TY  - JOUR
AB  - The reconstruction of complex skin defects challenges clinical practice, with autologous skin grafts (ASGs) as the traditional choice due to their high graft take rate and patient compatibility. However, ASGs have limitations such as donor site morbidity, limited tissue availability, and the necessity for multiple surgeries in severe cases. Bioengineered skin grafts (BSGs) aim to address these drawbacks through advanced tissue engineering and biomaterial science. This study conducts a systematic review to describe the benefits and shortcomings of BSGs and ASGs across wound healing efficacy, tissue integration, immunogenicity, and functional outcomes focusing on wound re-epithelialization, graft survival, and overall aesthetic outcomes. Preliminary findings suggest ASGs show superior early results, while BSGs demonstrate comparable long-term outcomes with reduced donor site morbidity. This comparative analysis enhances understanding of bioengineered alternatives in skin reconstruction, potentially redefining best practices based on efficacy, safety, and patient-centric outcomes, highlighting the need for further innovation in bioengineered solutions.
AU  - Dean, J.*
AU  - Hoch, C.C.*
AU  - Wollenberg, B.*
AU  - Navidzadeh, J.*
AU  - Maheta, B.*
AU  - Mandava, A.*
AU  - Knoedler, S.
AU  - Sherwani, K.
AU  - Baecher, H.
AU  - Schmitz, A.*
AU  - Alfertshofer, M.*
AU  - Heiland, M.*
AU  - Kreutzer, K.*
AU  - Koerdt, S.*
AU  - Knoedler, L.*
C1  - 73139
C2  - 56925
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - Advancements in bioengineered and autologous skin grafting techniques for skin reconstruction: A comprehensive review.
JO  - Front. Bioeng. Biotechnol.
VL  - 12
PB  - Frontiers Media Sa
PY  - 2025
SN  - 2296-4185
ER  - 

TY  - JOUR
AB  - Estimating spatiotemporal, kinematic, and kinetic movement variables with little obtrusion to the user is critical for clinical and sports applications. One possible approach is using a sparse inertial sensor setup, where sensors are not placed on all relevant body segments. Here, we investigated if movement variables can be estimated similarly accurate from sparse sensor setups as from a full lower-body sensor setup. We estimated the variables by solving optimal control problems with sagittal plane lower-body musculoskeletal models, in which we minimized an objective that combined tracking of accelerometer and gyroscope data with minimizing muscular effort. We created simulations for 10 participants at three walking and three running speeds, using seven sensor setups with between two and seven sensors located at the feet, shank, thighs, and/or pelvis. We found that differences between variables estimated from inertial sensors and those from optical motion capture were small for all sensor setups. Including all sensors did not necessarily lead to the smallest root mean square deviations (RMSDs) and highest coefficients of determination (   R 2    ). Setups without a pelvis sensor led to too much forward trunk lean and inaccurate spatiotemporal variables. Mean RMSDs were highest for the setup with two foot-worn inertial sensors (largest error in knee angle during running: 18 deg vs. 11 deg for the full lower-body setup), and ranged between 4.8-18 deg for the joint angles, between 1.0-5.4 BW BH% for the joint moments, and between 0.03 BW-0.49 BW for the ground reaction forces. We found strong or moderate relationships (   R 2  > 0.5  ) on average for all kinematic and kinetic variables, except for the hip and knee moment for five out of the seven setups. The large range of the coefficient of determination for most kinetic variables indicated individual differences in simulation quality. Therefore, we conclude that we can perform a comprehensive sagittal-plane motion analysis with sparse sensor setups as accurately as with a full sensor setup with sensors on the feet and on either the pelvis or the thighs. Such a sparse sensor setup enables comprehensive movement analysis outside the laboratory, by increasing usability of inertial sensors.
AU  - Dorschky, E.*
AU  - Nitschké, M.J.E.*
AU  - Mayer, M.*
AU  - Weygers, I.*
AU  - Gassner, H.*
AU  - Seel, T.*
AU  - Eskofier, B.M.
AU  - Koelewijn, A.D.*
C1  - 73592
C2  - 57123
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - Comparing sparse inertial sensor setups for sagittal-plane walking and running reconstructions.
JO  - Front. Bioeng. Biotechnol.
VL  - 13
PB  - Frontiers Media Sa
PY  - 2025
SN  - 2296-4185
ER  - 

TY  - JOUR
AB  - Portable measurement systems using inertial sensors enable motion capture outside the lab, facilitating longitudinal and large-scale studies in natural environments. However, estimating 3D kinematics and kinetics from inertial data for a comprehensive biomechanical movement analysis is still challenging. Machine learning models or stepwise approaches performing Kalman filtering, inverse kinematics, and inverse dynamics can lead to inconsistencies between kinematics and kinetics. We investigated the reconstruction of 3D kinematics and kinetics of arbitrary running motions from inertial sensor data using optimal control simulations of full-body musculoskeletal models. To evaluate the feasibility of the proposed method, we used marker tracking simulations created from optical motion capture data as a reference and for computing virtual inertial data such that the desired solution was known exactly. We generated the inertial tracking simulations by formulating optimal control problems that tracked virtual acceleration and angular velocity while minimizing effort without requiring a task constraint or an initial state. To evaluate the proposed approach, we reconstructed three trials each of straight running, curved running, and a v-cut of 10 participants. We compared the estimated inertial signals and biomechanical variables of the marker and inertial tracking simulations. The inertial data was tracked closely, resulting in low mean root mean squared deviations for pelvis translation (≤20.2 mm), angles (≤1.8 deg), ground reaction forces (≤1.1 BW%), joint moments (≤0.1 BWBH%), and muscle forces (≤5.4 BW%) and high mean coefficients of multiple correlation for all biomechanical variables (Formula presented.). Accordingly, our results showed that optimal control simulations tracking 3D inertial data could reconstruct the kinematics and kinetics of individual trials of all running motions. The simulations led to mutually and dynamically consistent kinematics and kinetics, which allows researching causal chains, for example, to analyze anterior cruciate ligament injury prevention. Our work proved the feasibility of the approach using virtual inertial data. When using the approach in the future with measured data, the sensor location and alignment on the segment must be estimated, and soft-tissue artifacts are potential error sources. Nevertheless, we demonstrated that optimal control simulation tracking inertial data is highly promising for estimating 3D kinematics and kinetics for a comprehensive biomechanical analysis.
AU  - Nitschké, M.J.E.*
AU  - Dorschky, E.*
AU  - Leyendecker, S.*
AU  - Eskofier, B.M.
AU  - Koelewijn, A.D.*
C1  - 70522
C2  - 55566
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - Estimating 3D kinematics and kinetics from virtual inertial sensor data through musculoskeletal movement simulations.
JO  - Front. Bioeng. Biotechnol.
VL  - 12
PB  - Frontiers Media Sa
PY  - 2024
SN  - 2296-4185
ER  - 

TY  - JOUR
AB  - Spheroids have become principal three-dimensional models to study cancer, developmental processes, and drug efficacy. Single-cell analysis techniques have emerged as ideal tools to gauge the complexity of cellular responses in these models. However, the single-cell quantitative assessment based on 3D-microscopic data of the subcellular distribution of fluorescence markers, such as the nuclear/cytoplasm ratio of transcription factors, has largely remained elusive. For spheroid generation, ultra-low attachment plates are noteworthy due to their simplicity, compatibility with automation, and experimental and commercial accessibility. However, it is unknown whether and to what degree the plate type impacts spheroid formation and biology. This study developed a novel AI-based pipeline for the analysis of 3D-confocal data of optically cleared large spheroids at the wholemount, single-cell, and sub-cellular levels. To identify relevant samples for the pipeline, automated brightfield microscopy was employed to systematically compare the size and eccentricity of spheroids formed in six different plate types using four distinct human cell lines. This showed that all plate types exhibited similar spheroid-forming capabilities and the gross patterns of growth or shrinkage during 4 days after seeding were comparable. Yet, size and eccentricity varied systematically among specific cell lines and plate types. Based on this prescreen, spheroids of HaCaT keratinocytes and HT-29 cancer cells were further assessed. In HaCaT spheroids, the in-depth analysis revealed a correlation between spheroid size, cell proliferation, and the nuclear/cytoplasm ratio of the transcriptional coactivator, YAP1, as well as an inverse correlation with respect to cell differentiation. These findings, yielded with a spheroid model and at a single-cell level, corroborate earlier concepts of the role of YAP1 in cell proliferation and differentiation of keratinocytes in human skin. Further, the results show that the plate type may influence the outcome of experimental campaigns and that it is advisable to scan different plate types for the optimal configuration during a specific investigation.
AU  - Vitacolonna, M.*
AU  - Bruch, R.*
AU  - Agaçi, A.*
AU  - Nürnberg, E.*
AU  - Cesetti, T.*
AU  - Keller, F.*
AU  - Padovani, F.
AU  - Sauer, S.*
AU  - Schmoller, K.M.
AU  - Reischl, M.*
AU  - Hafner, M.*
AU  - Rudolf, R.*
C1  - 71499
C2  - 56216
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - A multiparametric analysis including single-cell and subcellular feature assessment reveals differential behavior of spheroid cultures on distinct ultra-low attachment plate types.
JO  - Front. Bioeng. Biotechnol.
VL  - 12
PB  - Frontiers Media Sa
PY  - 2024
SN  - 2296-4185
ER  - 

TY  - JOUR
AB  - Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m2) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o−) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.
AU  - Doryab, A.
AU  - Taskin, M.B.*
AU  - Stahlhut, P.*
AU  - Schröppel, A.
AU  - Orak, S.
AU  - Voss, C.
AU  - Ahluwalia, A.*
AU  - Rehberg, M.
AU  - Hilgendorff, A.
AU  - Stöger, T.
AU  - Groll, J.*
AU  - Schmid, O.
C1  - 61397
C2  - 50208
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - A bioinspired in vitro lung model to study particokinetics of nano-/microparticles under cyclic stretch and air-liquid interface conditions.
JO  - Front. Bioeng. Biotechnol.
VL  - 9
PB  - Frontiers Media Sa
PY  - 2021
SN  - 2296-4185
ER  -