Matrix Formation Research Articles

Research progress on the role of adipocyte exosomes in cancer progression.

Exosomes, minute vesicles ubiquitously released by diverse cell types, serve as critical mediators in intercellular communication. Their pathophysiological relevance, especially in malignancies, has garnered significant attention. A meticulous exploration of the exosomal impact on cancer development has unveiled avenues for innovative and clinically valuable techniques. The cargo conveyed by exosomes exerts transformative effects on both local and distant microenvironments, thereby influencing a broad spectrum of biological responses in recipient cells. These membrane-bound extracellular vesicles (EVs) play a pivotal role in delivering bioactive molecules among cells and organs. Cellular and biological processes in recipient cells, ranging from stromal cell reprogramming to immunological responses, extracellular matrix formation, and modulation of cancer cell activation, expansion, and metastasis, are subject to exosome-mediated cell-to-cell communication. Moreover, exosomes have been implicated in endowing cancer cells with resistance to treatment. Extensive research has explored the potential of exosomes as therapeutic targets and diagnostic indicators. This comprehensive review seeks to provide an in-depth understanding of the pivotal components and roles of exosomes in tumorigenesis, growth, progression, and therapeutic responses. The insights into the multifaceted involvement of exosomes in malignant cancers are essential for the scientific community, fostering the development of novel therapeutic and diagnostic strategies in the relentless pursuit of cancer.

Proteolytic profiles of two isoforms of human AMBN expressed in E. coli by MMP-20 and KLK-4 proteases

Ameloblastin is a protein in biomineralization of tooth enamel. However recent results indicate that this is probably not its only role in an organism. Enamel matrix formation represents a complex process enabled via specific crosslinking of two proteins – the most abundant amelogenin and the ameloblastin (AMBN). The human AMBN (hAMBN) gene possesses 13 protein coding exons with alternatively spliced transcripts and the longest isoform about 447 amino acid residues. It has been described that AMBN molecules in vitro assemble into oligomers via a sequence encoded by exon 5. Enamel is formed by the processing of enamel proteins by two specific proteases - enamelysin (MMP-20) and kallikrein 4 (KLK-4). The scaffold made of AMEL and non-amelogenin proteins is cleaved and removed from the developed tooth enamel. The hAMBN is expressed in two isoforms (ISO I and II), which could lead to their different utilization determined by distinct proteolytic profiles. In this study, we compared proteolytic profiles of both isoforms of hAMBN expressed in E. coli after proteolysis by MMP-20, KLK-4, and their 1:2 mixture. Proteolysis products were analysed and cleavage sites were identified by mass spectrometry. The proteolytic profiles of two AMBN isoforms showed different results, although we have to determine that the analysed AMBN was not post-translationally modified as expressed in prokaryotic cells. These results may lead to the suggestion of potentially divergent roles of AMBN isoforms cleavage products in various cell signalling pathways such as calcium buffering or signalling cascades.

Harnessing 3D printed highly porous Ti-6Al-4V scaffolds coated with graphene oxide to promote osteogenesis.

Bone tissue engineering (BTE) strategies have been developed to address challenges in orthopedic and dental therapy by expediting osseointegration and new bone formation. In this study, we developed irregular porous Ti-6Al-4V scaffolds coated with reduced graphene oxide (rGO), specifically rGO-pTi, and investigated their ability to stimulate osseointegration in vivo. The rGO-pTi scaffolds exhibited unique irregular micropores and high hydrophilicity, facilitating protein adsorption and cell growth. In vitro assays revealed that the rGO-pTi scaffolds increased alkaline phosphatase (ALP) activity, mineralization nodule formation, and osteogenic gene upregulation in MC3T3-E1 preosteoblasts. Moreover, in vivo transplantation of rGO-pTi scaffolds in rabbit calvarial bone defects showed improved bone matrix formation and osseointegration without hemorrhage. These findings highlight the potential of combining rGO with irregular micropores as a promising BTE scaffold for bone regeneration.

A new procedure to induce aortic aneurysms in mice.

Aortic aneurysms (AAs) are a major public health challenge, featured by a progressive impairs in aortic wall integrity that drives to aortic dilation and, in end stage, to its rupture. Despite important advances in the surgical treatment of aortic aneurysms, there is currently no pharmacological intervention that prevents their development, reduces their expansion, or avoids their rupture. In addition to classic risk factors such age or gender, several heritable connective tissue disorders have been associated with AA developing, highlighting the role of extracellular matrix (ECM) genes alterations in the developing of AA. In this sense, we have recently demonstrated that global deletion of the cellular communicating network factor 2 (CCN2), previously known as connective tissue growth factor (CTGF) due to its role in the extracellular matrix formation, predisposes to early and lethal AAs development after Angiotensin II (Ang II) infusion in mice. Here, we detail the protocol to induce and detect AAs generation in inducible global CCN2 knockout mice after Ang II infusion which allow the characterization of CCN role in AA development and may help to the development of pharmacological target for AA treatment.

Минеральная плотность костной ткани у молодых пациентов с воспалительными заболеваниями кишечника

Inflammatory bowel diseases (IBD) are characterized by the development of various systemic manifestations. One of the significant extraintestinal manifestations of IBD is a decrease in mineral density (BMD) (demineralization) of bone tissue and osteoporosis (OP). The pathogenesis of decreased BMD is multifactorial: the activity of immune inflammation of the gastrointestinal mucosa, medication intake, malnutrition (low calcium intake), decreased muscle and fat mass, vitamin D deficiency, as well as other factors contribute to the development of osteoporosis in such patients. Despite various studies examining the prevalence of decreased BMD in patients with IBD, data vary widely, ranging from 17 to 77%. The purpose is to evaluate BMD, levels of bone resorption markers in young patients with IBD, and to evaluate the relationship between BMD and osteosynthesis markers. Materials and methods. 62 patients with a verified diagnosis of IBD were examined: 30 patients had Crohn’s disease (CD), 32 patients had ulcerative colitis (UC). All patients underwent a general clinical examination, a double-absorption X-ray densitometric study with determination of BMD and bone mineral content (BMC), as well as determination of bone resorption parameters — osteocalcin, Beta-Crosslaps (C-terminal telopeptides of type I collagen) and marker determination formation of bone matrix P1NP. The level of the mineral part of bone mass was measured using the bioimpedance method on the ABC-02 «MEDASS» apparatus. Results: Seven patients with IBD (11%) had low BMD for chronological age. The median values of BMD, osteocalcin, Beta-Crosslaps, and bone matrix formation marker P1NP in the general group of patients with IBD, as well as in the subgroups of patients with CD and UC are presented. A clinical example is presented. Conclusion. Diagnosis of osteoporosis in patients with IBD is difficult for several reasons. It is important to assess the presence of risk factors in conjunction with laboratory and instrumental examinations.

Platelet-Rich Plasma (PRP) in Dermatology: Cellular and Molecular Mechanisms of Action.

Platelet-rich plasma (PRP) therapy has gained attention in the scientific field due to its potential regenerative effects and great benefit-risk ratio. This review extensively explores the most studied mechanisms of this therapy according to the etiopathogenesis of skin diseases: cellular proliferation, matrix formation, regulation of inflammation, angiogenesis, collagen synthesis, and the remodeling of new tissue. Moreover, it draws on newly reported and lesser-known effects of PRP: its anti-apoptotic effects, immunological suppression, decrease in melanin synthesis, anti-microbial effects, overexpression of miR-155, antioxidant effects, and their involved pathways. This work aims to provide a complete update for understanding PRP's benefits and clinical relevance in wound healing, alopecia, pigmentary disorders, scars, rejuvenation, lichen sclerosus, and other inflammatory dermatoses, based on the current evidence. Furthermore, recent reports with novel indications for PRP therapy are highlighted, and new potential pathways correlated with the pathogenesis of skin diseases are explored.

Generation of porcine endometrial organoids and their use as a model for enhancing embryonic attachment and elongation.

Porcine endometrial organoids (EOs) were isolated and characterized, revealing distinctive features such as unique extracellular matrix formation, fusion into uterine bud-like structures, and facilitation of embryo elongation. The yield of EOs was significantly enhanced by cryopreservation medium supplemented with the rock inhibitor (Y-27632), resulting in reduced expression of apoptotic mRNAs and microRNAs. Endometrial organoids (EOs) are acceptable models for understanding maternal-embryonic cross talk. This study was conducted to generate EOs and optimize their cryopreservation and provide coculture modeling with embryos. The endometrial tissues were used for culturing the organoids inside domes of Matrigel®. To improve the long-term storage of EOs, 10 µM ROCK inhibitor (RI) was added to the cryopreservation medium. Day 7 parthenogenetically activated embryos were cocultured with EOs or EO outgrowths, and embryonic cell numbers and embryo attachment were monitored. Spherical EOs 100-300 µm in size can be retrieved on day 7 of culture, and larger EOs, approximately 1.5 mm in diameter, can be maintained in the Matrigel® dome for 21 days. The nuclear expression of Ki67 indicates that more than 80% of EOs nuclei were proliferative. EOs exhibit unique novel characters such as formation of extracellular matrix and ability for fusion. RI increased the yield and quality of organoids after freezing or thawing. The cell number of cocultured embryos increased five-fold, and the proportion of trophoblast outgrowths increased seven-fold compared with those of control embryos. The embryos cultured with EO-conditioned medium showed a better attachment rate than the other models, and - for the first time - we report embryonic elongation. Immunofluorescence staining of the attached embryos showed CDX2 in the periphery of EOs outgrowths. The 3D assembly and cryopreservation of EOs was optimized, and EO coculture supported embryo attachment, trophoblast outgrowth, and elongation, which would provide a valuable tool for studying the intricate processes involved in porcine embryo implantation.

Osteoinductive activity of photobiomodulation in an organotypic bone model

Photobiomodulation (PBM) is a technique that harnesses non-ionizing light at specific wavelengths, triggering the modulation of metabolic pathways, engendering favourable biological outcomes that reduce inflammation and foster enhanced tissue healing and regeneration. PBM holds significant promise for bone tissue applications due to its non-invasive nature and ability to stimulate cellular activity and vascularization within the healing framework. Notwithstanding, the impact of PBM on bone functionality remains largely undisclosed, particularly in the absence of influencing factors such as pathologies or regenerative therapies. This study aims to investigate the potential effects of PBM using red (660 nm) (RED) and near-infrared (808 nm) (NIR) wavelengths within an ex vivo bone culture system - the organotypic embryonic chicken femur model. A continuous irradiation mode was used, administering a total energy dose of 1.0 J, at an intensity of 100 mW for 10 s, which was repeated four times over the course of the 11-day culture period. The primary focus is on characterizing the expression of pivotal osteoblastic genes, the maturation and deposition of collagen, and the formation of bone mineral. Exposing femora to both RED and NIR wavelengths led to a notable increase in the expression of osteochondrogenic transcription factors (i.e., SOX9 and RUNX2), correlating with enhanced mineralization. Notably, NIR irradiation further elevated the expression of bone matrix-related genes and fostered enhanced deposition and maturation of fibrillar collagen. This study demonstrates that PBM has the potential to enhance osteogenic functionality within a translational organotypic bone culture system, with the NIR wavelength showing remarkable capabilities in augmenting the formation and maturation of the collagenous matrix.

Transcription of biochemical defenses by the harmful brown tide pelagophyte, Aureococcus anophagefferens, in response to the protozoan grazer, Oxyrrhis marina.

Aureococcus anophagefferens is a small marine pelagophyte that forms recurrent harmful brown tides blooms with adverse ecological and economic impacts. During blooms, A. anophagefferens experiences lower zooplankton grazing mortality than other phytoplankton potentially due to the synthesis of anti-predator compounds including extracellular polysaccharides. This study characterized the transcriptomic response of A. anophagefferens when exposed to the protozooplankton, Oxyrrhis marina, and assessed whether this response involved chemical cues. Transcriptomes were generated from A. anophagefferens populations grown at high (1×106 cells mL-1) and low (5×105 cells mL-1) cell densities incubated directly with O. marina or receiving only filtrate from co-cultures of A. anophagefferens and O. marina to evaluate the role of chemical cues. There were a greater number of genes differentially expressed in response to grazing in the lower concentration of A. anophagefferens compared to the high concentration treatment and in response to direct grazing compared to filtrate. KEGG pathway analysis revealed that direct grazer exposure led to a significant increase in transcripts of genes encoding secondary metabolite production (p < 0.001). There was broad transcriptional evidence indicating the induction of biosynthetic pathways for polyketides and sterols in response to zooplankton grazers, compounds associated with damage to marine organisms. In addition, exposure to O. marina elicited changes in the abundance of transcripts associated with carbohydrate metabolism that could support the formation of an extracellular polysaccharide matrix including genes related to glycoprotein synthesis and carbohydrate transport. Collectively, these findings support the hypothesis that A. anophagefferens can induce biochemical pathways that reduce grazing mortality and support blooms.

Micro- and nanostructure specific X-ray tomography reveals less matrix formation and altered collagen organization following reduced loading during Achilles tendon healing

Recovery of the collagen structure following Achilles tendon rupture is poor, resulting in a high risk for re-ruptures. The loading environment during healing affects the mechanical properties of the tendon, but the relation between loading regime and healing outcome remains unclear. This is partially due to our limited understanding regarding the effects of loading on the micro- and nanostructure of the healing tissue. We addressed this through a combination of synchrotron phase-contrast X-ray microtomography and small-angle X-ray scattering tensor tomography (SASTT) to visualize the 3D organization of microscale fibers and nanoscale fibrils, respectively. The effect of in vivo loading on these structures was characterized in early healing of rat Achilles tendons by comparing full activity with immobilization. Unloading resulted in structural changes that can explain the reported impaired mechanical performance. In particular, unloading led to slower tissue regeneration and maturation, with less and more disorganized collagen, as well as an increased presence of adipose tissue. This study provides the first application of SASTT on soft musculoskeletal tissues and clearly demonstrates its potential to investigate a variety of other collagenous tissues. Statement of significanceCurrently our understanding of the mechanobiological effects on the recovery of the structural hierarchical organization of injured Achilles tendons is limited. We provide insight into how loading affects the healing process by using a cutting-edge approach to for the first time characterize the 3D micro- and nanostructure of the regenerating collagen. We uncovered that, during early healing, unloading results in a delayed and more disorganized regeneration of both fibers (microscale) and fibrils (nanoscale), as well as increased presence of adipose tissue. The results set the ground for the development of further specialized protocols for tendon recovery.

ROS-scavenging materials for skin wound healing: advancements and applications.

The intricate healing process of skin wounds includes a variety of cellular and molecular events. Wound healing heavily relies on reactive oxygen species (ROS), which are essential for controlling various processes, including inflammation, cell growth, angiogenesis, granulation, and the formation of extracellular matrix. Nevertheless, an overabundance of reactive oxygen species (ROS) caused by extended oxidative pressure may result in the postponement or failure of wound healing. It is crucial to comprehend the function of reactive oxygen species (ROS) and create biomaterials that efficiently eliminate ROS to enhance the healing process of skin wounds. In this study, a thorough examination is presented on the role of reactive oxygen species (ROS) in the process of wound healing, along with an exploration of the existing knowledge regarding biomaterials employed for ROS elimination. In addition, the article covers different techniques and substances used in the management of skin wound. The future prospects and clinical applications of enhanced biomaterials are also emphasized, highlighting the potential of biomaterials that scavenge active oxygen to promote skin repair. This article seeks to enhance the understanding of the complex processes of ROS in the healing of wounds and the application of ROS-scavenging materials. Its objective is to create novel strategies for effective treatment skin wounds.

Cdc42 deletion yielded enamel defects by disrupting mitochondria and producing reactive oxygen species in dental epithelium

Developmental defects of enamel are common due to genetic and environmental factors before and after birth. Cdc42, a Rho family small GTPase, regulates prenatal tooth development in mice. However, its role in postnatal tooth development, especially enamel formation, remains elusive. Here, we investigated Cdc42 functions in mouse enamel development and tooth repair after birth. Cdc42 showed highly dynamic temporospatial patterns in the developing incisors, with robust expression in ameloblast and odontoblast layers. Strikingly, epithelium-specific Cdc42 deletion resulted in enamel defects in incisors. Ameloblast differentiation was inhibited, and hypomineralization of enamel was observed upon epithelial Cdc42 deletion. Proteomic analysis showed that abnormal mitochondrial components, phosphotransferase activity, and ion channel regulator activity occurred in the Cdc42 mutant dental epithelium. Reactive oxygen species accumulation was detected in the mutant mice, suggesting that abnormal oxidative stress occurred after Cdc42 depletion. Moreover, Cdc42 mutant mice showed delayed tooth repair and generated less calcified enamel. Mitochondrial dysfunction and abnormal oxygen consumption were evidenced by reduced Apool and Timm8a1 expression, increased Atp5j2 levels, and reactive oxygen species overproduction in the mutant repair epithelium. Epithelium-specific Cdc42 deletion attenuated ERK1/2 signaling in the labial cervical loop. Aberrant Sox2 expression in the mutant labial cervical loop after clipping might lead to delayed tooth repair. These findings suggested that mitochondrial dysfunction, up-regulated oxidative stress, and abnormal ion channel activity may be among multiple factors responsible for the observed enamel defects in Cdc42 mutant incisors. Overall, Cdc42 exerts multidimensional and pivotal roles in enamel development and is particularly required for ameloblast differentiation and enamel matrix formation.

A red blood cell‐derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery

AbstractThe tumour‐targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an “all‐in‐one” red blood cell (RBC)‐derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are “immolated” under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

SUMOylation is enriched in the nuclear matrix and required for chromosome segregation

As an important post-translational modification, SUMOylation plays critical roles in almost all biological processes. Although it has been well-documented that SUMOylated proteins are mainly localized in the nucleus and have roles in chromatin-related processes, we showed recently that the SUMOylation machinery is actually enriched in the nuclear matrix rather than chromatin. Here, we provide compelling biochemical, cellular imaging, and proteomic evidence that SUMOylated proteins are highly enriched in the nuclear matrix. We demonstrated that inactivation of SUMOylation by inhibiting SUMO-activating E1 enzyme or knockout of SUMO-conjugating E2 enzyme UBC9 have only mild effect on nuclear matrix composition, indicating that SUMOylation is neither required for nuclear matrix formation nor for targeting proteins to nuclear matrix. Further characterization of UBC9 knockout cells revealed that loss of SUMOylation did not result in significant DNA damage, but led to mitotic arrest and chromosome missegregation. Altogether, our study demonstrates that SUMOylated proteins are selectively enriched in the nuclear matrix and suggests a role of nuclear matrix in mediating SUMOylation and its regulated biological processes.

A Core Structural Protein That Builds the Locust Mandible with a Mechanical Gradient.

Natural materials, such as locust mandibles and squid beaks, define significant mechanical gradients that have been attributed to the chemical gradients of their specialized structural proteins (SPs). However, the mechanism by which SPs form chemical gradients in these materials remains unknown. In this study, a highly abundant histidine-rich structural protein (LmMHSP) was identified in the mandible of a migratory locust (Locusta migratoria). LmMHSP was proven by both in vivo and in vitro evidence to act as a core building block of the mandible with a variety of synergistic functions including chitin binding, matrix formation via liquid-liquid phase separation, chemical cross-linking, and metal coordination. Furthermore, we found that the SP gradient in the locust mandible stems from the chitin-binding activity of LmMHSP and different microstructures of chitin scaffolds in different regions. These findings advance our understanding of the formation mechanisms of natural biomaterials and have implications for the fabrication of biomimetic materials.

ИННОВАЦИОННЫЕ ПОДХОДЫ К СТРУКТУРИРОВАНИЮ И АНАЛИЗУ СИСТЕМЫ ТРУДОВОЙ МОТИВАЦИИ ПЕРСОНАЛА ПРЕДПРИЯТИЙ

The article emphasizes the influence of the structure of labor motivation on the effectiveness of personnel management and the efficiency of the company’s employees, confirming the relevance of the declared topic. The validity of the delineation of known approaches to the analysis of the structure of labor motivation of enterprise personnel into three conditional types (determinant, parametric, typological) is justified. An object approach to structuring the labor motivation system of personnel is proposed, the concept of which is adequate to the target targets of motivational monitoring, associated with ranking the objects of motivational monitoring (OMM) by the level of well-being and with assessing the effectiveness of management (targeted impact) of specialized divisions of the enterprise. The original methodological toolkit for monitoring the labor motivation system is presented and illustrated on conditional examples, the key elements of which are the development of a Map of expert assessments of the current state of IMM profile indicators and the formation of a summary matrix that accumulates the results of TSTI (current state-trend of change) — analysis.

Effects of hydroxyapatite bovine tooth graft (HAp-BTG) and polyethylene glycol (PEG) combinations in post extraction sockets on the amount of osteoid

Background: One of the actions in the field of tooth conservation such as hemisection can result in changes, especially in hard tissue due to the extraction of tooth roots and part of the tooth crown. After tooth extraction, socket wound healing will occur which ends with the process of osteogenesis. This process can reduce the dimensions of the socket due to alveolar bone resorption. Socket preservation can prevent dimension reduction and bone resorption to achieve maximum treatment results. The administration of Hydroxyapatite bovine tooth graft (HAp-BTG) into the post-extraction socket is expected to increase the formation of osteoid matrix which is important in the formation of new bone. Purpose: Proving the effect of adding a combination of HAp-BTG and PEG into the post-extraction socket on increasing the number of osteoid. Methods: 32 wistar rats were divided into control and treatment groups. Then the lower left incisor was extracted, the post-extraction socket was filled with PEG for the control group and a combination of HAp-BTG and PEG for the treatment group. On the 14th and 28th day the wistar rats were terminated and the mandibles were taken to make tissue preparations. HE staining was performed on the samples and observing the extent of the osteoid using a microscope with 400x magnification. Results: There was a significant difference between the control group and the treatment group on the 14th and 28th days. Conclusion: Administration of a combination of HAp-BTG and PEG into the post-extraction socket increased the number of osteoid on the 14th and 28th days.

Multifunctional photothermally responsive hydrogel as an effective whole-process management platform to accelerate chronic diabetic wound healing

The management of chronic diabetic wounds is a complex issue that requires wound repair, regulation of inflammatory levels, and intervention to prevent bacterial infection. To address this issue, we developed a multifunctional photothermally responsive hydrogel (PAG-CuS) as an effective platform for managing the entire wound-healing process, including promoting wound healing, providing anti-inflammatory therapy, and performing photothermal sterilization. Constructed through copolymerization of acrylic acid (AA), methacrylic anhydride-modified gelatin (GelMA), and lipoic acid sodium (LAS) coated copper sulfide nanoparticles (CuS@LAS), PAG-CuS possessed a porous three-dimensional structure that promoted cell adhesion and had a substantial water-holding capacity. Additionally, the internal CuS@LAS not only conferred photothermal antibacterial properties to the hydrogel but also served as physical cross-linking agents, thus enhancing its mechanical strength. Under the NIR-induced photothermal effect, the porous hydrogel liberates CuS@LAS, and later CuS@LAS expels LAS via micelle deassembly to eliminate intracellular ROS. This results in the down-regulation of MMP-9 expression, promoting ECM production and facilitating wound healing. Meanwhile, the release of Cu2+ from PAG-CuS could enhance CD31 expression in endothelial cells, promoting microvessel formation, which is crucial for wound healing. In the diabetic wound model of GK rats, the PAG-CuS hydrogel reduced ROS levels, increased microvessel count, improved epithelialization, and enhanced wound healing. Therefore, this versatile photothermal hydrogel has the potential to be applied in sterilization, scavenging free radicals, and promoting angiogenesis, making it an effective and comprehensive solution to manage the challenges of diabetic wounds. Statement of significanceAssessment of functional recovery and timely adjustment of treatment strategy is critical in the management of chronic diabetic wounds. In this work, we prepared PAG-CuS composite hydrogels by integrating in situ reduction, chemical crosslinking, and nanoenhancement techniques. The near-infrared light-induced photothermal effect of PAG-CuS gel rapidly kills bacteria at the lesion site, and the generated heat simultaneously promotes the multilevel release of LAS from the gel, which could regulate the levels of ROS and MMP-9 to promote extracellular matrix formation. In addition, the Cu2+ released from the gel can promote the formation of blood vessels to improve blood oxygenation. Therefore, this project proposes a synergistic solution to realize the whole process of management to accelerate chronic diabetic wound healing.

Ferroptosis induced by plasma-activated Ringer's lactate solution prevents oral cancer progression.

This study aimed to investigate the effect of plasma-activated Ringer's lactate solution (PAL) on oral squamous cell carcinoma (OSCC) cells and carcinogenic processes with a particular focus on iron and collagenous matrix formation. We used three OSCC cell lines, one keratinocyte cell line, and two fibroblast lines, and cell viability assays, immunoblotting, flow cytometry, and transmission electron microscopy were performed to evaluate the effect and type of cell death. The effect of PAL treatment on lysyl oxidase (LOX) expression was investigated invitro and invivo. Tamoxifen-inducible Mob1a/b double-knockout mice were used for the invivo experiment. PAL killed OSCC cells more effectively than the control nontumorous cells and suppressed cell migration and invasion. Ferroptosis occurred and the protein level of LOX was downregulated in cancer cells invitro and invivo. Additionally, PAL improved the survival rate of mice and suppressed collagenous matrix formation. We demonstrated that PAL specifically kills OSCC cells and that ferroptosis occurs invitro and invivo. Furthermore, PAL can prevent carcinogenesis and improve the survival rate of oral cancer, especially tongue cancer, by changing collagenous matrix formation via LOX suppression.

Gellan gum-based bi-polymeric hydrogel scaffolds loaded with Rosuvastatin calcium: A useful tool for tendon tissue regeneration

Statins have been long used in tissue engineering, besides their marketed hypolipidemic benefits. The aim of this research was to sustain the release of rosuvastatin calcium from bi-polymeric hydrogel scaffolds. A bi-polymer blend technique was used to enhance the mechanical properties of the fabricated hydrogels. Briefly, hydrogels were prepared via crosslinking gellan gum as the main polymer together with a secondary polymer in the presence of Ca2+. The fabricated hydrogels were assessed in terms of % swelling capacity, hydrolytic degradation and % drug released to determine the most efficient carrier system. The selected hydrogel exhibited a swelling capacity of 131.45±1.49 % following 3 weeks in an aqueous environment with a % weight loss of 15.73±1.86 % after 4 weeks post-equilibrium in aqueous medium. The results ensure a proper window for adequate drug diffusion and nutrient exchange. Sustained release was attained where 94.61±2.77 % of rosuvastatin was released at the 4-week mark. Later, FT-IR and DSC, were carried out and suggested the successful crosslinking and formation of new matrix. SEM images demonstrated the porous surface of the hydrogel while a Young's modulus of 888.558±73.549 kPa indicated the suitability of the hydrogel for soft tissue engineering. In-vivo testing involved implanting the selected hydrogel at precisely surgical cuts in the Achilles tendon of male Wistar Albino rats. Upon visual and microscopic evaluation, enhanced rates of fibrous tissue formation, vascularization and collagen expression were clearly noticed in the treatment group.