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The impact of orthopedic scaffolds on bone defect healing, particularly the late-stage bone remodeling process, is pivotal for the therapeutic outcome. This study applies fadditively manufactured scaffolds composed of hydroxyapatite-doped poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (HA-PELGA) with varying properties to treat rat calvarial defects, elucidating their significant role in bone remodeling by modulating physiological responses. We engineered two scaffolds with different polylactic acid (PLA) to polyglycolic acid (PGA) ratio (9/1 and 18/1) to vary in hydrophobicity, degradation rate, mechanical properties, and structural stability. These variations influenced physiological responses, including osteogenesis, angiogenesis, and immune reactions, thereby guiding bone remodeling. Our findings show that the HA-PELGA(18/1) scaffold, with a slower degradation rate, supported bulk bone formation due to a stable microenvironment. Conversely, the HA-PELGA(9/1) scaffold, with a faster degradation rate and more active interfaces, facilitated the formation of a thin bone layer and higher bone infiltration. This study demonstrates these degradable scaffolds help to promote bone healing and reveals how scaffold properties influence the bone remodeling process, offering a potential strategy to optimize scaffold design aiming at late-stage bone defect healing.

Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients’ quality of life and mental well-being. To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

Mineral ions play a crucial role in various biological processes in the human body, particularly in bone repair and regeneration. Supplementation with mineral ions offers several advantages over other therapies or treatments for bone repair and regeneration, such as higher biosafety, universal applicability, and compatibility with the immune system. Additionally, supplementation with mineral ions may avoid the need for invasive surgical procedures. The aim of this review is to provide a comprehensive overview of the functions of potentially beneficial mineral ions and their effects on bone regeneration and osteoporosis treatment. By examining previous studies, including in vitro cellular experiments, in vivo animal models, and clinical trials, this review compares the benefits and potential adverse effects of these mineral ions. Moreover, the review provides guidelines for suggested daily supplementation of these mineral ions to assist future preclinical and clinical studies in bone regeneration and osteoporosis treatment.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Abstract Background An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS‐related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. Methods The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients’ sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein–protein interaction (PPI) network and their expression was validated using clinical specimens. Results A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low‐risk group had a lower IC50 for the common chemotherapy drug, 5‐FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. Conclusion We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

Abstract Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals – the most successful orthopedic material – have yet to yield satisfactory results. Conventional bio‐inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non‐bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L‐PBF) technology. This in vivo study presents a comprehensive, side‐by‐side comparative analysis of the interactions between bone regeneration and additively manufactured bio‐inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in‐depth understanding of the metal scaffold‐assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the in vitro and in vivo performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn–Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn–Fe alloys showed outstanding antibacterial property. Taken together, Zn–Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.

In recent years, the shortage of available organs for transplant patients has grown exponentially across the globe. Consequently, the healthcare industry is in dire need of artificial substitutes. Many recent research studies and tissue engineering groups have decided to utilize 3D bioprinting to produce these artificial organs. This synthetic organ printing is made possible by advancements in the materials required for the constructs, the printing methodologies used to produce them, and the final physical structures’ varying properties. The cutting-edge research and technology related to 3D and 4D live cell bioprinting have recently allowed researchers to produce multiple types of artificial organs and tissues. These tissues can be utilized for drug screening and organ replacement applications. This article provides an extensive review of all the pertinent 3D live cell bioprinting technologies. First, we describe scaffolding methods and their comparison with the traditional technologies. Second, we explain the 3D bioprinting technology, its evolution, and its multiple types. Moreover, we describe the pros and cons of each bioprinting method. Third, we have discussed the critical bioink properties and their impact on the formation of 3D bioprinting models. In addition, we also describe the mechanical properties of bioprinters. Fourth, we have thoroughly discussed the various types of hydrogels and their properties. Every kind of hydrogel is utilized in specific applications, and we have presented a comprehensive list of its advantages and disadvantages. Fifth, we have discussed various applications of 3D bioprinting technology. We have considered a case study of human organs and elaborated on how bioprinters can revolutionize the organ replacement industry. Finally, we evaluated the possibility of 4D printing in the future organ industry, incorporating temporal factors into the bioprinting process.

Current single-cell tools are limited by the number of proteins they can analyse. Here the authors report a single-cell cyclic multiplex in situ tagging (CycMIST) method for functional proteome profiling of single cells, allowing multiple rounds of multiplexing of the same single cells on a microchip.

Abstract Alzheimer's disease (AD) is a progressive, neurodegenerative disease that has emerged as a leading risk factor for dementia associated with increasing age. Two‐dimensional (2D) cell culture and animal models, which have been used to analyze AD pathology and search for effective treatments for decades, have significantly contributed to our understanding of the mechanism of AD. Despite their successes, 2D and animal models can only capture a fraction of AD mechanisms due to their inability to recapitulate human brain‐specific tissue structure, function, and cellular diversity. Recently, the emergence of three‐dimensional (3D) cerebral organoids using tissue engineering and induced pluripotent stem cell technology has paved the way to develop models that resemble features of human brain tissue more accurately in comparison to prior models. In this review, we focus on summarizing key research strategies for engineering in vitro 3D human brain‐specific models, major discoveries from using AD cerebral organoids, and its future perspectives.

Bioceramics are a popular class of materials used in biomedical applications due to their mechanical stability and biocompatibility. They exist in a variety of fields including hip joints for orthopedics, tooth fillings for dentistry, and scaffolds for tissue engineering; however, the standard processes currently used to manufacture these ceramic products can be time-consuming and costly. In response, current literature alternatively proposes additive manufacturing (3D printing) strategies to fabricate bioceramic materials in a cost-effective and efficient manner. Herein, we briefly cover five common processes and materials used in additive manufacturing bioceramics: fused deposition modeling, material jetting, binder jetting, powder bed fusion, and vat photopolymerization. Furthermore, we discuss the potential of these 3D printed ceramic structures when applied to different biomedical technologies such as bone tissue scaffolds and structural implants.

The influence of genetic engineering on daily life is prominent, from genetically modified food to transgenic, antibiotic resistant plants. The direct manipulation of an organism's genotype has opened the door to a myriad of applications in an effort to treat chronic diseases. This paper proposes the unification of chimeric DNA technology and three-dimensional bioprinting to spark the development of new therapies. While studies of chimeric DNA, i.e. recombinant DNA, have been conducted since 1970, bioprinting is a budding method for tissue engineering and regenerative medicine. Both technologies are further described in the background section of this paper, and followed by a detailed analysis into current research, benefits, and limitations of 3D printed chimeric biomaterials. Major benefits include low-cost and effective treatments for cancer, bio-morphological nanostructures for targeted drug delivery, personalized medicine with the use of stem cells, and a significantly reduced rate of additional surgeries and transplant rejection after implantation. However, there are several shortcomings with current chimeric DNA applications, e.g. CAR-T cell therapies, and ethical dilemmas regarding the creation and regulation of human-animal chimeras. This review then presents future directions, in which inks made from chimeric DNA and live cells can be printed into bioactive engineered tissue, or biodegradable vehicles for targeted delivery of hiPSCs or CAR T-cells. Finally, this review concludes with a reaffirmation of its main points and the authors’ thoughts on the potential of 3D printed chimeric biomaterials.

Zinc (Zn) is a new generation of biodegradable metal as temporary biomedical implants with a promising degradation rate. However, its clinical applications have been limited because of the insufficient mechanical properties. Considering the degradation property and biocompatibility, we proposed Zn–Sr alloys after extrusion treatments to simultaneously improve the mechanical strength and ductility. The in vitro and in vivo degradation and biocompatibility were also evaluated using electrochemical and immersion corrosion tests, various cell and bacterial models, together with subcutaneous and femoral implantations in rats. Results showed that the extruded Zn-0.7Sr alloys exhibited two times higher mechanical strengths (∼120 ​MPa) and better ductility (∼10%) than the pure Zn counterparts. The Zn–Sr alloys provided enhanced in vitro and in vivo biocompatibility along with promising antibacterial properties.

In the advancing landscape of technology and novel material development, additive manufacturing (AM) is steadily making strides within the biomedical sector. Moving away from traditional, one-size-fits-all implant solutions, the advent of AM technology allows for patient-specific scaffolds that could improve integration and enhance wound healing. These scaffolds, meticulously designed with a myriad of geometries, mechanical properties, and biological responses, are made possible through the vast selection of materials and fabrication methods at our disposal. Recognizing the importance of precision in the treatment of bone defects, which display variability from macroscopic to microscopic scales in each case, a tailored treatment strategy is required. A patient-specific AM bone scaffold perfectly addresses this necessity. This review elucidates the pivotal role that customized AM bone scaffolds play in bone defect treatment, while offering comprehensive guidelines for their customization. This includes aspects such as bone defect imaging, material selection, topography design, and fabrication methodology. Additionally, we propose a cooperative model involving the patient, clinician, and engineer, thereby underscoring the interdisciplinary approach necessary for the effective design and clinical application of these customized AM bone scaffolds. This collaboration promises to usher in a new era of bioactive medical materials, responsive to individualized needs and capable of pushing boundaries in personalized medicine beyond those set by traditional medical materials.

As species extinction accelerates globally and biodiversity declines dramatically, identifying keystone species becomes an effective way to conserve biodiversity. In traditional approaches, it is considered that the extinction of species with high centrality poses the greatest threat to secondary extinction. However, the indirect effect, which is equally important as the local and direct effects, is not included. Here, we propose an optimized disintegration strategy model for quantitative food webs and introduced tabu search, a metaheuristic optimization algorithm, to identify keystone species. Topological simulations are used to record secondary extinctions during species removal and secondary extinction areas, as well as to evaluate food web robustness. The effectiveness of the proposed strategy is also validated by comparing it with traditional methods. Results of our experiments demonstrate that our strategy can optimize the effect of food web disintegration and identify the species whose extinction is most destructive to the food web through global search. The algorithm provides an innovative and efficient way for further development of keystone species identification in the ecosystem.

With the ongoing COVID-19 pandemic still escalating, many researchers are turning to nanotechnology as a method of treatment not only for this pandemic, but in preparation for the pandemics of the future. Given both a wide variety of biomaterials at their disposal and the recent rise of nanotechnology, scientists now have the means to release and distribute therapeutic drugs in a variety of ways. Such a variety permits medical professionals the ability to choose biomaterials and methods that would provide the best release and treatment methodologies for the viral ailment they are attempting to remedy. This integrative review discusses context of previous pandemics, viral pathogenesis, issues associated with the current state of antiviral delivery systems, numerous biomaterials used for this purpose, and further information regarding the ongoing global COVID-19 pandemic.

The advancements of 3D printing technology have been combined with the use of metallic biomaterials to create devices and products for the biomedical field. 3D printing has been a revolutionary process that makes the fabrication of metallic biomedical devices highly specific and simultaneously easier than other fabrication methods. The purpose and overall function of each medical device created is dependent on the type of metal used along with its fabrication method. In this review paper, the major characteristics of metallic biomaterials, including iron, magnesium, zinc, titanium, cobalt, and stainless steel, will be discussed. Major considerations of these metallic biomaterials include degradation rate, biocompatibility, and mechanical properties will be addressed. Importantly, various additive manufacturing processes will be described. Depending on the 3D printing method and the use of specific alloys, these properties can be altered to optimize their functionality for purposes such as bone implants, stents, and other devices.

Abstract The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.

Bone is a unique tissue that is capable of repairing itself after damage. However, there are certain instances of fractures and defects that require clinical intervention for proper alignment and healing. As with any implant, careful consideration of the material used to create the implants to treat these problems is needed. If the incorrect material is chosen, the implants themselves can lead to bone fractures or defects, or bone healing may not take place at all. All three classes of biomaterials–metals, ceramics, and polymers–have been used in the treatment of both bone fractures and bone defects, and each has its own unique benefits and limitations for its applications. Furthermore, composites of these different materials have also been created to try to take advantage of all the different benefits offered by each different material. This review highlights different materials that have been used for the development of internal fixators and bone graft substitutes to treat fracture and bone defects as well as their limitations and needed future research.

Hernia repair for primary and incisional hernia is the most commonly performed abdominal surgery done with extremely high costs. Treatment for hernia requires surgery to close the defect; however, there are post-operative complications like chronic pain, adhesion, and infection that are common. Hernia repair involves two types of biomaterials: a fixation biomaterial and a mesh biomaterial to close the defect. Synthetic meshes, mostly made from different polymers, provide adequate mechanical support but are associated with postoperative complications like infection. Biological meshes are derived from allografts and xenografts that are prone to less infection; however, their mechanical strength may be too weak depending the characteristics of the hernia defect. Novel meshes being developed try to combat the post-operative complications of current surgical meshes. Composite meshes that have two different surfaces have shown to have less adhesion effects but still produce varying inflammatory responses. Drug-loaded meshes are also a novel mesh that is designed to reduce infection with antibiotics. This review will highlight the different fixation methods as well as the pros and cons of different mesh options. Possible future improvements will be highlighted as well.

Molecular hydrogen recently attracted lots of attention in biomedical community because of its abilities to modulate signal transduction, protein phosphorylation, and gene expression that enable its anti-inflammatory, anti-allergy, and anti-apoptotic activities. However, controllable and local delivery of hydrogen molecules to tissues still remains challenging. Here, we propose a new method of delivering molecular hydrogen directly to human skin cells by designing a hydrogen-generating patch that releases hydrogen in surrounding environment as a product of chemical reaction of aluminum and carbon hydroxide in presence of water. We show that in the presence of molecular hydrogen the cells viability, expression of collagen, and migration efficiency of cells increase, thus suggesting that hydrogen can be used to promote better and faster healing of skin issues such as wounds and bruises.

Biodegradable implants are of great interest in orthopaedic applications but have been limited by low mechanical strength. Here, the authors examine systematically in detail the strengthening of biodegradable zinc by alloying with beneficial elements using mechanical, biodegradability and biocompatibility testing.

Metallic materials have been extensively applied in clinical practice due to their unique mechanical properties and durability. Recent years have witnessed broad interests and advances on surface functionalization of metallic implants for high-performance biofunctions. Calcium phosphates (CaPs) are the major inorganic component of bone tissues, and thus owning inherent biocompatibility and osseointegration properties. As such, they have been widely used in clinical orthopedics and dentistry. The new emergence of surface functionalization on metallic implants with CaP coatings shows promise for a combination of mechanical properties from metals and various biofunctions from CaPs. This review provides a brief summary of state-of-art of surface biofunctionalization on implantable metals by CaP coatings. We first glance over different types of CaPs with their coating methods and in vitro and in vivo performances, and then give insight into the representative biofunctions, i.e. osteointegration, corrosion resistance and biodegradation control, and antibacterial property, provided by CaP coatings for metallic implant materials. Keywords: Calcium phosphates, Metallic implant materials, Surface biofunctionalization, Osteointegration, Biodegradation

Metallic implant materials possess adequate mechanical properties such as strength, elastic modulus, and ductility for long term support and stability in vivo. Traditional metallic biomaterials, including stainless steels, cobalt-chromium alloys, and titanium and its alloys, have been the gold standards for load-bearing implant materials in hard tissue applications in the past decades. Biodegradable metals including iron, magnesium, and zinc have also emerged as novel biodegradable implant materials with different in vivo degradation rates. However, they do not possess good bioactivity and other biological functions. Bioactive glasses have been widely used as coating materials on the metallic implants to improve their integration with the host tissue and overall biological performances. The present review provides a detailed overview of the benefits and issues of metal alloys when used as biomedical implants and how they are improved by bioactive glass-based coatings for biomedical applications. Keywords: Bioactive glass coating, Metallic biomaterials, Biodegradation, Biocompatibility, Bioactivity. contents

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD); where Alzheimer’s accounts for 60–70% of cases of dementia and VaD accounts for 20% of all dementia cases. VaD is defined as a reduced or lack of blood flow to the brain that causes dementia. VaD is also known occasionally as vascular contributions to cognitive impairment and dementia (VCID) or multi-infarct dementia (MID). VCID is the condition arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior, and VaD is the most severe stage while MID is produced by the synergistic effects caused by multiple mini strokes in the brain irrespective of specific location or volume. There are also subtle differences in the presentation of VaD in males and females, but they are often overlooked. Since 1672 when the first case of VaD was reported until now, sex and gender differences have had little to no research done when it comes to the umbrella term of dementia in general. This review summarizes the fundamentals of VaD followed by a focus on the differences between sex and gender when an individual is diagnosed. In addition, we provide critical evidence concerning sex and gender differences with a few of the main risk factors of VaD including pre-existing health conditions and family history, gene variants, aging, hormone fluctuations, and environmental risk factors. Additionally, the pharmaceutical treatments and possible mitigation of risk factors is explored.

Abstract Tissue repair/regeneration, after implantation or injury, involves comprehensive physiological processes wherein immune responses play a crucial role to enable tissue restoration, amidst the immune cells early‐stage response to tissue damages. These cells break down extracellular matrix, clear debris, and secret cytokines to orchestrate regeneration. However, the immune response can also lead to abnormal tissue healing or scar formation if not well directed. This review first introduces the general immune response post injury, with focus on the major immune cells including neutrophils, macrophages, and T cells. Next, a variety of implant‐mediated immunomodulation strategies to regulate immune response through physical, chemical, and biological cues are discussed. At last, various scaffold‐facilitated regenerations of different tissue types, such as, bone, cartilage, blood vessel, and nerve system, by harnessing the immunomodulation are presented. Therefore, the most recent data in biomaterials and immunomodulation is presented here in a bid to shape expert perspectives, inspire researchers to go in new directions, and drive development of future strategies focusing on targeted, sequential, and dynamic immunomodulation elicited by implants.

The solid solution strengthening of Li, Mg, Al, Mn, Cu and Ag in biodegradable Zn-based alloys is quantitatively investigated by first-principles calculations based on density functional theory. The alloying effect on lattice parameters and elastic constants is determined. Mn is found to have the greatest impact on the lattice parameters and shear modulus, while Mg and Al exhibit the least. According to the theories proposed by Fleischer and Labusch, the strengthening capability of selected elements can be ranked as Mn > Li > Cu, Ag > Mg > Al. The different strengthening effect of solutes can be attributed to their valence electron structure. Analysis on experimental results indicates that ternary Zn-based alloys may satisfy the clinical requirements on mechanical properties with less secondary phase and suppressed mechanical instability.

Due to the advantages of high specific strength, specific stiffness, and excellent fatigue resistance, carbon fiber reinforced braided composites have been widely applied in engineering. Since the molding process of braided composites is complex and immature, substantial variability of the internal geometry exists in composites, in which the yarn path with uncertainty is a main factor, so it is necessary to establish an uncertainty model to study the influence of randomness of the yarn path on mechanical properties, which is significantly related to the fatigue resistance properties of composite. An uncertain mesoscopic model with uniform distribution of yarn paths is proposed. Assuming the yarn path is spatially varying in interval range, the variability of yarn path is represented geometrically in the unit cell of composite. The three-dimensional coordinates of the yarn trajectory are calculated, the meso-uncertainty models of 2-D and 2.5-D braided composites are established. The equivalent elastic parameters and the thermal expansion coefficients are obtained by applying homogenization method and temperature field boundary conditions to the mesoscopic model. The effect of yarn path uncertainty on the statistical characteristics of elastic and thermal parameters of braided composites was studied by using Monte-Carlo simulation. A simulation method for modeling yarn path uncertainty of braided composites is provided in this paper for predicting the statistical characteristics of the equivalent elastic and thermal parameters.

To accurately determine the temperature-dependent parameters of composites, a thermo-elastic parameter identification approach using thermal modal data is proposed in this article. The investigation is based on two hypotheses: (1) the structure is at steady-state temperature field, which means the temperature distribution is time independent; (2) temperature distribution can be determined in advance of thermo-elastic parameter identification, and thermal-related large deformation is not considered. The thermal-dependent elastic constants and thermal expansion coefficients are expressed as intermediate functions with the independent variable of temperature, perturbation method is adapted to calculate the sensitivity of thermal modal frequencies with respect to the intermediate variables, and variables with high sensitivity are selected as the identifying parameters. By constructing the intermediate function and calculating the relative sensitivity, thermo-elastic parameters are identified by minimizing the residual between experimental and analytical natural frequencies under thermal circumstance. Two different types of composite models are employed to verify the strategies of parameter identification. Results show that on the basis of the intermediate function, the proposed approach can be applied to identify the thermo-elastic parameters effectively.

Abstract Mg2+‐deficiency is linked to hypertension, Alzheimer's disease, stroke, migraine headaches, cardiovascular diseases, and diabetes, etc., but its exact role in these pathophysiological conditions remains elusive. Mg2+ can regulate vascular functions, yet the mechanistic insight remains ill‐defined. Data show that extracellular Mg2+ enters endothelium mainly through the TRPM7 channel and MagT1 transporter. Mg2+ can act as an antagonist to reduce Ca2+ signaling in endothelium. Mg2+ also reduces the intracellular reactive oxygen species (ROS) level and inflammation. In addition, Mg2+‐signaling increases endothelial survival and growth, adhesion, and migration. Endothelial barrier integrity is significantly enhanced with Mg2+‐treatment through S1P1‐Rac1 pathways and barrier‐stabilizing mediators including cAMP, FGF1/2, and eNOS. Mg2+ also promotes cytoskeletal reorganization and junction proteins to tighten up the barrier. Moreover, Mg2+‐deficiency enhances endothelial barrier permeability in mice, and Mg2+‐treatment rescues histamine‐induced transient vessel hyper‐permeability in vivo. In summary, Mg2+‐deficiency can cause deleterious effects in endothelium integrity, and Mg2+‐treatment may be effective in the prevention or treatment of vascular dysfunction.

Abstract Recently emerged metallic zinc (Zn) is a new generation of promising candidates for bioresorbable medical implants thanks to its essential physiological relevance, mechanical strength, and more matched degradation pace to that of tissue healing. Zn‐based metals exhibit excellent biocompatibility in various animal models. However, direct culture of cells on Zn metals yields surprisingly low viability, indicating high cytotoxicity of Zn. This contradicting phenomenon should result from the different degradation mechanisms between in vitro and in vivo. To solve this puzzle, the roles of all major players, i.e., zinc phosphate (ZnP), zinc oxide (ZnO), zinc hydroxide (Zn(OH)2), pH, and Zn2+, which are involved in the degradation process are examined. Data shows that ZnP, not ZnO or Zn(OH)2, significantly enhances its biocompatibility. The mild pH change during degradation also has no significant impact on cell viability. Collectively, ZnP appears to be the key to controlling the biocompatibility of Zn implants and could be applied as a novel surface coating to improve biocompatibility of different implants.

Magnesium (Mg)-based biodegradable materials are promising candidates for the new generation of implantable medical devices, particularly cardiovascular stents and orthopaedic implants. Mg-based cardiovascular stents represent the most innovative stent technology to date. However, these products still do not fully meet clinical requirements with regards to fast degradation rates, late restenosis, and thrombosis. Thus various surface coatings have been introduced to protect Mg-based stents from rapid corrosion and to improve biocompatibility. Similarly, different coatings have been used for orthopaedic implants, e.g., plates and pins for bone fracture fixation or as an interference screw for tendon-bone or ligament-bone insertion, to improve biocompatibility and corrosion resistance. Metal coatings, nanoporous inorganic coatings and permanent polymers have been proved to enhance corrosion resistance; however, inflammation and foreign body reactions have also been reported. By contrast, biodegradable polymers are more biocompatible in general and are favoured over permanent materials. Drugs are also loaded with biodegradable polymers to improve their performance. The key similarities and differences in coatings for Mg-based stents and orthopaedic implants are summarized.

Magnesium (Mg) alloys are promising scaffolds for the next generation of cardiovascular stents because of their better biocompatibility and biodegradation compared to traditional metals. However, insufficient mechanical strength and high degradation rate are still the two main limitations for Mg materials. Hydrofluoric acid (HF) treatment and collagen coating were used in this research to improve the endothelialization of two rare earth-based Mg alloys. Results demonstrated that a nanoporous film structure of fluoride with thickness of ~20 µm was formed on the Mg material surface, which improved the corrosion resistance. Primary human coronary artery endothelial cells (HCAECs) had much better attachment, spreading, growth and proliferation (the process of endothelialization) on HF-treated Mg materials compared to bare- or collagen-coated ones.

A muon facility—EMuS (Experimental Muon Source)—at China Spallation Neutron Source (CSNS) has been studied since 2007. CSNS, which is designed to deliver a proton beam power of 100 kW at Phase-I, and will serve multidisciplinary research based on neutron scattering techniques, has just completed construction, and is ready to open to general users from September 2018. As an additional platform to CSNS, EMuS aims to provide different muon beams for multiple applications, among which, magnetism study by μSR techniques is a core part. By using innovative designs, such as a long target in conical shape situating in superconducting capture solenoids and forward collection method, EMuS can provide very intense muon beams with a proton beam of 5 kW and 1.6 GeV, from surface muons, decay muons, and high momentum muons to slow muons. In this article, the design aspects of EMuS, including general design, target station, muon beamlines, and μSR spectrometer, as well as prospects for applications on magnetism studies, will be reviewed.

Magnesium (Mg) based alloys are the most advanced cardiovascular stent materials. This new generation of stent scaffold is currently under clinical evaluation with encouraging outcomes. All these Mg alloys contain a certain amount of rare earth (RE) elements though the exact composition is not yet disclosed. RE alloying can usually enhance the mechanical strength of different metal alloys but their toxicity might be an issue for medical applications. It is still unclear how RE elements will affect the magnesium (Mg) alloys intended for stent materials as a whole. In this study, we evaluated MgZnCaY-1RE, MgZnCaY-2RE, MgYZr-1RE, and MgZnYZr-1RE alloys for cardiovascular stents applications regarding their mechanical strength, corrosion resistance, hemolysis, platelet adhesion/activation, and endothelial biocompatibility. The mechanical properties of all alloys were significantly improved. Potentiodynamic polarization showed that the corrosion resistance of four alloys was at least 3-10 times higher than that of pure Mg control. Hemolysis test revealed that all the materials were non-hemolytic while little to moderate platelet adhesion was found on all materials surface. No significant cytotoxicity was observed in human aorta endothelial cells cultured with magnesium alloy extract solution for up to seven days. Direct endothelialization test showed that all the alloys possess significantly better capability to sustain endothelial cell attachment and growth. The results demonstrated the promising potential of these alloys for stent material applications in the future.

Magnesium (Mg) biomaterials are a new generation of biodegradable materials and have promising potential for orthopedic applications. After implantation in bone tissues, these materials will directly interact with extracellular matrix (ECM) biomolecules and bone cells. Type I collagen, the major component of bone ECM, forms the architecture scaffold that provides physical support for bone cell attachment. However, it is still unknown how Mg substrate affects collagen assembly on top of it as well as subsequent cell attachment and growth. Here, we studied the effects of collagen monomer concentration, pH, assembly time, and surface roughness of two Mg materials (pure Mg and AZ31) on collagen fibril formation. Results showed that formation of fibrils would not initiate until the monomer concentration reached a certain level depending on the type of Mg material. The thickness of collagen fibril increased with the increase of assembly time. The structures of collagen fibrils formed on semi-rough surfaces of Mg materials have a high similarity to that of native bone collagen. Next, cell attachment and growth after collagen assembly were examined. Materials with rough surface showed higher collagen adsorption but compromised bone cell attachment. Interestingly, surface roughness and collagen structure did not affect cell growth on AZ31 for up to a week. Findings from this work provide some insightful information on Mg-tissue interaction at the interface and guidance for future surface modifications of Mg biomaterials.