Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.

Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV—exosomes and matrix-bound nanovesicles (MBV)—both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation. Different phenotypes of human monocyte-derived macrophages (MDM) were used to study the anti-inflammatory properties of EV in vitro, and the medial meniscectomy-induced rat model of knee osteoarthritis (MMx) was used in vivo. The study found that both EV reduced pro-inflammatory cytokines IL-6 and TNF-α in MDM. However, exosomes showed superior results, preserving the extracellular matrix (ECM) of hyaline cartilage, and reducing synovitis more effectively than MBVs. Additionally, exosomes downregulated inflammatory markers (TNF-α, iNOS) and increased Arg-1 expression in macrophages and synovial fibroblasts, indicating a stronger anti-inflammatory effect. These results suggest UC-MSC exosomes as a promising therapeutic option for OA, with the potential for modulating inflammation and promoting joint tissue regeneration.

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a common condition in hip surgery, which is characterized by the death of bone cells due to disruption of the blood supply and ultimately irreversible destruction of the hip joint. As a result of the COVID-19 pandemic, a significant increase in the incidence of ONFH has been identified. To better understand the pathogenesis of ONFH in the context of COVID-19, our research aimed to determine pathomorphological changes in articular tissues specific to post-COVID-19 ONFH. Methods: Using morphological, morphometric, and statistical methods, the femoral heads after hip arthroplasty were retrospectively studied in patients with post-COVID-19 ONFH (n = 41) compared to a non-COVID-19 group of patients (n = 47). Results: Our results revealed that the key morphofunctional biomarkers of post-COVID-19 ONFH were clusters of mast cells, extensive areas of fibrosis, numerous arterial and venous thrombi, and giant cell granulomas. The potential relationship of those morphological features with the action of the SARS-CoV-2 coronavirus was discussed. Conclusions: Mast cells have been proposed as the leading players that may trigger the main molecular and cellular mechanisms in the development of post-COVID-19 ONFH and can be considered a diagnostic sign of the disease.

Titanium membranes and meshes are used for the repair of trauma, tumors, and hernia in dentistry and maxillofacial and abdominal surgery. But such membranes demonstrate the limited effectiveness of integration in recipients due to their bioinertness. In this study, we prepared titania oxide (by microarc oxidation) and/or HAp (by electrophoresis deposition) coatings with alginate soaking. We used annealing at 700 °C for 2.5 h for HAp crystallinity increasing with achievement of an acceptable Ca²⁺ release rate. The feedstock HAp and prepared coatings were characterized by X-ray diffraction, IR spectroscopy, electron and optical confocal microscopy, and thermal analysis, as well as the in vitro study of solubility in saline and in vivo tests with the animal model of subcutaneous implantation (with Wistar rats). Biocompatible compounds were found for all deposited coatings. We noted that the best biological response was detected for the annealed Ca-P/TiO₂ bilayer with alginate binding. In this case, the coating crystallinity was ≈40.5-50.0%. The Ca²⁺ release rate was 2.042 ± 0.058%/mm² at 168 h after immersion in saline. Thin and mature tissue capsules with minimal inflammation and vascularization were found in histological sections. We did not detect any unwanted responses around the implants, including inflammation infiltration, suppuration, bacterial infections, tissue lyses, and, finally, implant rejection. This information is expected to be useful for understanding the properties of bioactive ceramic coatings and improving the quality of medical care in dentistry and maxillofacial surgery and other applications of titanium membranes in medicine.

Background: Ditrosyl iron complexes (DNIC) are endogenous donors of nitric oxide. The possibility of their application to stimulate regeneration has been studied for more than 15 years. However, the most effective dose and form of delivery have not yet been determined. Purpose: The aim of this research was to develop a spray form of DNIC that accelerates wound healing. Methods: We prepared a series of DNIC sprays with spray dosages of 10, 50 and 100 μg. We modelled full-thickness skin wounds in 24 Wistar rats and treated them with distilled water (n = 6), 10 (n = 6), 50 (n = 6) and 100 μg (n = 6) for three post-operative days. On the fourth day, the excised wound tissues were studied by morphological, immunohistochemical and morphometric methods. Results: We demonstrated that 50 μg of DNIC spray had the most beneficial effect on wound healing: the thickness of the granulation tissue layer was 140% higher, vimentin positive fibroblasts predominated and the intensity of inflammation was significantly lower than in the control. There was a dose-dependent decrease in the functional activity of mast cells in the experimental groups compared to the control. Conclusion: DNIC spray is a potential effective dosage form for the treatment of large-area skin lesions. Graphical Abstract:

The formation of a dense fibrous capsule around the foreign body and its contracture is the most common complication of biomaterial implantation. The aim of our research is to find out how the surface of the implant influences the inflammatory and fibrotic reactions in the surrounding tissues. We made three types of implants with a remote surface topography formed of polylactide granules with different diameters: large (100–200 µm), medium (56–100 µm) and small (1–56 µm). We placed these implants in skin pockets in the ears of six chinchilla rabbits. We explanted the implants on the 7th, 14th, 30th and 60th days and performed optical coherence tomography, and histological, immunohistochemical and morphometric studies. We examined 72 samples and compared the composition of immune cell infiltration, vascularization, the thickness of the peri-implant tissues, the severity of fibrotic processes and α-SMA expression in myofibroblasts. We analyzed the scattering coefficient of tissue layers on OCT scans. We found that implants made from large granules induced a milder inflammatory process and slower formation of a connective tissue capsule around the foreign body. Our results prove the importance of assessing the surface texture in order to avoid the formation of capsular contracture after implantation.