Laser powder bed fusion is a complex process that requires understanding and control of multiple parameters to obtain parts with optimized microstructures and free of defects. Furthermore, refractory alloys add additional complexity due to their high melting temperatures. Thus, an optimization step for the production process was necessary to achieve materials with optimal properties. Through this optimization, two alloy compositions were obtained: TiNbZr (TaMo)15 and TiNbZr (TaMo)5 (hereafter referred to as TNZTM15 and TNZTM5). These alloys exhibit excellent mechanical properties, particularly TNZTM5, with an elastic modulus ranging between 55 and 77 GPa, lower than that of Ti and its alloys (110-120 GPa) and much closer to that of bone, which was one of the project’s objectives.

After post-treatments (conventional annealing or hot isostatic pressing), no loss of mechanical characteristics was observed, despite significant microstructural evolution (grain size, residual stresses, segregation dissolution). However, unlike hot isostatic pressing cycles, microhardness measurements revealed exceptional hardening after isochronous annealing. This is a first for this family of TNZTM alloys, markedly different from those produced by conventional methods. Further analysis conducted as part of A. Mourgout’s thesis (funded by CoCoA-Bio) indicated a potentially interesting effect of interstitial atoms. In particular, oxygen diffusion was found to be responsible for spinodal decomposition, which is attributed to the strong hardening observed. This result presents interesting prospects, such as the ability to control interstitial atom doping and achieve a material with a hardness (and thus elastic modulus) gradient. This opens a promising avenue in IMD design.

The second objective of the project was the functionalization of the developed alloys. To achieve this, the most optimized alloy, TNZTM5, was studied from both chemical and biological perspectives. Experimentally, all protocols were first optimized on the reference alloy prepared by arc melting and then transferred to the printed alloys. Electrochemical corrosion tests were conducted at 25°C and 37°C, in an aggressive medium (aqueous sodium chloride solution, NaCl 0.1 M) to accelerate chemical attack, as well as in two cell culture media: a high-glucose Dulbecco’s Modified Eagle Medium (DMEM) and a deoxygenated DMEM enriched with fetal bovine serum (FBS) to anticipate the chemical reactivity of the alloy in in vitro cellular test conditions. The obtained results confirm the fragility of the alloy when unalloyed Ta and/or Mo islands persist in its microstructure, as these dissolve at varying rates regardless of the environmental medium. They also show that the corrosion potential (Ecorr) of the alloy in DMEM or DMEM + FBS at 37°C is lower than in NaCl at 25°C, and that its impedance is higher in these media than in NaCl. Notably, optimizing TNZTM5 production by increasing the VED parameter (up to 550 J.mm-3) and especially by introducing a thermal post-treatment (annealing under ultra-pure argon up to 1000°C for 2 hours) reduces the proportion of unmelted islands and thus improves the alloy’s corrosion resistance. Pre-osteoblastic cells cultured in an alloy- conditioned medium showed no short-term cytotoxicity (≤120 hours of exposure). No negative effects on proliferation or cell morphology were observed within this timeframe. However, to confirm the biocompatibility of this alloy, as suggested by these preliminary results, further experiments must be conducted in compliance with ISO 10993-5 (cytotoxicity tests) and ISO 10993-12 (sample preparation). These tests should include prolong

Additionally, it will be essential to study the pro-inflammatory potential of ions released by the alloy over time. This can be evaluated by measuring the production of pro-Moreover, assessing the alloy’s hemocompatibility through standard tests, including hemolysis, platelet activation, and coagulation analysis, will be crucial. These evaluations are essential prerequisites given the objective of using these alloys as implantable medical devices. Parallel to this, robust strategies for chemical [F. Arjmand et al., Emergent Materials, 2024] and electrochemical [F. Arjmand et al., Emergent Materials, 2025 under revision] surface functionalization were developed, based on diazonium salt chemistry. These strategies enable the covalent grafting of functional chemical groups as “platforms” onto which complex biological functionalities can be added via peptides (e.g., osteoinductive or antimicrobial peptide grafting).

Finally, a machinability study was conducted to assess material removal behavior in relation to dental implant assembly areas. The tests demonstrated not only good machinability (material removal without significant degradation or tool breakage and without major deformation) but also surface roughness comparable to that of commercially available implants. Three machining methods were tested: conventional machining with a carbide tool, innovative machining with a diamond tool (with and without vibratory assistance, as used for hard materials). The conventional machining method yielded the best results, indicating that an economical production approach for implants is feasible. After determining the optimal cutting speed, three feed rates were tested for each machining method, and the resulting surface roughness was compared to the required roughness on the implant collar (Sa = 0.49 μm). Since the implant collar is positioned at the gum level, its roughness is critical to prevent infections. Among the tested feed rates, the ideal one was 127 mm/min, yielding a surface roughness of 0.548 μm, closest to the required value. The tool wear analysis suggests that material-induced wear is low. Future studies on tool edge sharpness will quantify wear levels more precisely. Chemical and biological functionalization will subsequently be performed on machined surfaces to compare results with those obtained on as-printed surfaces from laser fusion.

Impact and Potential Scientific, Economic, Social, and Cultural Outcomes of the Project

Metallurgical Perspective : While previous research has primarily focused on how alloying elements influence the microstructure and properties of MPEAs, the impact of post-treatment—particularly on fragile biphasic microstructures—has been relatively unexplored. This project demonstrated that post-processing plays a crucial role in refining microstructures and enhancing the properties of the produced alloys, especially considering common challenges such as porosity, segregation, and large grains that occur in cast alloys. Despite time-dependent microstructural changes, conventional annealing and hot isostatic pressing (HIP) post-treatments have shown improvements in mechanical properties compared to the as-manufactured state, which had already met the project’s objectives. The increase in hardness after annealing was attributed to the presence of interstitial atoms, particularly oxygen, during post-processing. This presence led to a spinodal decomposition observed at high temperatures and long durations. These findings open up new avenues for post-manufacturing microstructural optimization, including the possibility of controlling the type and concentration of interstitial elements (O, C, N…) to induce selective hardness modulation through diffusion of these interstitial atoms.

Functionalization Perspective : Enhancing cell-material interactions is a major goal in biomaterials research. Current bio-functionalization strategies using native proteins have limitations, necessitating the development of new methodologies. In this context, the use of synthetic peptides incorporating bioactive motifs or sequences from proteins represents a promising alternative. Moreover, combining different peptide sequences with complementary or synergistic effects allows targeting multiple biological functions on the biomaterial surface. To this end, the project developed a strategy based on peptide use to establish multifunctionality on alloy surfaces. We designed a methodology for modifying material surfaces by covalently attaching peptide motifs, creating a coating with synergistic properties for rapid endothelialization, osteoinduction, and/or antimicrobial activity. A combination of bioactive peptides was selected to develop a new generation of biomaterials with improved properties compared to those currently used in clinical practice. Thanks to the strong multidisciplinary approach of our consortium, a new

Methodological and Technical Innovation : The laser powder bed fusion (LPBF) additive manufacturing technique used in this project is becoming more widespread within the consortium and is successfully being extended to other applications, such as printing magnetic reluctance motor rotors using soft-chemistry synthesized alloy powders (ITODYS laboratory). The versatility of this technique in producing complex structures with little to no machining, while using only the exact amount of required material, reduces costs while improving the sustainability and environmental efficiency of functional device production. Furthermore, the use of hot isostatic pressing (HIP) during post-treatment could revive interest in this technique, particularly due to its potential for controlling the gas environment inside the furnace chamber. This opens possibilities for diffusing nitrogen interstitial atoms into the material under isostatic pressure, a technique that could be extended beyond biomedical applications to all refractory MPEAs.

Additionally, experimental advances in surface functionalization have been extended to the grafting of novel macromolecules of interest, such as peptides associated with succinyl-beta-cyclodextrin photosensitive groups. These allow metallic implant surfaces to gain osteoinductive properties while also enabling the controlled release of antimicrobial agents under external stimuli (e.g., light exposure). This approach has the potential to revolutionize the treatment of bone diseases and fractures in the long term (as part of a joint France-Italy PhD funded by the Horizon CY Initiative IDEX program of Cergy University).