Search Results (2,261)

Metastases are responsible for the majority of cancer-related deaths and remain one of the most complex and therapeutically challenging hallmarks of cancer. The metastatic cascade involves a multistep process by which cancer cells invade local tissue, enter and survive in circulation, extravasate, and ultimately colonize distant organs. Increasingly, the tumor microenvironment (TME), particularly the extracellular matrix (ECM), has emerged as a central regulator of these steps. Far from being a passive scaffold, the ECM actively influences cancer progression through its biochemical signals, structural properties, and dynamic remodeling. Among ECM components, collagens play a particularly pivotal role by mediating tumor cell adhesion, migration, invasion, survival, immune evasion, and therapeutic resistance. This narrative review synthesizes current knowledge of the dual roles of collagen in the metastatic process, with a focus on the cellular and molecular mechanisms. We highlight how altered ECM architecture and signaling contribute to metastatic niche formation and explore the potential of targeting ECM components as a strategy to enhance cancer therapy and improve patient outcomes. Full article

(1) Background: The extracellular matrix (ECM) is a natural scaffold for cells, creating a three-dimensional architecture composed of fibrous proteins (mainly collagen) and proteoglycans, which are synthesized by resident cells. In this study, a physiological hypoxic environment was utilized to enhance ECM production by human mesenchymal stem cells (hMSCs), a process relevant to tissue engineering and regenerative medicine. (2) Methods: hMSCs were treated with deferoxamine (DFO), a pharmaceutical hypoxia-mimetic agent that induces cellular responses similar to low-oxygen conditions through stabilization of hypoxia inducible factor-1α (HIF-1α). The time points 0 h 24 h, 3 h 24 h, and 24 h 24 h refer to DFO being added immediately after cell seeding (before cells adhesion), 3 h after cell seeding (during initial cells attachment), and 24 h after cell seeding (after focal adhesions formation and actin organization), respectively, to evaluate the influence of cell adhesion on ECM deposition. hMSCs incubated in culture media were subsequently exposed to DFO for 24 h. Samples were then subjected to cell viability tests, scanning electron microscopy (SEM), atomic force microscopy (AFM) and laser scanning confocal microscopy (CLSM) assessments. (3) Results: Viability tests indicated that DFO concentrations in the range of 0–300 µM were non-toxic over 24 h. The presence of collagen fibers in the DFO-derived ECM was confirmed with anti-collagen antibodies under CLSM. Increased ECM secretion was observed under the following conditions: 3 μM DFO (24 h 24 h), 100 μM DFO (0 h 24 h) and 300 μM DFO (3 h 24 h). SEM and AFM images revealed the morphology of various stages of collagen formation with both collagen fibrils and fibers identified. (4) Conclusions: Our preliminary study demonstrated enhanced ECM secretion by hMSC treated with DFO at concentrations of 3, 100, and 300 µM within a short cultivation period of 24–48 h without significant affecting cell viability. By mimicking physiological processes, it may be possible to stimulate endogenous tissue regeneration, for example, at an injury site. Full article

Wound healing remains a significant clinical challenge due to antibiotic-resistant pathogens, persistent inflammation, oxidative stress, and impaired tissue regeneration. Conventional therapies are often inadequate, necessitating alternative strategies. Plant bioactive compounds, including flavonoids, tannins, terpenoids, and alkaloids, offer antimicrobial, anti-inflammatory, antioxidant, and pro-angiogenic properties that directly address these challenges in wound healing therapy. However, their poor solubility, instability, and rapid degradation at the wound site limit clinical translation. Biomaterial-based scaffolds such as hydrogels, electrospun nanofibers, lyophilized dressings, and 3D-bioprinted constructs have emerged as promising delivery platforms to enhance bioavailability, stability, and sustained release of bioactive compounds while providing structural support for cell adhesion, proliferation, and tissue repair. This review was conducted through a structured literature search using PubMed, Scopus, and Web of Science databases, covering studies published between 1998 and 2025, with keywords including wound healing, phytochemicals, plant bioactive compounds, scaffolds, hydrogels, electrospinning, and 3D bioprinting. The findings highlight how incorporation of plant bioactive compounds onto scaffolds can combat resistant microbial infections, mitigate oxidative stress, promote angiogenesis, and accelerate tissue regeneration. Despite these promising outcomes, further optimization of scaffold design, standardization of bioactive formulations, and translational studies are needed to bridge laboratory research with clinical applications for next generation wound healing therapies. Full article

Postoperative adhesion remains a major clinical challenge, often leading to chronic pain, functional disorders, and recurrent surgeries. Herein, we developed a multifunctional gelatin–polyphenol hydrogel (GPP20) featuring rapid gelation (within 5 min), strong tissue adhesion (lasting > 24 h under physiological conditions), and intrinsic wound healing capacity to achieve integrated prevention of postoperative adhesion. GPP20 was fabricated via dynamic crosslinking between gelatin and tea polyphenol, endowing it with injectability, self-healing, biodegradability, and excellent mechanical properties (shear stress of 14.2 N). In vitro studies demonstrated that GPP20 exhibited effective ROS scavenging (82% ABTS scavenging capability), which protects cells against oxidative stress, while possessing excellent hemocompatibility and in vivo safety. Notably, GPP20 significantly reduced postoperative cecum–abdominal wall adhesions through both physical barrier effects and modulation of inflammation and collagen deposition, demonstrating a comprehensive integrated prevention strategy. Furthermore, in full-thickness wound models, GPP20 accelerated tissue regeneration (85% wound closure rate on day 10) by promoting macrophage polarization toward the M2 phenotype and stimulating angiogenesis, thereby enhancing collagen deposition and re-epithelialization. Collectively, these findings demonstrate that GPP20 integrates anti-adhesion efficacy with regenerative support, offering a facile and clinically translatable strategy for postoperative care and wound healing. Full article

Neural tissue injuries, including spinal cord damage and neurodegenerative diseases, pose a major clinical challenge due to the central nervous system’s limited regenerative capacity. Current treatments focus on stabilization and symptom management rather than functional restoration. Tissue engineering offers new therapeutic perspectives, particularly through the combination of electrospun nanofibrous scaffolds and mesenchymal stem cells (MSCs). Electrospun fibers mimic the neural extracellular matrix, providing topographical and mechanical cues that enhance MSC adhesion, viability, and neural differentiation. MSCs are multipotent stem cells with robust paracrine and immunomodulatory activity, capable of supporting regeneration and, under proper stimuli, acquiring neural-like phenotypes. This systematic review, following the PRISMA 2020 method, analyzes 77 selected articles from the last ten years to assess the potential of electrospun biopolymer scaffolds for MSC-mediated neural repair. We critically examine the scaffold’s composition (synthetic and natural polymers), fiber architecture (alignment and diameter), structural and mechanical properties (porosity and stiffness), and biofunctionalization strategies. The influence of MSC tissue sources (bone marrow, adipose, and dental pulp) on neural differentiation outcomes is also discussed. The results of a literature search show both in vitro and in vivo enhanced neural marker expression, neurite extension, and functional recovery when MSCs are seeded onto optimized electrospun scaffolds. Therefore, integrating stem cell therapy with advanced biomaterials offers a promising route to bridge the gap between neural injury and functional regeneration. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is a common and aggressive oral cancer with high recurrence and mortality rates, largely due to late diagnosis and metastasis. Epigenetic regulation, particularly aberrant DNA methylation, plays a critical role in cancer progression. Altered methylation patterns disrupt cancer-related gene regulation. Our previous study found that oral cancer patients exhibit increased synthesis of S-adenosyl-L-methionine, a key methyl donor for cytosine methylation. Therefore, the aim of this study was to explore the relationship between global DNA methylation and OSCC progression and to evaluate the impact of DNA methylation heterogeneity on oral cancer cells. Methods: Immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to examine 5-methylcytosine (5-mC) expression in OSCC clinical specimens and oral cancer cells. The DNA methyltransferase inhibitor 5-Aza-dC was used to assess the effects of DNA methylation on cell function and gene expression. RNA sequencing was used to identify key differentially expressed genes affected by 5-Aza-dC treatment. Cell migration was assessed using a wound closure assay. Protein and gene expression were analyzed using Western blotting and quantitative PCR. Results: An inverse relationship was found between 5-mC levels and cancer differentiation—poorly differentiated OSCC exhibited higher 5-mC levels. Additionally, higher 5-mC staining was observed at the invasion front of oral cancer tissues. In OSCC cells, 5-mC content correlated with migration ability. Furthermore, conditioned medium from cancer-associated fibroblasts enhanced both methylation levels and migration of OSCC cells. Treatment with 5-Aza-dC significantly increased epithelial differentiation, reduced epithelial-to-mesenchymal transition and cell adhesion-related genes, and inhibited OSCC cell migration. Conclusions: The findings highlight the critical role of DNA hypermethylation in OSCC progression, particularly in regulating differentiation, migration, and EMT. The interplay between the tumor microenvironment and epigenetic modifications underscores the complexity of OSCC biology and opens avenues for innovative therapeutic strategies. Full article

Intercellular junctions are involved in the regulation of epithelial function and remodeling in the female reproductive system; however, their importance in the avian oviduct is poorly known. The aim of this study was: first, to provide information on the expression and localization of key tight (occludin, claudin 1, 4, 5, junctional adhesion molecule [JAM] 2, 3) and adherens (E-cadherin, β-catenin) junction proteins in the hen oviduct, and second, to compare expression and localization of these molecules between laying and subjected to fasting-induced pause in laying hens. Tissue samples from all oviductal segments, i.e., infundibulum, magnum, isthmus, shell gland, and vagina were collected on the sixth day of the experiment from the control hens and hens that had been fasted for five consecutive days. Specific oviductal part-dependent expression patterns of examined genes (by quantitative real-time polymerase chain reaction [qRT-PCR]) and/or proteins (by Western blotting) were found, with the highest mRNA transcript and protein abundances in the infundibulum, shell gland, and vagina, and the lowest in the magnum. Fasting-induced partial regression of the oviduct was accompanied by alterations in mRNA transcript and protein abundances of examined molecules. Reduced staining intensity of immunoreaction (analyzed by immunofluorescence) for occludin, E-cadherin, and β-catenin proteins was observed in the oviduct of non-laying hens. Our results indicate the potential involvement of these proteins in controlling intercellular communication, cell signaling, paracellular permeability, and mucosal barrier functionality, which impact the functioning of the hen oviduct. Furthermore, our observations provide novel insights into the molecular composition of tight and adherens junctions and its contribution to the remodeling of the oviduct during its regression induced by fasting. Full article

Over the past years, with the growing interest in sustainable biomaterials, marine collagen has been emerging as an interesting alternative to bovine collagen. It is more easily absorbed by the body and has higher bioavailability. In this study, collagen was extracted from Dicentrarchus labrax (sea bass) skin, a fishery by-product, thus valorizing waste streams while reducing environmental impact. To overcome the intrinsic weak mechanical of collagen, it was combined with chitosan to produce composite scaffolds for skin tissue engineering. The incorporation of collagen proved crucial for scaffold performance: (i) it promoted the formation of an open-pore architecture, favorable for cell infiltration and proliferation; (ii) it enhanced swelling behavior suitable for exudate absorption and maintenance of a moist wound environment; (iii) by tuning the chitosan/collagen ratio, it enabled us to control the degradation rate; (iv) it conferred antioxidant properties; and (iv) by adjusting collagen/chitosan concentrations, it allowed fine-tuning of mechanical properties, ensuring sufficient strength to resist stresses encountered during wound healing. In vitro assays demonstrated that the scaffolds were non-cytotoxic and effectively supported mouse adipose tissue fibroblasts’ adhesion and proliferation. Finally, all formulations exhibited marked bactericidal activity against the human pathogen Staphylococcus aureus and the methicillin-resistant Staphylococcus aureus, with a Log reduction greater than 3 (a reduction of at least 99.9% in bacterial growth) compared to the control. Collectively, these findings highlight collagen not only as a sustainable resource but also as a functional component that drives the structural, physicochemical, biological, and antimicrobial performance of chitosan/collagen scaffolds for skin tissue engineering. Full article

Background/Objectives: Polymeric barrier membranes (BMs) are usually used in guided bone regeneration to isolate the bone defect from the surrounding tissue, favoring bone apposition. This study proposes a third-generation BM made of polycaprolactone (PCL), loaded with different concentrations of nano-hidroxyapatite (nHAP) and gentamicin (GEN), and fabricated by electrospinning. Methods: The mechanical properties of the polymer, together with the fabrication procedure, offer porosity with interconnectivity to permit cell adhesion and proliferation. Bacterial contamination of the BM can induce infection at the bone level, leading to unfavorable clinical outcomes of the regeneration procedure. Results: Therefore, BMs have been proposed as carriers for local GEN antibiotic therapy, demonstrating antibacterial properties against S. aureus, S. mutans, and P. aeruginosa, depending on the drug concentration, while being negligibly affected by the nHAP content. X-ray diffraction, FTIR-ATR, and SEM allowed for BM structural characterization, demonstrating the presence of GEN/nHAP and establishing the fiber diameter, which influences the mechanical properties in dry and wet conditions and the drug release behaviorA BM cytotoxicity assessment, performed over 1 and 5 days, revealed that a high nHAP concentration provided protection against cytotoxicity, in contrast to GEN, and that cell proliferation and cell adhesion increased in the presence of nHAP. The BM’s bioactivity was demonstrated by mineralization after 21 days in simulated body fluid in an SEM/EDX analysis. Conclusions: The electrospun 15 wt.% nHAP and 2 wt.% GEN-loaded third-generation BM could be a promising alternative for guided bone regeneration. Full article

Hydrogels have emerged as promising biomaterials for oral tissue regeneration thanks to their high-water content, excellent biocompatibility, and ability to mimic native tissue environments. These versatile materials can be tailored to support cell adhesion, proliferation, and differentiation, making them suitable for repairing both soft and hard oral tissues. When engineered from natural polymers and enriched with bioactive agents, hydrogels offer enhanced regenerative potential. Biopolymer-based hydrogels, derived from materials such as chitosan, alginate, collagen, hyaluronic acid, and gelatin, are particularly attractive due to their biodegradability, bioactivity, and structural similarity to the extracellular matrix, creating an optimal microenvironment for cell growth and tissue remodeling. Recent innovations have transformed these systems into multifunctional platforms capable of supporting targeted regeneration of periodontal tissues, alveolar bone, oral mucosa, dental pulp, and dentin. Integration of bioactive molecules, particularly essential oils, bio-derived constituents, cells, or growth factors, has introduced intrinsic antimicrobial, anti-inflammatory, and antioxidant functionalities, addressing the dual challenge of promoting tissue regeneration while at the same time attenuating microbial contamination in the oral environment. This review explores the design strategies, material selection, functional properties, and biomedical applications in periodontal therapy, guided tissue regeneration, and implant integration of natural polymer-based hydrogels enriched with bioactive factors, highlighting their role in promoting oral tissue regeneration. In addition, we discuss current challenges related to mechanical stability, degradation rates, and clinical translation, while highlighting future directions for optimizing these next-generation bioactive hydrogel systems in regenerative dentistry. Full article

Collagen, which has osteoconductive potential, has been widely used as a scaffold material for bone repair and regeneration for more than the last three decades. Recently, collagen has been combined with other materials to produce collagen-based bone grafting materials with enhanced bone repair and regeneration capacities. However, varied results have been obtained with collagen-based grafting materials. Methods: To elucidate the mechanisms underlying the enhanced bone engineering capacity of these materials, we critically reviewed the current literature on the complex hierarchical structure and properties of native collagen molecules. Results: This review highlights the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, particularly those related to bone repair and regeneration. Conclusions: This article sheds light on the interactions between collagen and cell receptor molecules to mediate biological pathways. In addition, this article clarifies the mechanisms of cell adhesion-mediated bone regeneration. The findings may guide future research on collagen-based biomaterials. Full article

The use of advanced wound dressings can significantly support the skin healing process by maintaining optimal conditions for tissue regeneration. In this study, foam-like dressings composed of agarose and chitosan, enriched with vitamin C, were developed using a simple and cost-effective freeze-drying method. Three types of chitosan with varying molecular weights (low, medium, high) were used to investigate their impact on the biological, physicochemical, and mechanical properties of the resulting foams. All fabricated biomaterials were biocompatible, non-toxic, and did not promote cell adhesion to their surfaces. The foams exhibited highly porous, hydrophilic microstructures with excellent fluid absorption capacity (~20 mL/g) and sustained vitamin C release over the first 24 h. Chitosan molecular weight had no significant effect on biological properties, but influenced samples’ wettability and mechanical parameters. The hydrophilic character of samples was observed in all tested biomaterials, with the strongest enhancement of hydrophilicity noted for the low molecular weight variant. The highest tensile strength was observed in samples prepared with medium molecular weight chitosan. The results indicate that among the analyzed variants, agarose-chitosan foam biomaterials containing medium molecular weight chitosan exhibited the most favorable properties, making them the most promising candidates for the treatment of wounds with excessive exudate. Full article

Wound healing is a complex, multifaceted biological process that plays a vital role in recovery and overall quality of life. However, conventional wound care methods often prove insufficient, resulting in delayed healing, higher infection risk, and other complications. In response, biomaterials—especially hydrogels—have gained attention for their advanced wound management capabilities, which support wound healing by maintaining moisture, mimicking the extracellular matrix (ECM), and enabling targeted drug delivery triggered by wound-specific signals. They frequently carry antimicrobial or anti-inflammatory agents, promote blood vessel and nerve regeneration, and are biocompatible with customizable properties suited to different healing stages. Natural hydrogels, derived from polysaccharides, proteins, and peptides, offer several advantages over synthetic options, including inherent bioactivity, enzymatic degradability, and cell-adhesive qualities that closely resemble the native ECM. These features facilitate cell interaction, modulate inflammation, and speed up tissue remodeling. Moreover, natural hydrogels can be engineered as delivery systems for therapeutic agents like antimicrobial compounds, nanoparticles, growth factors, and exosomes. This review discusses recent advances in the use of natural hydrogels as multifunctional wound dressings and delivery platforms, with a focus on their composition, mechanisms of action, and potential for treating chronic and infected wounds by incorporating antimicrobial and regenerative additives such as silver and zinc oxide nanoparticles. Full article

Peripheral artery disease is a common manifestation of atherosclerosis, characterized by insufficient tissue perfusion and chronic ischemia. Arteriogenesis and angiogenesis are essential endogenous mechanisms to restore blood flow and limit ischemic injury. The metalloprotease ADAMTS13, known for cleaving ultra-large von Willebrand factor, has been implicated in thrombotic and inflammatory regulation. However, its role in ischemic vascular remodeling remains unclear. Using a murine hind limb ischemia model, we investigated the effect of ADAMTS13 deficiency on arteriogenesis and angiogenesis by comparing male ADAMTS13^−/− and wild-type control mice. Perfusion recovery, vascular cell proliferation, immune cell infiltration, and thrombotic activity were evaluated using laser Doppler measurements, immunohistochemical analysis of adductor and gastrocnemius muscle tissues, and in vivo microscopy. ADAMTS13 deficiency did not impair perfusion recovery, collateral artery growth, or capillarization. While platelet adhesion was slightly increased in ADAMTS13^−/− mice, no thrombotic occlusions were observed. Inflammatory responses, including macrophage and neutrophil infiltration as well as macrophage polarization, were largely unaffected. Despite previous in vitro evidence indicating an angiogenic role for ADAMTS13, its absence did not compromise angiogenesis in vivo. Our findings suggest that ADAMTS13 does not play a critical role in ischemia-related angiogenesis and arteriogenesis under sterile conditions and may be relevant only in contexts involving acute and sufficiently strong thromboinflammatory stimuli. Full article

Bovine anaplasmosis is a serious health problem in the livestock industry. Currently, there is a lack of information regarding the molecular mechanisms by which Anaplasma marginale adheres and invades bovine erythrocytes. Even more is unknown about how it binds to tick gut cells when the tick feeds on infected blood. In other pathogens, enolase has been shown to play a significant role in adhesion to host tissue, serving as the first step in invasion and colonization. Therefore, the elucidation of the role of the moonlighting protein enolase AmEno15 of A. marginale in the adhesion to erythrocytes, tick gut tissue, and plasminogen is addressed in this work. We explored the role of A. marginale recombinant AmEno15 in the adhesion to spectrin, stomatin, fibronectin, and plasminogen. Firstly, we modeled AmEno15 tridimensionally and performed a molecular dynamics approach to determine whether AmEno15 could bind to the proteins mentioned above. Then, we expressed recombinant AmEno15 and performed a microplate binding assay using fixed concentrations of the erythrocyte proteins, fibronectin, and plasminogen, as well as variable concentrations of AmEno15. We found that AmEno15 binds to all assessed proteins in a specific and concentration-dependent manner. Spectrin and fibronectin-AmEno15 binding occurs at high concentrations, while stomatin and plasminogen-AmEno15 binding occurs at lower concentrations. Our findings bring us closer to understanding the role of the moonlighting protein enolase and suggest its participation in the A. marginale adhesion and invasion processes, providing a basis for the control of tick-borne diseases. Full article