Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration.

Features of the extracellular matrix, along with biochemical factors, have a momentous impress in making genes on and/or off. The interaction of cells and the extracellular matrix is mediated by integrins. Therefore, these molecules have pivotal roles in regulating cell behaviors. Integrins include a group of molecules with a variety of characteristics that can affect different molecular cascades. Considering the importance of these molecules in tissue regeneration after injury, it is necessary to know well the integrins involved in the process of connecting cells to the extracellular matrix in each tissue.With the increase in life expectancy, bone tissue engineering has received more attention from researchers. Integrins are critical components in osteoblast differentiation, survival, and bone mechanotransduction. During osteogenic differentiation in stem cells, specific integrins facilitate multiple signaling pathways through their cytoplasmic domain, leading to the induction of osteogenic differentiation. Also, due to the importance of using biomaterials in bone tissue engineering, efforts have been made to design and use biomaterials with maximum interaction with integrins. Notably, the use of RGD peptide or fibronectin for surface modification is a well-established and commonly employed approach to manipulate integrin activity.This review article looks into integrins' role in bone development and regeneration. It then goes on to explore the complex mechanisms by which integrins contribute to these processes. In addition, this review discusses the use of natural and synthetic biomaterials that target integrins to promote bone regeneration.

Fabricating Multiphasic Angiogenic Scaffolds Using Amyloid/Roxadustat-Assisted High-Temperature Protein Printing.

Repairing multiphasic defects is cumbersome. This study presents new soft and hard scaffold designs aimed at facilitating the regeneration of multiphasic defects by enhancing angiogenesis and improving cell attachment. Here, the nonimmunogenic, nontoxic, and cost-effective human serum albumin (HSA) fibril (HSA-F) was used to fabricate thermostable (up to 90 °C) and hard printable polymers. Additionally, using a 10.0 mg/mL HSA-F, an innovative hydrogel was synthesized in a mixture with 2.0% chitosan-conjugated arginine, which can gel in a cell-friendly and pH physiological environment (pH 7.4). The presence of HSA-F in both hard and soft scaffolds led to an increase in significant attachment of the scaffolds to the human periodontal ligament fibroblast (PDLF), human umbilical vein endothelial cell (HUVEC), and human osteoblast. Further studies showed that migration (up to 157%), proliferation (up to 400%), and metabolism (up to 210%) of these cells have also improved in the direction of tissue repair. By examining different in vitro and ex ovo experiments, we observed that the final multiphasic scaffold can increase blood vessel density in the process of per-vascularization as well as angiogenesis. By providing a coculture environment including PDLF and HUVEC, important cross-talk between these two cells prevails in the presence of roxadustat drug, a proangiogenic in this study. In vitro and ex ovo results demonstrated significant enhancements in the angiogenic response and cell attachment, indicating the effectiveness of the proposed design. This approach holds promise for the regeneration of complex tissue defects by providing a conducive environment for vascularization and cellular integration, thus promoting tissue healing.

Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach.

BACKGROUND: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis. METHODS: Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure. RESULTS: Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin. CONCLUSION: These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.

Droplet-based microfluidics: an efficient high-throughput portable system for cell encapsulation.

One of the goals of tissue engineering and regenerative medicine is restoring primary living tissue function by manufacturing a 3D microenvironment. One of the main challenges is protecting implanted non-autologous cells or tissues from the host immune system. Cell encapsulation has emerged as a promising technique for this purpose. It involves entrapping cells in biocompatible and semi-permeable microcarriers made from natural or synthetic polymers that regulate the release of cellular secretions. In recent years, droplet-based microfluidic systems have emerged as powerful tools for cell encapsulation in tissue engineering and regenerative medicine. These systems offer precise control over droplet size, composition, and functionality, allowing for creating of microenvironments that closely mimic native tissue. Droplet-based microfluidic systems have extensive applications in biotechnology, medical diagnosis, and drug discovery. This review summarises the recent developments in droplet-based microfluidic systems and cell encapsulation techniques, as well as their applications, advantages, and challenges in biology and medicine. The integration of these technologies has the potential to revolutionise tissue engineering and regenerative medicine by providing a precise and controlled microenvironment for cell growth and differentiation. By overcoming the immune system's challenges and enabling the release of cellular secretions, these technologies hold great promise for the future of regenerative medicine.

Collagen: The superior material for full-thickness oral mucosa tissue engineering.

BACKGROUND: Tissue engineering has significantly progressed in developing full-thickness oral mucosa constructs designed to replicate the natural oral mucosa. These constructs serve as valuable in vitro models for biocompatibility testing and oral disease modeling and hold clinical potential for replacing damaged or lost oral soft tissue. However, one of the major challenges in tissue engineering of the oral mucosa is the identification of an appropriate scaffold with optimal porosity, interconnected porous networks, biodegradability, and biocompatibility. These characteristics facilitate cell migration, nutrient delivery, and vascularization. Various biomaterials have been investigated for constructing tissue-engineered oral mucosa models; collagen has demonstrated superior outcomes compared with other materials. HIGHLIGHT: This review discusses the different types of tissue-engineered oral mucosa developed using various materials and includes articles published between January 2000 and December 2022 in PubMed and Google Scholar. The review focuses on the superiority of collagen-based scaffolds for tissue engineering of oral mucosa, explores in vitro applications, and discusses potential clinical applications. CONCLUSION: Among the various scaffold materials used for engineering the connective tissue of the oral mucosa, collagen-based scaffolds possess excellent biological properties, offering high-quality oral mucosa constructs and high resemblance to the native human oral mucosa in terms of histology and expression of various differentiation markers.

Evaluating osteogenic potential of a 3D-printed bioceramic-based scaffold for critical-sized defect treatment: an in vivo and in vitro investigation.

The integration of precision medicine principles into bone tissue engineering has ignited a wave of research focused on customizing intricate scaffolds through advanced 3D printing techniques. Bioceramics, known for their exceptional biocompatibility and osteoconductivity, have emerged as a promising material in this field. This article aims to evaluate the regenerative capabilities of a composite scaffold composed of 3D-printed gelatin combined with hydroxyapatite/tricalcium phosphate bioceramics (G/HA/TCP), incorporating human dental pulp-derived stem cells (hDPSCs). Using 3D powder printing, we created cross-shaped biphasic calcium phosphate scaffolds with a gelatin layer. The bone-regenerating potential of these scaffolds, along with hDPSCs, was assessed through in vitro analyses and in vivo studies with 60 rats and critical-sized calvarial defects. The assessment included analyzing cellular proliferation, differentiation, and alkaline phosphatase activity (ALP), and concluded with a detailed histological evaluation of bone regeneration. Our study revealed a highly favorable scenario, displaying not only desirable cellular attachment and proliferation on the scaffolds but also a notable enhancement in the ALP activity of hDPSCs, underscoring their pivotal role in bone regeneration. However, the histological examination of calvarial defects at the 12-wk mark yielded a rather modest level of bone regeneration across all experimental groups. The test and cell group exhibited significant bone formation compared to all other groups except the control and cell group. This underscores the complexity of the regenerative process and paves the way for further in-depth investigations aimed at improving the potential of the composite scaffolds.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

Studying the electrical, mechanical, and biological properties of BCZT-HA composites.

The piezoelectric properties of natural bone and their influence on bone growth have inspired researchers to study a range of bio-piezoelectric composite materials. By exploring these materials, researchers aim to understand better, how piezoelectricity can be controlled to promote bone growth and tissue regeneration. In this work, the prominent piezoelectric material, (Ba, Zr) TiO3 -x(Ba,Ca)TiO3 , abbreviated as BCZT, was selected as a possible bone growth enhancer in hydroxyapatite (HA) scaffolds. Initially, BCZT and hydroxyapatite (HA) powders were synthesized using the sol-gel method. Subsequently, various composite samples of BCZT-xHA were prepared using the conventional solid-state method. After sintering the samples at 1300°C, the phase structure, microstructure, density, and electrical properties were characterized. The samples' compressive strength was determined by analyzing the outcomes of basic compression tests. The biological behavior of the samples in terms of in vitro simulated body fluid immersion and MTT tests were evaluated. Our results revealed that among the BCZT-xHA samples, the BCZT-20HA sample had the best composition, considering its electrical, mechanical, and biological properties. A d33 value of 10 pC/N, dielectric permittivity of 110, and the g33 equal to 10.27 mV m/N resulted in the output voltage of 1.03 V. The results of the MTT assay test confirmed the noncytotoxic nature of the samples with the highest optical density in the BCZT-20HA sample.

Deep eutectic solvent-based ferrofluid for highly efficient preconcentration and determination of metronidazole by vortex-assisted liquid-phase microextraction under experimental design optimization.

To determine metronidazole in water samples, we developed an environmentally friendly, efficient, and straightforward ferrofluid-based liquid-liquid microextraction sample pretreatment technique. It is coupled with a high-performance liquid chromatography-ultraviolet analytical technique known for its sensitivity, speed, and precision. The magnetic separation of metronidazole-containing ferrofluid from the matrix was effortlessly achieved through the application of an external magnetic field, eliminating the need for centrifugation. Response surface optimization was employed to systematically determine the key experimental parameters influencing extraction efficiency, including pH, NaCl concentration, ferrofluid volume, and vortex duration. With a low detection limit (0.116 ng mL-1), a broad linear range between 0.5 and 700 ng mL-1 was achieved at optimal conditions. Additionally, acceptable spiking recoveries (94.3-97.3 %) and RSD values (≤3.7 %) for intra- and inter-day precision were attained in water samples. In conclusion, the effectiveness of the vortex and ferrofluid combination, along with the convenience of collection and elimination of the need for centrifugation, bestows a highly valuable technique for determining metronidazole in water samples.

The Need for Smart Materials in an Expanding Smart World: MXene-Based Wearable Electronics and Their Advantageous Applications.

As a result of the transformation of inflexible electronic structures into flexible and stretchy devices, wearable electronics now provide great advantages in a variety of fields, including mobile healthcare sensing and monitoring, human-machine interfaces, portable energy storage and harvesting, and more. Because of their enriched surface functionalities, large surface area, and high electrical conductivity, transition metal nitrides and carbides (also known as MXenes) have recently come to be extensively considered as a group of functioning two-dimensional nanomaterials as well as exceptional fundamental elements for forming flexible electronics devices. This Review discusses the most recent advancements that have been made in the field of MXene-enabled flexible electronics for wearable electronics. The emphasis is placed on extensively established nonstructural features in order to highlight some MXene-enabled electrical devices that were constructed on a nanometric scale. These attributes include devices configured in three dimensions: printed materials, bioinspired structures, and textile and planar substrates. In addition, sample applications in electromagnetic interference (EMI) shielding, energy, healthcare, and humanoid control of machinery illustrate the exceptional development of these nanodevices. The increasing potential of MXene nanoparticles as a new area in next-generation wearable electronic technologies is projected in this Review. The design challenges associated with these electronic devices are also discussed, and possible solutions are presented.

Magnetic hydrogel applications in articular cartilage tissue engineering.

Articular cartilage defects afflict millions of individuals worldwide, presenting a significant challenge due to the tissue's limited self-repair capability and anisotropic nature. Hydrogel-based biomaterials have emerged as promising candidates for scaffold production in artificial cartilage construction, owing to their water-rich composition, biocompatibility, and tunable properties. Nevertheless, conventional hydrogels typically lack the anisotropic structure inherent to natural cartilage, impeding their clinical and preclinical applications. Recent advancements in tissue engineering (TE) have introduced magnetically responsive hydrogels, a type of intelligent hydrogel that can be remotely controlled using an external magnetic field. These innovative materials offer a means to create the desired anisotropic architecture required for successful cartilage TE. In this review, we first explore conventional techniques employed for cartilage repair and subsequently delve into recent breakthroughs in the application and utilization of magnetic hydrogels across various aspects of articular cartilage TE.

Enhancing bone tissue engineering with 3D-Printed polycaprolactone scaffolds integrated with tragacanth gum/bioactive glass.

Tissue-engineered bone substitutes, characterized by favorable physicochemical, mechanical, and biological properties, present a promising alternative for addressing bone defects. In this study, we employed an innovative 3D host-guest scaffold model, where the host component served as a mechanical support, while the guest component facilitated osteogenic effects. More specifically, we fabricated a triangular porous polycaprolactone framework (host) using advanced 3D printing techniques, and subsequently filled the framework's pores with tragacanth gum-45S5 bioactive glass as the guest component. Comprehensive assessments were conducted to evaluate the physical, mechanical, and biological properties of the designed scaffolds. Remarkably, successful integration of the guest component within the framework was achieved, resulting in enhanced bioactivity and increased strength. Our findings demonstrated that the scaffolds exhibited ion release (Si, Ca, and P), surface apatite formation, and biodegradation. Additionally, in vitro cell culture assays revealed that the scaffolds demonstrated significant improvements in cell viability, proliferation, and attachment. Significantly, the multi-compartment scaffolds exhibited remarkable osteogenic properties, indicated by a substantial increase in the expression of osteopontin, osteocalcin, and matrix deposition. Based on our results, the framework provided robust mechanical support during the new bone formation process, while the guest component matrix created a conducive micro-environment for cellular adhesion, osteogenic functionality, and matrix production. These multi-compartment scaffolds hold great potential as a viable alternative to autografts and offer promising clinical applications for bone defect repair in the future.

The Potential Therapeutic Effects of Platelet-Derived Biomaterials on Osteoporosis: A Comprehensive Review of Current Evidence.

Osteoporosis is a chronic multifactorial condition that affects the skeletal system, leading to the deterioration of bone microstructure and an increased risk of bone fracture. Platelet-derived biomaterials (PDBs), so-called platelet concentrates, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), have shown potential for improving bone healing by addressing microstructural impairment. While the administration of platelet concentrates has yielded positive results in bone regeneration, the optimal method for its administration in the clinical setting is still debatable. This comprehensive review aims to explore the systemic and local use of PRP/PRF for treating various bone defects and acute fractures in patients with osteoporosis. Furthermore, combining PRP/PRF with stem cells or osteoinductive and osteoconductive biomaterials has shown promise in restoring bone microstructural properties, treating bony defects, and improving implant osseointegration in osteoporotic animal models. Here, reviewing the results of in vitro and in vivo studies, this comprehensive evaluation provides a detailed mechanism for how platelet concentrates may support the healing process of osteoporotic bone fractures.

Clinical Trials of Mesenchymal Stem Cells for the Treatment of COVID 19.

Mesenchymal Stem Cells (MSCs) are being investigated as a treatment for a novel viral disease owing to their immunomodulatory, anti-inflammatory, tissue repair and regeneration characteristics, however, the exact processes are unknown. MSC therapy was found to be effective in lowering immune system overactivation and increasing endogenous healing after SARS-CoV-2 infection by improving the pulmonary microenvironment. Many studies on mesenchymal stem cells have been undertaken concurrently, and we may help speed up the effectiveness of these studies by collecting and statistically analyzing data from them. Based on clinical trial information found on clinicaltrials. gov and on 16 November 2020, which includes 63 clinical trials in the field of patient treatment with COVID-19 using MSCs, according to the trend of increasing studies in this field, and with the help of meta-analysis studies, it is possible to hope that the promise of MSCs will one day be realized. The potential therapeutic applications of MSCs for COVID-19 are investigated in this study.

Data-driven supervised machine learning to predict the compressive response of porous PVA/Gelatin hydrogels and in-vitro assessments: Employing design of experiments.

The purpose of this study is to design and evaluate a series of porous hydrogels by considering three independent variables using the Box-Behnken method. Accordingly, concentrations of the constituent macromolecules of the hydrogels, Polyvinyl Alcohol and Gelatin, and concentration of the crosslinking agent are varied to fabricate sixteen different porous samples utilizing the lyophilization process. Subsequently, the porous hydrogels are subjected to a battery of tests, including Fourier Transform Infrared spectroscopy, morphology assessment, pore-size study, porosimetry, uniaxial compression, and swelling measurements. Additionally, in-vitro cell assessments are performed by culturing mouse fibroblast cells (L-929) on the hydrogels, where viability, proliferation, adhesion, and morphology of the L-929 cells are monitored over 24, 48, and 72 h to evaluate the biocompatibility of these biomaterials. To better understand the mechanical behavior of the hydrogels under compressive loadings, Deep Neural Networks (DNNs) are implemented to predict and capture their compressive stress-strain responses as a function of the constituent materials' concentrations and duration of the performed mechanical tests. Overall, this study emphasizes the importance of considering multiple variables in the design of porous hydrogels, provides a comprehensive evaluation of their mechanical and biological properties, and, particularly, implements DNNs in the prediction of the hydrogels' stress-strain responses.

Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine.

The utilization of growth factors in the process of tissue regeneration has garnered significant interest and has been the subject of extensive research. However, despite the fervent efforts invested in recent clinical trials, a considerable number of these studies have produced outcomes that are deemed unsatisfactory. It is noteworthy that the trials that have yielded the most satisfactory outcomes have exhibited a shared characteristic, namely, the existence of a mechanism for the regulated administration of growth factors. Despite the extensive exploration of drug delivery vehicles and their efficacy in delivering certain growth factors, the development of a reliable predictive approach for the delivery of delicate growth factors like Vascular Endothelial Growth Factor (VEGF) remains elusive. VEGF plays a crucial role in promoting angiogenesis; however, the administration of VEGF demands a meticulous approach as it necessitates precise localization and transportation to a specific target tissue. This process requires prolonged and sustained exposure to a low concentration of VEGF. Inaccurate administration of drugs, either through off-target effects or inadequate delivery, may heighten the risk of adverse reactions and potentially result in tumorigenesis. At present, there is a scarcity of technologies available for the accurate encapsulation of VEGF and its subsequent sustained and controlled release. The objective of this review is to present and assess diverse categories of VEGF administration mechanisms. This paper examines various systems, including polymeric, liposomal, hydrogel, inorganic, polyplexes, and microfluidic, and evaluates the appropriate dosage of VEGF for multiple applications.

Fabrication and evaluation of PLA/MgAl2O4 scaffolds manufactured through 3D printing method.

In this study, we synthesized magnesium aluminate spinel (MgAl2O4) with a particle size ranging from 35 to 70 nm using a facile combustion approach. Then, we used a 3D printing (FDM) machine to produce PLA/x wt% MgAl2O4 (x = 0, 2, 4, 6, and 8) scaffolds. To investigate the crystal structure, microstructure, biodegradability, and thermal characteristics of the produced materials, we employed X-ray diffraction analysis (XRD), field emission scanning electron microscope (FESEM), Inductively Coupled Plasma (ICP), Simultaneous Thermal Analysis (STA), and compressive strength analyses. The results showed that PLA/6 wt% MgAl2O4 scaffolds possess the highest amounts of compressive strength. We evaluated the bio-activation and biodegradability of scaffolds by immersing them in simulated body fluid (SBF) for four weeks. Interestingly, the highest strength was achieved in PLA/6 wt% MgAl2O4 scaffolds, while the improper dispersion of ceramic particles happened on the polymer substrate in cases where x>6. ICP analysis showed that the addition of spinel nanoparticles to PLA increased the biodegradability of the scaffolds. Our FESEM results supported this finding and also revealed that the dispersion of ceramic particles on the polymer substrate was not uniform in cases where x>6. Also, according to the results of STA, the presence of MgAl2O4 nanoparticles effectively reduces the rate of thermal decomposition from 95 to 85 percent.

3D-bioprinting of patient-derived cardiac tissue models for studying congenital heart disease.

Introduction: Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies. Methods: To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521. Results: Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including spontaneous contraction. Contraction remained consistent during 30 days of culture based on displacement measurements. Furthermore, tissue constructs demonstrated progressive maturation based on sarcomere structure and gene expression analysis. Gene expression analysis also revealed enhanced maturation in 3D constructs compared to 2D cell culture. Discussion: This combination of patient-derived cardiomyocytes and 3D-bioprinting represents a promising platform for studying congenital heart disease and evaluating individualized treatment strategies.

Moving beyond nanotechnology to uncover a glimmer of hope in diabetes medicine: Effective nanoparticle-based therapeutic strategies for the management and treatment of diabetic foot ulcers.

Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.

Lithium metasilicate glass-ceramic fabrication using spark plasma sintering.

Background: The digital dentistry, requires materials with wo opposite properties of machining ability and also enough hardness. The main objective of this experimental study was to investigate the fabrication feasibility of the lithium metasilicate glass-ceramic in partially crystalized stated using the spark plasma sintering (SPS) method. Materials and Methods: In this study, SPS for the first time was used to fabricate primary lithium metasilicate glass-ceramic (LMGC) blocks. The raw materials were mixed and melted and then quenched in water and the resulted frits were grinded. The resulting powder was sintered by SPS at 660, 680, and 700°C. Results: Scanning Electron Microscope (SEM), X-ray diffraction (XRD), and Vicker's microhardness assay were used to evaluate the properties of samples. Statistical comparison of the obtained data was performed by ANOVA, followed by the post hoc test of Duncan. Microstructural studies by SEM and XRD showed that all samples were composed of lithium metasilicate phase in a glassy matrix. With increasing the sintering temperature, the number and size of lithium metasilicate particles increased and higher mechanical properties have been achieved. However, the sintered sample at 700°C has less processing ability than the samples sintered at 660 and 680°C. Conclusion: The optimum sintering temperature for glass frit consolidation was determined by SPS at 680°C.