Machine learning-guided exploration and experimental assessment of unreported compositions in the quaternary Ti-Zr-Cu-Pd biocompatible metallic glass system.

Due to their outstanding elastic limit, biocompatible Ti-based bulk metallic glasses (BMGs) are candidate materials to decrease the size of medical implants and therefore reduce their invasiveness. However, the practical use of classical Ti-BMGs in medical applications is in part hindered by their high copper content: more effort is thus required to design low-copper Ti-BMGs. In this work, in line with current rise in AI-driven tools, machine learning (ML) approaches, a neural-network ML model is used to explore the glass-forming ability (GFA) of unreported low-copper compositions within the biocompatible Ti-Zr-Cu-Pd system. Two types of models are trained and compared: one based on the alloy composition only, and a second based on various features derived from the alloying elements. Contrary to expectation, the predictive power of both models in evaluating GFA is similar. The compositional space identified by ML as promising is experimentally assessed, finding unfortunately low GFA. These results indicate that the ML approach may be premature for specific composition tuning of amorphous metallic materials. We emphasise that the development of ML tools in GFA prediction requires an improvement of the dataset, in terms of homogeneity, size and GFA descriptors, which must be supported by increased reporting of high-quality experimental GFA measurements, both positive and negative. STATEMENT OF SIGNIFICANCE: Biocompatible Ti-based bulk metallic glasses (BMGs) are candidate materials for use in the next generation of minimally invasive dental implants where improved mechanical properties, such as high strength are required. Despite promising in vitro/vivo evaluations, implementation of alloys for practical applications is partly hindered by the presence of copper as the main alloying element. Recent studies have presented AI-guided and machine learning strategies as appealing approaches to understand and describe the glass forming ability (GFA) of BMG-forming compositions. In this work, we employ and evaluate the capacity of a machine-learning model to explore low-copper compositional spaces in the biocompatible Ti-Zr-Cu-Pd system. Our results highlight the limits of such a computational approach and suggest improvements for future designing routes.

A simple and effective approach to prepare injectable macroporous calcium phosphate cement for bone repair: Syringe-foaming using a viscous hydrophilic polymeric solution.

In this study, we propose a simple and effective strategy to prepare injectable macroporous calcium phosphate cements (CPCs) by syringe-foaming via hydrophilic viscous polymeric solution, such as using silanized-hydroxypropyl methylcellulose (Si-HPMC) as a foaming agent. The Si-HPMC foamed CPCs demonstrate excellent handling properties such as injectability and cohesion. After hardening the foamed CPCs possess hierarchical macropores and their mechanical properties (Young's modulus and compressive strength) are comparable to those of cancellous bone. Moreover, a preliminary in vivo study in the distal femoral sites of rabbits was conducted to evaluate the biofunctionality of this injectable macroporous CPC. The evidence of newly formed bone in the central zone of implantation site indicates the feasibility and effectiveness of this foaming strategy that will have to be optimized by further extensive animal experiments. STATEMENT OF SIGNIFICANCE: A major challenge in the design of biomaterial-based injectable bone substitutes is the development of cohesive, macroporous and self-setting calcium phosphate cement (CPC) that enables rapid cell invasion with adequate initial mechanical properties without the use of complex processing and additives. Thus, we propose a simple and effective strategy to prepare injectable macroporous CPCs through syringe-foaming using a hydrophilic viscous polymeric solution (silanized-hydroxypropyl methylcellulose, Si-HPMC) as a foaming agent, that simultaneously meets all the aforementioned aims. Evidence from our in vivo studies shows the existence of newly formed bone within the implantation site, indicating the feasibility and effectiveness of this foaming strategy, which could be used in various CPC systems using other hydrophilic viscous polymeric solutions.

A novel injectable, cohesive and toughened Si-HPMC (silanized-hydroxypropyl methylcellulose) composite calcium phosphate cement for bone substitution.

This study reports on the incorporation of the self-setting polysaccharide derivative hydrogel (silanized-hydroxypropyl methylcellulose, Si-HPMC) into the formulation of calcium phosphate cements (CPCs) to develop a novel injectable material for bone substitution. The effects of Si-HPMC on the handling properties (injectability, cohesion and setting time) and mechanical properties (Young's modulus, fracture toughness, flexural and compressive strength) of CPCs were systematically studied. It was found that Si-HPMC could endow composite CPC pastes with an appealing rheological behavior at the early stage of setting, promoting its application in open bone cavities. Moreover, Si-HPMC gave the composite CPC good injectability and cohesion, and reduced the setting time. Si-HPMC increased the porosity of CPCs after hardening, especially the macroporosity as a result of entrapped air bubbles; however, it improved, rather than compromised, the mechanical properties of composite CPCs, which demonstrates a strong toughening and strengthening effect. In view of the above, the Si-HPMC composite CPC may be particularly promising as bone substitute material for clinic application.

Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties.

Since their initial formulation in the 1980s, calcium phosphate cements (CPCs) have been increasingly used as bone substitutes. This article provides an overview on the chemistry, kinetics of setting and handling properties (setting time, cohesion and injectability) of CPCs for bone substitution, with a focus on their mechanical properties. Many processing parameters, such as particle size, composition of cement reactants and additives, can be adjusted to control the setting process of CPCs, concomitantly influencing their handling and mechanical performance. Moreover, this review shows that, although the mechanical strength of CPCs is generally low, it is not a critical issue for their application for bone repair--an observation not often realized by researchers and clinicians. CPCs with compressive strengths comparable to those of cortical bones can be produced through densification and/or homogenization of the cement matrix. The real limitation for CPCs appears to be their low fracture toughness and poor mechanical reliability (Weibull modulus), which have so far been only rarely studied.

The influence of different cellulose ethers on both the handling and mechanical properties of calcium phosphate cements for bone substitution.

The influence of cellulose ether additives (CEAs) on the performance of final calcium phosphate cement (CPC) products is thoroughly investigated. Four CEAs were added into the liquid phase of apatitic CPCs based on the hydrolysis of α-tricalcium phosphate, to investigate the influence of both molecular weight and degree of substitution on the CPCs' properties, including handling (e.g. injectability, cohesion, washout resistance and setting time), microstructure (e.g. porosity and micromorphology) and mechanical properties (e.g. fracture toughness and compressive strength). The results showed that even a small amount of CEAs modified most of these CPCs' features, depending on the structural parameters of the CEAs. The CEAs dramatically improved the injectability, cohesion and washout resistance of the pastes, prolonged the final setting time and increased the porosity of CPCs. Moreover, the CEAs had an evident toughening effect on CPCs, and this effect become more significant with increasing molecular weight and mass fraction of CEAs, inducing a significant tolerance to damage. Overall, the molecular weight of CEAs played a major role compared to their degree of substitution in CPCs' performances.