Search Results (559)

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements. Full article

Osteochondral lesions of the talus (OLTs) present a significant clinical challenge, often leading to pain, dysfunction, and joint degeneration. Traditional treatments, including microfracture and grafting, have limitations in their ability to fully restore osteochondral integrity. Recent advances in tissue engineering have introduced heparin-conjugated fibrin hydrogel (HCFH) as a promising scaffold for regenerative therapy. By supporting mesenchymal stem cell (MSC) proliferation and controlled growth factor release, HCFH enhances cartilage and bone repair. A 21-year-old female presented with chronic right ankle pain and instability following a sports injury, with MRI revealing an osteochondral lesion in the lateral dome of the talus and an anterior talofibular ligament injury. Treatment included autologous MSC isolation, HCFH synthesis, arthroscopic debridement, microfracture, and implantation of MSC-loaded HCFH, while postoperative rehabilitation involved four weeks of restricted weight-bearing- and physiotherapy. At 12 months, her visual analog scale (VAS) score decreased from 60 to 40, indicating clinical improvement, and her American Orthopaedic Foot and Ankle Society (AOFAS) score increased from 69 to 77. Serial MRI scans showed progressive cartilage regeneration with near-complete defect filling. This case highlights the potential of MSC-loaded HCFH in treating OLTs. The observed improvements in pain relief, function, and cartilage regeneration suggest that this technique may overcome the limitations of conventional treatments. Further studies with larger cohorts and long-term follow-up are necessary to confirm its clinical efficacy. Full article

In vitro chondrocyte expansion is key to all tissue engineering (TE) strategies using adult differentiated articular chondrocytes. Unfortunately, high proliferation rates in vitro can cause a progressive loss of chondrocyte phenotype (dedifferentiation) during culture passages. This can impair the quality of newly formed tissue after implantation because dedifferentiated chondrocytes mainly produce fibrocartilage, which hinders successful cartilage repair. Freshly isolated chondrocytes from equine articular cartilage were grown as a primary culture on tissue culture dishes and on 2D chitosan or chitosan/hyaluronic acid films. To evaluate chondrocyte differentiation during in vitro expansion, morphological observations, gene expression of chondrocyte phenotype markers, and LC-MS/MS shotgun proteomics were performed. All types of 2D cultures showed significantly reduced differentiation compared with freshly isolated cells, but chondrocytes grown on biomaterials maintained a rounded morphology and the gene expression of differentiation markers. Interestingly, pairwise proteomics comparison revealed a remarkable number of differentially expressed proteins, highlighting the different dynamics occurring in each experimental condition at the protein level. Based on novel insights into differentiation-dedifferentiation mechanisms, hypotheses were generated to explore new markers implicated in dedifferentiation and the role of biomaterials in this process by investigating the biological pathways associated with the reduced phenotype. Full article

Magnetic hydrogels are stimulus-responsive hydrogels with rapid response when placed in a magnetic field. Their properties include those of conventional hydrogels such as biocompatibility, viscoelasticity, and a high content of water, with the addition of magnetic actuation, magnetothermal conductivity, and magnetic resonance conferred by the magnetic particles. Their use in the biomedical field is constantly growing, with various applications such as drug delivery, hyperthermia treatment, theranostic, and tissue engineering. Since the research field of magnetic hydrogels is very dynamic, it is important to review the literature regularly to highlight the most recent insights of the field. In this review, we focused on the latest advances of magnetic hydrogels and give a large overview on their types, fabrication, properties, and applications in hyperthermia, drug delivery, wound healing, MRI, sensors, and tissue engineering (neural, cartilage, bone, and cardiac tissues). We concluded this review with challenges and future developments of magnetic hydrogels. Full article

Background/Objectives: Osteoarthritis (OA) is a prevalent age-related degenerative joint disease causing cartilage damage, leading to a debilitating lifestyle. However, there are currently no drugs on the market that promote cartilage repair, and advanced cases often require arthroplasty. Increasing evidence suggests that exosomes, the smallest extracellular vesicles (30–150 nm) secreted by all cell types, are involved in the pathological process of OA and play a crucial and complex role in its progression. This review aims to provide in-depth insights into exosome biology, isolation techniques, their role in OA pathophysiology, and their clinical therapeutic potential. Methods: We systematically reviewed studies published since 2020 on exosomes in OA, focusing on their biological properties, isolation techniques, pathological roles, and therapeutic applications. Results: Exosomes derived from synovial fluid, chondrocytes, synoviocytes, and mesenchymal stem cells regulate key processes in OA progression, including inflammation, apoptosis, extracellular matrix degradation, and regeneration. Various cell-derived exosomes show therapeutic potential for cartilage damage/OA. However, their mechanisms of action have not been fully investigated. Moreover, emerging methodologies, such as utilizing novel materials for exosome delivery, potentially facilitate the development of more effective and personalized therapeutic interventions. Conclusions: Exosomes exert dual roles in OA pathogenesis and therapy. Although challenges remain regarding their sources, dosage, delivery, and standardization, exosome-based strategies represent a promising cell-free therapeutic approach with potential applications in personalized and precision medicine. Full article

A subset of chondrocytes in various human cartilage tissues, including neoplastic, regenerative, and normal cartilage, expresses α-smooth muscle actin (α-SMA), a protein typically found in smooth muscle cells. These α-SMA-containing chondrocytes, termed myochondrocytes and myochondroblasts, may play important roles in cartilage physiology, regeneration, and structural integrity, particularly in auricular and articular cartilage. This review synthesizes current knowledge regarding the terminology, distribution, and biological significance of these cells across normal, osteoarthritic, transplanted, and neoplastic cartilage. We summarize key findings from immunohistochemical studies using markers such as S-100, α-SMA, and SOX9, along with ultrastructural confirmation of myofilament bundles via electron microscopy. Current evidence suggests that myochondrocytes exhibit enhanced regenerative potential and contribute to matrix remodeling. Furthermore, their presence reflects the inherent cellular heterogeneity of cartilage, potentially arising from transdifferentiation processes involving fibroblasts, mesenchymal stem cells, or chondroblasts. Finally, TGF-β1 and PDGF-BB are identified as a critical modulator of α-SMA expression and chondrocyte phenotype. A deeper understanding of nature and function of myochondrocytes and myochondroblasts may improve interpretations of cartilage pathology and inform strategies for tissue engineering and cartilage repair. This review highlights the need for further investigation into the molecular regulation and functional roles of these cells in both physiological and pathological contexts. Full article

Articular cartilage (AC) is a specialised connective tissue covering joint surfaces. It enables smooth movement, distributes mechanical loads, and protects the underlying bone. In response to loading, AC adapts by modifying both its thickness and composition. AC is organised in different zones, with low cellularity and a high abundance of extracellular matrix (ECM). Mechanical overloading or immobilisation can lead to structural changes, potentially resulting in osteoarthritis (OA), for which no causal treatment currently exists. However, smaller defects can be treated using chondrocyte/cartilage transplantation or tissue engineering. A better understanding of the molecular composition of AC at different locations is essential to improve such therapeutic approaches. For this purpose, we performed a comprehensive analysis of porcine femoral knee cartilage at eight defined anatomical sites. Cartilage thickness and proteoglycan (PG) content were analysed histologically, while specific ECM proteins were assessed by proteomics and validated by immunohistochemistry and Western blot. Significant differences were identified, particularly between medial and lateral compartments, in terms of cartilage thickness, PG abundance, and ECM composition. Some proteins also showed zone-specific localisation patterns. These structural differences likely reflect adaptation to mechanical loading and should be considered to optimise future cartilage repair and tissue engineering strategies. Full article

Natural biomaterials are widely used in the construction of cartilage tissue engineering due to their excellent biocompatibility, easy degradation, and ability to degrade products to be absorbed by the human body. However, due to their poor mechanical properties, it is usually necessary to composite them with other materials to prepare biological scaffolds that meet the expected requirements. This study used freeze-drying technology to introduce calcium polyphosphate fibres (CPPFs) into a chitosan (CS) matrix to prepare composite scaffolds with better performance. CPPF was used as a filler and inorganic skeleton in the CS/CPPF composite to improve the properties of the CS-based scaffold. With little change in porosity, the compressive strength of the CS/CPPF composite scaffold increased from 0.172 MPa of chitosan to 0.332 MPa with the increase in CPPF addition. The water absorption rate of the composite scaffold decreased from 1297.42% to 935.37%. In vitro degradation experiments revealed that CPPF accelerated the degradation of the scaffold and generated calcium phosphate and nano-hydroxyapatite compounds during the degradation process. According to our cytotoxicity testing, the CS/CPPF composite scaffolds exhibited good biocompatibility and could enhance cell proliferation. This method of incorporating CPPF into CS provides important reference values for the application of CPPF in other natural bone tissue engineering scaffold materials. Full article

Extracellular matrix proteins have a complex assembly in tissue and it is believed that not only the chemical structure, but also their location, plays an important role in cellular functions. Collagen is one of the main components of the extracellular matrix and the oriented arrangement of collagen fibrils in tissues such as bone, cartilage, tendons, and cornea has a significant impact on various tissue functions. In the body, the orientation of extracellular matrix proteins is determined by cells. Oriented collagen fibrils can not only promote directed cell migration, but also stimulate cells to secrete an extracellular matrix with an oriented structure. However, the creation of collagen fibrils with an oriented structure in vitro is still associated with a number of limitations. Such limitations are primarily because the mechanisms regulating cellular functions in the orientation of extracellular matrix proteins, including collagen, are still unknown. Currently, only physical ways of organizing collagen fibrils in a certain direction are known. We hope that the description of the orientation of collagen fibrils in this review will allow readers to better understand the processes that occur with molecules. The study of methods and conditions for obtaining oriented collagen fibrils can help to obtain tissue biomimetic materials with complex properties identical to native tissues. Therefore, we discuss here various methods and conditions for obtaining oriented collagen fibrils in vitro using mechanical, electric, magnetic, and other fields. The prospects of application in tissue engineering and scientific problems of oriented collagen fibrils are also described. Full article

This review covers the roles of cartilage oligomeric matrix protein (COMP), an established biomarker of cartilage breakdown in pathological tissues in osteoarthritis, and in emerging areas in extracellular matrix and vascular remodeling associated with trauma, fibrosis and cancer. COMP is produced by chondrocytes, tenocytes, myofibroblasts, and in some specialized tissue contexts, endothelial and vascular smooth muscle cells. COMP expression by tendon and cartilage cells is sensitive to weight bearing and tensional mechanical stimulation. Vascular smooth muscle cells are sensitive to shear forces which regulate COMP expression in vascular tissues in atherosclerosis and in carotid stenosis. COMP is a multivalent bridging molecule that stabilizes tissues. It facilitates the signaling of TGF-β and BMP-2 in chondrogenesis, osteogenesis, tissue fibrosis, vascular and ECM remodeling and tumor development by providing a multimeric environment through which growth factor binding and receptor activation can occur. Engineered COMP proteins have been used as molecular templates in the development of chimeric therapeutic proteins of potential application in repair biology. Tie2 (Angiopoietin-1 receptor, Tyrosine-protein kinase receptor TEK), when activated by an engineered COMP-inspired angiopoietin-2 pentamer, is a potent angiogenic molecule of obvious application in wound healing. COMP’s multifunctional properties show it is much more than a biomolecular marker protein through its ability to participate in many biological processes. Further studies are warranted to fully explore the biology of this fascinating molecule, particularly in the wound repair processes. Full article

Background/Objectives: Mesenchymal stem cells (MSCs) offer promising prospects for novel treatment modalities in cellular therapies and artificial organ production. Despite a surge in artificial tissue research, there is a dearth of comprehensive studies detailing the entire process from stem cells to tissue production, coupled with a scarcity. This study, however, presents the utility of extra-embryonic MSCs derived from placental tissue, traditionally considered as medical waste. Methods: Within a 3-dimensional cell culture system, histological assessments, and comprehensive optimization studies, the entire process required for artificial tissue production is addressed. Results: The results obtained are encouraging regarding the advancement of cellular therapies and artificial tissue engineering. However, challenges such as biopolymer degradation highlight the necessity for multistep approaches. Each analysis within this study delves into the discussion and optimization of key steps in artificial tissue production. Conclusions: Consequently, this study not only represents one of the first of its kind but also lays the groundwork for future investigations into relevant clinical applications. Full article

Soft tissues exhibit remarkable stretchability, fracture toughness, and stress–relaxation ability. They possess a large water content to support cellular processes. Mimicking such a combination of mechanical and physical properties in hydrogels is important for tissue engineering applications but remains challenging. This work aims to develop a hydrogel that can combine excellent mechanical properties with cellular viability. The research focused on polyvinyl alcohol (PVA)/agar double-network (DN) hydrogels, fabricated by thermal gelation and freeze–thawing methods. Their mechanical properties were characterized through tension, compression, fracture, and stress–relaxation tests, and their cellular viability was measured through cytotoxicity tests. The results show that the PVA/agar DN gels are highly stretchable (>200%) and compressible (>30%) while containing high water content. The incorporation of agar by 6 wt% improved the fracture toughness of hydrogels from 1 to 1.76 kJ/m². The degree of stress–relaxation, a key indicator of gel viscoelastic properties, improved by roughly 170% with an increase in agar content from 0 to 6 wt%. Cytotoxicity analysis showed that the gels, being physically cross-linked, were able to promote cellular proliferation. This work shows that tough and viscoelastic PVA/agar DN gels are suitable for soft tissue engineering applications, especially cartilage repair. Full article

Cellulose nanocrystals (CNCs), derived from renewable cellulose sources, have emerged as a versatile class of nanomaterial with exceptional mechanical strength, tuneable surface chemistry and inherent biocompatibility. In the scenario of contemporary commercial hydrogel products, which are expensive and rely on synthetic materials, the sustainable origin and unique physicochemical properties have positioned CNCs as promising sustainable functional building blocks for next-generation hydrogels in biomedical applications. Over the past decade, CNC-based hydrogels have gained momentum as soft biomaterials capable of interacting with diverse tissue types, predominantly demonstrated through in vitro cell line studies. This review critically examines the current landscape of research on biomedical applications of CNC-based hydrogels, focusing on their biomedical utility across 22 systematically screened studies. It revealed applications spanning around bone and cartilage tissue engineering, wound healing, medical implants and sensors, and drug delivery. We highlight the predominance of microcrystalline cellulose as the CNC source and sulfuric acid hydrolysis as the preferred extraction method, with several studies incorporating surface modifications to enhance functionality. Despite growing interest, there remains a lack of data for transitioning towards human clinical studies and commercialisation. Hence, this review highlights the pressing need for scalable, sustainable, and affordable CNC-based hydrogel systems that can democratise access to advanced biomedical technologies. Full article

Orofacial Mesenchymal Stem Cells (OMSCs) are an attractive and promising tool for tissue regeneration, with their potential for craniofacial bone repair being a primary focus of research. A key advantage driving their clinical interest is their accessibility from tissues that are often discarded, such as exfoliated deciduous teeth, which circumvents the ethical concerns and donor site morbidity associated with other stem cell sources. The high proliferation ability and multi-differentiation capacity of OMSCs make them a unique resource for tissue engineering. Recently, OMSCs have been explored in the restoration of the heart and skin, treatment of oral mucosal lesions, and regeneration of hard connective tissues such as cartilage. Beyond their direct regenerative capabilities, OMSCs possess potent immunomodulatory functions, enabling them to regulate the immune system in various inflammatory disorders through the secretion of cytokines. This review offers an in-depth update regarding the therapeutic possibilities of OMSCs, highlighting their roles in the regeneration of bone and various tissues, outlining their immunomodulatory capabilities, and examining the essential technologies necessary for their clinical application. Full article

Articular cartilage regeneration remains a major challenge due to its limited self-repair capacity. Bone marrow-derived skeletal stem cells (SSCs) and mesenchymal stem cells (MSCs) are promising candidates for cartilage engineering, although they differ in their chondrogenic potential. This study explored whether co-culturing SSCs and MSCs in three-dimensional (3D) organoid systems under cartilage physioxia (5% O₂) and chondrogenic induction could improve cartilage tissue formation. SSCs, MSCs, and SSC–MSC co-cultures were characterized for morphology, phenotype, and differentiation capacity. Organoids were generated and cultured for 10 days, followed by analysis of morphology, viability, gene expression (SOX9, RUNX2, ACAN, COL2A1, COL10A1, PRG4, and PDPN), chondrocyte-associated antigens (CD44, CD105, CD146, and PDPN), and cartilage ECM proteins (aggrecan, collagen types I, II, and X, and PRG4). SSCs showed robust chondrogenic and osteogenic potential, while MSCs exhibited a balanced multipotency. Co-culture-derived organoids enhanced chondrogenesis and reduced adipogenesis, with higher expression of cartilage-specific ECM and lower hypertrophic marker levels. These findings highlight the functional synergy between SSCs and MSCs in co-culture, promoting the formation of stable, cartilage-like structures under physioxia. The approach offers a promising strategy for generating preclinical models and advancing regenerative therapies for hyaline cartilage repair. Full article