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.

Current developments in bioequivalent technology have led to the creation of excellent models that mimic the structure and function of human organs. These models are based on the original tissues and organs of the human body, but they lack the complex interaction with the extensive network of vasculature, and this is a major challenge for these models. A functional vasculature is essential for oxygen, nutrient, and waste exchange. It is also responsible for inductive biochemical exchange, and provides a structural pattern for organ growth. In vitro systems, containing no perfusable vessels, suffer from the quick formation of a necrotic core of organoids, and further development does not occur due to increased metabolic demands. Another key limitation of 3D-based techniques is the absence of accurate architectural structures and large-scale tissue sizes. Recently, new 3D bioprinting methods have been developed for organoids and spheroids as living building blocks. These methods aim to address some of the challenges associated with 3D technologies. In this review, we discuss recent strategies for vascularization via organoids and spheroids, which are used as structural units in bioprinting to recreate natural organs and tissues with ever-increasing accuracy in structure and function.

Periodontitis is a prevalent chronic inflammatory disease that leads to the progressive destruction of periodontal tissues and remains the primary cause of tooth loss worldwide. Despite advances in regenerative approaches—including stem cell therapy, scaffold-based tissue engineering, and guided tissue regeneration—the complete and functional restoration of the periodontal ligament remains a major clinical challenge. Stem-cell-based therapies and advanced biomaterials have emerged as promising strategies in regenerative medicine, offering potential for restoring periodontal structure and function. Among cells, periodontal-ligament-derived stem cells (PDLSCs) show exceptional regenerative potential due to their ability to differentiate into cementoblasts, osteoblasts, and other cell types essential for periodontal repair. In recent years, a variety of biomaterials with distinct specifications and properties have been utilized to repair periodontal damage. In addition to the inherent properties of biomaterials, the morphology and structural characteristics of these materials as bioequivalents for periodontal regeneration are also critical considerations. Furthermore, recent studies emphasize that mechanical stimulation plays a considerable role in directing stem cell differentiation, gene expression, matrix organization, and modulating inflammatory responses in periodontal regeneration. Canonical parameter ranges for systematic analysis indicate that cyclic stretch strain of 1–20% at 0.1–0.5 Hz (6–30 cycles/min) typically increases the expression of osteogenic markers (RUNX2, ALP, OCN) and matrix components (Col1) in PDLSCs. Conversely, higher values (>15%) often bias the response toward inflammatory pathways (IL-6, PGE2). Static compression above 2 g/cm² consistently stimulates the secretion of pro-inflammatory cytokines (IL-6, IL-8) and alters the RANKL/OPG balance in favor of osteoclastogenesis. Significant heterogeneity in response across studies will be analyzed by examining key methodological variables, including specific loading regimens (duration, frequency patterns) and culture conditions (e.g., serum/osteogenic supplements), which critically modulate mechanotransduction outcomes. This review summarizes current progress in periodontal regenerative medicine, emphasizing cellular and biomaterial considerations, as well as biofabrication techniques, with a particular focus on the influence of mechanical forces on PDLSCs. We discuss cellular responses to mechanical stimuli, including changes in gene expression, cytoskeletal organization, proliferation, and differentiation. Combining biological knowledge with advances in bioprinting and the study of mechanobiology, we finally discuss promising opportunities for improving periodontal regeneration that can be applied in the future in clinical practice.

Most tissues and organs are based on cells of the epithelial and mesenchymal phenotypes. Epithelial cells build protective barriers, have a key role in absorption and secretion, and participate in metabolism. Characterized by high plasticity and ability to migrate, mesenchymal cells ensure structural support, promote tissue restoration and are important for matrix remodeling. Interaction between these two cell types is critical for maintaining the body integrity and functioning.

To simulate the wound, titanium sealing rings were used, which mechanically compressed the skin to create a local ischemic wound. A day after, the rings were removed, and the epidermis of the skin was excised. The wound was treated one day and 2 weeks after the wound infliction. For this purpose, a combined ink was applied to the wound surface using a portable Biogan bioprinter (the prototype was developed by the authors). An adapted passive mixer allowed uniform mixing of the bioink based on a fibrin-gelatin hydrogel and spheroids derived from human adipose MSCs. Wound closure rates were assessed over 36 days, followed by histological analysis. The use of inks based on fibrin-gelatin hydrogel and spheroids from adipose MSCs significantly accelerated healing, as evidenced by the reduction in the wound area compared to the control group and hydrogel-only group, as well as the complete restoration of all skin layers by day 36. The therapeutic effect of the developed approach was due to the spheroids in the bioinks and not to the hydrogel. The use of the developed mixer did not reduce the cell viability and ensured convenient ink application to the wound surface.