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Investigating the influence of different cellular mechanical and physical properties on cells in vitro is important for assessing cellular activities like differentiation, proliferation, and migration. Evaluating the mechanical response of the cells lodged on a scaffold due to variations in substrate roughness, substrate elasticity, fluid flow, and the shapes of the cells is the main goal of the study. In this comprehensive analysis, a combination of the fluid structure interaction method and the submodeled finite element technique was employed to anticipate the mechanical responses across various cells at the interface between cells and the substrate. Fluid inlet velocity, substrate roughness, and substrate material were varied in this analysis. Different cell shapes were considered along with various components such as cell membrane, cytoplasm, nucleus, and cytoskeletons. This analysis shows the effect of these individual parameters on the elastic strain and strain energy density of cells at the cell‐substrate interface. The results highlight that substrate roughness has a more significant impact on the mechanical response of cells at the interface than substrate elasticity. However, effect of the substrate elasticity becomes crucial for extremely soft substrate materials. The results of this research can be applied to identify the optimal parameters for fluid flow and create a suitable condition for cell culture. [ABSTRACT FROM AUTHOR]

Both cell migration and osteogenic differentiation are critical for successful bone regeneration. Therefore, understanding the mechanobiological aspects that govern these two processes is essential in designing effective scaffolds that promote faster bone regeneration. Studying these two factors at different locations is necessary to manage bone regeneration in various sections of a scaffold. Hence, a multiscale computational model was used to observe the mechanical responses of osteoblasts placed in different positions of the trabecular bone and gyroid scaffold. Fluid shear stresses in scaffolds at cell seeded locations (representing osteogenic differentiation) and strain energy densities in cells at cell substrate interface (representing cell migration) were observed as mechanical response parameters in this study. Comparison of these responses, as two critical factors for bone regeneration, between the trabecular bone and gyroid scaffold at different locations, is the overall goal of the study. This study reveals that the gyroid scaffold exhibits higher osteogenic differentiation and cell migration potential compared to the trabecular bone. However, the responses in the gyroid only mimic the trabecular bone in two out of nine positions. These findings can guide us in predicting the ideal cell seeded sites within a scaffold for better bone regeneration and in replicating a replaced bone condition by altering the physical parameters of a scaffold. [ABSTRACT FROM AUTHOR]

Clinical success of regenerative medicine for treating deep‐tissue skin injuries depends on the availability of skin grafts. Though bioengineered constructs are tested clinically, lack of neovascularization provide only superficial healing. Thus constructs, which promotes wound healing and supports vascularization has gained priority in tissue engineering. In this study, chitosan‐collagen‐fibrinogen (CCF) scaffold was fabricated using freeze‐drying method without using any chemical crosslinkers. CCF scaffolds proved cytocompatibility and faster healing in in vitro scratch assay of primary human adult dermal fibroblasts cells with progressively increasing vascular endothelial growth factor‐A and reducing vascular endothelial growth factor receptor 1 expressions. Skin regeneration evaluated on in vivo full thickness wound model confirmed faster remodeling with angiogenic signatures in CCF scaffold‐implanted mice. Histopathological observations corroborated with stereo‐zoom and SS‐optical coherence tomography images of wound sites to prove the maturation of healing‐bed, after 12 days of CCF implantation. Therefore, it is concluded that CCF scaffolds are promising for skin tissue regeneration and demonstrates pro‐angiogenic potential. [ABSTRACT FROM AUTHOR]

This study focuses on the development of theranostic, dual drug‐loaded nanocarriers to propose a proof‐of‐principle therapeutic approach in the treatment of pancreatic ductal adenocarcinoma (PDAC). The nanoconstructs consist of a core of zinc oxide nanocrystals doped with gadolinium, useful as a potential contrast agent in magnetic resonance imaging applications. After functionalizing their surface with amino‐propyl groups, the physical adsorption of two hydrophobic drugs is performed: Vismodegib and Sorafenib. Their synergistic use might improve PDAC treatment and stroma depletion when co‐delivered in the tumor microenvironment for future in vivo applications. To enhance the nanoconstructs' biostability, the ensemble is coated by a lipid bilayer and a tumor targeting peptide is incorporated on the outer shell surface. As a first proof of concept, the resulting nanoconstructs are tested against two pancreatic cancer cell lines, showing a modest increase in treatment efficacy compared to the free drug counterparts and proving to spare healthy pancreatic cells. In a second testing set, the dual‐drug loaded nanoconstructs are tested on both cell lines previously sensitized to a first‐line chemotherapeutic drug, Gemcitabine, showing an improved treatment response. From these preliminary results, the nanotheranostic platforms might constitute a good starting point for future PDAC therapy and diagnosis studies. [ABSTRACT FROM AUTHOR]

The natural bone is a biological example of a polymer–ceramic composite with a higher volume fraction of nanosized ceramic (around 65% hydroxyapatite) dispersed in polymer (collagenous) matrix. The loading of a dental implant involves the biomechanical interactions of the implant with such natural composites in the jaw bones of human subjects. In particular, the insertion torque responses of the dental implant are related to the implant design, in particular the external thread morphology, which influences the primary stability of the implant. In this study, the effect of the bone properties (polyurethane‐based synthetic bone, porcine and human cadaver lumbar bone) and clinically relevant implant driving protocols on the insertion and removal torques of newly designed implant variants (hybrid threads with macro‐ and micro‐threads) were assessed, quantitatively and qualitatively. It was observed that torque response increased with an increase in bone density, irrespective of the implant designs. The torque response of the implants in both synthetic and natural bones was benchmarked with the commercially available implant. The implants with bone cutting partial macro‐threads at the apical end without inter thread gap exhibited comparable clinically relevant results with respect to control implants and were found to be most suitable for implantation into natural bone. [ABSTRACT FROM AUTHOR]

The recognition of hydroxyapatite (HAp) as the major bone mineral triggered significant research in bone tissue engineering applications. Although laboratory‐scale development involves the synthesis of HAp in different routes, scalability with uncompromised quality remains a major challenge. This article reports a large‐scale wet precipitation‐based synthesis of phase‐pure HAp using indigenously customized stirred tank reactors. The different synthesis parameters, like pH, reaction time, stirring rate, precursor addition, were tailored, together with the post‐synthesis mechano‐chemical treatment (aging induced Ostwald ripening) and calcinations, as the technology is matured to manufacture HAp powders in large volume. At least three batches of HAp were produced in the pilot‐scale reactor with reproducible values of phase purity, compositional fingerprint, particle size distribution, flowability, etc. The post‐calcination bluish tint was strategically addressed by adopting a proprietary calcination protocol. This batch process can produce around 200 kg/month of phase‐pure and highly crystalline (91–94%) HAp using stirred tank reactors of different working volumes. Extensive scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses reveal the particle size of as‐synthesized HAp powders with hexagonal crystal structure in the range of 20.47 ± 4.95 nm , while individual crystallite size in range of 22.3 ± 3.2 nm (XRD based Debye‐Scherrer analysis). TEM‐based SADP analysis confirms the highly crystalline hexagonal structure of as‐synthesized HAp. The spray‐dried powders with spherical shape having narrow size distribution (35–40 μm) could also be manufactured in large batches. The spray‐dried HAp powders could be coated on clinically used stainless steel femoral stem implants using atmospheric plasma spray coating technique. [ABSTRACT FROM AUTHOR]

Umbilical cord‐derived mesenchymal stem cells (UCDMSC) are attractive candidates for cell‐based regenerative medicine. However, they are susceptible to replicative senescence during repetitive passaging for in‐vitro expansion and induced senescence in an oxidative, inflammatory microenvironment in vivo. Aim of this study is to investigate if honey‐incorporated matrices can be employed to reduce senescence of UCDMSC. Matrices were prepared by electrospinning solutions of honey with poly‐vinyl alcohol (PVA). PVA:honey matrices exhibited free radical scavenging activity. Culture of UCDMSC on PVA:honey matrices showed improvement in cell proliferation compared to pure PVA nanofibres. Expression of vimentin indicated that mesenchymal phenotype is preserved after culturing on these matrices. Further, UCDMSC were serially subcultured and cells of two passages (P2 and P6) were evaluated for reactive oxygen species (ROS) load and senescence parameters. P6 cells showed a higher ROS load and β‐galactosidase (β‐gal) positive senescent cells compared to P2. However, culturing on PVA:honey substrates significantly reduced both ROS and β‐gal markers compared to cells on PVA substrates. Honey contains several antioxidant and anti‐inflammatory components, which can reduce the ROS‐related senescence. Thus, it is concluded that honey containing nanofibres can be effective substrates for stem cell‐based wound healing and regenerative medicine. [ABSTRACT FROM AUTHOR]

Photosensitizer‐functionalized reduced graphene oxide (rGO) nanoparticles are promising materials for photodynamic therapy in cancer management. In this study, rGO is synthesized by a green route employing glucose as the reducing agent and functionalized with photosensitizer, protoporphyrin IX (PPIX) in a convenient, single‐step procedure. PPIX‐functionalized rGO exhibits photodynamic effect against cancer cells (HeLa) at 0.001 mg mL−1 under visible light illumination (635 nm). A 50% elimination of HeLa cells after 5 min irradiation is observed while very low phototoxicity (80% cell viability) is noted against normal dermal fibroblast cells. A positive correlation with ROS accumulation and increased expression of caspase‐3 in PPIX‐functionalized rGO‐treated cancer cells is also established. The results evidence a simple and cost‐effective route for developing photosensitizer‐functionalized rGO for effective and selective killing of cancer cells. [ABSTRACT FROM AUTHOR]

Surface‐enhanced Raman spectroscopy (SERS) is rapidly emerging as a bioanalytical tool for cancer diagnosis and therapy. The SERS‐based molecular diagnostics have progressed from proof‐of‐concept studies towards analysis in animal models as well as for in vitro clinical diagnostics in the last decade. Recently, SERS has also been implemented in screening, diagnosis, and staging of clinical cancer samples. Moreover, in vivo SERS imaging has been implemented for mapping the extent of tumor growth and metastasis; SERS nanoparticles have also enabled image‐guided therapies strongly indicating SERS technology can significantly complement the practice of oncology. Despite the progress, widespread clinical translation of SERS nanoparticles is still challenging. Current SERS strategies in diagnostic oncology require further development and standardization to progress from bench‐top to point‐of‐care applications. The present review critically analyzes the current state of the art about various strategies for SERS‐based cancer detection and staging from cellular metabolites, exosomes, circulating tumor cells, extracellular fluids, and cancer cells. [ABSTRACT FROM AUTHOR]

Stem cells are a promising cell source for regenerative medicine due to their characteristics of self‐renewal and differentiation. The intricate balance between these two cell fates is maintained by precisely controlled symmetric and asymmetric cell divisions. Asymmetric division has a fundamental importance in maintaining tissue homeostasis and in the development of multi‐cellular organisms. For example, during development, asymmetric cell divisions are responsible for the formation of the body axis. Mechanistically, mitotic spindle dynamics determine the assembly and separation of chromosomes and regulate the orientation of cell division. Interestingly, symmetric and asymmetric cell division is not mutually exclusive and a range of factors are involved in such cell‐fate decisions, the measurement of which can provide efficient and reliable information on the regenerative potential of a cell. The balance between self‐renewal and differentiation in stem cells is controlled by various biophysical and biochemical cues. Although the role of biochemical factors in asymmetric stem cell division has been widely studied, the effect of biophysical cues in stem‐cell self‐renewal is not comprehensively understood. Herein, we review the biological relevance of stem‐cell asymmetric division to regenerative medicine and discuss the influences of various intrinsic and extrinsic biophysical cues in stem‐cell self‐renewal. This review particularly aims to inform the clinical translation of efforts to control the self‐renewal ability of stem cells through the tuning of various biophysical cues. [ABSTRACT FROM AUTHOR]

A rapid method for qualitative and quantitative assaying of l-lactate in milk is described. The method is based on oxidation of lactate by lactate oxidase with the simultaneous formation of H2O2 which subsequently oxidises 2, 4, 6-tribromo 3-hydroxy benzoic acid ( TBHBA) in the presence of peroxidase. Oxidised TBHBA then reacts with 4-amino antipyrine to obtain magenta colour (λmax = 523 nm). In the qualitative assay, colour change becomes visible in raw milk samples spiked with 300 mg lactate/L. The absorbance increases linearly up to 1000 mg/L. The method can be used for rapid assessment of the hygienic quality of milk. [ABSTRACT FROM AUTHOR]

The identification of a new class of luminogens based on pyrrolo-quinoxaline embedded coumarin (PQC) structures is reported. The reaction relies on the gold-catalyzed hydroarylation reaction of appropriately substituted aryl alkynoates that produces molecules that exhibit solvatochromism and aggregation-induced emission enhancement (AIEE) phenomena. The application of PQCs for live cell imaging has also been demonstrated. [ABSTRACT FROM AUTHOR]

ABSTRACT Honey is known as a popular healing agent against tropical infections and wounds. However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing under hypoxic condition is still not explored. In this study, we examined whether honey dilution have wound healing potential under hypoxic stress. The antioxidant potential and healing efficacy of honey dilution on in vitro wound of human epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2), and normoxia is explored by nitro blue tetrazolium assay. The cell survival % quantified by MTT assay to select four honey dilutions like 10, 1, 0.1, and 0.01 v/v% and the changes in cellular function was observed microscopically. Further, the cell proliferation, migration, cell-cell adhesion, and relevant gene expression were studied by flow cytometry, migration/scratch assay, immunocytochemistry, and reverse transcription-polymerase chain reaction, respectively. The expression pattern of cardinal molecular features viz. E-cadherin, cytoskeletal protein F-actin, p63, and hypoxia marker Hif 1α were examined. Honey dilution in 0.1% v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%). Its wound healing potential was quantified by immunocytochemistry and real-time PCR for the associated molecular features that were responsible for cell proliferation and migration. Our data showed that honey dilution can be effective in hypoxic wound healing. Additionally, it reduced superoxide generation and supplied favorable bioambience for cell proliferation, migration, and differentiation during hypoxic wound healing. These findings may reveal the importance of honey as an alternative and cost effective therapeutic natural product for wound healing in hypoxic condition. [ABSTRACT FROM AUTHOR]

The 2-stage smelting reduction process for ironmaking without post combustion is analyzed by a thermochemical model based on materials and energy balances at steady state. The influence of various parameters like composition of hot metal and its tapping temperature, degree of metallization, slag basicity, heat losses, coal rank, proportion of limestone to dolomite, etc., on the technological parameters like coal rate, flux rate, slag rate, oxygen rate and the export gas amount is studied. The commercial scale data of a corex plant are used to verify the model predictions. The model is found to predict the plant data satisfactorily. The effect of metallization, stag basicity, heat loss and the proportion of limestone to dolomite is presented in terms of incremental changes on the coal rate, slag rate, flux rate, oxygen rate and the export energy. Further, it is shown that in the combination of the COREX+DRI-unit, the maximum metallization of sponge iron depends on the type of coal used in the corex process. [ABSTRACT FROM AUTHOR]