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
• biokompatibilní materiály chemie   MeSH
• myši MeSH
• polyestery * chemie   MeSH
• poréznost MeSH
• testování materiálů MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury * chemie   MeSH
• vstřebatelné implantáty MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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
• buněčná diferenciace * fyziologie   MeSH
• kmenové buňky * cytologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   fyziologie   MeSH
• regenerativní lékařství * metody   MeSH
• tkáňové inženýrství metody   MeSH
• tuková tkáň * cytologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Targeting ubiquitin E3 ligases is therapeutically attractive; however, the absence of an active-site pocket impedes computational approaches for identifying inhibitors. In a large, unbiased biochemical screen, we discover inhibitors that bind a cryptic cavity distant from the catalytic cysteine of the homologous to E6-associated protein C terminus domain (HECT) E3 ligase, SMAD ubiquitin regulatory factor 1 (SMURF1). Structural and biochemical analyses and engineered escape mutants revealed that these inhibitors restrict an essential catalytic motion by extending an α helix over a conserved glycine hinge. SMURF1 levels are increased in pulmonary arterial hypertension (PAH), a disease caused by mutation of bone morphogenetic protein receptor-2 (BMPR2). We demonstrated that SMURF1 inhibition prevented BMPR2 ubiquitylation, normalized bone morphogenetic protein (BMP) signaling, restored pulmonary vascular cell homeostasis, and reversed pathology in established experimental PAH. Leveraging this deep mechanistic understanding, we undertook an in silico machine-learning-based screen to identify inhibitors of the prototypic HECT E6AP and confirmed glycine-hinge-dependent allosteric activity in vitro. Inhibiting HECTs and other glycine-hinge proteins opens a new druggable space.

• MeSH
• alosterická regulace účinky léků   MeSH
• lidé MeSH
• myši MeSH
• plicní arteriální hypertenze farmakoterapie   MeSH
• receptory morfogenetických kostních proteinů typu II MeSH
• signální transdukce účinky léků   MeSH
• ubikvitinace účinky léků   MeSH
• ubikvitinligasy * antagonisté a inhibitory   metabolismus   chemie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: German-speaking surgeons have left a deep imprint on the history of diagnostics and treatment of proximal femur fractures. Some of the studies published in German have fell into oblivion, others are cited until today, although sometimes quite inaccurately. The cause of such inaccuracies are citations from secondary sources due to unavailability of the original or inability to read it because of a language barrier. In the current literature, globally predominated by English articles, the "German history" of treatment of proximal femur fractures remains undervalued. The aim of the present article is to point out its contribution. MATERIALS AND METHODS: Literature search was performed in original publications and historical sources. RESULTS: The German-speaking surgeons have considerably contributed to the development of the treatment of proximal femur fractures. The analyzed period between 1847 and 1970 may be divided into three basic periods. In the first period (1847-1896), the German-speaking surgeons (Langenbeck, Trendelenburg, König, Heine, Dolinger) were the first worldwide to start treating the fractures of proximal femur operatively. In the second period (1897-1935), mainly in the 1930s, the initiative in Europe was taken over by surgeons publishing studies in France and in Belgium. Overseas, American surgeons were coming to the forefront. In Germany, only Pauwels developed the first biomechanical classification of femoral neck fractures. In the third period (1936-1970), mainly in the 1940s and 1950s, implants were designed (Pohl, Künstcher), based on close collaboration between German engineers and surgeons, that served as a model for a dynamic hip screw and a proximal femoral nail, which are currently the implants of choice in the treatment of trochanteric fractures. CONCLUSION: The historical contribution of German-speaking surgeons to understanding the issue of proximal femur fractures and their operative treatment is far more significant than presented in the historical studies published in English.

• MeSH
• femur chirurgie   MeSH
• fraktury krčku femuru * chirurgie   MeSH
• fraktury kyčle * chirurgie   MeSH
• fraktury proximálního femuru * MeSH
• kostní hřeby MeSH
• lidé MeSH
• vnitřní fixace fraktury MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This study develops and characterizes novel biodegradable soft hydrogels with dual porosity based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers cross-linked by hydrolytically degradable linkers. The structure and properties of the hydrogels are designed as scaffolds for tissue engineering and they are tested in vitro with model mesenchymal stem cells (rMSCs). Detailed morphological characterization confirms dual porosity suitable for cell growth and nutrient transport. The dual porosity of hydrogels slightly improves rMSCs proliferation compared to the hydrogel with uniform pores. In addition, the laminin coating supports the adhesion of rMSCs to the hydrogel surface. However, hydrogels modified by heptapeptide RGDSGGY significantly stimulate cell adhesion and growth. Moreover, the RGDS-modified hydrogels also affect the topology of proliferating rMSCs, ranging from single-cell to multicellular clusters. The 3D reconstruction of the hydrogels with cells obtained by laser scanning confocal microscopy (LSCM) confirms cell penetration into the inner structure of the hydrogel and its corresponding microstructure. The prepared biodegradable oligopeptide-modified hydrogels with dual porosity are suitable candidates for further in vivo evaluation in soft tissue regeneration.

• MeSH
• buněčná adheze MeSH
• hydrogely * chemie   MeSH
• mezenchymální kmenové buňky * MeSH
• poréznost MeSH
• tkáňové inženýrství MeSH
• tkáňové podpůrné struktury chemie   MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Age-at-death estimation is usually done manually by experts. As such, manual estimation is subjective and greatly depends on the past experience and proficiency of the expert. This becomes even more critical if experts need to evaluate individuals with unknown population affinity or with affinity that they are not familiar with. The purpose of this study is to design a novel age-at-death estimation method allowing for automatic evaluation on computers, thus eliminating the human factor. METHODS: We used a traditional machine-learning approach with explicit feature extraction. First, we identified and described the features that are relevant for age-at-death estimation. Then, we created a multi-linear regression model combining these features. Finally, we analysed the model performance in terms of Mean Absolute Error (MAE), Mean Bias Error (MBE), Slope of Residuals (SoR) and Root Mean Squared Error (RMSE). RESULTS: The main result of this study is a population-independent method of estimating an individual's age-at-death using the acetabulum of the pelvis. Apart from data acquisition, the whole procedure of pre-processing, feature extraction and age estimation is fully automated and implemented as a computer program. This program is a part of a freely available web-based software tool called CoxAGE3D, which is available at https://coxage3d.fit.cvut.cz/. Based on our dataset, the MAE of the presented method is about 10.7 years. In addition, five population-specific models for Thai, Lithuanian, Portuguese, Greek and Swiss populations are also given. The MAEs for these populations are 9.6, 9.8, 10.8, 10.5 and 9.2 years, respectively. Our age-at-death estimation method is suitable for individuals with unknown population affinity and provides acceptable accuracy. The age estimation error cannot be completely eliminated, because it is a consequence of the variability of the ageing process of different individuals not only across different populations but also within a certain population.

• MeSH
• acetabulum * diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• software * MeSH
• soudní antropologie * metody   MeSH
• strojové učení * MeSH
• určení kostního věku * metody   MeSH
• zobrazování trojrozměrné * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The aim of this study was to develop multifunctional magnetic poly(ε-caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three-step approach. Then, a series of PCL-based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow-derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS-2 osteoblast-like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• Escherichia coli účinky léků   MeSH
• kosti a kostní tkáň MeSH
• krysa rodu rattus MeSH
• kyselina askorbová * chemie   farmakologie   MeSH
• lidé MeSH
• magnetické nanočástice chemie   MeSH
• nádorové buněčné linie MeSH
• nanokompozity chemie   MeSH
• osteoblasty metabolismus   cytologie   MeSH
• osteosarkom patologie   MeSH
• polyestery * chemie   MeSH
• Staphylococcus aureus * účinky léků   růst a vývoj   MeSH
• testování materiálů MeSH
• tkáňové inženýrství * MeSH
• tkáňové podpůrné struktury chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Previously, a new biodegradable poly(ester urethane urea) was synthesized based on polycaprolactone-diol and fish gelatin (PU-Gel). In this work, the potential of this new material for neural tissue engineering is evaluated. Membranes with randomly oriented fibers and with aligned fibers are produced using electrospinning and characterized regarding their mechanical behavior under both dry and wet conditions. Wet samples exhibit a lower Young's modulus than dry ones and aligned membranes are stiffer and more brittle than those randomly oriented. Cyclic tensile tests are conducted and high values for recovery ratio and resilience are obtained. Both membranes exhibited a hydrophobic surface, measured by the water contact angle (WCA). Human mesenchymal stem cells from umbilical cord tissue (UC-MSCs) and human neural stem cells (NSCs) are seeded on both types of membranes, which support their adhesion and proliferation. Cells stained for the cytoskeleton and nucleus in membranes with aligned fibers display an elongated morphology following the alignment direction. As the culture time increased, higher cell viability is obtained on randomfibers for UC-MSCs while no differences are observed for NSCs. The membranes support neuronal differentiation of NSCs, as evidenced by markers for a neuronal filament protein (NF70) and for a microtubule-associated protein (MAP2).

• MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• buněčná adheze účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   účinky léků   metabolismus   MeSH
• nervové kmenové buňky * cytologie   účinky léků   metabolismus   MeSH
• pevnost v tahu MeSH
• polyestery * chemie   farmakologie   MeSH
• polyurethany * chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• testování materiálů MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• viabilita buněk účinky léků   MeSH
• želatina * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH