Student Projects

This master’s thesis project focuses on the automation and optimization of a melt electrowriting (MEW) platform used for the fabrication of fibrous scaffolds for osteochondral tissue engineering. The student will work with an open-source MEWron system and contribute to improving its stability, controllability, and reproducibility, with particular emphasis on pressure and high-voltage control. Building on extensive existing work in the lab on multiscale PCL scaffolds for cartilage-mimicking applications, the project can be extended (depending on progress) toward the introduction of stiffer, bone-relevant materials and the design of layered osteochondral scaffolds with effective mechanical coupling between soft and stiff regions. The project is modular and can be adapted in scope for a master’s thesis, semester project, or internship.

The goal of this project is to establish a robust and flexible MEW-based workflow that allows: - reliable and reproducible fibrous scaffold fabrication, - improved control over key MEW process parameters, - and the development of mechanically integrated, layered osteochondral scaffolds.

Alessio Amicone - aamicone@ethz.ch Jaka Pižorn - jpizorn@ethz.ch

Degenerative changes of vertebral bone marrow, known as Modic changes, are associated with pain and damage to the vertebral endplates. Stem cell injections close to the affected endplates have been proposed as a potential therapeutic strategy, requiring controlled and localized delivery of cells dispersed in a fluid within the porous vertebral body. More generally, minimally invasive procedures such as vertebral augmentation rely on the injection of fluids into porous vertebral bone, typically involving highly viscous cements to restore mechanical stability (Li et al. 2020). In this context, extensive experimental and numerical studies have shown that cement viscosity, injectability, pressure and spreading within the trabecular structure are strongly interrelated, highlighting the importance of fluid rheology and porous-medium properties in determining clinical outcomes (Koh et al. 2016, Ahmadian et al. 2022, Teo et al. 2007, Baroud et al. 2004, Trivedi et al. 2023, Bleiler et al. 2014). At the macroscopic scale, trabecular bone can be modelled as a porous continuum governed by Darcy’s law and its extensions for multiphase flow using the Theory of Porous Media (Ehlers et al. 2002), characterized by effective porosity and permeability. In previous work, a 2D Darcy-scale multiphase transient model of fluid injection in porous bone was developed to investigate pressure evolution, phases distribution and the effect of spatially varying permeability. While this 2D framework provided valuable insight, recent studies have shown that model dimensionality (2D vs 3D) can influence macroscopic flow predictions, even when the same Darcy-scale assumptions are adopted (Marafini et al. 2020). In this context, permeability is the key structural parameter controlling flow in porous media (Widmer et al. 2013, Bleiler et al. 2014), yet its representation is often simplified. The availability of micro-CT imaging of trabecular bone offers the opportunity to derive image-based porosity and permeability estimates, which can be upscaled and implemented in macroscopic Computational Fluid Dynamics (CFD) models as spatially varying isotropic or anisotropic permeability fields (Teo et al. 2011). This enables a systematic comparison between simplified (uniform or literature-based) permeability assumptions and micro-CT permeability representations. In addition, the rheology of both the resident phase and the injected fluid affects injectability and spreading (Trivedi et al. 2023). Bone marrow has been shown to exhibit non-Newtonian, shear-dependent behavior, commonly described using Carreau-type models (Davis et al. 2015, Jansen et al. 2015, Gunkan et al. 2008), while in Modic type 1 changes marrow can be replaced by fibrotic tissue with altered rheological properties (Modic et al. 1988, Modic et al. 2007). Since the final application involves delivery of viable cells, the rheology of the injected fluid is also critical, as non-Newtonian or viscoelastic carriers may improve injectability and reduce damaging mechanical stresses during flow (Amer et al. 2015, Amer et al. 2018, Aguado et al. 2012). The aim of this master’s thesis is therefore to extend the existing 2D framework to a 3D Darcy-scale multiphase model of fluid injection in porous vertebral bone, incorporating micro-CT–derived porosity and permeability information, and to perform a systematic parametric study to identify which modelling and physical parameters most strongly influence injectability and spatial spreading, with the goal of enabling targeted delivery.

i. Develop a 3D Darcy-scale multiphase CFD model of fluid injection in porous vertebral bone, extending an existing 2D framework. ii. Use micro-CT data to derive porosity and permeability estimates and implement them as spatially varying isotropic and anisotropic permeability fields in the 3D model. iii. Perform a parametric sensitivity analysis to assess how injectability and fluid localization are affected.

Elisa Rosano’ elisa.rosano@hest.ethz.ch Insititute for Biomechanics / Professorship Stephen Ferguson / Laboratory for Orthopaedic Technology (ETHZ)/ Location ETH Zentrum campus, GLC building

Degenerative changes of vertebral bone marrow (Modic changes) are associated with pain and endplates damage. Stem cell injections near the endplates have been proposed, requiring tools capable of reaching defined regions inside the vertebral body along the endplates. Clinically, a pedicular approach is minimally invasive and compatible with existing workflows, e.g. vertebral augmentation. However, conventional straight instruments can only access a limited region in front of the pedicle and struggle to reach distributed targets along the inferior endplate. Superelastic (SE) NiTi shape memory alloy (SMA) wires can undergo large, reversible strains and are already used in devices that navigate (e.g., endovascular procedures, endoscopic guidewires) and cut hard tissues (e.g., endodontic files). Prior work by Cuscieri et al. 1991 and Wiebking et al. has demonstrated the potential of SMA in creating controlled curved cutting paths. Therefore, the aim of this project is to assess the feasibility of employing a pre‑curved SE cutting wire that is temporarily straightened within a cannula to reach the vertebral body. After exiting the cannula into trabecular bone, the wire recovers its prescribed curvature, transmits torque, and cuts without plastic deformation. We will exploit the superelastic response of NiTi (Af < 37 °C, target range = 20–30 °C) and appropriate heat-treatment-defined curvature (R) to design and test SMA cutting wires with diameter (d) on the order of a few millimeters. Analytical calculations and finite element (FE) simulations will be used to select feasible combinations of d and R that keep strains within the superelastic plateau while providing sufficient cutting stiffness and torque transmission. Experimentally, bone-mimicking materials will be used to assess cutting ability, torque response, and guidewire-like failure modes such as lag, whip and kinking (Yamauchi et al. 2011). Axial rotation and insertion depth will be exploited to reach different targets along the endplate from a single pedicular access; alternative steering concepts (e.g., deflectable tips) may also be explored.

i. Develop an analytical and FE-based approach to design pre-curved superelastic NiTi wires (diameter d, curvature R) that remain within the admissible superelastic strain range during straightening in a cannula and recovery in bone-mimicking material. ii. Experimentally investigate the ability of SE NiTi wires to generate effective curved cutting paths in trabecular bone-like samples, including assessment of torque transmission, flexural rigidity, and cutting performance without failure modes such as kinking, permanent set, or fracture.

Elisa Rosano’ elisa.rosano@hest.ethz.ch Insititute for Biomechanics / Professorship Stephen Ferguson / Laboratory for Orthopaedic Technology (ETHZ) / Location ETH Zentrum campus, GLC building

Please send your CV, academic transcripts, and a short motivation letter to Dr. Xiaoyu Du (xiaoyu.du@hest.ethz.ch) if you are interested.