Nanoparticles-assisted aptamer biosensing for the detection of environmental pathogens.

Given the importance of public health, it is crucial to develop quick, targeted, highly sensitive, and accurate technologies to monitor pathogenic microbes in response to the growing concerns of food and environmental safety. Although conventional approaches for microbiological detection are available, they are laborious, and often skill demanding. Therefore, such approaches are incompetent in the on-site or high-throughput assessment of pathogenic microbes. Numerous efforts have been made to develop biosensors that use nucleic acid aptamer as the biorecognition element, which would avoid the abovementioned limitations. Incorporating nanomaterials (NMs) into aptamer-based biosensors (aptasensors) improves their sensitivity and specificity, opening exciting possibilities for various applications, such as bioanalysis of food and environmental samples. Over the last decade, nanomaterial-conjugated aptasensors have seen a steadily rising demand. To this end, the main goal of this study is to demonstrate the novelty in the design of nanomaterial-conjugated aptasensors and how they can be used to detect different pathogenic microbes in water and food. The intent of this paper is to evaluate the cutting-edge techniques that have appeared in nano-aptasensors throughout the past few years, such as manufacturing procedures, analytical credibility, and sensing mechanisms. Additionally, the fundamental performance parameters of aptasensing techniques (such as detection limits, and sensing ranges response) were also used to evaluate their practical applicability. Finally, it is anticipated that this study will inspire innovative ideas and techniques for the construction and use of aptasensors for monitoring pathogenic microorganisms in food, drinks, recreational water, and wastewater.

An Injectable Hydrogel Composing Anti-Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment Remodeling in Rheumatoid Arthritis.

Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized HA macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) can display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, the introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogenesis, and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model.

Mussel bioinspired, silver-coated and insulin-loaded mesoporous polydopamine nanoparticles reinforced hyaluronate-based fibrous hydrogel for potential diabetic wound healing.

Diabetes wounds take longer to heal due to extended inflammation, decreased angiogenesis, bacterial infection, and oxidative stress. These factors underscore the need for biocompatible and multifunctional dressings with appropriate physicochemical and swelling properties to accelerate wound healing. Herein, insulin (Ins)-loaded, and silver (Ag) coated mesoporous polydopamine (mPD) nanoparticles were synthesized (Ag@Ins-mPD). The nanoparticles were dispersed into polycaprolactone/methacrylated hyaluronate aldehyde dispersion, electrospun to form nanofibers, and then photochemically crosslinked to form a fibrous hydrogel. The nanoparticle, fibrous hydrogel, and nanoparticle-reinforced fibrous hydrogel were characterized for their morphological, mechanical, physicochemical, swelling, drug-release, antibacterial, antioxidant, and cytocompatibility properties. The diabetic wound reconstruction potential of nanoparticle-reinforced fibrous hydrogel was studied using BALB/c mice. The results indicated that Ins-mPD acted as a reductant to synthesize Ag nanoparticles on their surface, held antibacterial and antioxidant potential, and their mesoporous properties are crucial for insulin loading and sustained release. The nanoparticle-reinforced scaffolds were uniform in architecture, porous, mechanically stable, showed good swelling, and possessed superior antibacterial, and cell-responsive properties. Furthermore, the designed fibrous hydrogel scaffold demonstrated good angiogenic, anti-inflammatory, increased collagen deposition, and faster wound repair capabilities, therefore, it could be used as a potential candidate for diabetic wound treatment.

Donor-Acceptor Engineering for Tailoring Highly Efficient Photosensitizers for Image-Guided Antitumor Photodynamic Therapy.

Photosensitizers (PSs) have greatly flourished as a promising tool for photodynamic therapy owing to their integration of both in situ diagnosis and treatment in a single nanoplatform. However, there is still a need to explore synthesis pathways that can result in high-performance PSs with good reproducibility, high yield, less dark toxicity, and an attractive therapeutic index. Therefore, by exploiting the precise molecular engineering guideline, this work unveils a straightforward protocol to fabricate three homologous PSs (TPA-T-RS, TPA-Ts-RS, and TPA-Ts-RCN) with aggregation-induced emission (AIE) characteristics. Through slight structural tuning, the PSs are capable of anchoring to the cell membrane, mitochondria, and lysosome, and effectively generating reactive oxygen species (ROS). More importantly, TPA-Ts-RCN proved an intuitively appealing imaging-guided photodynamic therapy (PDT) effect. This work is expected to add a promising dimension to the field of architecting AIE PSs for image-guided photodynamic therapy.

GelMA-catechol coated FeHAp nanorods functionalized nanofibrous reinforced bio-instructive and mechanically robust composite hydrogel scaffold for bone tissue engineering.

Critical bone defects complicate tissue graft-based surgeries, raising healthcare expenditures and underscoring scaffold-based tissue-engineering strategies to support bone reconstruction. Our study highlighted that the phase-compatible combination of inorganic nanorods, nanofibers, and hydrogels is promising for developing biomimetic and cell-instructive scaffolds since the bone matrix is a porous organic/inorganic composite. In brief, methacrylated gelatin (GelMA) was reacted with dopamine to form catechol-modified GeLMA (GelMA-C). The GelMA-C was nanocoated onto an iron-doped hydroxyapatite (FeHAp) nanorod via metal-catechol network coordination. The modified nanorod (FeHAp@GelMA-C) was loaded onto GelMA-based nanofibers. The nanorods loaded pre-fibers were electrospun onto GelMA solution and photochemically crosslinked to fabricate a fiber-reinforced hydrogel. The structural, mechanical, physicochemical, biocompatibility, swelling properties, osteogenic potential, and bone remodelling potential (using rat femoral defect model) of modified nanorods, simple hydrogel, and nanorod-loaded fiber-reinforced hydrogel were studied. The results supported that the interface interaction between GelMA-C/nanorods, nanorods/nanofibers, nanorods/hydrogels, and nanofiber/hydrogels significantly improved the microstructural and mechanical properties of the scaffold. Compared to pristine hydrogel, the nanorod-loaded fiber-reinforced scaffold better supported cellular responses, osteogenic differentiation, matrix mineralization, and accelerated bone regeneration. The nanorod-loaded fiber-reinforced hydrogel proved more biomimetic and cell-instructive for guided bone reconstruction.

An osteogenic, antibacterial, and anti-inflammatory nanocomposite hydrogel platform to accelerate bone reconstruction.

Fabricating an organic-inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague-Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues.

Spectrum of Dyslipidemias in Treatment-Naïve Human Immunodeficiency Virus-Infected Patients Presenting to an HIV Clinic of a Tertiary Care Hospital.

Introduction HIV/AIDS is a major communicable disease worldwide, especially in developing countries where disease prevalence is over 90%. The National AIDS Control Programme of Pakistan reported around 160,000 HIV cases (140,000-190,000) with a 5% prevalence among traditional risks groups. HIV infection is thought to affect lipids metabolism adversely, thus resulting in increased morbidity and mortality. The aim of the study was to find out the frequency and types of dyslipidemia in patients with HIV not taking anti-retroviral therapy, presenting to an HIV clinic at a tertiary care hospital. Methods This cross-sectional study was conducted at the HIV clinic of Jinnah Hospital from January 2020 to July 2020. A total of 280 treatment-naïve patients, fulfilling the inclusion protocol, were included through non-probability consecutive sampling after informed consent. Blood samples of 5 mL were taken using aseptic measures and following standard procedure after ensuring overnight fasting by a nurse and were sent immediately to the pathology laboratory of Allama Iqbal Medical College. The results of the lipid profile were collected the next day and noted in the proforma. Dyslipidemia and type of dyslipidemia were recorded as per operational definition. Data were analyzed by SPSS software, version 27.0 (IBM Corp., Armonk, NY). Cross-tabulation was done to assess the relationship of gender, BMI, and family history on dyslipidemia, and a chi-square test was applied to check statistical significance. Results Among 280 treatment-naïve HIV-infected patients, the majority of patients were females (52%). The mean duration of HIV was 9.31 + 2.13 months. About 55% of patients had a BMI of more than 25 kg m2. A family history of dyslipidemia was found in 62% of the patients. Dyslipidemia was observed in 70% of patients with maximum derangement seen in total cholesterol level (62%). After applying the chi-square test, a significant relation was identified between BMI and family history with dyslipidemia in HIV-infected individuals (p-value = 0.00). Conclusion A considerable proportion of treatment-naïve HIV patients have underlying dyslipidemia with a significant relationship with higher BMI and a family history of dyslipidemia. The findings of this study highlight the importance of early screening for dyslipidemia in HIV patients.

Biomimetic porous scaffolds containing decellularized small intestinal submucosa and Sr2+/Fe3+co-doped hydroxyapatite accelerate angiogenesis/osteogenesis for bone regeneration.

The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+co-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr2+/Fe3+and ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis bothin vitroandin vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to acceleratein vivovascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.

Electrospun tannin-rich nanofibrous solid-state membrane for wastewater environmental monitoring and remediation.

Heavy metal, organic dyes, and bacterial contamination in water endanger human/animals' health, and therefore, the detection, adsorption, and capturing of contaminants are essential for environmental safety. Ligand-rich membranes are promising for sensors, adsorption, and bacterial decontamination. Herein, tannin (TA)-reinforced 3-aminopropyltriethoxysilane (APTES) crosslinked polycaprolactone (PCL) based nanofibrous membrane (PCL-TA-APTES) was fabricated via electrospinning. PCL-TA-APTES nanofibers possess superior thermal, mechanical, structural, chemical, and aqueous stability properties than the un-crosslinked membrane. It changed its color from yellowish to black in response to Fe2+/3+ ions due to supramolecular iron-tannin network (FeTA) interaction. Such selective sensing has been noticed after adsorption-desorption cycles. Fe3+ concentration, solution pH, contact time, and ligand concentration influence FeTA coordination. Under optimized conditions followed by image processing, the introduced membrane showed a colorimetric linear relationship against Fe3+ ions (16.58 µM-650 µM) with a limit of detection of 5.47 µM. The PCL-FeTA-APTES membrane could restrain phenolic group oxidation and result in a partial water-insoluble network. The adsorption filtration results showed that the PCL-FeTA-APTES membrane can be reused and had a higher methylene blue adsorption (32.04 mg/g) than the PCL-TA-APTES membrane (14.96 mg/g). The high capture efficiency of nanocomposite against Fe3+-based S. aureus suspension than Fe3+-free suspension demonstrated that Fe3+-bounded bacterium adhered to the nanocomposite through Fe3+/TA-dependent biointerface interactions. Overall, high surface area, rich phenolic ligand, porous microstructure, and super-wetting properties expedite FeTA coordination in the nanocomposite, crucial for Fe2+/3+ ions sensing, methylene blue adsorption-filtration, and capturing of Fe3+-bounded bacterium. These multifunctional properties could promise nanocomposite membrane practicability in wastewater and environmental protection.

Heavy Metal Ions Detection Using Nanomaterials-Based Aptasensors.

Heavy metals ions as metallic pollutants are a growing global issue due to their adverse effects on the aquatic ecosystem, and human health. Unfortunately, conventional detection methods such as atomic absorption spectrometry exhibit a relatively low limit of detection and hold numerous disadvantages, and therefore, the development of an efficient method for in-situ and real-time detection of heavy metal residues is of great importance. The aptamer-based sensors offer distinct advantages over antibodies and emerged as a robust sensing platform against various heavy metals due to their high sensitivity, ease of production, simple operations, excellent specificity, better stability, low immunogenicity, and cost-effectiveness. The nucleic acid aptamers in conjugation with nanomaterials can bind to the metal ions with good specificity/selectivity and can be used for on-site monitoring of metal ion residues. This review aimed to provide background information about nanomaterials-based aptasensor, recent advancements in aptamer conjunction on nanomaterials surface, the role of nanomaterials in improving signal transduction, recent progress of nanomaterials-based aptasening procedures (from 2010 to 2022), and future perspectives toward the practical applications of nanomaterials-based aptasensors against hazardous metal ions for food safety and environmental monitoring.

Multifaceted tannin crosslinked bioinspired dECM decorated nanofibers modulating cell-scaffold biointerface for tympanic membrane perforation bioengineering.

Tympanic membrane (TM) perforation leads to persistent otitis media, conductive deafness, and affects life quality. Ointment medication may not be sufficient to treat TM perforation (TMP) due to the lack of an underlying tissue matrix and thus requiring a scaffold-based application. The engineering of scaffold biointerface close to the matrix via tissue-specific decellularized extracellular matrix (dECM) is crucial in instructing cell behaviour and regulating cell-material interaction in the bioengineering domain. Herein, polycaprolactone (PCL) and TM-dECM (from Sprague-Dawley rats) were combined in a different ratio in nanofibrous form using an electrospinning process and crosslinked via tannic acid. The histological and biochemical assays demonstrated that chemical and enzymatic decellularization steps removed cellular/immunogenic contents while retaining collagen and glycosaminoglycan. The morphological, physicochemical, thermomechanical, contact angle, and surface chemical studies demonstrated that the tannin crosslinked PCL/dECM nanofibers fine-tune biophysical and biochemical properties. The multifaceted crosslinked nanofibers hold the tunable distribution of dECM moieties, assembled into a spool-shaped membrane, and could easily insert into perforated sites. The dECM decorated fibers provide a preferable biomimetic matrix for L929 fibroblast adhesion, proliferation, matrix adsorption, and f-actin saturation, which could be crucial for bioengineering. Overall, dECM patterning, surface hydrophilicity, interconnected microporosities, and multifaceted nanofibrous biosystem modulate cell-scaffold performance and could open opportunities to reconstruct TMP in a biomimetic fashion.

Bioactive Sr2+/Fe3+co-substituted hydroxyapatite in cryogenically 3D printed porous scaffolds for bone tissue engineering.

Developing multi-doped bioceramics that possess biological multifunctionality is becoming increasingly attractive and promising for bone tissue engineering. In this view innovative Sr2+/Fe3+co-substituted nano-hydroxyapatite with gradient doping concentrations fixed at 10 mol% has been deliberately designed previously. Herein, to evaluate their therapeutic potentials for bone healing, novel gradient SrFeHA/PCL scaffolds are fabricated by extrusion cryogenic 3D printing technology with subsequent lyophilization. The obtained scaffolds exhibit desired 3D interconnected porous structure and rough microsurface, along with appreciable release of bioactive Sr2+/Fe3+from SrFeHA components. These favorable physicochemical properties render printed scaffolds realizing effective biological applications bothin vitroandin vivo, particularly the moderate co-substituted Sr7.5Fe2.5HA and Sr5Fe5HA groups exhibit remarkably enhanced bioactivity that not only promotes the functions of MC3T3 osteoblasts and HUVECs directly, but also energetically manipulates favorable macrophages activation to concurrently facilitate osteogenesis/angiogenesis. Moreover,in vivosubcutaneous implantation and cranial defects repair outcomes further confirm their superior capacity to dictate immune reaction, implants vascularization andin situbone regeneration, mainly dependent on the synergetic effects of released Sr2+/Fe3+. Accordingly, for the first time, present study highlights the great potential of Sr7.5Fe2.5HA and Sr5Fe5HA for ameliorating bone regeneration process by coupling of immunomodulation with enhanced angio- and osteogenesis and hence may provide a new promising alternative for future bone tissue engineering.

Antidiabetic and Hypolipidemic Potential of Green AgNPs against Diabetic Mice.

Green nanotechnology-based approaches have been acquired as environmentally friendly and cost effective with many biomedical applications. The present study reports the synthesis of silver nanoparticles (AgNPs) from the leaves of Emblica phyllanthus, characterized by UV-Vis spectroscopy, EDX, SEM, AFM, and XRD. The acute and chronic antidiabetic and hypolipidemic potential of AgNPs was studied in alloxan-induced diabetic mice. A total of 11 groups (G1-G11, n = 6) of mice were treated with different concentrations (150 and 300 mM) and sizes of AgNPs and compared with those treated with standard glibenclamide. A significant decrease (P > 0.05) in the glucose level was achieved for 30, 45, and 65 nm after 15 days of treatment compared to the diabetic control. The oral administration of optimal AgNPs reduced the glucose level from 280.83 ± 4.17 to 151.17 ± 3.54 mg/dL, while the standard drug glibenclamide showed the reduction in glucose from 265.5 ± 1.43 to 192 ± 3.4 mg/dL. Histopathological studies were performed in dissected kidney and liver tissues of the treated mice, which revealed significant recovery in the liver and kidney after AgNP treatment. Acute toxicity study revealed that AgNPs were safe up to a size of 400 nm and the raw leaf extract of Emblica phyllanthus was safe up to 2500 mg/kg b.w. This study may help provide more effective and safe treatment options for diabetes compared to traditionally prescribed antidiabetic drugs.

Synthesis and Characterization of Sintered Sr/Fe-Modified Hydroxyapatite Bioceramics for Bone Tissue Engineering Applications.

In the current study, Sr/Fe co-substituted hydroxyapatite (HAp) bioceramics were prepared by the sonication-assisted aqueous chemical precipitation method followed by sintering at 1100 °C for bone tissue regeneration applications. The sintered bioceramics were analyzed for various structural and chemical properties through X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy, which confirmed the phase purity of HAp and Sr/Fe co-substitution into its lattice. The Vickers hardness measurement, high blood compatibility (less than 5% hemolysis), and ability to support the adhesion, proliferation, and osteogenic differentiation of human mesenchymal stem cells suggest the suitability of Sr/Fe:HAp bioceramics for bone implant applications. The physicochemical analysis revealed that the developed Sr/Fe:HAp bioceramics exhibited a polyphasic nature (HAp and ßTCP) with almost identical structural morphology having a particle size less than 0.8 µm. The dielectric constant (ε') and dielectric loss (ε″) were potentially affected by the incorporated foreign ions together with the polyphasic nature of the material. The Sr/Fe co-substituted samples demonstrated extended drug (5-fluorouracil and amoxicillin) release profiles at the pH of physiological medium. The multifunctional properties of the developed HAp bioceramics enabled them to be an auspicious candidate for potential biomedical applications, including targeted drug-delivery applications, heating mediator in hyperthermia, and bone tissue repair implants.

Impact of structural features of Sr/Fe co-doped HAp on the osteoblast proliferation and osteogenic differentiation for its application as a bone substitute.

The potential of external ions doped biomaterials has been extensively explored; however, the co-doped biomaterials remain typically unexplored for their biological properties for precise biomedical applications. The current study was aimed to explore the impact of structural features of Sr/Fe co-doped hydroxyapatite (HAp) bionanomaterial on osteoblastic proliferation and osteogenic differentiation for its application as a bone substitute. A 10 mol% isomorphous co-doping of strontium and iron with respect to calcium was carried into HAp in the solid solution. Raman spectroscopy verified the presence of major functional groups of apatite structure together with the carbonate peaks. The Sr/Fe co-doped HAp bionanomaterials showed slightly negative zeta potential (at neutral pH), versatile DLS particle size (140-205 nm), high BET surface area (186 m2/g), and narrow width pore size (13-19 nm). TG/DTA analysis showed low thermal stability of the Sr/Fe co-doped HAp groups. The nanoparticles showed an initial burst release of amoxicillin for 15 h followed by extended-release up to 81 h and demonstrated an excellent antibacterial activity by producing inhibition zones of 17.6 ± 0.3 mm and 19.5 mm ± 0.4 mm for Escherichia coli and Staphylococcus aureus. Live/dead cell staining and MTT assay confirmed the non-toxic nature of Sr/Fe co-doped HAp bionanomaterial towards MC3T3-E1 cells. Further, an improved ALP activity, increased calcium deposition, enhanced RUNX2 expression, and regulated OPN and OCN expression levels suggest in MC3T3-E1 cells demonstrate the maturation of osteoblasts. This study provides the unique advantages of the co-doping approach for the applications Sr/Fe co-doped HAp bionanomaterials as a bone substitute.

Cryogenic free-form extrusion bioprinting of decellularized small intestinal submucosa for potential applications in skin tissue engineering.

A novel strategy of cryogenic 3D bioprinting assisted by free-from extrusion printing has been developed and applied to printing of a decellularized small intestinal submucosa (dSIS) slurry. The rheological properties, including kinetic viscosity, storage modulus (G'), and loss modulus (G″), were appropriate for free-from extrusion printing of dSIS slurry. Three different groups of scaffolds, including P500, P600, and P700, with filament distances of 500, 600, and 700 µm, respectively were fabricated at a 5 mm s-1 working velocity of the platform (V xy) and 25 kPa air pressure of the dispensing system (P) at -20 °C. The fabricated scaffolds were crosslinked via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) which resulted in a polyporous microstructure. The variations in the filament diameter and pore size were evaluated in the initial frozen state after printing, the lyophilized state, and after immersion in a PBS solution. The Young's modulus of the P500, P600, and P700 scaffolds was measured in wet and dry states for EDC-crosslinked scaffolds. The cell experiment results showed improved cell adhesion, viability, and proliferation both on the surface and within the scaffold, indicating the biocompatibility and suitability of the scaffold for 3D cell models. Further, gene and protein expression of normal skin fibroblasts on dSIS scaffolds demonstrated their ability to promote the production of some extracellular matrix proteins (i.e. collagen I, collagen III, and fibronectin) in vitro. Overall, this study presents a new potential strategy, by combining cryogenic 3D bioprinting with decellularized extracellular matrix materials, to manufacture ideal scaffolds for skin tissue engineering applications.

Catechins-Modified Selenium-Doped Hydroxyapatite Nanomaterials for Improved Osteosarcoma Therapy Through Generation of Reactive Oxygen Species.

Osteosarcoma is the most common bone cancer with limited therapeutic options. It can be treated by selenium-doped hydroxyapatite owing to its known antitumor potential. However, a high concentration of Se is toxic toward normal and stem cells whereas its low concentration cannot effectively remove cancer cells. Therefore, the current study was aimed to improve the anticancer activity of Se-HAp nanoparticles through catechins (CC) modification owing to their high cancer therapeutic value. The sequentially developed catechins modified Se-HAp nanocomposites (CC/Se-HAp) were characterized for various physico-chemical properties and antitumor activity. Structural analysis showed the synthesis of small rod-like single phase HAp nanoparticles (60 ± 15 nm), which effectively interacted with Se and catechins and formed agglomerated structures. TEM analysis showed the internalization and degradation of CC/Se-HAp nanomaterials within MNNG/HOS cells through a non-specific endocytosis process. Cell toxicity analysis showed that catechins modification improved the antitumor activity of Se-HAp nanocomposites by inducing apoptosis of human osteosarcoma MNNG/HOS cell lines, through generation of reactive oxygen species (ROS) which in turn activated the caspase-3 pathway, without significantly affecting the growth of human normal bone marrow stem cells (hBMSCs). qPCR and western blot analyses revealed that casp3, p53, and bax genes were significantly upregulated while cox-2 and PTK-2 were slightly downregulated as compared to control in CC/Se-HAp-treated MNNG/HOS cell lines. The current study of combining natural biomaterial (i.e., catechins) with Se and HAp, can prove to be an effective therapeutic approach for bone cancer therapy.

Electrospinning of Polycaprolactone/Pluronic F127 dissolved in glacial acetic acid: fibrous scaffolds fabrication, characterization and in vitro evaluation.

Abstracts The Polycaprolactone (PCL) fibrous scaffolds in nano to micro scale have been considered as excellent templates for cell culture and tissue growth. The hydrophobic nature of the PCL, however, yields low initial cell seeding density, heterogeneous cell spreading and slow cell growth rate. Therefore, in this study the surface hydrophilic fibrous scaffolds were directly fabricated by the electrospinning of PCL solutions with small quantities (0.5-5%) of Pluronic F127 (PEO100-PPO65-PEO100) dissolved in benign solvent of glacial acetic acid. The clear and miscible solutions were achieved by controlling the proper F127 content in the blend solutions. The continuous and smooth fibers with average diameters from 0.71 to 1.43 µm made up the fibrous scaffolds in non-woven mode. Then the water wetting angle of the scaffolds could be adjusted from 126° to 0° by varying F127 content owing to its hydrophilic PEO chains presented on surface the blended fibers. Finally, it was demonstrated that the blended fibrous scaffolds with the F127 content less than 1% exhibited better cell attachment, proliferation and spreading performance than those of pure PCL scaffolds.