The project

Methodology

The initial phase focuses on the design and development of the core innovation: an electromagnetic-responsive shape memory 4D nanocomposite fibrous hydrogel.

This begins with molecular dynamics simulations (using GROMACS) to predict the shape memory behaviour of the polyurethane (PU) structure, optimizing the actuation temperature to the physiological range of 32-35°C.

The innovative biomaterial will be synthesized by incorporating bioactive polysaccharides (chitosan and chondroitin sulphate) and peptidomimetic antimicrobial motifs (AMP) to enhance healing and prevent colonization.

A key technical step is the optimization of the in situ synthesis (in solid phase) of magnetic nanoparticles (MNPs) and polypyrrole within the polymer blend, using an eco-sustainable process designed for scalability.

The second phase concentrates on industrialization, 4D programming, and digital integration. The nanocomposite fibrous hydrogel scaffold is manufactured using centrifugal spinning technology, a sustainable and high-yield method. The resulting fibres are assembled into a yarn and undergo shape memory programming.

This process allows the scaffold to be rolled for implantation via minimally invasive surgery (MIS) equipment, facilitating its delivery and subsequent recovery into a predefined “cage structure” upon reaching body temperature to envelop the tendon. To ensure compliance with GMP (Good Manufacturing Practice) standards and promote production robustness, an automated centrifugal spinning equipment and a Digital Twin (software program) will be designed and developed.

This Digital Twin, assisted by an AI framework, simulates and optimizes the manufacturing process. Additionally, the hydrogel is loaded with an anti-inflammatory drug (NSAID or corticosteroid) to ensure its controlled release during the acute phase of inflammation and pain post-surgery, targeted for approximately 15 days.

The final phase involves stringent preclinical characterization and strategic translation. Rigorous validation includes characterizing the structural, magnetic, and mechanical properties (aiming for ultimate tensile strength 5–10 MPa) and verifying a slow degradation rate (expected not higher than 30% in 3 months, supporting healing for at least 6 weeks). In vitro tests assess mechanotransduction pathways (quantifying gene expression like YAP1 and Tenascin C) and antimicrobial/antibiofilm properties.

In vivo preclinical evaluation is performed using both a small animal model (rats) and a clinically relevant large animal model (sheep, for total Achilles tendon rupture) under GLP (Good Laboratory Practice) conditions. The entire development is guided by the SSbD framework, including quantitative assessments via LCA, LCC, and S-LCA to ensure safety and sustainability.

Final exploitation is secured through regulatory planning (MDR/EMA), economic evaluation via a Cost-Effectiveness Model, and user feedback integrated through PPIE methods. Furthermore, a feasibility study will investigate developing a Digital Twin software program for tendon lesion and scaffold geometry in view of a personalized approach.