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Materials engineered to elicit targeted cellular responses in regenerative medicine must display bioligands with precise spatial and temporal control. Although materials with temporally regulated presentation of bioadhesive ligands using external triggers, such as light and electric fields, have recently been realized for cells in culture, the impact of in vivo temporal ligand presentation on cell–material responses is unknown. Here, we present a general strategy to temporally and spatially control the in vivo presentation of bioligands using cell-adhesive peptides with a protecting group that can be easily removed via transdermal light exposure to render the peptide fully active. We demonstrate that non-invasive, transdermal time-regulated activation of cell-adhesive RGD peptide on implanted biomaterials regulates in vivo cell adhesion, inflammation, fibrous encapsulation, and vascularization of the material. This work shows that triggered in vivo presentation of bioligands can be harnessed to direct tissue reparative responses associated with implanted biomaterials. Transdermal light-triggered activation of cell-adhesive peptides on the surface of implanted hydrogels alters cell–material interactions, such as cell adhesion and spatial patterning, and fibrous encapsulation and vascularization of the material.

Two-dimensional (2D) molybdenum disulfide (MoS₂) nanomaterials are an emerging class of biomaterials that are photoresponsive at near-infrared wavelengths (NIR). Here, we demonstrate the ability of 2D MoS₂ to modulate cellular functions of human stem cells through photothermal mechanisms. The interaction of MoS₂ and NIR stimulation of MoS₂ with human stem cells is investigated using whole-transcriptome sequencing (RNA-seq). Global gene expression profile of stem cells reveals significant influence of MoS₂ and NIR stimulation of MoS₂ on integrins, cellular migration, and wound healing. The combination of MoS₂ and NIR light may provide new approaches to regulate and direct these cellular functions for the purposes of regenerative medicine as well as cancer therapy.

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS 2 ) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS 2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS 2 -PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS 2 -PEG nanoflakes under the irradiation. These results thus suggest that the MoS 2 -PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

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.

Cell morphology determines cell behavior, signal transduction, protein-protein interaction, and responsiveness to external stimuli. In cancer, these functions profoundly contribute to resistance mechanisms to radio- and chemotherapy. With regard to this aspect, this study compared the genome wide gene expression in exponentially growing cell lines from different tumor entities, lung carcinoma and squamous cell carcinoma, under more physiological three-dimensional (3D) versus monolayer cell culture conditions. Whole genome cDNA microarray analysis was accomplished using the Affymetrix HG U133 Plus 2.0 gene chip. Significance analysis of microarray (SAM) and t-test analysis revealed significant changes in gene expression profiles of 3D relative to 2D cell culture conditions. These changes affected the extracellular matrix and were mainly associated with biological processes like tissue development, cell adhesion, immune system and defense response in contrast to terms related to DNA repair, which lacked significant alterations. Selected genes were verified by semi-quantitative RT-PCR and Western blotting. Additionally, we show that 3D growth mediates a significant increase in tumor cell radio- and chemoresistance relative to 2D. Our findings show significant gene expression differences between 3D and 2D cell culture systems and indicate that cellular responsiveness to external stress such as ionizing radiation and chemotherapeutics is essentially influenced by differential expression of genes involved in the regulation of integrin signaling, cell shape and cell-cell contact.

Radiation resistance presents a significant challenge in the treatment of triple-negative breast cancer (TNBC). To investigate the molecular adaptations associated with radiation therapy resistance, MDA-MB-231 cells were subjected to a repeated radiation (RR) regimen totaling 57 Gy over 11 weeks, followed by clonal selection. The resulting radiation-adapted cells (MDA-MB-231RR) were analyzed using whole-transcriptome RNA sequencing, revealing substantial dysregulation of pathways related to cell adhesion, mitochondrial function, and epithelial–mesenchymal transition (EMT). These transcriptional changes were corroborated by functional assays. MDA-MB-231RR cells exhibited reduced expression of adhesion receptors (ITGB1, ITGA2, ITGA6) and extracellular matrix proteins (fibronectin, collagen, laminins), accompanied by significantly impaired cell adhesion to fibronectin, collagen, and laminin substrates. Mitochondrial dysfunction was supported by downregulation of oxidative phosphorylation genes (MTCO1, MTND1) and confirmed by JC-1 dye assays demonstrating a marked reduction in mitochondrial membrane potential. EMT-associated changes included increased mesenchymal markers and loss of epithelial markers (CTNNB1, SNAI2, CK19), consistent with enhanced migratory potential. Taken together, this study delineates key molecular features of radiation adaptation in TNBC, providing a foundation for the development of targeted therapies to overcome treatment resistance.

Low-intensity pulsed ultrasound (LIPUS) is a widely used non-invasive approach with therapeutic purposes since it provides physical stimulation with minimal thermal effects. The skin epithelium is the first barrier of the human body that interfaces with LIPUS and is subjected to the highest intensity. Little is known about the impact of LIPUS on the skin surface. This work investigates the biological effects of one-hour exposure to 1 MHz LIPUS on human keratinocytes HaCaT and tumoral SK-MEL-28 skin cells. Specifically, we evaluated the cellular state immediately after LIPUS treatment by analyzing cytogenetic endpoints and the response of cytoskeleton and cell junction proteins. Herein we demonstrate that LIPUS induces genomic damage as shown by an increase of chromosome malsegregation and a consequent decrease of cellular proliferation. The mechanical stimulus produced by LIPUS is also transmitted to the cytoskeletal compartment, inducing the expression and re-organization of junction proteins (i.e., E-cadherin and Desmosomes) and intermediate filaments (i.e., F-actin and Cytokeratins) with impact on cell morphology and cell adhesion. These in vitro results highlight the different outcomes following the cytogenetic damage and the resilience response exerted by the cytoskeleton upon mechanical stress, laying the foundation for future in vivo investigations.

The ubiquitous presence of solar UV radiation in human life is essential for vitamin D production but also leads to skin photoaging, damage, and malignancies. Photoaging and skin cancer have been extensively studied, but the effects of UV on the critical mechanical barrier function of the outermost layer of the epidermis, the stratum corneum (SC), are not understood. The SC is the first line of defense against environmental exposures like solar UV radiation, and its effects on UV targets within the SC and subsequent alterations in the mechanical properties and related barrier function are unclear. Alteration of the SC’s mechanical properties can lead to severe macroscopic skin damage such as chapping and cracking and associated inflammation, infection, scarring, and abnormal desquamation. Here, we show that UV exposure has dramatic effects on cell cohesion and mechanical integrity that are related to its effects on the SC’s intercellular components, including intercellular lipids and corneodesmosomes. We found that, although the keratin-controlled stiffness remained surprisingly constant with UV exposure, the intercellular strength, strain, and cohesion decreased markedly. We further show that solar UV radiation poses a double threat to skin by both increasing the biomechanical driving force for damage while simultaneously decreasing the skin’s natural ability to resist, compromising the critical barrier function of the skin.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of the cellular stress response, but the biological functions of the related Nrf3 protein are largely unknown. Here we demonstrate a novel pro-apoptotic function of Nrf3 in mouse and human keratinocytes. In response to UV irradiation, Nrf3-deficient keratinocytes were protected from apoptosis in vitro and in vivo. The protective function was also seen under oxidative or hyperosmotic stress conditions, but not when apoptosis was induced by disruption of cell–matrix interactions. Mechanistically, we show that Nrf3-deficient keratinocytes exhibit stronger cell–cell and cell-matrix adhesion, which correlates with higher cell surface integrin levels and enhanced activation of focal adhesion kinase. Nrf3-deficient cells also formed more and larger focal adhesions and exhibited a higher motility. These results suggest that the strong expression of Nrf3 in basal keratinocytes promotes their elimination in response to DNA damage-inducing agents, thereby preventing accumulation of mutated stem and transit amplifying cells in the epidermis.

Peri-implantitis is an unsolved but critical problem with dental implants. It is postulated that creating a seal of gingival soft tissue around the implant neck is key to preventing peri-implantitis. The objective of this study was to determine the effect of UV surface treatment of titanium disks on the adhesion strength and retention time of oral connective tissues as well as on the adherence of mucosal fibroblasts. Titanium disks with a smooth machined surface were prepared and treated with UV light for 15 min. Keratinized mucosal tissue sections (3 × 3 mm) from rat palates were incubated for 24 h on the titanium disks. The adhered tissue sections were then mechanically detached by agitating the culture dishes. The tissue sections remained adherent for significantly longer (15.5 h) on the UV-treated disks than on the untreated control disks (7.5 h). A total of 94% of the tissue sections were adherent for 5 h or longer on the UV-treated disks, whereas only 50% of the sections remained on the control disks for 5 h. The adhesion strength of the tissue sections to the titanium disks, as measured by tensile testing, was six times greater after UV treatment. In the culture studies, mucosal fibroblasts extracted from rat palates were attached to titanium disks by incubating for 24, 48, or 96 h. The number of attached cells was consistently 15–30% greater on the UV-treated disks than on the control disks. The cells were then subjected to mechanical or chemical (trypsinization) detachment. After mechanical detachment, the residual cell rates on the UV-treated surfaces after 24 and 48 h of incubation were 35% and 25% higher, respectively, than those on the control surfaces. The remaining rate after chemical detachment was 74% on the control surface and 88% on the UV-treated surface for the cells cultured for 48 h. These trends were also confirmed in mouse embryonic fibroblasts, with an intense expression of vinculin, a focal adhesion protein, on the UV-treated disks even after detachment. The UV-treated titanium was superhydrophilic, whereas the control titanium was hydrophobic. X-ray photoelectron spectroscopy (XPS) chemical analysis revealed that the amount of carbon at the surface was significantly reduced after UV treatment, while the amount of TiOH molecules was increased. These ex vivo and in vitro results indicate that the UV treatment of titanium increases the adhesion and retention of oral mucosa connective tissue as a result of increased resistance of constituent fibroblasts against exogenous detachment, both mechanically and chemically, as well as UV-induced physicochemical changes of the titanium surface.