Nanomaterials-Based Hybrid Bioink Platforms in Advancing 3D Bioprinting Technologies for Regenerative Medicine.

3D bioprinting is recognized as the ultimate additive biomanufacturing technology in tissue engineering and regeneration, augmented with intelligent bioinks and bioprinters to construct tissues or organs, thereby eliminating the stipulation for artificial organs. For 3D bioprinting of soft tissues, such as kidneys, hearts, and other human body parts, formulations of bioink with enhanced bioinspired rheological and mechanical properties were essential. Nanomaterials-based hybrid bioinks have the potential to overcome the above-mentioned problem and require much attention among researchers. Natural and synthetic nanomaterials such as carbon nanotubes, graphene oxides, titanium oxides, nanosilicates, nanoclay, nanocellulose, etc. and their blended have been used in various 3D bioprinters as bioinks and benefitted enhanced bioprintability, biocompatibility, and biodegradability. A limited number of articles were published, and the above-mentioned requirement pushed us to write this review. We reviewed, explored, and discussed the nanomaterials and nanocomposite-based hybrid bioinks for the 3D bioprinting technology, 3D bioprinters properties, natural, synthetic, and nanomaterial-based hybrid bioinks, including applications with challenges, limitations, ethical considerations, potential solution for future perspective, and technological advancement of efficient and cost-effective 3D bioprinting methods in tissue regeneration and healthcare.

Polymeric Nanoparticles for Wound Healing.

Skin injury is one of the most prevalent lesions in humans, and many such wounds, including deep burns and chronic skin wounds, are notoriously difficult to heal. It has been established by medical practitioners that current wound therapies are not perfectly effective and are far from satisfactory. Meanwhile, nanotechnologies have made it possible to develop pharmaceutical formulations that can elevate the effectiveness of conventional pharmacotherapies to entirely new heights. Most nanostructured biomaterials used to treat wounds, including those that have helped establish this fascinating subject, have been polymeric. The bibliographic analysis presented here shows a steady growth in the research output of studies on the use of polymeric nanoparticles in wound healing therapies. This article provides an overview of polymeric nanoparticles for the treatment of wounds with an emphasis on different chemistries and polymer-drug combinations that have been proven the most effective. The wound age, pathophysiology, wound healing treatments of the present and past, as well as the physicochemical nature and methods for the synthesis of polymeric nanoparticles, are all covered in the opening parts of the review. The existing polymeric nano-drug delivery systems with the greatest promise for wound healing and skin regeneration are subsequently addressed and their potentials summarized.

Understanding the Association Between Obesity and Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Introduction Obstructive sleep apnea (OSA) represents a sleep-related impairment linked to upper airway function. The question of whether OSA drives obesity or if shared underlying factors contribute to both conditions remains unresolved. Hence, this present study aims to understand the interplay between obstructive sleep apnea syndrome (OSAS) and obesity through in-depth analysis of anthropometric data within control subjects and OSA patients. Methodology A case-control study was conducted, which included 40 cases and 40 matched healthy controls. Study participants with reported symptoms of snoring, daytime drowsiness, or both were included in the study. All the study participants underwent comprehensive anthropometric assessments such as height, weight, body mass index (BMI), neck circumference, waist circumference, hip circumference, waist-to-hip ratio, skin-fold thickness, and thickness measurements of biceps, triceps, suprailiac, and subscapular muscles. Results Within the OSA group, significant disparities emerged in mean age, waist circumference, waist-to-hip ratio, and diverse fat accumulations encompassing visceral, subcutaneous, trunk, and subcutaneous leg fat. Notably, skin-fold thickness at specific sites - biceps, triceps, subscapula, and suprailiac - demonstrated considerable augmentation relative to the control group. Furthermore, mean values associated with height, weight, BMI, neck circumference, fat percentage, subcutaneous arm fat, entire arm composition, and trunk skeletal muscle either equaled or exceeded those in the control group. However, statistical significance was not attained in these comparisons. Conclusion This investigation underscored a pronounced correlation between numerous endpoints characterizing OSA patients and markers of obesity. Consequently, addressing altered levels of obesity-linked anthropometric variables through pharmacological interventions might hold promise as a pivotal strategy for improving symptoms associated with OSA.

Oxidative Stress in Wistar Rats Under Acute Restraint Stress and Its Modulation by Antioxidants and Nitric Oxide Modulators.

BACKGROUND: Several pathogenic conditions leading to morbidity, including cancer, aging, diabetes, reperfusion injury, cardiovascular disease, and neurological disorders, are known to be exacerbated by oxidative stress. Antioxidant therapy is effective in the treatment of such disorders and appears to be a potential therapeutic technique to reduce oxidative stress. The aim of our study is to investigate the antioxidant effects of L-ascorbic acid and nitric oxide (NO) modulators on rats suffering from oxidative stress induced by acute restraint stress (RSx1). METHODOLOGY: In this in vivo study, Wistar rats were subjected to one hour of restraint stress on day 21 to induce oxidative stress. Superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase, glutathione (GSH), and malondialdehyde (MDA) were used to assess the antioxidant effects. IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. was used for data analysis. RESULTS: Compared to vehicle groups, acute restraint stress (RSx1) dramatically increased MDA levels while decreasing GSH, SOD, total antioxidant capacity, and catalase. L-NAME, 7-NI, AG (50 mg/kg each), and L-ascorbic acid (200 mg/kg) reversed the changes in SOD, MDA, GSH, total antioxidant capacity, and catalase levels. The NO precursor L-arginine (1000 mg/kg) and NO synthase inhibitors followed the same trend. CONCLUSION: Our study findings highlight the complex role of antioxidants and NO modulators in the pathogenesis of diseases, as evidenced by the reversal of oxidative stress indicators. Antioxidant therapy, with its potential to mitigate oxidative stress, emerges as a viable treatment option for a range of pathological conditions associated with oxidative stress.

Clinical, laboratory profile and outcomes in children with snakebite from Eastern India.

Background: Snakebite remains a significant public health problem worldwide, particularly in rural areas with unexpected morbidity and mortality. This study evaluated the clinical, laboratory profile and outcomes in children with snake bites from Eastern India. Methods: This was a retrospective case record-based study between January 2017 and December 2021. The clinical features, complications, laboratory profiles and outcomes were analysed. Results: Thirty children with snake bites were admitted during this study period. There was a male predominance with a ratio of 2.3:1. The mean age of presentation was 10.4 years. About 60% of bites occurred during the rainy season between July and September. Most bites (96%) were on lower limbs, predominantly showing vasculotoxic features followed by neurotoxic and a combined presentation. In this study, around 53% received anti-snake venom (ASV) before reaching our centre; the median time to reach our centre was 13 h. Complications such as acute kidney injury (AKI), cellulitis, shock and coagulation abnormalities were common in those who arrived early (before 6 h) than in those who reached late (after 6 h). Similarly, the mean duration of hospital stay was less for those seeking medical attention early as compared to those reaching late for treatment (4.7 days vs. 7.2 days). Twenty-six out of 30 (86.7%) were discharged without any sequelae, 3 (10%) children were left against medical advice and one died. Conclusions: Snakebite remains a major health problem in children causing significant morbidity and mortality. Children, in general, especially males, are particularly vulnerable because of their playful and explorative nature and considerable time spent in outdoor activities. Preventive measures, education about avoiding traditional first aid methods and early administration of ASV reduce complications, duration of hospital stay and avoid the use of antibiotics.

Assessment of Leptin Levels and Their Correlation With the Severity of Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Background Obstructive sleep apnea (OSA) is characterized by a combination of structural issues in the upper airway and imbalances in the respiratory control system. While numerous studies have linked OSA with obesity, it remains uncertain whether leptin, a hormone associated with fat, plays a role in the functional and anatomical defects that lead to OSA. Therefore, the aim of this study was to investigate whether leptin levels could be used as a predictor of OSA syndrome (OSAS). Methodology A case-control observational study was conducted, enrolling study participants who reported obesity (BMI > 30) within the range of >30 to <35 kg/m2, along with a short neck and a history of snoring, excessive daytime drowsiness, fatigue, or insomnia. Leptin levels and fasting blood sugar (FBS) were measured in all individuals. Additionally, the study evaluated the severity of OSAS using indicators such as the STOP BANG scores, apnea-hypopnea index, uvula grade score, and Epworth Sleepiness Scale scores. Results A total of 80 participants (40 cases and 40 controls) were included in the study. The mean leptin and FBS levels were significantly higher in cases compared to controls. Moreover, leptin levels exhibited a significant correlation with the severity indices of OSAS. Conclusion The study findings indicate that individuals with higher leptin levels tend to exhibit more severe OSAS symptoms. Furthermore, these elevated leptin levels contribute to the worsening of various OSA symptoms. Larger controlled studies have suggested that pharmacologically restoring the altered leptin levels may serve as a beneficial adjunct to treatment for alleviating OSAS symptoms.

Contemporary updates on bioremediation applications of graphene and its composites.

Graphene, a 2D single-layered carbon sp2 hybrid substance set in a honeycomb network, is widespread in many carbon-based materials. Due to its extraordinary optical, electrical, thermal, mechanical, and magnetic competences as well as its significant specific surface area, it has attracted a lot of interest recently. Synthesizing graphene refers to any process for creating or extracting the material, depending on the desired purity, size, and efflorescence of the finished good. Numerous methods have been employed for graphene synthesis categorized as top-down procedures and bottom-up procedures. Graphene finds its implementations in various industries such as electronics, energy, chemical, transport, defence, and biomedical areas such as accurate biosensing. It has been widely used in water treatment as a binder for organic contaminants and heavy metals. Many researches have fixated on creating various modified graphene, graphene oxide composites, graphene nanoparticle composites and semiconductor hybrids of graphene for contaminant removal from water. In this review, we have tried to address various production methods for graphene and its composites along with their advantages and disadvantages. Furthermore, we have presented a summary on graphene's outstanding immobilization of a variety of contaminants like toxic heavy metals, organic dyes, inorganic pollutants and pharmaceutical wastes. Additionally, a development of graphene-based microbial fuel cell (MFC) has been evaluated in an effort to produce ecological wastewater treatment and bioelectricity.

Angiogenic stimulation strategies in bone tissue regeneration.

Current tissue engineering strategies in bone repair and regeneration have limitations regarding tissue rejection, insufficient blood supply, and tissue integration. Specific host response results in isolation, degeneration, and subsequent loss of function of the implanted/scaffold biomaterial. Therefore, strategies to increase the interplay between angiogenesis and complex bone tissue formation are required to develop fully functional vascularized bone tissue. Angiogenesis is essential for oxygen/nutrient supply, waste removal, endothelial/stem cell homing, and the release of mitogenic/angiogenic/osteogenic factors. Hence, the challenge lies in understanding the complex interdependence of angiogenesis with neo-bone formation. Therefore, recent bone tissue regeneration strategies have focused on biomaterial development concerning induction of neovascularization and subsequent angiogenesis. Scaffold architecture (macro/micro/nano) scales, culture conditions (3-Dimension, hypoxia, etc), stimuli-dependent delivery of angiofactors, and gene delivery may significantly modulate vascularization in tissue-engineered products. Therefore, the current review discusses the key mechanisms/steps involved in defining the relationship between angiogenic and osteogenic factors. The recent strategies incorporating the above understanding in the development of bone tissue-engineered constructs are also deliberated. Eventually, these strategies may give the potential way forward to develop a bioengineered, vascularized bone tissue construct for implant applications.

Emerging role and promise of nanomaterials in organoid research.

Organoids are 3D stem cell-derived self-organization of cells. Organoid bioengineering helps recreate and tailor their architecture in vitro to generate mini organ-like properties, providing the opportunity to study fundamental cell behavior in heterogeneous populations and as a tool to model various diseases. Nanomaterials (NMs) are becoming indispensable in regenerative medicine and in developing treatment modalities for various diseases. Therefore, organoid-NM interactions are set to gain traction for the development of advanced diagnostics and therapeutics. Here, we discuss the interactions of NMs with distinctive organoid types, organoid matrices, trafficking and cargo delivery, organs-on-a-chip, bioprinting, downstream therapeutic implications, and future approaches.

A designer cell culture insert with a nanofibrous membrane toward engineering an epithelial tissue model validated by cellular nanomechanics.

Engineered platforms for culturing cells of the skin and other epithelial tissues are useful for the regeneration and development of in vitro tissue models used in drug screening. Recapitulating the biomechanical behavior of the cells is one of the important hallmarks of successful tissue generation on these platforms. The biomechanical behavior of cells profoundly affects the physiological functions of the generated tissue. In this work, a designer nanofibrous cell culture insert (NCCI) device was developed, consisting of a free-hanging polymeric nanofibrous membrane. The free-hanging nanofibrous membrane has a well-tailored architecture, stiffness, and topography to better mimic the extracellular matrix of any soft tissue than conventional, flat tissue culture polystyrene (TCPS) surfaces. Human keratinocytes (HaCaT cells) cultured on the designer NCCIs exhibited a 3D tissue-like phenotype compared to the cells cultured on TCPS. Furthermore, the biomechanical characterization by bio-atomic force microscopy (Bio-AFM) revealed a markedly altered cellular morphology and stiffness of the cellular cytoplasm, nucleus, and cell-cell junctions. The nuclear and cytoplasmic moduli were reduced, while the stiffness of the cellular junctions was enhanced on the NCCI compared to cells on TCPS, which are indicative of the fluidic state and migratory phenotype on the NCCI. These observations were corroborated by immunostaining, which revealed enhanced cell-cell contact along with a higher expression of junction proteins and enhanced migration in a wound-healing assay. Taken together, these results underscore the role of the novel designer NCCI device as an in vitro platform for epithelial cells with several potential applications, including drug testing, disease modeling, and tissue regeneration.

Nanostructured polymer scaffold decorated with cerium oxide nanoparticles toward engineering an antioxidant and anti-hypertrophic cardiac patch.

Reactive oxygen species (ROS) are generated in reperfused ischemic heart tissue after myocardial infarction (MI). A compensatory attempt of the heart to enhance its functional performance after MI is to undergo cardiomyocyte hypertrophy. In the past, reducing the levels of ROS in the cardiomyocytes has been linked to suppression of cardiac hypertrophy. Notably, cerium oxide nanoparticles (nCe) have been used extensively to protect the cells from oxidative damage by efficiently scavenging cellular ROS. Furthermore, fibrous matrices such as nanofibers are emerging as promising substrates for engineering implantable cardiac patches. In this study, we describe the fabrication of nCe-decorated polycaprolactone (PCL) and PCL-gelatin blend (PCLG) nanofibers prepared using electrospinning. Characterization by X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, atomic force microscopy, and contact angle goniometry confirmed the presence of nCe on PCL or PCLG nanofibers (PCLG-Ce) of ≈300 nm fiber diameter. nCe-based PCLG scaffolds were cytocompatible with a variety of cell types, including primary cells. Primary cardiomyocytes cultured on nCe-decorated PCLG nanofibers showed marked reduction in the ROS levels when subjected to H2O2 induced oxidative stress. Interestingly, we found that nCe-decorated PCLG nanofibers can suppress agonist-induced cardiac hypertrophy. Overall, the results of this study suggest the potential of nCe-decorated PCLG nanofibers as a cardiac patch with antioxidant and anti-hypertrophic properties.

Revascularization and limb salvage following critical limb ischemia by nanoceria-induced Ref-1/APE1-dependent angiogenesis.

In critical limb ischemia (CLI), overproduction of reactive oxygen species (ROS) and impairment of neovascularization contribute to muscle damage and limb loss. Cerium oxide nanoparticles (CNP, or 'nanoceria') possess oxygen-modulating properties which have shown therapeutic utility in various disease models. Here we show that CNP exhibit pro-angiogenic activity in a mouse hindlimb ischemia model, and investigate the molecular mechanism underlying the pro-angiogenic effect. CNP were injected into a ligated region of a femoral artery, and tissue reperfusion and hindlimb salvage were monitored for 3 weeks. Tissue analysis revealed stimulation of pro-angiogenic markers, maturation of blood vessels, and remodeling of muscle tissue following CNP administration. At a dose of 0.6 mg CNP, mice showed reperfusion of blood vessels in the hindlimb and a high rate of limb salvage (71%, n = 7), while all untreated mice (n = 7) suffered foot necrosis or limb loss. In vitro, CNP promoted endothelial cell tubule formation via the Ref-1/APE1 signaling pathway, and the involvement of this pathway in the CNP response was confirmed in vivo using immunocompetent and immunodeficient mice and by siRNA knockdown of APE1. These results demonstrate that CNP provide an effective treatment of CLI with excessive ROS by scavenging ROS to improve endothelial survival and by inducing Ref-1/APE1-dependent angiogenesis to revascularize an ischemic limb.

Ceria-incorporated MTA for accelerating odontoblastic differentiation via ROS downregulation.

OBJECTIVE: Odontoblast differentiation from dental pulp stem cells (DPSCs) is involved in a cascade of key biological events for maintaining pulp-dentin homeostasis, repair and regeneration. A pulp regeneration biomaterial (mineral trioxide aggregate (MTA)) increased intracellular reactive oxygen species (ROS) levels during differentiation, ameliorating the differentiating of DPSCs into odontoblasts. Here, ceria nanoparticles (CNP) were incorporated as an insoluble antioxidant into commercially available MTA (CMTA), and the odontoblastic differentiation of human DPSCs was investigated. METHODS: The CMTA was fabricated from MTA and CNP conjugation up to 4wt%, and the compressive strength, surface morphology after setting and setting time were investigated. Furthermore, the alkaline phosphatase (ALP) assay, Alizarin Red staining (ARS) and quantitative real-time polymerase chain reaction (qPCR) were performed to evaluate odontoblastic differentiation in an indirect co-culture system using inserts with pores. To reveal the underlying mechanism, the ROS levels and ion release were measured. Statistical analysis was performed by one-way analysis of variance with a Tukey post hoc test (P<0.05). RESULTS: CMTA significantly elevated the odontoblastic differentiation of hDPSCs measured by ALP activity, ARS, and odontoblastic gene expression, whereas the other physico-mechanical properties were relatively maintained. Upregulation of gene expression from CMTA was reversed with hydrogen peroxide. CMTA could reduce the increased intracellular ROS levels of hDPSCs by approximately 70% during differentiation, similar to when an antioxidant was used, without changing the ion release and pH of the media. SIGNIFICANCE: CMTA could be useful dental materials for regenerating dentin-pulp complexes by instructing intracellular ROS during differentiation to achieve beneficial biological functions. This study suggests a new direction of dental nanomaterials in treating pulp-dentin complexes.

Differential chondro- and osteo-stimulation in three-dimensional porous scaffolds with different topological surfaces provides a design strategy for biphasic osteochondral engineering.

Bone/cartilage interfacial tissue engineering needs to satisfy the differential properties and architectures of the osteochondral region. Therefore, biphasic or multiphasic scaffolds that aim to mimic the gradient hierarchy are widely used. Here, we find that two differently structured (topographically) three-dimensional scaffolds, namely, "dense" and "nanofibrous" surfaces, show differential stimulation in osteo- and chondro-responses of cells. While the nanofibrous scaffolds accelerate the osteogenesis of mesenchymal stem cells, the dense scaffolds are better in preserving the phenotypes of chondrocytes. Two types of porous scaffolds, generated by a salt-leaching method combined with a phase-separation process using the poly(lactic acid) composition, had a similar level of porosity (~90%) and pore size (~150 µm). The major difference in the surface nanostructure led to substantial changes in the surface area and water hydrophilicity (nanofibrous ≫ dense); as a result, the nanofibrous scaffolds increased the cell-to-matrix adhesion of mesenchymal stem cells significantly while decreasing the cell-to-cell contracts. Importantly, the chondrocytes, when cultured on nanofibrous scaffolds, were prone to lose their phenotype, including reduced chondrogenic expressions (SOX-9, collagen type II, and Aggrecan) and glycosaminoglycan content, which was ascribed to the enhanced cell-matrix adhesion with reduced cell-cell contacts. On the contrary, the osteogenesis of mesenchymal stem cells was significantly accelerated by the improved cell-to-matrix adhesion, as evidenced in the enhanced osteogenic expressions (RUNX2, bone sialoprotein, and osteopontin) and cellular mineralization. Based on these findings, we consider that the dense scaffold is preferentially used for the chondral-part, whereas the nanofibrous structure is suitable for osteo-part, to provide an optimal biphasic matrix environment for osteochondral tissue engineering.

Combinatory Cancer Therapeutics with Nanoceria-Capped Mesoporous Silica Nanocarriers through pH-triggered Drug Release and Redox Activity.

In the field of nanomedicine, drug-loaded nanocarriers that integrate nanotechnology and chemotherapeutics are widely used to achieve synergistic therapeutic effects. Here, we prepared mesoporous silica nanoparticles capped with cerium oxide nanoparticles (COP@MSN) wherein a pH trigger-responsive mechanism was used to control drug release and intracellular drug delivery. We blocked the mesopores of the carboxyl-functionalized MSN with aminated COP. These pores could be opened in acidic conditions to release the loaded drug, thus establishing a pH-responsive drug release system. We loaded doxorubicin (DOX) as anticancer biomolecule into the pores of MSN and capped with COP. The COP@DOX-MSN system showed a typical drug release profile in an acidic medium, which, however, was not observed in a neutral medium. In vitro studies using cancer cell line (HeLa) proved that the COP@DOX-MSN entered efficiently into HeLa cells and released DOX to the level sufficient for cytotoxicity. The cytotoxic effect of COP in cancer cells was facilitated by the pro-oxidant property of COPs, which considerably raised the reactive oxygen species (ROS) level, thereby leading to cellular apoptosis. The combination of DOX with COP (COP@DOX-MSN) showed even higher ROS level, demonstrating a cytotoxic synergism of drug and nanoparticle in terms of ROS generation. Collectively, the COP@DOX-MSN is considered useful for cancer treatment with the combined capacity of pH-controlled drug delivery, chemotherapeutics, and redox activity.

Energy Management in Smart Cities Based on Internet of Things: Peak Demand Reduction and Energy Savings.

Around the globe, innovation with integrating information and communication technologies (ICT) with physical infrastructure is a top priority for governments in pursuing smart, green living to improve energy efficiency, protect the environment, improve the quality of life, and bolster economy competitiveness. Cities today faces multifarious challenges, among which energy efficiency of homes and residential dwellings is a key requirement. Achieving it successfully with the help of intelligent sensors and contextual systems would help build smart cities of the future. In a Smart home environment Home Energy Management plays a critical role in finding a suitable and reliable solution to curtail the peak demand and achieve energy conservation. In this paper, a new method named as Home Energy Management as a Service (HEMaaS) is proposed which is based on neural network based Q-learning algorithm. Although several attempts have been made in the past to address similar problems, the models developed do not cater to maximize the user convenience and robustness of the system. In this paper, authors have proposed an advanced Neural Fitted Q-learning method which is self-learning and adaptive. The proposed method provides an agile, flexible and energy efficient decision making system for home energy management. A typical Canadian residential dwelling model has been used in this paper to test the proposed method. Based on analysis, it was found that the proposed method offers a fast and viable solution to reduce the demand and conserve energy during peak period. It also helps reducing the carbon footprint of residential dwellings. Once adopted, city blocks with significant residential dwellings can significantly reduce the total energy consumption by reducing or shifting their energy demand during peak period. This would definitely help local power distribution companies to optimize their resources and keep the tariff low due to curtailment of peak demand.

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal-Dosed Cerium Oxide Nanoparticles.

Spinal cord injury (SCI) produces excess reactive oxygen species (ROS) that can exacerbate secondary injury and lead to permanent functional impairment. Hypothesizing that cerium oxide nanoparticles (CONPs) as an effective ROS scavenger may offset this damaging effect, it is first demonstrated in vitro that CONPs suppressed inducible nitric oxide synthase (iNOS) generation and enhanced cell viability of hydrogen peroxide (H2O2)-insulted cortical neurons. Next, CONPs are administered at various does (50-4000 µg mL-1) to a contused spinal cord rat model and monitored the disease progression for up to eight weeks. At one day postinjury, the number of iNOS+ cells decreases in the treated groups compared with the control. At one week, the cavity size and inflammatory cells are substantially reduced, and the expression of proinflammatory and apoptotic molecules is downregulated with a concurrent upregulation of anti-inflammatory cytokine. By eight weeks, the treated groups show significantly improved locomotor functions compared with the control. This study shows for the first time that injection of optimal-dosed CONPs alone into contusion-injured spinal cord of rats can reduce ROS level, attenuate inflammation and apoptosis, and consequently help locomotor functional recovery, adding a promising and complementary strategy to the other treatments of acute SCI.

Nano-shape varied cerium oxide nanomaterials rescue human dental stem cells from oxidative insult through intracellular or extracellular actions.

Cerium oxide nanomaterials (CeNMs), due to their excellent scavenging properties of reactive oxygen species (ROS), have gained great promise for therapeutic applications. A high level of ROS often degrades the potential of stem cells in terms of survivability, maintenance and lineage differentiation. Here we hypothesize the CeNMs may play an important role in protecting the capacity of stem cells against the oxidative insult, and the suppression mechanism of ROS level may depend on the internalization of CeNMs. We synthesized CeNMs with different directional shapes (aspect ratios) by a pH-controlled hydrothermal method, and treated them to stem cells derived from human dental pulp at various doses. The short CeNMs (nanoparticles and nanorods) were internalized rapidly to cells whereas long CeNMs (nanowires) were slowly internalized, which led to different distributions of CeNMs and suppressed the ROS levels either intracellularly or extracellularly under the H2O2-exposed conditions. Resultantly, the stem cells, when dosed with the CeNMs, were rescued to have excellent cell survivability; the damages in intracellular components including DNA fragmentation, lipid rupture and protein degradation were significantly alleviated. The findings imply that the ROS-scavenging events of CeNMs need special consideration of aspect ratio-dependent cellular internalization, and also suggest the promising use of CeNMs to protect stem cells from the ROS-insult environments, which can ultimately improve the stem cell potential for tissue engineering and regenerative medicine uses. STATEMENT OF SIGNIFICANCE: Oxidative stress governs many stem cell functions like self-renewal and lineage differentiation, and the biological conditions involving tissue repair and disease cure where stem cell therapy is often needed. Here we demonstrate the unique role of cerium oxide nanomaterials (CeNMs) in rescuing stem cell survivability, migration ability, and intracellular components from oxidative stress. In particular, we deliver a novel finding that nano-morphologically varied CeNMs show different mechanisms in their scavenging reactive oxygen species either intracellularly or extracellularly, and this is related with their different cellular internalizations. We used human dental pulp stem cells for the model study and proved the CeNMs were effective in controlling ROS level by means of scavenging intracellularly or extracellularly, which ultimately led to improving the intact therapeutic potential of stem cells. This work touches an important biological issue of nanomaterial interactions with stem cells under the conditions related with oxidative stress and the resultant damage. The correlation of shape factor in therapeutic nanomaterials with stem cell interaction and the oxidative stress-related functions will provide informative ideas in the design of CeNMs for cellular therapy.

Osteopromoting Reservoir of Stem Cells: Bioactive Mesoporous Nanocarrier/Collagen Gel through Slow-Releasing FGF18 and the Activated BMP Signaling.

Providing an osteogenic stimulatory environment is a key strategy to construct stem cell-based bone-equivalent tissues. Here we design a stem cell delivering gel matrix made of collagen (Col) with bioactive glass nanocarriers (BGn) that incorporate osteogenic signaling molecule, fibroblast growth factor 18 (FGF18), a reservoir considered to cultivate and promote osteogenesis of mesenchymal stem cells (MSCs). The presence of BGn in the gel was shown to enhance the osteogenic differentiation of MSCs, possibly due to the therapeutic role of ions released. The mesoporous nature of BGn was effective in loading FGF18 at large quantity, and the FGF18 release from the BGn-Col gel matrix was highly sustainable with almost a zero-order kinetics, over 4 weeks as confirmed by the green fluorescence protein signal change. The released FGF18 was effective in accelerating osteogenesis (alkaline phosphatase activity and bone related gene expressions) and bone matrix formation (osteopontin, bone sialoprotein, and osteocalcin production) of MSCs. This was attributed to the bone morphogenetic protein (BMP) signaling pathway, where the FGF18 release stimulated the endogenous secretion of BMP2 and the downstream signal Smad1/5/8. Taken together, the FGF18-BGn/Col gel is considered an excellent osteopromoting depot to support and signal MSCs for bone tissue engineering.

C-Dot Generated Bioactive Organosilica Nanospheres in Theranostics: Multicolor Luminescent and Photothermal Properties Combined with Drug Delivery Capacity.

Biocompatible nanomaterials that allow for labeling cells and tissues with the capacity to load and deliver drug molecules hold great promise for the therapeutic-diagnostic purposes in tissue repair and disease cure. Here a novel nanoplatform, called C-dot bioactive organosilica nanosphere (C-BON), is introduced to have excellent theranostic potential, such as controlled drug delivery, visible-light imaging, and NIR photothermal activity. C-dots with a few nanometers were in situ generated in the Ca-containing organosilica mesoporous nanospheres through the sol-gel and thermal-treatment processes. The C-BON exhibited multicolor luminescence over a wide visible-light range with strong emissions and high photostability over time and against acidity and the possible in vivo optical imaging capacity when injected in rat subcutaneous tissues. Moreover, the C-BON showed a photothermal heating effect upon the irradiation of near-infrared. The C-BON, thanks to the high mesoporosity and existence of Ca(2+) ions, demonstrated excellent loading capacity of anticancer drug doxorubicin (as high as 90% of carrier weight) and long-term (over a couple of weeks) and pH/NIR-dependent release ability. The C-BON preserved the compositional merit of Ca-Si glass, having excellent bioactivity and cell compatibility in vitro. Taken all, the multifunctional properties of C-BON-multicolor luminescence, photothermal activity, and high drug loading and controlled release-together with its excellent bioactivity and cell compatibility potentiate the future applications in theranostics (chemotherapy and photothermal therapy with optical imaging).