Publications

The last decade has witnessed great progress in the field of adoptive cell therapies, with the authorization of Kymriah (tisagenlecleucel) in 2017 by the Food and Drug Administration (FDA) as a crucial stepstone. Since then, five more CAR-T therapies have been approved for the treatment of hematological malignancies. While this is a great step forward to treating several types of blood cancers, CAR-T cell therapies are still associated with severe side-effects such as Graft-versus-Host Disease (GvHD), cytokine release syndrome (CRS) and neurotoxicity. Because of this, there has been continued interest in Natural Killer cells which avoid these side-effects while offering the possibility to generate allogeneic cell therapies. Similar to T-cells, NK cells can be genetically modified to improve their therapeutic efficacy in a variety of ways. In contrast to T cells, viral transduction of NK cells remains inefficient and induces cytotoxic effects. Viral vectors also require a lengthy and expensive product development process and are accompanied by certain risks such as insertional mutagenesis. Therefore, non-viral transfection technologies are avidly being developed aimed at addressing these shortcomings of viral vectors. In this review we will present an overview of the potential of NK cells in cancer immunotherapies and the non-viral transfection technologies that have been explored to engineer them.Copyright © 2023 Elsevier Inc. All rights reserved.

JTD Keywords: adoptive cell therapy, cancer immunotherapy, immunotherapy, messenger-rna delivery, nanoparticle, nk cells, non -viral engineering, sonoporation, t-cell, transfection, ultrasound, Adoptive cell therapy, Cancer immunotherapy, Cell engineering, Natural-killer-cells, Nk cells, Non-viral engineering

Individual biohybrid microrobots have the potential to perform biomedical in vivo tasks such as remote-controlled drug and cell delivery and minimally invasive surgery. This work demonstrates the formation of biohybrid sperm-templated clusters under the influence of an external magnetic field and essential functionalities for wireless actuation and drug delivery. Ferromagnetic nanoparticles are electrostatically assembled around dead sperm cells, and the resulting nanoparticle-coated cells are magnetically assembled into three-dimensional biohybrid clusters. The aim of this clustering is threefold: First, to enable rolling locomotion on a nearby solid boundary using a rotating magnetic field; second, to allow for noninvasive localization; third, to load the cells inside the cluster with drugs for targeted therapy. A magneto-hydrodynamic model captures the rotational response of the clusters in a viscous fluid, and predicts an upper bound for their step-out frequency, which is independent of their volume or aspect ratio. Below the step-out frequency, the rolling velocity of the clusters increases nonlinearly with their perimeter and actuation frequency. During rolling locomotion, the clusters are localized using ultrasound images at a relatively large distance, which makes these biohybrid clusters promising for deep-tissue applications. Finally, we show that the estimated drug load scales with the number of cells in the cluster and can be retained for more than 10 h. The aggregation of microrobots enables them to collectively roll in a predictable way in response to an external rotating magnetic field, and enhances ultrasound detectability and drug loading capacity compared to the individual microrobots. The favorable features of biohybrid microrobot clusters place emphasis on the importance of the investigation and development of collective microrobots and their potential for in vivo applications.

JTD Keywords: drug delivery, magnetic actuation, microrobot aggregation, sperm, Driven, Drug delivery, Magnetic actuation, Magnetotactic bacteria, Microrobot aggregation, Microrobots, Motion, Movement, Propulsion, Sperm, Sphere, Ultrasound, Wall

© BME-PT. Ultrasound micromolding (USM) preparation of hybrid scaffolds based on polylactide (PLA) and hydroxyapatite (HAp) particles has been evaluated. PLA was stable under the applied ultrasound source since a minimum degradation was detected. Porous materials were achieved using polyethylene glycol (PEG) and NaCl salts to the initial PLA and the subsequent leaching of the micromolded specimens. To avoid cavitation and decomposition problems during micromolding, it was necessary to use HAp free of typical synthesis impurities like carbonate and nitrate compounds. Compact PLA/HAp pieces allowed a maximum HAp load of 60 wt%, while porous specimens could be obtained with a maximum load of 38 wt%. Physical characterization of new scaffolds was performed by X-ray diffraction, spectroscopic and calorimetric techniques, stress-strain tests and contact angle measurements. Results indicated that a degree of porosity of 35% and relatively good mechanical properties could be achieved (i.e., 580 MPa, 4%, and 15.6 MPa for the Young modulus, elongation at break, and tensile strength, respectively). Scaffolds showed the positive effect of HAp and porosity on cell proliferation; this latter was 40% higher than that detected for non-porous PLA specimens.

JTD Keywords: apatite, conformation, fabrication, hydroxyapatite, micropieces, polymers, porous scaffolds, proliferation, tissue, ultrasound micromolding, vibration, Composite scaffolds, Hydroxyapatite, Micropieces, Porous scaffolds, Processing technologies, Ultrasound micromolding

Cardiac motion estimation is an important diagnostic tool for detecting heart diseases and it has been explored with modalities such as MRI and conventional ultrasound (US) sequences. US cardiac motion estimation still presents challenges because of complex motion patterns and the presence of noise. In this work, we propose a novel approach to estimate cardiac motion using ultrafast ultrasound data. Our solution is based on a variational formulation characterized by the L 2-regularized class. Displacement is represented by a lattice of b-splines and we ensure robustness, in the sense of eliminating outliers, by applying a maximum likelihood type estimator. While this is an important part of our solution, the main object of this work is to combine low-rank data representation with topology preservation. Low-rank data representation (achieved by finding the k-dominant singular values of a Casorati matrix arranged from the data sequence) speeds up the global solution and achieves noise reduction. On the other hand, topology preservation (achieved by monitoring the Jacobian determinant) allows one to radically rule out distortions while carefully controlling the size of allowed expansions and contractions. Our variational approach is carried out on a realistic dataset as well as on a simulated one. We demonstrate how our proposed variational solution deals with complex deformations through careful numerical experiments. The low-rank constraint speeds up the convergence of the optimization problem while topology preservation ensures a more accurate displacement. Beyond cardiac motion estimation, our approach is promising for the analysis of other organs that exhibit motion.

JTD Keywords: Cardiac analysis, Low-rank representation, Motion estimation, Topology preservation, Ultrafast ultrasound