for two potential clinical applications, craniosynostosis treatment and skin expansion. The ambitious goal of this project is to reach prototype medical devices tested in preclinical animal models. To reach long-term impact as actual products that can be used to treat human patients, significant resources and time beyond the project will be needed to perform further research and advance through clinical trials. On the technical side, this will require follow-up research, testing with end-users, and demonstration in a real-life environment with patients. On the business side, this will require activities such as business plan development, legal advice and intellectual property right (IPR) protection, and a supportive regulatory framework to reach a commercially viable product.

Schematic showing an overview of the BIOMET4D project.