Search Results (916)

Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article

Background and Objectives: Posterior chamber phakic implantable contact lenses (Phakic-ICL) are widely used for refractive correction due to their efficacy and safety, including minimal corneal endothelial cell loss. The Collamer-based EVO+ Visian implantable contact lens (ICL), manufactured from Collamer, which is a blend of collagen and hydroxyethyl methacrylate (HEMA), has demonstrated excellent long-term biocompatibility and optical clarity. Recently, hydrophilic acrylic Phakic-ICLs, such as the Implantable Phakic Contact Lens (IPCL), have been introduced. This study investigated the material differences among Phakic-ICLs and their interaction with fibronectin (FN), which has been reported to adhere to intraocular lens (IOL) surfaces following implantation. The aim was to compare Collamer, IPCL, and LENTIS lenses (used as control) in terms of FN distribution and cell adhesion using a small number of explanted Phakic-ICLs. Materials and Methods: Three lens types were analyzed: a Collamer Phakic-ICL (EVO+ Visian ICL), a hydrophilic acrylic IPCL, and a hydrophilic acrylic phakic-IOL (LENTIS). FN distribution and cell adhesion were evaluated across different regions of each lens. An in vitro FN-coating experiment was conducted to assess its effect on cell adhesion. Results: All lenses demonstrated minimal FN deposition and cellular adhesion in the central optical zone. A thin FN film was observed on the haptics of Collamer lenses, while FN adhesion was weaker or absent on IPCL and LENTIS surfaces. Following FN coating, Collamer lenses supported more uniform FN film formation; however, this did not significantly enhance cell adhesion. Conclusions: Collamer, which contains collagen, promotes FN film formation. Although FN film formation was enhanced, the low cell-adhesive properties of HEMA resulted in minimal cell adhesion even with FN presence. This characteristic may contribute to the long-term transparency and biocompatibility observed clinically. In contrast, hydrophilic acrylic materials used in IPCL and LENTIS demonstrated limited FN interaction. These material differences may influence extracellular matrix protein deposition and biocompatibility in clinical settings, warranting further investigation. Full article

Hyaluronic acid (HA) is a key extracellular matrix component of vertebrates, where it mediates cell adhesion, immune regulation, and tissue remodeling through its interaction with specific receptors. Although HA has been detected in a few invertebrate species, the lack of fundamental components of the molecular HA pathway poses relevant objections about its functional role in these species. Mining genomic and transcriptomic data, we considered the conservation of the gene locus encoding for the extracellular link protein (XLINK) in marine mussels as well as its expression patterns. Structural and phylogenetic analyses were undertaken to evaluate possible similarities with vertebrate orthologs and to infer the origin of this gene in invertebrates. Biochemical analysis was used to quantify HA in tissues of Mytilus galloprovincialis. As a result, we confirm that the mussel can produce HA (up to 1.02 ng/mg in mantle) and that its genome encodes two XLINK gene loci. These loci are conserved in Mytilidae species and show a complex evolutionary path. Mussel XLINK genes appeared to be expressed during developmental stages in three mussel species, ranking in the top 100 expressed genes in M. trossulus at 17 h post-fertilization. In conclusion, the presence of HA and an active gene with the potential to bind HA suggests that mussels have the potential to synthesize and use HA and are among the few invertebrates encoding this gene. Full article

Tissue remodeling of human endometrium occurs during the menstrual cycle to prepare for embryo adhesion and invasion. The ovarian steroid hormones 17β-estradiol and progesterone control the menstrual cycle to achieve the receptive state during the “window of implantation” (WOI). Here, we focus on the human endometrial epithelium and its changes in polarity, adhesion, cytoskeletal organization and the underlying extracellular matrix enabling embryo implantation. The adhesion and invasion of the trophoblast via the apical plasma membrane of epithelial cells is a unique cell biological process, which is coupled to partial epithelial–mesenchymal transition (EMT). Given the fundamental species differences during implantation, we restrict the review mainly to the human situation and focus on cell culture systems to study the interaction between human trophoblast and endometrial cells. We summarize current knowledge based on the relatively scarce in vivo data and the steadily growing in vitro observations using various cell culture systems. Full article

Cell adhesion molecules (CAMs) are cell-surface-localized proteins mediating interactions of cells with other cells and the extracellular matrix. CAMs influence cell behavior and survival by inducing various intracellular signaling cascades that regulate diverse cellular processes including cytoskeleton remodeling and gene expression. Here, we review the evidence demonstrating that the levels, subcellular distribution, and binding affinities of CAMs of several major families including integrins, cadherins, immunoglobulin superfamily, and selectins are regulated by intracellularly generated or extracellular reactive oxygen species (ROS). Remarkably, CAMs themselves induce ROS production in response to binding to their ligands by activating lipoxygenases or NADPH oxidases or influencing ROS generation in mitochondria. CAM-dependent ROS production is essential for CAM-mediated cell adhesion and CAM-dependent intracellular signaling. Importantly, CAMs also protect cells from the ROS-induced cell death by stimulating the synthesis of antioxidants and suppressing the cell death signaling. A better understanding of the role ROS play in controlling CAM functions and mechanisms of this control may pave the way to modulating the functions of CAMs in various disorders associated with abnormal cell adhesion. Full article

Extracellular polymeric substances (EPS) are multifunctional biopolymers that have significant biotechnological potential. In this study, forty-seven strains of Rhodococcus actinomycetes were screened for EPS production and the content of its main components: carbohydrates, lipids, proteins, and nucleic acids. The Rhodococcus strains produced lipid-rich EPS (15.6 mg·L⁻¹ to 71.7 mg·L⁻¹) with carbohydrate concentrations varying from 0.6 mg·L⁻¹ to 58.2 mg·L⁻¹ and low amounts of proteins and nucleic acids. Biofilms of R. ruber IEGM 231 were grown on nitrocellulose filters in the presence of n-hexane, n-hexadecane, or diesel fuel. The distribution of β-polysaccharides, glycoconjugates, and proteins between cells and the extracellular matrix was examined using fluorescence microscopy. The observed release of β-polysaccharides into the biofilm matrix in the presence of n-hexane and diesel fuel was regarded as an adaptation to the assimilation of these toxic hydrocarbons by Rhodococcus cells. Atomic force microscopy of the dried EPS film revealed adhesion forces between 1.0 and 20.0 nN, while some sites were highly adhesive (F_a ≥ 20.0 nN). EPS biosynthetic genes were identified, with two glycosyltransferases correlating with an increase in carbohydrate production. The production of EPS by Rhodococcus cells exhibited strain-specific rather than species-specific patterns, reflecting a high genetic diversity of these bacteria. Full article

The intervertebral disc, an anatomical compartment interposed between vertebral bodies, plays a key role in spine flexibility and compression loading. It comprises three tissues: the nucleus pulposus, the annulus fibrosus, and the end plates. Degeneration-related changes in the extracellular matrix of the nucleus pulposus upon ageing or pathological conditions prompted the present investigation into the impact of proteoglycan reduction, the main constituent of the healthy nucleus pulposus, on its physicochemical properties and cellular phenotypical changes. To mimic the native extracellular matrix, three-dimensional NP-mimicking constructs were developed using a biomimetic hydrogel composed of collagen type I, collagen type II, and proteoglycans. This system was fabricated using a bottom-up approach, employing highly pure monomeric collagen types I and II, which were induced to form a reconstituted fibrillar structure closely resembling the natural NP microenvironment. A comprehensive physicochemical characterization was conducted at varying proteoglycan percentages using scanning electron microscopy (SEM), FTIR, rheological tests, and water retention property analysis. The effect of microenvironment changes on the phenotype of nucleus pulposus cells was studied by their encapsulation within the various collagen–proteoglycan hydrogels. The morphological and immunochemistry analysis of the cells was performed to study the cell–matrix adhesion pathways and the expression of the cellular regulator hypoxia-inducible factor 1 alpha. These were linked to the analysis of the synthesis of healthy or pathological extracellular matrix components. The findings reveal that the reduction in proteoglycan content in the nucleus pulposus tissue triggers a pathological pathway, impairing the rheological and water retention properties. Consequently, the cell phenotypes are altered, inducing the synthesis of collagen type I rather than securing the natural physiological remodelling process by the synthesis of collagen type II and proteoglycans. Identifying the proteoglycan content threshold that triggers these pathological phenotypical changes could provide new diagnostic markers and early therapeutic strategies for intervertebral disc degeneration. Full article

Background/Objectives: Osteopontin (OPN) is a 34 kDa protein that is extensively phosphorylated and rich in aspartic acid, produced by a single-copy gene, and altered by post-translational processes. In several diseases, OPN has been discovered to play a direct role in immunological and inflammatory responses. It is also important in kidney stone disease, preeclampsia, cardiovascular disease, endometriosis, and cancer, among other pathological conditions. It is a crucial extracellular matrix molecule involved in oncology, due to its ability to bridge the gap between inflammation and carcinogenesis. Methods: Our systematic review has as PICO “Does Osteopontin have possible etiological and prognostic correlations in patients affected by endometrial carcinoma?” Based on online data collected from PubMed, Scholar, Embase, Scopus, and other sources, a preliminary analysis was conducted. A keyword search for “Osteopontin” AND “tumors”, “endometrial cancer”, and other related terms was used to identify the publications. The relevance of scientific research was used to select articles in English. Results: For our systematic review, the citation search yielded nine articles on the topic. At the endometrial level, OPN plays a role in a variety of biological processes, including angiogenesis, metastasis, altered tissue remodeling, immunological responses, cell adhesion, and migration. Conclusions: With established direct correlations and a potential role in the assessment of the diagnosis and prognosis of the disease, OPN participates in endometrial cancer, drawing more and more attention from researchers. Full article

Glaucoma is a leading cause of irreversible blindness, normally associated with dysfunction and degeneration of the trabecular meshwork (TM) as the primary cause. Trabecular meshwork stem cells (TMSCs) have emerged as promising candidates for TM regeneration toward glaucoma therapies, yet their molecular characteristics remain poorly defined. In this study, we performed a comprehensive transcriptomic comparison of human TMSCs and human TM cells (TMCs) using RNA sequencing and microarray analyses, followed by qPCR validation. A total of 465 differentially expressed genes were identified, with 254 upregulated in TMSCs and 211 in TMCs. A functional enrichment analysis revealed that TMSCs are associated with development, immune signaling, and extracellular matrix remodeling pathways, while TMCs are enriched in structural, contractile, and adhesion-related functions. A network topology analysis identified CXCL3, CXCL6, and BMP2 as robust TMSC-specific hub genes, and LMOD1 and BGN as TMC-specific markers, with expression patterns confirmed by qPCR. These findings define distinct molecular signatures of TMSCs and TMCs, providing reliable biomarkers for cell identity and a foundation for future stem cell-based therapies targeting TM dysfunction in glaucoma. Full article

The aim of this in vitro study is to investigate the adhesion, proliferation, and differentiation of human adipose-derived mesenchymal stem cells (hASC) on Trabecular Titanium scaffolds manufactured with different manufacturing processes (EBM and SLM). The in vitro adhesion and proliferation of hASC on titanium scaffolds with WST assays have been carried out. The comparison of the gene expression profiles of typical bone genes (Alp, Bglap, Col1a1, and Osx) through real-time PCR assays and the evaluation of extracellular matrix composition with immunofluorescence and SEM analysis have been performed. In addition, the possible osteoinductive properties of the two scaffolds have been investigated through real-time PCR and ALP assays. Data showed that Trabecular Titanium supports human adipose-derived mesenchymal stem cell colonization and induces differentiation in bone with the deposition of the abundant extracellular mineralized matrix regardless of the manufacturing process, proving that the micro- and macro-design features are the key factors responsible for the osteoinduction behavior. These features can only be achieved through tailored 3D printing process parameters. Full article

Chronic diabetic wounds affect 15–20% of patients and are characterized by impaired healing due to disrupted hemostasis, inflammation, proliferation, and extracellular matrix (ECM) remodeling. Low-level light therapy (LLLT) has emerged as a promising noninvasive strategy for enhancing tissue regeneration. Here, we developed a multispectral pulsed LED system combining red and near-infrared light to stimulate wound healing. In vitro photostimulation of human keratinocytes and fibroblasts on biomimetic hydrogels enhanced adhesion, spreading, migration, and proliferation via increased focal adhesion kinase (pFAK), paxillin, and F-actin expression. In vivo, daily LED treatment of streptozotocin-induced diabetic wounds accelerated closure and improved ECM remodeling. Histological and molecular analyses revealed elevated levels of MMPs, interleukins, collagen, fibronectin, FGF2, and TGF-β1, supporting regenerative healing without excessive fibrosis. These findings demonstrate that multispectral pulsed photobiomodulation enhances diabetic wound healing through focal adhesion-mediated cell migration and ECM remodeling, offering a cost-effective and clinically translatable approach for chronic wound therapy. Full article

Three-dimensional (3D) in vitro adipocyte models provide physiologically relevant platforms for studying adipogenesis and obesity-related metabolic dysfunction. However, long-term adipocyte culture is often hindered by limited cell–matrix adhesion and spheroid detachment. Previously, we demonstrated that elastin-like polypeptide (ELP)–polyethyleneimine (PEI) coatings functionalized with a trivalent RGD motif enhanced spheroid retention during frequent media changes. The present study investigates the long-term functional consequences of RGD incorporation over a 28-day culture period. 3T3-L1 preadipocytes were seeded, differentiated, and matured on ELP-PEI or ELP-(RGD)₃-PEI coatings. Spheroid morphology, triglyceride content, expression of PPAR-γ, adiponectin, HIF-1α genes, and insulin-stimulated glucose uptake were assessed. Both coatings supported initial spheroid formation, but only ELP-PEI maintained the 3D architecture and supported adipogenic maturation and insulin responsiveness. ELP-(RGD)₃-PEI promoted early retention but led to spheroid disassembly by mid-culture; notably, by day 28, cells reaggregated into abnormally large spheroids with impaired metabolic function, likely due to continued proliferation. These findings highlight the critical role of extracellular matrix-mediated cell–cell versus cell–substrate interactions in maintaining 3D culture fidelity. While RGD enhances adhesion, it disrupts spheroid integrity and compromises adipogenic and metabolic maturation. Taken together, ELP-PEI coatings offer a more conducive microenvironment for long-term 3D adipocyte culture and hold promise for modeling obesity-associated metabolic dysfunction in vitro. Full article

Peripheral nerve injuries (PNIs) present a significant clinical challenge due to the inherently limited regenerative capacity of the adult nervous system. Conventional therapeutic strategies, such as nerve autografting and systemic pharmacological interventions, are often limited by donor site morbidity, restricted graft availability, and suboptimal drug bioavailability. In this context, gelatin-based hydrogels have emerged as a promising class of biomaterials due to their excellent biocompatibility, biodegradability, and structural similarity to the native extracellular matrix. These hydrogels could offer a highly tunable platform capable of supporting cellular adhesion, promoting axonal elongation, and enabling localized and sustained release of therapeutic agents. This narrative review synthesizes recent advances in the application of gelatin-based hydrogels for peripheral nerve regeneration, with a particular focus on their use as delivery vehicles for neurotrophic factors, stem cells, and pharmacologically active compounds. Additionally, this review provides a foundation for extending our ongoing preclinical study, evaluating the neuroregenerative effects of alpha-lipoic acid, B-complex vitamins, and a deproteinized hemoderivative in a murine PNI model. Although systemic administration has demonstrated promising neuroprotective effects, limitations related to local drug availability and off-target exposure highlight the need for site-specific delivery strategies. In this regard, gelatin hydrogels might represent an excellent candidate for localized, controlled drug delivery. The review concludes by discussing formulation techniques, manufacturing considerations, biological performance, and key translational and regulatory aspects. Full article

Zebrafish is a well-recognized model for studying human genetic disorders. Recently, we proposed the homozygous cdkl5^sa21938 mutant zebrafish as a model of CDKL5 deficiency disorder (CDD), a developmental epileptic encephalopathy with diverse symptoms. This study aimed to explore Cdkl5-associated molecular mechanisms in zebrafish and assess their similarity to those in mammals. We conducted RNA sequencing on whole cdkl5^−/− zebrafish and wild-type siblings at 5 and 35 days post-fertilization (dpf) to compare their gene expression profiles. Most significant differentially expressed genes (DEGs) were related to muscle, neuronal, and visual systems which are affected in CDD. Gene Ontology analysis revealed downregulated DEGs enriched in muscle development, extracellular matrix, and actin cytoskeleton functions at both stages, while upregulated DEGs were enriched in eye development functions at 35 dpf. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed enrichment of downregulated DEGs in focal adhesion and extracellular matrix (ECM)-receptor interaction pathways at both stages. Neuronal development DEGs were mainly downregulated at both stages, while synaptic signaling DEGs were upregulated at 35 dpf. Crossing cdkl5^−/− mutants with the Hb9:GFP transgenic line showed fewer motor neuron cells with shorter axons compared to the wild type, which may explain the impaired motor phenotype observed in zebrafish and CDD patients. Moreover, we identified key downregulated DEGs related to cartilage development at both stages and bone development at 35 dpf, potentially explaining the skeletal defects seen in zebrafish and CDD individuals. In conclusion, Cdkl5 loss in zebrafish leads to dysregulation of genes involved in CDKL5-associated functions in mammals, providing new insights into its less studied functions and phenotypes. Full article

Both biochemical cues and the electrophysiological microenvironment play a pivotal role in influencing cell behaviors. In this study, collagen/polypyrrole biomimetic electroactive composite coatings with a fiber network structure were constructed on the surface of titanium substrates by hot alkali treatment and stepwise electrochemical deposition. Materialistic characterization and electrochemical performance tests demonstrated that the titanium electrodes modified with collagen/polypyrrole composite coatings exhibited the surface morphology of a collagen film layer, and their electroactivity was significantly enhanced. Cellular experiments demonstrated that the collagen in the composite coatings could provide good biomimetic biochemical cues as a main extracellular matrix component, which have a substantial effect in promoting cell adhesion, proliferation, and osteogenic differentiation. Furthermore, under exogenous electrical signals, the polypyrrole coating has the capacity to facilitate an appropriate electrophysiological microenvironment, thereby promoting osteogenic differentiation. The collagen/polypyrrole composite coating exhibited a better effect in promoting osteogenic differentiation among all samples by simultaneously providing the appropriate biochemical cues and electrophysiological microenvironments. This work demonstrates the feasibility of synergistic pro-osteogenesis by biochemical cues and an electrophysiological microenvironment, which is instructive for the field of bone tissue engineering. Full article