EEF1A2 promotes HIF1A mediated breast cancer angiogenesis in normoxia and participates in a positive feedback loop with HIF1A in hypoxia.

BACKGROUND: The eukaryotic elongation factor, EEF1A2, has been identified as an oncogene in various solid tumors. Here, we have identified a novel function of EEF1A2 in angiogenesis. METHODS: Chick chorioallantoic membrane, tubulogenesis, aortic ring, Matrigel plug, and skin wound healing assays established EEF1A2's role in angiogenesis. RESULT: Higher EEF1A2 levels in breast cancer cells enhanced cell growth, movement, blood vessel function, and tubule formation in HUVECs, as confirmed by ex-ovo and in-vivo tests. The overexpression of EEF1A2 could be counteracted by Plitidepsin. Under normoxic conditions, EEF1A2 triggered HIF1A expression via ERK-Myc and mTOR signaling in TNBC and ER/PR positive cells. Hypoxia induced the expression of EEF1A2, leading to a positive feedback loop between EEF1A2 and HIF1A. Luciferase assay and EMSA confirmed HIF1A binding on the EEF1A2 promoter, which induced its transcription. RT-PCR and polysome profiling validated that EEF1A2 affected VEGF transcription and translation positively. This led to increased VEGF release from breast cancer cells, activating ERK and PI3K-AKT signaling in endothelial cells. Breast cancer tissues with elevated EEF1A2 showed higher microvessel density. CONCLUSION: EEF1A2 exhibits angiogenic potential in both normoxic and hypoxic conditions, underscoring its dual role in promoting EMT and angiogenesis, rendering it a promising target for cancer therapy.

White to brown adipocyte transition mediated by Apigenin via VEGF-PRDM16 signaling.

The dysregulated energy metabolism in white adipose tissues results in derangement of biological signaling resulting in obesity. Lack of vascularization in these white adipose tissues is one of the major reasons for dysregulated energy metabolism. Not much work has been done in this direction to understand the role of angiogenesis in white adipose tissue metabolism. In the present study, we evaluated the effect of angiogenic modulator in the metabolism of white adipocyte (WAC). Bioactive Apigenin was selected and its angiogenic ability was studied. Apigenin was shown to be highly proangiogenic hence the effect of Apigenin on de novo and trans-differentiation of WAT was studied. Apigenin showed enhanced de novo differentiation and trans-differentiation of mouse WAC into brown-like phenotype. To understand the effect of Apigenin on adipose tissue vasculature, coculture studies were conducted. Cross talk between endothelial cell and adipocytes were observed in coculture studies. Gene expression studies of cocultured cells revealed that browning of WAC occurred by triggering the expression of Vascular endothelial growth factor A. The study provides a new insight for inducing metabolic shift in WACs by modulation of angiogenesis in WAC microenvironment by the upregulation of PRDM16 cascade to trigger browning for the treatment of obesity.

Decorin mediated biomimetic PCL-gelatin nano-framework to impede scarring.

Scars occur as a result of fibrosis after tissue damage or surgery and reports suggest that excessive Transforming growth factor-ß (TGF-ß) activity during the process of wound healing leads to progressive fibrosis. Decorin is an extracellular matrix (ECM) protein which regulates collagen fibrillogenesis. However, targeted delivery and effective protein therapy remains a challenge owing to degradation byproteases. Hence, we aimed to deliver Decorin in a sustainable mode for the reduction of TGF-ß levels and subsequent scar formation. Herein, we have fabricated PCL-Gelatin bio-mimetic scaffolds to optimize the bio-activity and provide localized delivery of recombinant Decorin. The degradation and drug release patterns reveals that this biomaterial is biodegradable and offers sustained release of the recombinant Decorin. Decorin loaded nanofiber displayed lower adhesion and proliferation rates in in-vitro conditions. Moreover, Decorin loaded scaffolds demonstrated morphological changes in cells, specifically targeting the myofibroblast. The expression of TGF-ß was also scrutinized to understand the effect of Decorin loaded nanofibers. Besides, in the in-vitro fibrotic model, Decorin loaded nanofibers efficiently reduced the expression of ECM related proteins. Therefore, we report the sustained delivery of the recombinant Decorin from nanofiber dressing to potentially obstruct scar formation during the process of wound healing.

Regulatory significance of CULLIN2 in neuronal differentiation and regeneration.

BACKGROUND: Scaffold proteins coordinate multiple signalling pathways by integrating various proteins but the role of these proteins in neuronal pathways remains to be elucidated. The present study focused to evaluate the expression of the scaffold protein CULLIN2 in neuronal cells. METHODS: The neuronal precursor cell line N2A was differentiated to neurons in-vitro with retinoic acid and biochemical assays were used to understand the gene expression profiling of CULLIN2. Moreover, neddylation inhibitor MLN4924 was used to inhibit the activity of CULLIN2 and the downstream substrates were validated. Finally, the role of CULLIN2 in nerve regeneration was evaluated in an in vivo zebrafish model. RESULTS: Experimental data showed that the neuronal cells N2A have lower expression of CULLIN2 compared to skin cell lines (HaCaT and A431) and inactivation with the neddylation inhibitor resulted in cell death. Furthermore differentiating the neural precursor cell line into neurons with retinoic acid enhanced the expression of CULLIN2. Examining downstream signalling molecules with the neddylation inhibitor illuminates that MLN4924 treatment influences the cytokine signalling cascade (JAK-STAT) in neuronal cells. Moreover, for the first time, we show that the ubiquitin ligase protein CULLIN2 is perturbed in neural regeneration. Expression profile of CULLIN2 was significantly decreased in response to a nerve injury in Zebra fish and as the nerve regenerates there is corresponding reduction in the mRNA levels. CONCLUSION: During differentiation CULLIN2 is upregulated whereas during regeneration there is significant downregulation. Thus, our findings reveal a crucial role of the scaffold protein CULLIN2 in nerve differentiation and regeneration which can be vital for the treatment of nerve injury.

Lanthanum oxide nanoparticle-collagen bio matrix induced endothelial cell activation for sustained angiogenic response for biomaterial integration.

Rare earth lanthanum oxide nanoparticle reinforced collagen biomatrix that elicited the endothelial cell activation to promote angiogenesis for biomaterial integration was developed and evaluated in the present study. The structural integrity of collagen was not compromised on crosslinking of lanthanum oxide nanoparticle to collagen biomolecule. As-synthesised collagen biomatrix was shown to have improved mechanical strength, a lesser susceptibility to proteolytic degradation and good swelling properties. Superior cytocompatibility, hemocompatibility and minimal ROS generation was observed with Lanthanum oxide nanoparticle reinforced collagen bio matrix. The Lanthanum oxide nanoparticle reinforced collagen bio matrix elicited endothelial cell activation eliciting pro-angiogensis as observed in tube formation and aortic arch assays. The bio-matrix promoted the infiltration and proliferation of endothelial cells which is an unexplored domain in the area of tissue engineering that is very essential for biomaterial integration into host tissue. The wound healing effect of Lanthanum oxide nanoparticle stabilized collagen showed enhanced cell migration in vitro in cells maintained in Lanthanum oxide nanoparticle reinforced collagen bio matrix. The study paves the way for developing rare earth-based dressing materials which promoted biomatrix integration by enhancing vascularisation for tissue regenerative applications in comparison with traditional biomaterials.

Applications of molybdenum oxide nanoparticles impregnated collagen scaffolds in wound therapeutics.

INTRODUCTION: The highly complex pathophysiology of the wound micro-environment demands the development of a multi-faceted system which would enhance the wound healing cascade. Incorporation of nanotechnology in wound therapeutics has opened up new avenues to tourment the diseased condition. Amongst the various types of nanoparticles molybdenum oxide nanoparticles posses various inherent properties that makes it a versatile material to be used in healing. Incorporation of Molybdenum nanoparticles into collagen scaffolds would provide a synergistic and sequential healing process ensuring the formation of a fully functional tissue. MATERIALS AND METHODS: The physico-chemical characterization of the synthesized materials were done using SEM and FT-IR techniques. The bicompatibility and cell proliferation were tested using HaCaT cell lines. Pro-angiogenic ability of the scaffold was tested using CAM assay and Chick aortic arch assay. Finally the in-vivo wound healing ability of the material was tested by creating wound of about 6 cm2 on the dorsal side of Wistar rats and observed for about 21 days. RESULTS: The characterization of the scaffold revealed the presence MoO3 nanoparticles and their structural integrity within the scaffold. The synthesized MoO3-collagen nanocomposite was found to be biocompatible and hemocompatible. The in-vitro studies demonstrated that the MoO3-collagen scaffold significantly increased the cell adhesion and migration to nearly 2 fold. The MoO3 embedded collagen sheets synergistically favoured neovascularization and re-epithelization,which would potentially enhance therapeutic efficiency of the scaffold. The nanocomposite also encouraged results in in-vivo analysis, the Wistar rats treated with MoO3-collagen scaffolds showed complete healing in about 15 days. CONCLUSION: The fabricated MoO3-collagen scaffold was found to play an important role in all major events of wound healing such as adhesion, migration, proliferation and angiogenesis. The in-vivo healing assay also proved that the healing rate of animals treated with the samples was comparatively faster. Further research using various trace elements would open up promising avenues in healing therapeutics.

Mesoporous silica incorporated PCL/Curcumin nanofiber for wound healing application.

Electrospinning, a recent fast-emerging technique highly applicable in the production of nanofibers has gained vast recognition owing to its explicit applications in various domains. Amongst which, the production of nanoscaffolds for wound healing applications has been focused recently due to advantages over conventional wound healing methods. In the present research, a composite nanoscaffold comprising SBA-15 (Santa Barbara Amorphous), amine functionalized SBA-15 polycaprolactone (PCL) and curcumin was investigated for its potentiality in wound healing therapeutics. The high biocompatibility and cell adhesion of amine functionalized SBA-15 and the widely explored antimicrobial properties of curcumin added benefit for the wound healing target. The prepared highly interconnected electrospun fibers with porous structure were characterized through various studies such as FTIR, XRD, SEM and EDAX. Further, antibacterial studies against both Gram positive (Bacillus subtilis) and Gram negative (Escherichia coli) strains revealed an improved zone of inhibition. Major invitro studies such as cell migration, proliferation, bio-compatibility was experimented through cell adhesion and live and dead assay using Swiss 3T6 cell lines. In vivo studies on female Wister rats using the fabricated nanofibers incorporated with curcumin and amine functionalized SBA-15 showed 99% scar-less wound healing within 21 days. Re-epithelization of tissue, collagen deposition and formation of granulation tissue were observed from the results of Hematoxylin-Eosin and Masson's tri-chrome staining. From the observations, it can be concluded that the fabricated nanoscaffold could be an effective substrate for wound healing therapeutics.

A critical appraisal of humanized alternatives to fetal bovine serum for clinical applications of umbilical cord derived mesenchymal stromal cells.

OBJECTIVE: The study is aimed to verify the possibility of using humanized alternatives to fetal bovine serum (FBS) such as umbilical cord blood plasma (CBP) and AB+ plasma to support the long-term growth of mesenchymal stromal cells (MSCs) derived from the umbilical cord. We hypothesized that umbilical CBP would be a potential substitute to FBS, especially for small scale autologous clinical transplantations. METHODS: The MSCs were cultured for six consecutive passages to evaluate xeno-free media's ability to support long-term growth. Cell proliferation rates, colony-forming-unit (CFU) efficiency and population doublings of expanded MSCs, were investigated. Ex vivo expanded MSCs were further characterized using flow cytometry and quantitative PCR. The impact of cryopreservation and composition of cryomedium on phenotype, viability of MSC was also assessed. RESULTS: Our results on cell proliferation, colony-forming unit efficiency suggested that the expansion of the cells was successfully carried out in media supplemented with humanized alternatives. MSCs showed lower CFU counts in FBS (~ 25) than humanized alternatives (~ 35). The gene expression analysis revealed that transcripts showed significant differential expression by two to three folds in the FBS group compared with MSCs grown in medium with humanized alternatives (p < 0.05). In addition, MSCs grown in a medium with FBS had more osteogenic activity, a signature of unwanted differentiation. The majority of ex vivo expanded MSCs at early and late passages expressed CD44+, CD73+, CD105+, CD90+, and CD166+ in all the experimental groups tested (~ 90%). In contrast to the other MSC surface markers, expression levels of STRO-1+ (~ 21-10%) and TNAP+ (~ 29-11%) decreased with the increase in passage number for MSCs cultured in a FBS-supplemented medium (p < 0.05). CONCLUSION: Our results established that CBP supported culture of umbilical cord tissue-derived MSCs and is a safer Xeno free replacement to FBS. The use of CBP also enables the storage of umbilical cord tissue derived MSCs in patient-specific conditions to minimize adverse events if cells are delivered directly to the patient.

Effect of magnesium ascorbyl phosphate on collagen stabilization for wound healing application.

Wound healing is a complex process which requires appropriate structural support for restoration of tissue continuity and function. Collagen can act as a template for cellular activities but poor physico-chemical properties necessitates the stabilization of collagen without impairing its structure and function. This study investigates the effect of magnesium ascorbyl phosphate (MAP) on collagen with reference to physico-chemical properties. Incorporation of MAP enhanced the rate of collagen fibrillation signifying increased interaction at reduced time interval. MAP did not induce any changes in the secondary structure of collagen while there was an increase in shear viscosity with increase in shear stress at different shear rate. MAP stabilized collagen film exhibited higher denaturation temperature and showed an increase in Young's Modulus when compared with that of collagen film. In vivo studies showed complete wound closure on day 16 in case of stabilized collagen film. Mechanical properties of healed skin revealed that MAP collagen film treated rat skin completely regained its properties similar to that of normal skin thereby making them a potential candidate for wound healing application.

3 D nano bilayered spatially and functionally graded scaffold impregnated bromelain conjugated magnesium doped hydroxyapatite nanoparticle for periodontal regeneration.

Chronic periodontal disease affect the tissues supporting around the teeth like gingival tissue, connective tissue, alveolar bone and periodontal ligaments. Hitherto, periodontal treatment was targeted to selectively repopulate the defect site with cell that has capability to regenerate lost tissue by promoting the concept of guided tissue regeneration but it requires second surgery due to non- biodegradability. The use of polymeric biodegradable nanofibrous coated scaffold that have the ability to deliver bioactives required for regeneration to occur is relatively a newer concept. The functionalization of polymeric scaffold with Bromelain and magnesium doped hydroxyapatite nanoparticle enhanced the mechanical, physico-chemical, thermal and biological properties of the scaffold by imitating the intricate extracellular matrix (ECM) architecture which provided the necessary bioactive cues that offered control over cellular functions by showing antibacterial potential, hemocompatibility and increasing the proliferation and migration rate in vitro. In addition, in ovo chicken chorioallantoic membrane assay and ex vivo aortic ring assay confirmed the efficacy of the developed scaffold by encouraging angiogenesis required for maintaining its viability after implanting onto the infected area. Further, the scaffold positively interacted with the host and actively contributed to the process of tissue regeneration in vivo in Wistar rat model.

Design and fabrication of electrospun SBA-15-incorporated PVA with curcumin: a biomimetic nanoscaffold for skin tissue engineering.

Fabricating and designing a scaffold is a complex and highly challenging process in the current scenario. The present study deals with the design and fabrication of electrospun Santa Barbara Amorphous (SBA)-15-incorporated polyvinyl alcohol (PVA) with curcumin, which can be used as a biomimetic nanoscaffold for skin tissue engineering. Curcumin was selected due to its effective anti-microbial and anti-inflammatory properties. SBA-15 was selected for its characteristic drug-carrying potential. Fourier transform infrared spectroscopy and x-ray diffraction characterizations of the fabricated nanofiber demonstrated the interaction of PVA, SBA-15 and curcumin. The scanning electron microscopy results depicted that the nanofiber was highly interconnected with a porous structure mimicking the extracellular matrix. The nanofibrous scaffold showed a higher percentage of cell migration, proliferation, cytocompatibility and biocompatibility with absence of cytotoxicity which was evidenced from the results of MTT assay, cell adhesion and live/dead assay using HaCaT cells. The results of the anti-bacterial test depicted that the synthesized nanofiber forms a potent material for skin wound-healing therapeutics. The in vitro drug release study performed over a period of 80 h revealed a sustained release pattern of curcumin from the SBA-15-incorporated PVA nanofiber. Finally, the in vivo results confirmed that SBA-15-incorporated PVA nanofiber with curcumin showed efficient wound-healing activities.

Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action.

Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies revealed that the IC50 vales of molybdenum trioxide (MoO3) particles against skin cancer cells (melanoma and non-melanoma) were around 200-300 µg. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl2. Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO3 nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO3 nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes.

Bi-faceted delivery of phytochemicals through chitosan nanoparticles impregnated nanofibers for cancer therapeutics.

Drug delivery through nanotechnological approaches has predominantly gained significance owing to the enhanced bioavailability, stability and targeted sequel. Multiple drug delivery is also on its stride to achieve holistic therapeutic regime. In our quest for such a treatment for cancer we selected two phytochemicals namely resveratrol (RS) and ferulic acid (FA) that have gained wide attention in the field of medicine due to their array of properties. Albeit their multifaceted application their therapeutic potential is mired due to its physicochemical instability and low bioavailability. Therefore, in the present study combinatorial effect of these compounds in cancer therapeutics have been scrutinized by fabricating chitosan nanoparticle loaded polycaprolactone nanofibers for delivering RS and FA. The materials were physico-chemical characterized. The nanoparticle incorporation within the nanofibers was corroborated through FITC tagging. The anti-cancer effect of drug loaded nanofibers were studied using A431 cells which displayed 30% and 50% reduction in the cell viability when treated with nanoparticles and nanofibrous scaffold. In congruence, the anti-angiogenic potential of the scaffold was elucidated using Chick chorioallantoic membrane assay and aortic ring assay. Thus, the nanofibrous delivery system opens up new venue in the field of cancer therapeutics with reduced side effects and efficient cancer targeting.

Electrospun gelatin-polyethylenimine blend nanofibrous scaffold for biomedical applications.

In this study, gelatin-polyethylenimine blend nanofibers (GEL/PEI) were fabricated via electrospinning with different ratios (9:1, 6:1, 3:1) to integrate the properties of both the polymers for evaluating its biomedical application. From scanning electron microscopy, the average diameter of blend nanofibers (265 ± 0.074 nm to 340 ± 0.088 nm) was observed to be less than GEL nanofibers (403 ± 0.08 nm). The incorporation of PEI with gelatin resulted in improved thermal stability of nanofibers whereas the Young's modulus was observed to be higher at 9:1 ratio when compared with other ratios. The in vitro studies showed that the GEL/PEI nanofibers with 9:1 ratio promoted better cell adhesion and viability. GEL/PEI nanofibers with 9:1 and 6:1 showed hemolysis within the permissible limits. From the results, it could be interpreted that GEL/PEI nanofibers with 9:1 ratio proved to be a better scaffold thereby making them a potential candidate for tissue engineering applications.

Nanofiber-Mediated Sustained Delivery of Triiodothyronine: Role in Angiogenesis.

Angiogenesis is a vital component of the orchestrated wound healing cascade and tissue regeneration process, which has a therapeutic prominence in treatment of ischemic vascular diseases and certain cardiac conditions. Based on its eminence, several strategies using growth factors have been studied to initiate angiogenesis. However, growth factors are expensive and have short half-life. In this work, sustained release of triiodothyronine, which plays a crucial role in stimulating growth factors and other signaling pathways that are instrumental in initiating angiogenesis, has been attempted through electrospun polycaprolactone nanofibers. This delivery system enabled the slow and sustained delivery of triiodothyronine into the micro-environment, reducing seepage of excess into systemic circulation and eliminating the necessity of repeated dosage forms. It was observed that triiodothyronine-incorporated nanofibers exhibited favorable interaction with cells (phalloidin staining of actin filaments) and also enhanced the rate of endothelial proliferation, migration, and adhesion. The angiogenic potential of these nanofibers was further corroborated through chorioallantoic membrane and rat aortic ring assay (demonstrating cell sprouting area of 3.3 ± 0.71 mm2 compared to 1.2 ± 0.01 mm2 in control). The nanofiber matrix thus fabricated demonstrated a vibrant therapeutic potential to induce angiogenesis. Triiodothyronine also plays a significant role in wound healing independent of initiating angiogenesis. This further substantiates the positive impact of this delivery system as a dressing material for chronic wound therapeutics, ischemic vascular diseases, and certain cardiac conditions.

Strategic design of peptide-decorated aligned nanofibers impregnated with triiodothyronine for neural regeneration.

Nerve injuries are often debilitating as its regeneration occurs in a slow and laborious manner. Remediation of nerve injury is a colossal task as functional restoration in larger gaps seldom occurs due to the complex nerve regeneration mechanism. A nanofiber-based graft material has been fabricated to provide topographical and biochemical cues to encourage neural differentiation. Laminin plays a crucial role in supporting peripheral nerve regeneration and hence aligned polyvinyl cinnamate nanofibers surface-conjugated with laminin-derived cell-adhesion peptides have been fabricated to improve selective neural adhesion and regeneration. Further, triiodothyronine has been encapsulated within the nanofibers enabling its sustained release so as to bolster regeneration and reinstate the lost functionality to the damaged nerve. The fabricated nanofibers were characterized for its physicochemical, morphological, and topographical properties. Nanofibers were biocompatible, improved cell adhesion rate, and illustrated favourable interaction with cells. Gene expression (showed 9.5 and 4.1 fold increase in ß-tubulin and MAP 2 expression, respectively) and protein expression (immunofluorescence, flow cytometry, and western blot) studies confirmed the positive influence of the scaffold over cell differentiation. The studies were extrapolated to adult zebrafish model with a surgical incision in posterior lateral line. The biocomposite treated group showed earlier functional restoration of the nerve compared with control groups detected by touch-evoked response. Thus, the combination of aligned nanofibers providing topographical cue, along with the peptides and triiodothyronine serving as biochemical cues, has a robust potential to restore functionality to the injured nerve, thereby opening avenues for fabrication of regenerative nerve grafts.

Praseodymium-Cobaltite-Reinforced Collagen as Biomimetic Scaffolds for Angiogenesis and Stem Cell Differentiation for Cutaneous Wound Healing.

The present study describes the fabrication of collagen reinforced with praseodymium-cobaltite nanoparticles for wound healing applications. Praseodymium-cobaltite nanoparticles (PCNP) reinforced with collagen resulted in an increased thermal stability and decreased proteolytic susceptibility to collagen. Circular dichroism spectroscopy and ATR-FTIR (attenuated total reflection Fourier transform infrared) spectroscopy analyses confirm the intact structural integrity of the collagen sheets after cross-linking with praseodymium-cobaltite nanoparticles. Cross-linked collagen has shown to possess biocompatibility, less protein adsorption behavior, and hemocompatibility, which are the desirable properties of a wound dressing material. The nanoparticle cross-linked collagen sheets provided a proper matrix elasticity that promotes mesenchymal stem cell attachment and angiogenesis. Further, the scaffold promoted tube formation in endothelial cells. The enhancement of angiogenesis is considered to be brought about by the therapeutic potential of nanoparticle formulation. Praseodymium-cobaltite nanoparticle cross-linking increased the ductility of collagen sheets for the pro-angiogenic and stem cell differentiation ability. Also, the praseodymium-cobaltite cross-linked collagen sheets have been shown to induce a mild level of ROS (reactive oxygen species) generation in the DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) assay, which is beneficial for angiogenesis as well as wound healing. This study paves the way for exploring the therapeutic potential of rare-earth-based nanoparticles for tissue engineering applications as an alternative for traditional wound healing materials.

Generation of clinical-grade red blood cells from human umbilical cord blood mononuclear cells.

A xeno-free method for ex vivo generation of red blood cells (RBCs) is attempted in order to replicate for large-scale production and clinical applications. An efficient milieu was formulated using injectable drugs substituting the animal-derived components in the culture medium. Unfractionated mononuclear cells isolated from human umbilical cord blood were used hypothesizing that the heterogeneous cell population could effectively contribute to erythroid cell generation. The strategy adopted includes a combination of erythropoietin and other injectable drugs under low oxygen levels, which resulted in an increase in the number of mature RBCs produced in vitro. The novelty in this study is the addition of supplements to the medium in a stage-specific manner for the differentiation of unfractionated umbilical cord blood mononuclear cells (MNCs) into erythropoietic lineage. The erythropoietic lineage was well established by day 21, wherein the mean cell count of RBCs was found to be 21.36 ± 0.9 × 108 and further confirmed by an upregulated expression of CD235a+ specific to RBCs. The rationale was to have a simple method to produce erythroid cells from umbilical cord blood isolates in vitro by mitigating the effects of multiple erythroid-activating agents and batch to batch variability.

Strategic design of cardiac mimetic core-shell nanofibrous scaffold impregnated with Salvianolic acid B and Magnesium l-ascorbic acid 2 phosphate for myoblast differentiation.

The major loss of myocardial tissue extracellular matrix after infarction is a serious complication that leads to heart failure. Regeneration and integration of damaged cardiac tissue is challenging since the functional restoration of the injured myocardium is an incredible task. The injured micro environment of myocardium fails to regenerate spontaneously. The emergence of nano-biomaterials would be a promising approach to regenerate such a damaged cardiomyocytes tissue. Here, we have fabricated a dual bioactive embedded nanofibrous cardiac patch via coaxial electrospinning technique, to mimic the topographical and chemical cues of the natural cardiac tissue. The proportion and the concentration of the polymers were optimized for tailored delivery of bioactives from a spatio-temporally designed scaffold. The functionalization of polymeric core shell nanofibrous scaffold with dual bioactives enhanced the physico-chemical and bio-mechanical properties of the scaffolds that has resulted in a 3-dimensional topography mimicking the natural cardiac like extracellular matrix. The sustained delivery of bioactive signals, improved cell adhesion, proliferation, migration and differentiation could be attributed to its highly interconnected nanofibrous matrix with good extended morphology. Further, the expression of cardiac specific markers were found to increase on investigation of mRNA by real time PCR studies and proteins by immunofluorescence and western blotting techniques, confirming cell - biomaterial interactions. Flow cytometry analysis authenticated a potent mitochondrial membrane potential of cells treated with nanocomposite. In addition, in ovo studies in chicken chorioallantoic membrane assay confirm the efficacy of the developed scaffold in inducing angiogenesis required for maintaining its viability after transplantation onto the infarcted zone. These promising results demonstrate the potential of the composite nanofibrous scaffold as an effective biomaterial substrate for cardiac regeneration providing cues for development of novel cardiac therapeutics.

Selectivity and sensitivity of molybdenum oxide-polycaprolactone nanofiber composites on skin cancer: Preliminary in-vitro and in-vivo implications.

Cancer nanomedicine has emerged as a revolution in the last decade opening up promising strides for the cancer treatment. The major challenge in these therapeutic approaches resides in the failure of clinical trials owing to the immunological cancer microenvironment. Therefore, the success of next generation nanomedicine depends on tunable physicochemical nanomaterial design and corresponding clinical trials by integrating targeted delivery with mitigated toxicity. The present study deals with the fabrication of nanofibrous scaffold impregnated with molybdenum nanoparticles for targeted skin cancer therapeutics. Molybdenum oxide, a transitional metal oxide is gaining rapid importance due to its vital role in cellular and molecular metabolism. Polycaprolactone nanofibers were chosen as a matrix to localize the nanoparticles topically facilitating selective apoptosis of the tumor cells over the normal cells with mitigated side effects. The scaffold was designed to tailor the physicochemical, mechanical and biological suitability for skin cancer (melanoma and non melanoma). The designed scaffold was found to reduce more than 50% cell viability of the cancer cells selectively through apoptosis as confirmed using AO/PI staining and the probable mechanism could be attributed to the induction of mitochondria dependent apoptosis as observed by JC1 dye staining. In-vivo trials in zebra fish were found to reduce cancer progression by more than 30% in 14 days. The fabricated molybdenum trioxide nano constructs not only serve as tunable targeted systems but also open venues capable of ferrying chemotherapeutic drugs sparing normal cells alleviating the trauma due to side effects.