Institut für Medizintechnik und Medizininformatik

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3D-printed LEGO®-inspired titanium scaffolds for patient-specific regenerative medicine
(Elsevier, 2023) Lee, Seunghun S.; Du, Xiaoyu; Smit, Thijs; Bissacco, Elisa G.; Seiler, Daniel; de Wild, Michael; Ferguson, Stephen J.
Despite the recent advances in 3D-printing, it is often difficult to fabricate implants that optimally fit a defect size or shape. There are some approaches to resolve this issue, such as patient-specific implant/scaffold designs based on CT images of the patients, however, this process is labor-intensive and costly. Especially in developing countries, affordable treatment options are required, while still not excluding these patient groups from potential material and manufacturing advances. Here, a selective laser melting (SLM) 3D-printing strategy was used to fabricate a hierarchical, LEGO®-inspired Assemblable Titanium Scaffold (ATS) system, which can be manually assembled in any shape or size with ease. A surgeon can quickly create a scaffold that would fit to the defect right before the implantation during the surgery. Additionally, the direct inclusion of micro- and macroporous structures via 3D-printing, as well as a double acid-etched surface treatment (ST) in the ATS, ensure biocompatibility, sufficient nutrient flow, cell migration and enhanced osteogenesis. Three different structures were designed (non-porous:NP, semi-porous:SP, ultra-porous:UP), 3D-printed with the SLM technique and then surface treated for the ST groups. After analyzing characteristics of the ATS such as printing quality, surface roughness and interconnected porosity, mechanical testing and finite element analysis (FEA) demonstrated that individual and stacked ATS have sufficient mechanical properties to withstand loading in a physiological system. All ATS showed high cell viability, and the SP and UP groups demonstrated enhanced cell proliferation rates compared to the NP group. Furthermore, we also verified that cells were well-attached and spread on the porous structures and successful cell migration between the ATS units was seen in the case of assemblies. The UP and SP groups exhibited higher calcium deposition and RT-qPCR proved higher osteogenic gene expression compared to NP group. Finally, we demonstrate a number of possible medical applications that reveal the potential of the ATS through assembly. © 2023 The Authors
01A - Beitrag in wissenschaftlicher Zeitschrift
A baseline wander tracking system for artifact rejection in long-term electrocardiography
(IEEE, 2016) Niederhauser, Thomas; Marisa, Thanks; Kohler, Lukas; Haeberlin, Andreas; Wildhaber, Reto; Abächerli, Roger; Goette, Josef; Jacomet, Marcel; Vogel, Rolf
Long-term electrocardiogram (ECG) signals might suffer from relevant baseline disturbances during physical activity. Motion artifacts in particular are more pronounced with dry surface or esophageal electrodes which are dedicated to prolonged ECG recording. In this paper we present a method called baseline wander tracking (BWT) that tracks and rejects strong baseline disturbances and avoids concurrent saturation of the analog front-end. The proposed algorithm shifts the baseline level of the ECG signal to the middle of the dynamic input range. Due to the fast offset shifts, that produce much steeper signal portions than the normal ECG waves, the true ECG signal can be reconstructed offline and filtered using computationally intensive algorithms. Based on Monte Carlo simulations we observed reconstruction errors mainly caused by the non-linearity inaccuracies of the DAC. However, the signal to error ratio of the BWT is higher compared to an analog front-end featuring a dynamic input ranges above 15 mV if a synthetic ECG signal was used. The BWT is additionally able to suppress (electrode) offset potentials without introducing long transients. Due to its structural simplicity, memory efficiency and the DC coupling capability, the BWT is dedicated to high integration required in long-term and low-power ECG recording systems.
01A - Beitrag in wissenschaftlicher Zeitschrift
A graphical simulation software for instruction in cardiovascular mechanics physiology
(2011) Wildhaber, Reto; Verrey, François; Wenger, Roland H
Background Computer supported, interactive e-learning systems are widely used in the teaching of physiology. However, the currently available complimentary software tools in the field of the physiology of cardiovascular mechanics have not yet been adapted to the latest systems software. Therefore, a simple-to-use replacement for undergraduate and graduate students' education was needed, including an up-to-date graphical software that is validated and field-tested.
01A - Beitrag in wissenschaftlicher Zeitschrift
A novel route to molecular self-assembly. Self-intermixed monolayer phases
(Wiley, 18.10.2002) de Wild, Michael; Berner, Simon; Suzuki, Hitoshi; Yanagi, Hisao; Schlettwein, Derck; Ivan, Stanislav; Baratoff, Alexis; Guentherodt, Hans-Joachim; Jung, Thomas A.
The stars and stripes: A novel route to highly perfect molecular self-assembly is presented. Depending on the relative surface (Ag(111)) coverage of the two species, subphthalocyanine and C60 (green and yellow in the colored STM image) on an surface, well-ordered intermixed monolayers consisting of 1D chains with 1 nm width or 2D hexagonal patterns are formed. The structural parameters and schematic binary "phase diagram" of this system are deduced from detailed room-temperature STM studies. The most important underlying interactions and the relevant properties of the molecules are discussed qualitatively.
01A - Beitrag in wissenschaftlicher Zeitschrift
A survey of practice patterns for adaptive particle therapy for interfractional changes
(Elsevier, 04/2023) Trnkova, Petra; Zhang, Ye; Toshito, Toshiyuki; Heijmen, Ben; Richter, Christian; Aznar, Marianne C.; Albertini, Francesca; Bolsi, Alessandra; Daartz, Juliane; Knopf, Antje; Bertholet, Jenny
01A - Beitrag in wissenschaftlicher Zeitschrift
Algorithm for real-time analysis of intracoronary electrocardiogram
(Frontiers, 07.09.2022) Bigler, Marius Reto; Kieninger-Gräfitsch, Andrea; Waldmann, Frédéric; Seiler, Christian; Wildhaber, Reto
Since its first implementation in 1985, intracoronary (ic) electrocardiogram (ECG) has shown ample evidence for its diagnostic value given the higher sensitivity for myocardial ischemia detection in comparison to surface ECG. However, a lack of online systems to quantitatively analyze icECG in real-time prevents its routine use. The present study aimed to develop and validate an autonomous icECG analyzing algorithm.
01A - Beitrag in wissenschaftlicher Zeitschrift
All-inside meniscal repair devices compared with their matched inside-out Vertical mattress suture repair. Introducing 10,000 and 100,000 loading cycles
(SAGE, 01.09.2014) Rosso, Claudio; Müller, Sebastian; Buckland, Daniel M.; Schwenk, Tanja; Zimmermann, Simon; de Wild, Michael; Valderrabano, Victor
All-inside arthroscopic meniscal repairs are favored by most clinicians because of their lower complication rate and decreased morbidity compared with inside-out techniques. Until now, only 1000 cycles have been used for biomechanical testing. Hypothesis: All-inside meniscal repairs will show inferior biomechanical response to cyclic loading (up to 100,000 cycles) and load-to-failure testing compared with inside-out suture controls. Study Design: Controlled laboratory study. Methods: Bucket-handle tears in 72 porcine menisci were repaired using the Omnispan and Fast-Fix 360 (all-inside devices) and Orthocord 2-0 and Ultrabraid 2-0 sutures (matched controls). Initial displacement, displacement after cyclic loading (100, 500, 1000, 2000, 5000, 10,000, and 100,000 cycles) between 5 and 20 N, ultimate load to failure, and mode of failure were recorded, as well as stiffness. Results: Initial displacement and displacement after cyclic loading were not different between the groups. The Omnispan repair demonstrated the highest load-to-failure force (mean 6 SD, 151.3 6 21.5 N) and was significantly stronger than all the other constructs (Orthocord 2-0, 105.5 6 20.4 N; Ultrabraid 2-0, 93.4 6 22.5 N; Fast-Fix 360, 76.6 6 14.2 N) (P \ .0001 for all). The Orthocord vertical inside-out mattress repair was significantly stronger than the Fast-Fix 360 repair (P = .003). The Omnispan (30.8 6 3.5 N/mm) showed significantly higher stiffness compared with the Ultrabraid 2-0 (22.9 6 6.9 N/mm, P \ .0001) and Fast-Fix 360 (23.7 6 3.9 N/mm, P = .001). The predominant mode of failure was suture failure. Conclusion: All-inside meniscal devices show comparable biomechanical properties compared with inside-out suture repair in cyclic loading, even after 100,000 cycles. Clinical Relevance: Eight to 10 weeks of rehabilitation might not pose a problem for all repairs in this worst-case scenario.
01A - Beitrag in wissenschaftlicher Zeitschrift
An approach towards bronchoscopic-based gene therapy using electrical field accelerated plasmid droplets
(IEEE, 2012) Hradetzky, David; Boehringer, Stephan; Geiser, Thomas; Gazdhar, Amiq
Idiopathic pulmonary fibrosis (IPF) is a devastating disease affecting the distal lung, due to failure of the alveolar epithelium to heal after micro-injuries, leading to inefficient gas exchange and resulting in death. Therapeutic options are very limited. A new therapeutic approach based on gene therapy restores the self-healing process within the lung in the experimental setup. A basic requirement of this therapy is the successful transduction of genes into the alveolar epithelium in the distal part of the lung, for which a new therapeutic instrument is required. In this paper we present the concept and first experimental results of a device which uses an electrical field to accelerate the charged droplets of plasmid suspension toward the tissue and which overcomes cell membrane with its impact energy. The aim is to develop a therapeutic device capable of being integrated into minimally invasive procedures such as bronchoscopy.
04B - Beitrag Konferenzschrift
Assessing the grain structure of highly X-ray absorbing metallic alloys
(De Gruyter, 07/2014) Bormann, Therese; Beckmann, Felix; Schinhammer, Michael; Deyhle, Hans; de Wild, Michael; Müller, Bert
Selective laser melting allows the fabrication of NiTi implants with pre-defined, complex shapes. The control of the process parameters regulates the arrangement of the granular microstructure of the NiTi alloy. We prepared specimens with elongated grains, which build a sound basis for diffraction contrast tomography experiments using synchrotron radiation and for electron backscatter diffraction measurements. Both approaches reveal the orientation and size of the individual grains within the specimen. Still, electron backscatter diffraction is confined to two-dimensional cross-sections while diffraction contrast tomography reveals these microstructural features in three dimensions. We demonstrate that the grains in the selective laser melted specimen, which are oriented along the building direction, do not exhibit a well-defined planar grain orientation but are twisted. These twisted grains give rise to diffraction spots observable for several degrees of specimen rotation simultaneously to the acquisition of tomography data.
01A - Beitrag in wissenschaftlicher Zeitschrift
Assessing the morphology of selective laser melted NiTi-scaffolds for a three-dimensional quantification of the one-way shape memory effect
(03/2013) Bormann, Therese; de Wild, Michael; Beckmann, Felix; Müller, Bert; Goulbourne, Nakhiah C.; Naguib, Hani E.
NiTi is promising for the use as bone scaffold, because the pseudoelasticity or the one- and two-way shape memory effect in the physiological window can mechanically stimulate the adherent cells. Such stimuli can enhance osseo integration and might reduce stress shielding associated with load bearing implants. The present study is based on the additive manufacturing technique of selective laser melting (SLM) to fabricate three-dimensional NiTi scaffolds. We demonstrate that the morphology of the scaffolds can be quantified using synchrotron radiation-based micro computed tomography (SRµCT) and sophisticated registration software. Comparing the CAD file with the SLM scaffolds, quality factors are derived. With respect to the CAD file, the overlap corresponds to (92.5 ± 0.6) %. (7.4 ± 0.42) % of material was missing and (48.9 ± 2.3) % of excess material found. This means that the actual scaffold is less porous than expected, a fact that has to be considered for the scaffold design. In order to quantify the shape memory effect during the shape recovery process, we acquired radiographs rotating an initially deformed scaffold in angular steps of 0.2 degree during controlled heating. The continuously acquired radiographs were combined to tomography data, showing that the quality factors evolved with temperature as the scaffold height, measured by conventional thermo-mechanical analysis. Furthermore, the data comprise the presence of compressive and tensile local strains in the three-dimensional scaffolds to be compared with the physiological situation.
04B - Beitrag Konferenzschrift
Assessment of the impact of static field inhomogeneity on the performance of miniaturized NMR devices
(IEEE, 2023) Baumgarten, Guilherme; Madec, Morgan; Nguyen, Duc-Vinh; Werling, Lucas; Pascal, Joris; Gajendramurthy, Chunchesh Malangi; Bertani, Philippe; Djukic, Jean-Pierre; Hebrard, Luc
01A - Beitrag in wissenschaftlicher Zeitschrift
Augmented feedback system to support physical therapy of non-specific low back pain
(Springer, 2010) Brodbeck, Dominique; Degen, Markus; Stanimirov, Michael; Kool, Jan; Scheermesser, Mandy; Oesch, Peter; Neuhaus, Cornelia; Fred, Ana; Filipe, Joaquim; Gamboa, Hugo
Low back pain is an important problem in industrialized countries. Two key factors limit the effectiveness of physiotherapy: low compliance of patients with repetitive movement exercises, and inadequate awareness of patients of their own posture. The Backtrainer system addresses these problems by real-time monitoring of the spine position, by providing a framework for most common physiotherapy exercises for the low back, and by providing feedback to patients in a motivating way. A minimal sensor configuration was identified as two inertial sensors that measure the orientation of the lower back at two points with three degrees of freedom. The software was designed as a flexible platform to experiment with different hardware, and with various feedback modalities. Basic exercises for two types of movements are provided: mobilizing and stabilizing. We developed visual feedback - abstract as well as in the form of a virtual reality game - and complemented the on-screen graphics with an ambient feedback device. The system was evaluated during five weeks in a rehabilitation clinic with 26 patients and 15 physiotherapists. Subjective satisfaction of subjects was good, and we interpret the results as encouraging indication for the adoption of such a therapy support system by both patients and therapists.
04B - Beitrag Konferenzschrift
Augmenting adaptive immunity. Progress and challenges in the quantitative engineering and analysis of adaptive immune receptor repertoires
(Royal Society of Chemistry, 2019) Brown, Alex J.; Snapkov, Igor; Akbar, Rahmad; Pavlović, Milena; Miho, Enkelejda; Sandve, Geir K.; Greiff, Victor
The adaptive immune system is a natural diagnostic sensor and therapeutic. It recognizes threats earlier than clinical symptoms manifest and neutralizes antigens with exquisite specificity. Recognition specificity and broad reactivity are enabled via adaptive B- and T-cell receptors: the immune receptor repertoire. The human immune system, however, is not omnipotent. Our natural defense system sometimes loses the battle to parasites and microbes and even turns against us in the case of cancer and (autoimmune) inflammatory disease. A long-standing dream of immunoengineers has been, therefore, to mechanistically understand how the immune system “sees”, “reacts” and “remembers” (auto)antigens. Only very recently, experimental and computational methods have achieved sufficient quantitative resolution to start querying and engineering adaptive immunity with high precision. Specifically, these innovations have been applied with the greatest fervency and success in immunotherapy, autoimmunity and vaccine design. The work here highlights advances, challenges and future directions of quantitative approaches which seek to advance the fundamental understanding of immunological phenomena, and reverse engineer the immune system to produce auspicious biopharmaceutical drugs and immunodiagnostics. Our review shows how the merger of fundamental immunology, computational immunology and (digital) biotechnology advances both immunological knowledge and immunoengineering methodologies.
01A - Beitrag in wissenschaftlicher Zeitschrift
Author Correction. The dengue-specific immune response and antibody identification with machine learning
(Nature, 20.01.2024) Natali, Eriberto Noel; Horst, Alexander; Meier, Patrick; Greiff, Victor; Nuvolone, Mario; Babrak, Lmar Marie; Fink, Katja; Miho, Enkelejda
Dengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.
01A - Beitrag in wissenschaftlicher Zeitschrift
Automatische Datenextraktion aus Anamnesebögen
(Hochschule für Life Sciences FHNW, 2024) Kamber, Lukas; Kahraman, Abdullah; Universität Zürich
11 - Studentische Arbeit
Autonomous state space models for recursive signal estimation beyond least squares
(IEEE, 2017) Zalmai, Nour; Wildhaber, Reto; Loeliger, Hans-Andrea
The paper addresses the problem of fitting, at any given time, a parameterized signal generated by an autonomous linear state space model (LSSM) to discrete-time observations. When the cost function is the squared error, the fitting can be accomplished based on efficient recursions. In this paper, the squared error cost is generalized to more advanced cost functions while preserving recursive computations: first, the standard sample-wise squared error is augmented with a sampledependent polynomial error; second, the sample-wise errors are localized by a window function that is itself described by an autonomous LSSM. It is further demonstrated how such a signal estimation can be extended to handle unknown additive and/or multiplicative interference. All these results rely on two facts: first, the correlation function between a given discrete-time signal and a LSSM signal can be computed by efficient recursions; second, the set of LSSM signals is a ring.
04B - Beitrag Konferenzschrift
Backtrainer. Computer-aided therapy system with augmented feedback for the lower back
(SciTePress, 2009) Brodbeck, Dominique; Degen, Markus; Stanimirov, Michael; Kool, Jan; Scheermesser, Mandy; Oesch, Peter; Neuhaus, Cornelia; Azevedo, Luis; Londral, Ana
Low back pain is an important problem in industrialized countries. Two key factors limit the effectiveness of physiotherapy: low compliance of patients with repetitive movement exercises, and inadequate awareness of patients of their own posture. The Backtrainer system addresses these problems by real-time monitoring of the spine position, by providing a framework for most common physiotherapy exercises for the low back, and by providing feedback to patients in a motivating way. A minimal sensor configuration was identified as two inertial sensors that measure the orientation of the lower back at two points with three degrees of freedom. The software was designed as a flexible platform to experiment with different hardware, and with various feedback modalities. Basic exercises for two types of movements are provided: mobilizing and stabilizing. We developed visual feedback - abstract as well as in the form of a virtual reality game - and complemented the on-screen graphics with an ambient feedback device. The system was evaluated during five weeks in a rehabilitation clinic with 26 patients and 15 physiotherapists. Subjective satisfaction of subjects was good, and we interpret the results as encouraging indication for the adoption of such a therapy support system by both patients and therapists.
04B - Beitrag Konferenzschrift
Bioinformatic and statistical analysis of adaptive immune repertoires
(Cell Press, 10/2015) Greiff, Victor; Miho, Enkelejda; Menzel, Ulrike; Reddy, Sai T.
High-throughput sequencing (HTS) of immune repertoires has enabled the quantitative analysis of adaptive immune responses and offers the potential to revolutionize research in lymphocyte biology, vaccine profiling, and mono clonal antibody engineering. Advances in sequencing technology coupled to an exponential decline in sequencing costs have fueled the recent over whelming interest in immune repertoire sequencing. This, in turn, has sparked the development of numerous methods for bioinformatic and statistics-driven interpretation and visualization of immune repertoires. Here, we review the current literature on bioinformatic and statistical analysis of immune reper toire HTS data and discuss underlying assumptions, applicability, and scope. We further highlight important directions for future research, which could propel immune repertoire HTS to becoming a standard method for measuring adaptive immune responses.
01A - Beitrag in wissenschaftlicher Zeitschrift
Biomechanical evaluation of the interfacial strength of a chemically modified sandblasted and acid-etched titanium surface
(Wiley, 06/2006) Ferguson, Stephen J.; Broggini, Nina; Wieland, Marco; de Wild, Michael; Rupp, Frank; Geis-Gerstorfer, Jürgen; Cochran, David L.; Buser, Daniel
The functional capacity of osseointegrated dental implants to bear load is largely dependent on the quality of the interface between the bone and implant. Sandblasted and acid-etched (SLA) surfaces have been previously shown to enhance bone apposition. In this study, the SLA has been compared with a chemically modified SLA (modSLA) surface. The increased wettability of the modSLA surface in a protein solution was verified by dynamic contact angle analysis. Using a well-established animal model with a splitmouth experimental design, implant removal torque testing was performed to determine the biomechanical properties of the bone-implant interface. All implants had an identical cylindrical shape with a standard thread configuration. Removal torque testing was performed after 2, 4, and 8 weeks of bone healing (n = 9 animals per healing period, three implants per surface type per animal) to evaluate the interfacial shear strength of each surface type. Results showed that the modSLA surface was more effective in enhancing the interfacial shear strength of implants in comparison with the conventional SLA surface during early stages of bone healing. Removal torque values of the modSLA-surfaced implants were 8-21% higher than those of the SLA implants (p = 0.003). The mean removal torque values for the modSLA implants were 1.485 N m at 2 weeks, 1.709 N m at 4 weeks, and 1.345 N m at 8 weeks; and correspondingly, 1.231 N m, 1.585 N m, and 1.143 N m for the SLA implants. The bone-implant interfacial stiffness calculated from the torque-rotation curve was on average 9-14% higher for the modSLA implants when compared with the SLA implants (p = 0.038). It can be concluded that the modSLA surface achieves a better bone anchorage during early stages of bone healing than the SLA surface; chemical modification of the standard SLA surface likely enhances bone apposition and this has a beneficial effect on the interfacial shear strength.
01A - Beitrag in wissenschaftlicher Zeitschrift
Biomimetic modification of titanium dental implant model surfaces using the RGDSP-peptide sequence. A cell morphology study
(Elsevier, 07/2006) Schuler, Martin; Owen, Gethin Rh.; Hamilton, Douglas W.; de Wild, Michael; Textor, Marcus; Brunette, Donald M.; Tosatti, Samuele G.P.
Surface topography and (bio)chemistry are key factors in determining cell response to an implant. We investigated cell adhesion and spreading patterns of epithelial cells, fibroblasts and osteoblasts on biomimetically modified, smooth and rough titanium surfaces. The RGD bioactive peptide sequence was immobilized via a non-fouling poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) molecular assembly system, which allowed exploitation of specific cell–peptide interactions even in the presence of serum. As control surfaces, bare titanium and bio-inactive surfaces (scrambled RDG and unfunctionalized PLL-g-PEG) were used. Our findings demonstrated that surface topography and chemistry directly influenced the attachment and morphology of all cell types tested. In general, an increase in cell number and more spread cells were observed on bioactive substrates (containing RGD) compared to bio-inactive surfaces. More fibroblasts were present on smooth than on rough topographies, whereas for osteoblasts the opposite tendency was observed. Epithelial cell attachment did not follow any regular pattern. Footprint areas for all cell types were significantly reduced on rough compared to smooth surfaces. Osteoblast attachment and footprint areas increased with increasing RGD-peptide surface density. However, no synergy (interaction) between RGD-peptide surface density and surface topography was observed for osteoblasts neither in terms of attachment nor footprint area.
01A - Beitrag in wissenschaftlicher Zeitschrift