Resonance-Based microwave technique for body implant sensing

There is an increasing need for safe and simple techniques for sensing devices and prostheses implanted inside the human body. Microwave wireless inspection may be an appropriate technique for it. The implanted device may have specific characteristics that allow to distinguish it from its environment. A new sensing technique based on the principle of differential resonance is proposed and its basic parameters are discussed. This technique allows to use the implant as a signal scattering device and to detect changes produced in the implant based on the corresponding change in its scattering signature. The technique is first tested with a canonic human phantom and then applied to a real in vivo clinical experiment to detect coronary stents implanted in swine animalsPeer ReviewedPostprint (published version

Silk-reinforced collagen hydrogels with raised multiscale stiffness for mesenchymal cells 3D culture

Type I collagen hydrogels are of high interest in tissue engineering. With the evolution of 3D bioprinting technologies, a high number of collagen-based scaffolds have been reported for the development of 3D cell cultures. A recent proposal was to mix collagen with silk fibroin derived from Bombyx mori silkworm. Nevertheless, due to the difficulties in the preparation and the characteristics of the protein, several problems such as phase separation and collagen denaturation appear during the procedure. Therefore, the common solution is to diminish the concentration of collagen although in that way the most biologically relevant component is reduced. In this study, we present a new, simple, and effective method to develop a collagen-silk hybrid hydrogel with high collagen concentration and with increased stiffness approaching that of natural tissues, which could be of high interest for the development of cardiac patches for myocardial regeneration and for preconditioning of mesenchymal stem cells (MSCs) to improve their therapeutic potential. Sericin in the silk was preserved by using a physical solubilizing procedure that results in a preserved fibrous structure of type I collagen, as shown by ultrastructural imaging. The macro- and micromechanical properties of the hybrid hydrogels measured by tensile stretch and atomic force microscopy, respectively, showed a more than twofold stiffening than the collagen-only hydrogels. Rheological measurements showed improved printability properties for the developed biomaterial. The suitability of the hydrogels for 3D cell culture was assessed by 3D bioprinting bone marrow-derived MSCs cultured within the scaffolds. The result was a biomaterial with improved printability characteristics that better resembled the mechanical properties of natural soft tissues while preserving biocompatibility owing to the high concentration of collagen. Impact statement In this study, we report the development of silk microfiber-reinforced type I collagen hydrogels for 3D bioprinting and cell culture. In contrast with previously reported studies, a novel physical method allowed the preservation of the silk sericin protein. Hydrogels were stable, showed no phase separation between the biomaterials, and they presented improved printability. An increase between two- and threefold of the multiscale stiffness of the scaffolds was achieved with no need of using additional crosslinkers or complex methods, which could be of high relevance for cardiac patches development and for preconditioning mesenchymal stem cells (MSCs) for therapeutic applications. We demonstrate that bone marrow-derived MSCs can be effectively bioprinted and 3D cultured within the stiffened structures.This work was supported in part by the Spanish Ministry of Sciences, Innovation and Universities (DPI2017-83721-P and PGC2018-097323-A-I00) and by the Marie Sklodowska- Curie Action, Innovative Training Networks 2018, EU Grant Agreement no. 812772.Peer ReviewedPostprint (published version

Ex vivo assessment and in vivo validation of non-invasive stent monitoring techniques based on microwave spectrometry

Some conditions are well known to be directly associated with stent failure, including in-stent re-occlusion and stent fracture. Currently, identification of these high-risk conditions requires invasive and complex procedures. This study aims to assess microwave spectrometry (MWS) for monitoring stents non-invasively. Preliminary ex vivo data are presented to move to in vivo validation. Fifteen mice were assigned to receive subcutaneous stent implantations (n¿=¿10) or sham operations (n¿=¿5). MWS measurements were carried out at 0, 2, 4, 7, 14, 22, and 29 days of follow-up. Additionally, 5 stented animals were summited to micro-CT analyses at the same time points. At 29 days, 3 animals were included into a stent fracture subgroup and underwent a last MWS and micro-CT analysis. MWS was able to identify stent position and in-stent stenosis over time, also discerning significant differences from baseline measures (P¿<¿0.001). Moreover, MWS identified fractured vs. non-fractured stents in vivo. Taken together, MWS emerges as a non-invasive, non-ionizing alternative for stent monitoring. MWS analysis clearly distinguished between in-stent stenosis and stent fracture phenomena.Peer ReviewedPostprint (published version

Ex vivo assessment and in vivo validation of non-invasive stent monitoring techniques based on microwave spectrometry

Some conditions are well known to be directly associated with stent failure, including in-stent re-occlusion and stent fracture. Currently, identification of these high-risk conditions requires invasive and complex procedures. This study aims to assess microwave spectrometry (MWS) for monitoring stents non-invasively. Preliminary ex vivo data are presented to move to in vivo validation. Fifteen mice were assigned to receive subcutaneous stent implantations (n = 10) or sham operations (n = 5). MWS measurements were carried out at 0, 2, 4, 7, 14, 22, and 29 days of follow-up. Additionally, 5 stented animals were summited to micro-CT analyses at the same time points. At 29 days, 3 animals were included into a stent fracture subgroup and underwent a last MWS and micro-CT analysis. MWS was able to identify stent position and in-stent stenosis over time, also discerning significant differences from baseline measures (P < 0.001). Moreover, MWS identified fractured vs. non-fractured stents in vivo. Taken together, MWS emerges as a non-invasive, non-ionizing alternative for stent monitoring. MWS analysis clearly distinguished between in-stent stenosis and stent fracture phenomena

A simple low-cost electrocardiogram synchronizer

Electrocardiogram (ECG) synchronization is useful to avoid the effects of cardiac motion in medical measurements, and is widely used in standard medical imaging. A number of medical equipment include embedded commercial synchronizers. However, the use of independent synchronization modules is sometimes needed when several non-integrated instruments are used, or in the development of new medical instruments and procedures. We present a simple low-cost ECG synchronizer module based on an Arduino controller board that converts the ECG signal into a transistor-transistor-logic (TTL) one, allowing real-time medical measurements triggered at specific phases of the cardiac cycle. The device and conversion algorithm developed is optimized in vitro using synthetic and human ECG signals, and tested in vivo on three swine specimens. Error rates during the in vivo testing stage remain below the 2% of the cycles in all animals and critical false positives are less than 1%, which is sufficient for most applications. Possible algorithm updates are discussed if its performance needs to be improved.This research was funded by grants from the Instituto de Salud Carlos III [PI18/00256], the Fundació La MARATÓ de TV3 (20153530/31), the Sociedad Española de Cardiología, and the Generalitat de Catalunya [2017-SGR-483]. This work was also funded by CaixaImpulse (CI20/00230), and the Red de Terapia Celular—TerCel [RD16/0011/0006] and CIBER Cardiovascular [CB16/11/00403] projects, as part of the Plan Nacional de I+D+I, and cofunded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). F.M. acknowledges support from the Catalan Government through COFUND and the Unidad de Excelencia Maria de Maeztu MDM-2016-0600.Peer ReviewedPostprint (published version

Resonance-Based microwave technique for body implant sensing

There is an increasing need for safe and simple techniques for sensing devices and prostheses implanted inside the human body. Microwave wireless inspection may be an appropriate technique for it. The implanted device may have specific characteristics that allow to distinguish it from its environment. A new sensing technique based on the principle of differential resonance is proposed and its basic parameters are discussed. This technique allows to use the implant as a signal scattering device and to detect changes produced in the implant based on the corresponding change in its scattering signature. The technique is first tested with a canonic human phantom and then applied to a real in vivo clinical experiment to detect coronary stents implanted in swine animalsPeer Reviewe