Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions.
- MeSH
- Biocompatible Materials chemistry MeSH
- Mice MeSH
- Polyesters * chemistry MeSH
- Porosity MeSH
- Materials Testing MeSH
- Tissue Engineering methods MeSH
- Tissue Scaffolds * chemistry MeSH
- Absorbable Implants MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The alveolar-capillary interface is the key functional element of gas exchange in the human lung, and disruptions to this interface can lead to significant medical complications. However, it is currently challenging to adequately model this interface in vitro, as it requires not only the co-culture of human alveolar epithelial and endothelial cells but mainly the preparation of a biocompatible scaffold that mimics the basement membrane. This scaffold should support cell seeding from both sides, and maintain optimal cell adhesion, growth, and differentiation conditions. Our study investigates the use of polycaprolactone (PCL) nanofibers as a versatile substrate for such cell cultures, aiming to model the alveolar-capillary interface more accurately. We optimized nanofiber production parameters, utilized polyamide mesh UHELON as a mechanical support for scaffold handling, and created 3D-printed inserts for specialized co-cultures. Our findings confirm that PCL nanofibrous scaffolds are manageable and support the co-culture of diverse cell types, effectively enabling cell attachment, proliferation, and differentiation. Our research establishes a proof-of-concept model for the alveolar-capillary interface, offering significant potential for enhancing cell-based testing and advancing tissue-engineering applications that require specific nanofibrous matrices.
The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry-Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.
Tools for post-operative localization of deep brain stimulation (DBS) electrodes may be of major benefit in the evaluation of the stimulation area. However, little is known about their precision. This study compares 3 different software packages used for DBS electrode localization. T1-weighted MRI images before and after the implantation of the electrodes into the subthalamic nucleus for DBS in 105 Parkinson's disease patients were processed using the pipelines implemented in Lead-DBS, SureTune4, and Brainlab. Euclidean distance between active contacts determined by individual software packages and in repeated processing by the same and by a different operator was calculated. Furthermore, Dice coefficient for overlap of volume of tissue activated (VTA) was determined for Lead-DBS. Medians of Euclidean distances between estimated active contact locations in inter-software package comparison ranged between 1.5 mm and 2 mm. Euclidean distances in within-software package intra- and inter-rater assessments were 0.6-1 mm and 1-1.7 mm, respectively. Median intra- and inter-rater Dice coefficients for VTAs were 0.78 and 0.75, respectively. Since the median distances are close to the size of the target nucleus, any clinical use should be preceded by careful review of the outputs.
- MeSH
- Deep Brain Stimulation * methods instrumentation MeSH
- Electrodes, Implanted * MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Subthalamic Nucleus surgery MeSH
- Parkinson Disease * therapy MeSH
- Aged MeSH
- Software MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
T-cell engagers represent a transformative approach to cancer immunotherapy leveraging bispecific and multispecific antibody constructs to redirect T-cell cytotoxicity toward malignant cells. These molecules bridge T cells and tumor cells by simultaneously binding CD3 on T cells and tumor-associated antigens on cancer cells, thereby enabling precise immune targeting even in immunologically "cold" tumors. Recent advancements include conditional T-cell engagers activated by tumor microenvironment proteases to minimize off-tumor toxicity as well as T-cell receptor-based engagers targeting intracellular antigens via MHC presentation. Clinical successes, such as Kimmtrak in metastatic uveal melanoma, underscore good potential of these modalities, while challenges persist in the management of cytokine release syndrome, neurotoxicity, and tumor resistance. Emerging multispecific engagers are aimed at enhancing efficacy via incorporation of costimulatory signals, thus offering a promising trajectory for next-generation immunotherapies. T-cell engagers are also gaining attention in the treatment of autoimmune disorders, where they can be designed to selectively modulate pathogenic immune responses. By targeting autoreactive T or B cells, T-cell engagers hold promise for restoring immune tolerance in such conditions as HLA-B*27-associated autoimmunity subtypes, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Engineering strategies that incorporate inhibitory receptors or tissue-specific antigens may further refine T-cell engagers' therapeutic potential in autoimmunity, by minimizing systemic immunosuppression while preserving immune homeostasis.
- MeSH
- Immunotherapy * methods MeSH
- Humans MeSH
- Tumor Microenvironment immunology MeSH
- Neoplasms * immunology therapy MeSH
- Antibodies, Bispecific therapeutic use immunology MeSH
- Receptors, Antigen, T-Cell immunology metabolism MeSH
- T-Lymphocytes * immunology metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Adipose-derived stem cells (ADSCs) are mesenchymal stem cells (MSCs) derived from adipose tissue with mesenchymal lineage differentiation potential and remarkable potential in regenerative medicine. ADSCs are easily sourced from adipose tissue, share regenerative characteristics akin to other MSCs. Their convenient adherence to plastic culture flasks, coupled with their capacity for in vitro expansion and multi-lineage differentiation, underscores their promise as a robust tool for tissue repair and enhancement. The accessibility of human adipose tissue and the development of minimally invasive isolation protocols have further propelled the autologous use of ADSCs, fueling excitement in both organ repair and regenerative medicine. Consequently, research in ADSCsis experiencing rapid growth. A detailed overview of the current landscape of ADSCs isolation and differentiation capacity including the latest advancements in ADSCs usage, encompassing ongoing clinical investigations are important considerations to understand their potential to shape the landscape of regenerative medicine.
- MeSH
- Cell Differentiation * physiology MeSH
- Stem Cells * cytology MeSH
- Humans MeSH
- Mesenchymal Stem Cells * cytology physiology MeSH
- Regenerative Medicine * methods MeSH
- Tissue Engineering methods MeSH
- Adipose Tissue * cytology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Stem cells derived from adipose tissue are gaining popularity in the field of regenerative medicine due to their adaptability and clinical potential. Their rapid growth, ability to differentiate, and easy extraction with minimal complications make adipose-derived stem cells (ADSCs) a promising option for many treatments, particularly those targeting bone-related diseases. This study analyzed gene expression in canine ADSCs subjected to long-term culture and osteogenic differentiation. METHODS: ADSCs were isolated from discarded surgical waste and cultured for 14 days with and without differentiation media to assess osteogenic changes. RNA sequencing (RNA-seq) and bioinformatical analysis were performed to obtain comprehensive transcriptomic data. A total of 17793 genes were detected and GO enrichment analysis was performed on the differentially expressed genes to identify significantly up- and downregulated Biological Process (BP) GO terms across each comparison. RESULTS: The upregulation of apoptosis-regulating genes and genes related to circulatory system development suggest an induction of these processes, while the downregulation of neurogenesis and gliogenesis genes points to reciprocal regulation during osteogenic differentiation of canine ADSCs. DISCUSSION: These findings underscore the potential of ADSCs in bone regeneration and offer valuable insights for advancing tissue engineering, however further studies, including proteomic analyses, are needed to confirm these patterns and their biological significance.
- Publication type
- Journal Article MeSH
... PAPPAS -- 5 Engineering Design of the LCS Knee Replacement 39 -- M.J. ... ... HAAS -- 19 Navigation and Soft-Tissue Balancing of LCSTKA 333 -- J.M. Strauss, J.-L. Briard, W. ...
... -- Bikote:286883088 -- Contents -- The Biomaterial Collagen -- Collagen-Based Biomaterials and -- Tissue ... ... Engineering *3 -- B. ... ... Losel -- Mineral Biomaterials -- New Developments in Implant Coatings: -- Biomimetics and Tissue Engineering ...
This report summarizes the ASEV-CzeSEV Joint Meeting on Extracellular Vesicles (EVs), held at the Medical University of Vienna in September 2024. The conference focused on introducing and expanding EV research and infrastructure within the Czech Republic and Austria, highlighting areas for collaboration. Key sessions featured research on EV-based diagnostics, tissue regeneration, interspecies communication and therapeutic applications, with an emphasis on shared resources and cross-border partnerships. The program included oral and poster presentations on EV engineering, new isolation techniques, and potential clinical applications, as well as industry updates on the latest EV technologies. The meeting concluded with awards for outstanding presentations reflecting the quality of work presented. Following the conference, a dedicated workshop was held on flow cytometry analysis of EVs, allowing participants to deepen their technical expertise in EV characterization. This report captures the main discussions, findings, and collaborative opportunities explored at the ASEV-CzeSEV meeting, signaling strong regional support for advancing EV research.
- Publication type
- Journal Article MeSH
