Gold Nanoparticle Promoted Formation and Biological Properties of Injectable Hydrogels.

Acceleration of gelation in the biological environment and improvement of overall biological properties of a hydrogel is of enormous importance. Biopolymer stabilized gold (Au) nanoparticles (NPs) exhibit cytocompatibility and therapeutic activity. Hence, in situ gelation and subsequent improvement in the property of a hydrogel by employing Au NPs is an attractive approach. We report that stable Au NPs accelerate the conventional nucleophilic substitution reaction of activated halide-terminated poly(ethylene glycol) and tertiary amine functional macromolecules, leading to the rapid formation of injectable nanocomposite hydrogels in vivo and ex vivo with improved modulus, cell adhesion, cell proliferation, and cytocompatibility than that of a pristine hydrogel. NP surfaces with low chain grafting density and good colloidal stability are crucial requirements for the use of these NPs in the hydrogel formation. Influence of the structure of the amine functional prepolymer, the spacer connecting the halide leaving groups of the substrate, and the structure of the stabilizer on the rate promoting activity of the NPs have been evaluated with model low-molecular-weight substrates and macromolecules by 1H NMR spectroscopy, rheological experiments, and density functional theory. Results indicate a significant effect of the spacer connecting the halide leaving group with the macromolecule. The Au nanocomposite hydrogels show sustained co-release of methotrexate, an anti-rheumatic drug, and the Au NPs. This work provides insights for designing an injectable nanocomposite hydrogel system with multifunctional property. The strategy of the use of cytocompatible Au NPs as a promoter provides new opportunity to obtain an injectable hydrogel system for biological applications.

Health benefits of resveratrol: Evidence from clinical studies.

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5'-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

Layered Double Hydroxide Nanoparticles for Efficient Gene Delivery for Cancer Treatment.

The use of cationic polymer based gene delivery vectors has several limitations such as low transfection efficiency, high toxicity, and inactivation by serum. The present work provides an inorganic based nanocarrier for efficient gene delivery and a method for preparing the same through a facile coprecipitation technique. The vehicle showed high loading capacity of DNA and can release the loaded DNA in a controlled pH-responsive manner. The developed gene delivery vehicle offers remarkable protection against DNase I and also provides protection against thermal damage. This vehicle also demonstrated efficient cellular uptake performance. Transfection and expression of plasmid gene encoding GFP proteins is achieved successfully by this LDH based vehicle. More interestingly, the developed Li-Al LDH efficiently induces GFP-p53 mediated apoptosis in HeLa cells exclusively sparing the normal tissue cells like NIH-3T3. The study demonstrates the potential of the developed inorganic based nanocarrier as a promising nonviral gene vector for tumor treatment.

Nanoparticle-Induced Controlled Drug Delivery Using Chitosan-Based Hydrogel and Scaffold: Application to Bone Regeneration.

The novel chitosan nanohybrid hydrogel and scaffold have been developed with high mechanical strength and tailor the drug release ability for their applications in the biomedical arena. Nanohybrid hydrogels are prepared in dilute acetic acid medium using two different types of two-dimensional-layered nanoparticles. Scaffolds are prepared through lyophilization of hydrogels. Highly porous, open, and 3D interconnected morphologies are observed in the nanohybrid scaffolds, as opposed to the thick wall, smaller pore dimension in pure chitosan. The interaction between the nanoparticles and chitosan chains are elucidated using different spectroscopic techniques, which in turn are responsible for the uniform distribution of the nanoparticle in the chitosan matrix. Nanohybrids are found to be highly mechanically stable in both states (hydrogel and scaffold), as compared to pure chitosan because of the good reinforcing ability of 2D nanoparticles. Sustained drug release has been achieved in nanohybrid in vitro, as compared to the pure chitosan hydrogel/scaffold, mainly due to greater interactions between the components and the better barrier effect of 2D nanoparticles. Cytotoxicity of the nanohybrids is verified using NIH 3T3 mouse embryonic fibroblast cells for their possible use as controlled drug delivery vehicles. Nanohybrids are found to be nontoxic in nature and more biocompatible as compared to pure chitosan, as observed through cell viability and cell imaging studies. Interestingly, cell growth occurs within the pores of the nanohybrid scaffold, vis-à-vis the surface proliferation noticed in the pure chitosan scaffold. Better biocompatibility, hydrophilic nature, and sustained delivery with location specific cell growth make this nanohybrid hydrogel unique for biomedical uses. The bone regeneration rate is found to be significantly higher for the nanohybrid scaffold as compared to blank/pure chitosan without any side effect, suggesting nanohybrid systems are superior biomaterials.

Biomaterials for Interfacing Cell Imaging and Drug Delivery: An Overview.

This feature article provides an overview of different kinds of futuristic biomaterials which have the potential to be used for fluorescent imaging and drug delivery, often simultaneously. The synthesis route or preparation process, fluorescence property, release profile, biocompatibility, bioimaging, and mechanistic approaches are vividly discussed. These include bioimaging with fluorescently doped quantum dots, mesoporous silica, noble metals, metal clusters, hydrophilic/hydrophobic polymers, semiconducting polymer dots, carbon/graphene dots, dendrimers, fluorescent proteins, and other nanobiomaterials. Another section discusses the controlled and targeted drug, gene, or biologically active material delivery using various vehicles such as micelles, 2D nanomaterials, organic nanoparticles, polymeric nanohybrids, and chemically modified polymers. In the last section, we discuss biomaterials, which can deliver biologically active molecules, and imaging the cell/tissue.

Highly selective fluorescence 'turn off' sensing of picric acid and efficient cell labelling by water-soluble luminescent anthracene-bridged poly(N-vinyl pyrrolidone).

A novel, water-soluble, luminescent anthracene-bridged AA-type bi-arm poly(N-vinylpyrrolidone) (ATC-PNVP) was synthesized using a click reaction between alkyne-terminated PNVP and 9,10-bis(azidomethyl)anthracene. The resultant anthracene-bridged PNVP (ATC-PNVP) was characterized using 1H NMR, FTIR, UV-Vis, and fluorescence spectroscopic methods and GPC analysis. ATC-PNVP showed effective fluorescence properties in an aqueous medium. It showed highly selective "turn off" sensing behaviour towards picric acid, a common nitro-aromatic explosive, with a wide linear range of detection of 0.01-0.3 mM and LOD value of 0.006 mM in water. ATC-PNVP-based paper sensors also showed very effective detection of picric acid in the concentration range 0.001-1.0 mM. Its binding with bovine serum albumin (BSA) was studied using steady-state, synchronous and 3D fluorescence spectroscopy and this study showed effective quenching of the intrinsic fluorescence of BSA and occurrence of a FRET-type interaction. Furthermore, this luminescent ATC-PNVP was efficiently used as a fluorescence microscopy labelling agent in NIH-3T3 and HeLa cells, and showed greater uptake and hence better fluorescent labelling in the cytosols of the tested cells than free 9,10-bis(azidomethyl) anthracene. The cell viability study also showed a very good biocompatible and non-toxic nature of ATC-PNVP at lower working concentrations towards each of the types of cells tested.

Engineered Cellular Uptake and Controlled Drug Delivery Using Two Dimensional Nanoparticle and Polymer for Cancer Treatment.

Two major problems in chemotherapy, poor bioavailability of hydrophobic anticancer drug and its adverse side effects causing nausea, are taken into account by developing a sustained drug release vehicle along with enhanced bioavailability using two-dimensional layered double hydroxides (LDHs) with appropriate surface charge and its subsequent embedment in polymer matrix. A model hydrophobic anticancer drug, raloxifene hydrochloride (RH), is intercalated into a series of zinc iron LDHs with varying anion charge densities using an ion exchange technique. To achieve significant sustained delivery, drug-intercalated LDH is embedded in poly(ε-caprolactone) (PCL) matrix to develop intravenous administration and to improve the therapeutic index of the drug. The cause of sustained release is visualized from the strong interaction between LDH and drug, as measured through spectroscopic techniques, like X-ray photoelectron spectroscopy, infrared, UV-visible spectroscopy, and thermal measurement (depression of melting temperature and considerable reduction in heat of fusion), using differential scanning calorimeter, followed by delayed diffusion of drug from polymer matrix. Interestingly, polymer nanohybrid exhibits long-term and excellent in vitro antitumor efficacy as opposed to pure drug or drug-intercalated LDH or only drug embedded PCL (conventional drug delivery vehicle) as evident from cell viability and cell adhesion experiments prompting a model depicting greater killing efficiency (cellular uptake) of the delivery vehicle (polymer nanohybrid) controlled by its better cell adhesion as noticed through cellular uptake after tagging of fluorescence rhodamine B separately to drug and LDH. In vivo studies also confirm the sustained release of drug in the bloodstream of albino rats using polymer nanohybrid (novel drug delivery vehicle) along with a healthy liver vis-à-vis burst release using pure drug/drug-intercalated LDHs with considerable damaged liver.

Sustained release of herbal drugs using biodegradable scaffold for faster wound healing and better patient compliance.

Electrospun scaffold has been developed using biodegradable polymer and age old herbal drug for efficient wound healing patch with much better patient compliance. Positively charged smaller particle size (40 nm) of the drug has been prepared for greater penetration through epidermal barrier to enhance the wound healing activity of drug. Controlled drug release has been understood in terms of interactions between the components through spectroscopic techniques and calorimetric studies. In-vivo study using albino rats shows better wound healing efficiency of scaffold in terms of higher wound area contraction, minimum inflammation, faster epithelialization and vascularization. Cellular studies also endorse the scaffold as better biomaterial. Clinical studies also demonstrate fast healing of different type of wounds in presence of all three wound dressing materials with histological evidences. The complete biodegradation of the patch confirms its green nature of the developed patch.

Brominated Graphene as Mimetic Peroxidase for Sulfide Ion Recognition.

Brominated graphene (GBR) with ∼3% bromine content has shown novel peroxidase mimetic activity toward 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. Optimum activity has been observed at pH 4.48 and after a minimum ∼30 min of equilibration time. Among the different analytes studied using the sensor combining TMB, H2O2, and GBR in phosphate buffer of pH 4.48, the S2- ion has effectively shown a short duration of sensing (∼2 min) within the detection range of 0.04-1 mM. A calibration curve for S2- ion estimation has been constructed with the experimental linearity in 0.04-0.4 mM range and having the limit of detection (LOD) value of 25.3 µM. A standard addition experiment has validated the method. A paper strip sensor has been fabricated for successful detection of S2- ion.

Tailored Chemical Properties of 4-Arm Star Shaped Poly(d,l-lactide) as Cell Adhesive Three-Dimensional Scaffolds.

Biodegradable poly(lactic acid) (PLA) is widely used to fabricate 3D scaffolds for tissue regeneration. However, PLA lacks cell adhering functional moieties, which limit its successful application in tissue engineering. Herein, we have tailored the cell adhesive properties of star shaped poly(d,l-lactide) (ss-PDLLA) by grafting gelatin to their 4 arms. Grafting of gelatin on PDLLA backbone was confirmed by 1H NMR and FTIR. The synthesized star shaped poly(d,l-lactide)-b-gelatin (ss-pLG) exhibited enhanced wettability and protein adsorption. The modification also facilitated better cell adhesion and proliferation on their respective polymer coated 2D substrates, compared to their respective unmodified ss-PDLLA. Further, 3D scaffolds were fabricated from gelatin grafted and unmodified polymers. The fabricated scaffolds were shown to be cytocompatible to 3T3-L1 cells and hemocompatible to red blood cells (RBCs). Cell proliferation was increased up to 2.5-fold in ss-pLG scaffolds compared to ss-PDLLA scaffolds. Furthermore, a significant increase in cell number reveals a high degree of infiltration of cells into the scaffolds, forming a viable and healthy 3D interconnected cell community. In addition to that, burst release of docetaxal (DTX) was observed from ss-pLG scaffolds. Hence, this new system of grafting polymers followed by fabricating 3D scaffolds could be utilized as a successful approach in a variety of applications where cell-containing depots are used.

Osteoconductive Amine-Functionalized Graphene-Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization.

Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis.

Ordered Mesoporous Silica Delivering siRNA as Cancer Nanotherapeutics: A Comprehensive Review.

Nanosized mesoporous silica has emerged as a promising flexible platform delivering siRNA for cancer treatment. This ordered mesoporous nanosized silica provides attractive features of well-defined and tunable porosity, structure, high payload, and multiple functionalizations for targeted delivery and increasing biocompatibility over other polymeric nanocarriers. Moreover, it also overcomes the lacunae associated with traditional administration of drugs. Chemically modified porous silica matrix efficiently entraps siRNA molecules and prevents their enzymatic degradation and premature release. This Review discusses the synthesis of silica using the sol-gel approach and the advantages with different silica mesostructure. Herein, the factors affecting the synthesis of silica at nanometer scale, shape, porosity and nanoparticle surface modification are also highlighted to attain the desired nanostructured silica carriers. Additional emphasis is given to chemically modified silica delivering siRNA, where the silica nanoparticle surface was modified with different chemical moieties such as amine modified with (3-aminoropyl) triethoxysilane, polyethylenimine, chitosan, poly(ethylene glycol), and cyclodextrin polymer modification to attain high therapeutic loading, improved dispersibility and biocompatibility. Upon systemic administration, ordered mesoporous nanosized silica encounters blood cells, immune cells, and organs mainly of the reticuloendothelial system (RES). Thereby, biocompatibility and biodistribution of silica based nanocarriers are deliberated to design principles for smart and efficacious nanostructured silica-siRNA carriers and their clinical trial status. This Review further reports the future scopes and challenges for developing silica nanomaterial as a promising siRNA delivery vehicle demanding FDA approval.

Core-Shell Structure of Photopolymer-Grafted Polyurethane as a Controlled Drug Delivery Vehicle for Biomedical Application.

Functionalized ultraviolet photocurable bisphenol A-glycerolate dimethacrylates with tailorable size have been synthesized as the core, which have further been grafted using the diisocyanate chain end of polyurethane (PU) as the shell to create a core-shell structure of tunable size for a controlled drug delivery vehicle. The core-shell structure has been elucidated through spectroscopic techniques like 1H NMR, FTIR, and UV-vis and their relative shape and size through TEM and AFM morphology. The greater cross-link density of the core is reflected in the higher glass transition temperature, and the improved thermal stability of the graft copolymer is proven from its thermogravimetric analyses. The flow behavior and enhanced strength of the graft copolymers have been revealed from rheological measurements. The graft copolymer exhibits sustained release of the drug, as compared to pure polyurethane and photopolymer, arising from its core-shell structure and strong interaction between the copolymer and drug, as observed through a significant shifting of absorption peaks in FTIR and UV-vis measurements. Biocompatibility has been tested for the real application of the novel graft copolymer in medical fields, as revealed from MTT assay, cell imaging, and cell adhesion studies. The efficacy of controlled release from a graft copolymer has been verified from the gradual cell killing and ∼70% killing in 3 days vs meager cell killing of ∼25% very quickly in 1 day, followed by the increased cell viability of the system treated with the pure drug. The mechanism of slow and controlled drug release from the core-shell structure has been explored. The fluorescence images support the higher cell-killing efficiency as opposed to a pure drug or a drug embedded in polyurethane. Cells seeded on 3D scaffolds have been developed by embedding a graft copolymer, and fluorescence imaging confirms the successful growth of cells within the scaffold, realizing the potential of the core-shell graft copolymer in the biomedical arena.

Doxorubicin-Intercalated Li-Al-Based LDHs as Potential Drug Delivery Nanovehicle with pH-Responsive Therapeutic Cargo for Tumor Treatment.

Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li-Al (M+/M3+)-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M+1-x M3+x (OH)]2x+[(Am-)2x/m. n(H2O)]2x-, which is fully biodegradable and works in connection with the therapeutic interaction between LDH nanocarriers and anticancerous doxorubicin (DOX). Compositional variation of Li and Al in LDHs has been used as a nanoplatform, which provides a functional balance between circulation lifetime, drug loading capacity, encapsulation efficiency, and tumor-specific uptake to act as self-regulatory therapeutic cargo to be released intracellularly. First-principle analyses based on DFT have been employed to investigate the interaction of bonding and electronic structure of LDH with DOX and assess its capability and potential for a superior drug carrier. Following the internalization into cancer cells, nanoformulations are carried to the nucleus via lysosomes, and the mechanistic pathways have been revealed. Additionally, in vitro along with in vivo therapeutic assessments on melanoma-bearing mice show a dimensional effect of nanoformulation for better biocompatibility and excellent synergetic anticancer activity. Further, the severe toxic consequences associated with traditional chemotherapy have been eradicated by using injectable hydrogel placed just beneath the tumor site, and regulated release of the drug has been confirmed through protein expression applying various markers. However, Li-Al-based LDH nanocarriers open up new design options for multifunctional nanomedicine, which has intriguing potential for use in cancer treatment through sustained drug delivery.

Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration.

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

Induced Piezoelectricity in Cotton-Based Composites for Energy-Harvesting Applications.

A flexible and easily processable polymer composite is developed from naturally occurring piezoelectric materials for efficient energy-harvesting applications. Tomato peel (TP)- and cotton (CTN)-based poly(vinylidene fluoride) (PVDF) composites have been prepared and the role of induced electroactive phases have been explored through structural, thermal, and morphological analyses for their applications in energy production. The mechanism of induced piezoelectricity is vividly demonstrated using electromechanical responses and characteristic changes due to induction phenomena. The CTN-based composite generates a maximum output voltage and current of 65 V and 2.1 µA, respectively, as compared to the maximum output voltage and current of 23 V and 0.7 µA in TP-based composites due to the significant induction of the piezoelectric phase in the presence of suitable electroactive cotton. The fabricated device is able to store charges in capacitors and converts the external stress through different motions of the human body to generate a considerable output, which describes the applicability of the material and justifies the potential as an efficient and sustainable biomechanical energy harvester.

3D bioprinting and its innovative approach for biomedical applications.

3D bioprinting or additive manufacturing is an emerging innovative technology revolutionizing the field of biomedical applications by combining engineering, manufacturing, art, education, and medicine. This process involved incorporating the cells with biocompatible materials to design the required tissue or organ model in situ for various in vivo applications. Conventional 3D printing is involved in constructing the model without incorporating any living components, thereby limiting its use in several recent biological applications. However, this uses additional biological complexities, including material choice, cell types, and their growth and differentiation factors. This state-of-the-art technology consciously summarizes different methods used in bioprinting and their importance and setbacks. It also elaborates on the concept of bioinks and their utility. Biomedical applications such as cancer therapy, tissue engineering, bone regeneration, and wound healing involving 3D printing have gained much attention in recent years. This article aims to provide a comprehensive review of all the aspects associated with 3D bioprinting, from material selection, technology, and fabrication to applications in the biomedical fields. Attempts have been made to highlight each element in detail, along with the associated available reports from recent literature. This review focuses on providing a single platform for cancer and tissue engineering applications associated with 3D bioprinting in the biomedical field.

Piezoelectric nanogenerators for self-powered wearable and implantable bioelectronic devices.

One of the recent innovations in the field of personalized healthcare is the piezoelectric nanogenerators (PENGs) for various clinical applications, including self-powered sensors, drug delivery, tissue regeneration etc. Such innovations are perceived to potentially address some of the unmet clinical needs, e.g., limited life-span of implantable biomedical devices (e.g., pacemaker) and replacement related complications. To this end, the generation of green energy from biomechanical sources for wearable and implantable bioelectronic devices gained considerable attention in the scientific community. In this perspective, this article provides a comprehensive state-of-the-art review on the recent developments in the processing, applications and associated concerns of piezoelectric materials (synthetic/biological) for personalized healthcare applications. In particular, this review briefly discusses the concepts of piezoelectric energy harvesting, piezoelectric materials (ceramics, polymers, nature-inspired), and the various applications of piezoelectric nanogenerators, such as, self-powered sensors, self-powered pacemakers, deep brain stimulators etc. Important distinction has been made in terms of the potential clinical applications of PENGs, either as wearable or implantable bioelectronic devices. While discussing the potential applications as implantable devices, the biocompatibility of the several hybrid devices using large animal models is summarized. This review closes with the futuristic vision of integrating data science approaches in developmental pipeline of PENGs as well as clinical translation of the next generation PENGs. STATEMENT OF SIGNIFICANCE: Piezoelectric nanogenerators (PENGs) hold great promise for transforming personalized healthcare through self-powered sensors, drug delivery systems, and tissue regeneration. The limited battery life of implantable devices like pacemakers presents a significant challenge, leading to complications from repititive surgeries. To address such a critical issue, researchers are focusing on generating green energy from biomechanical sources to power wearable and implantable bioelectronic devices. This comprehensive review critically examines the latest advancements in synthetic and nature-inspired piezoelectric materials for PENGs in personalized healthcare. Moreover, it discusses the potential of piezoelectric materials and data science approaches to enhance the efficiency and reliability of personalized healthcare devices for clinical applications.

Evaluation of anticancer activity of Gmelina asiatica leaves, in-vitro and in-silico studies.

Cervical cancer poses a major threat to women's health worldwide, constituting the fourth most prevalent cancer among the female population. High-risk variants of human papillomavirus (HPV) with its oncogenic proteins are a necessary cause of cervical cancer. Due to the resistance of cancer cells to the current treatment, there is a need for new medicines with new strategies to treat cervical cancer. Gmelina asiatica Linn. is a medicinal plant with various traditional uses and biological activities. Its anticancer potential against breast cancer and lymphoma has been demonstrated in the literature. In view of this, our study aims to investigate the anticancer activity of Gmelina asiatica leaves against cervical cancer. Various extracts of Gmelina asiatica leaves were prepared by soxhletation and maceration methods. The cytotoxic activity of the extracts was evaluated through in-vitro studies against SiHa cell line using MTT assay and fluorescence imaging. The most potent extract (GAME) phytochemical profile was analysed by UHPLC-HRMS. Further, in-silico studies were performed on its phytoconstituents against E6 oncoprotein, and the DFT studies were conducted on the active component to assess the physicochemical properties. In-vitro studies revealed that methanolic extract (GAME) showed the highest inhibition on the SiHa cell line compared to the other extracts and the control (p < 0.0001). In-silico studies indicated high affinity with stable interaction of the compound 5 (JC5ABDR) at E6 binding sites. This study revealed the importance of Gmelina asiatica plant as a potential source of anticancer molecules with a specific mode of action against cervical cancer.Communicated by Ramaswamy H. Sarma.

3D Printing of a Biocompatible Nanoink Derived from Waste Animal Bones.

Direct ink writing (DIW) additive manufacturing is a versatile 3D printing technique for a broad range of materials. DIW can print a variety of materials provided that the ink is well-engineered with appropriate rheological properties. DIW could be an ideal technique in tissue engineering to repair and regenerate deformed or missing organs or tissues, for example, bone and tooth fracture that is a common problem that needs surgeon attention. A critical criterion in tissue engineering is that inserts must be compatible with their surrounding environment. Chemically produced calcium-rich materials are dominant in this application, especially for bone-related applications. These materials may be toxic leading to a rejection by the body that may need secondary surgery to repair. On the other hand, there is an abundance of biowaste building blocks that can be used for grafting with little adverse effect on the body. In this work, we report a bioderived ink made entirely of calcium derived from waste animal bones using a benign process. Calcium nanoparticles are extracted from the bones and the ink prepared by mixing with different biocompatible binders. The ink is used to print scaffolds with controlled porosity that allows better growth of cells. DIW printed parts show better mechanical properties and biocompatibility that are important for the grafting application. Degradation tests and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay study were done to examine the biocompatibility of the extracted materials. In addition, discrete element modeling and computational fluid dynamics numerical methods are used in Rocky and Ansys software programs. This work shows that biowaste materials if well-engineered can be a never-ending source of raw materials for advanced application in orthopedic grafting.