A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.

Long-term drug delivery using implantable electrospun woven polymeric nanotextiles.

A woven nanotextile implant was developed and optimized for long-term continuous drug delivery for potential oncological applications. Electrospun polydioxanone (PDS) nanoyarns, which are twisted bundles of PDS nanofibres, were loaded with paclitaxel (PTX) and woven into nanotextiles of different packing densities. A mechanistic modeling of in vitro drug release proved that a combination of diffusion and matrix degradation controlled the slow PTX-release from a nanoyarn, emphasizing the role of nanostructure in modulating release kinetics. Woven nanotextiles, through variations in its packing density and thereby architecture, demonstrated tuneable PTX-release. In vivo PTX-release, pharmacokinetics and biodistribution were evaluated in healthy BALB/c mice by suturing the nanotextile to peritoneal wall. The slow and metronomic PTX-release for 60 days from the loosely woven implant was extremely effective in enhancing its residence in peritoneum, in contrast to intraperitoneal injections. Such an implantable matrix offers a novel platform for therapy of solid tumors over prolonged durations.

Predictors of Outcome in Patients with Neovascular Age-Related Macular Degeneration Switched from Ranibizumab to 8-Weekly Aflibercept.

PURPOSE: The purpose of this study was to evaluate the outcomes over 12 months in patients with neovascular age-related macular degeneration (nAMD) with insufficient response to ranibizumab who were switched directly to 8-weekly fixed dosing of aflibercept without a loading phase. DESIGN: Retrospective interventional study. PARTICIPANTS: Consecutive patients with nAMD who were switched from pro re nata (PRN) intravitreal ranibizumab to 8-weekly fixed aflibercept because of persistent disease activity from November 1, 2013, to September 30, 2014, were included. METHODS: Demographic data, visual acuity (VA), and spectral-domain optical coherence tomography characteristics over time were evaluated to determine the prognostic indicators of final visual outcome at 12 months. MAIN OUTCOME MEASURES: The VA, central subfield thickness (CST), presence of macular fluid at month 12 compared with baseline, and the definition of prognostic indicators of final visual outcome at month 12. RESULTS: A total of 431 patients (447 eyes) were included in this study. There was no statistically significant difference in VA between baseline and month 12 (P = 0.79), whereas the CST significantly decreased at month 12 compared with baseline (P < 0.001). At the 12-month follow-up, 48.3% of eyes had no macular fluid compared with 8.5% at baseline. The mean number of injections at month 12 was 6.8±1.75. Poor prognostic indicators included increasing age, increasing CST, the presence of intraretinal fluid, pigment epithelial detachment, and subfoveal thickening. CONCLUSIONS: Patients who have not yet "responded" to PRN ranibizumab seem to exhibit retinal dehydration after switching to aflibercept, whereas there was no demonstration of VA benefit. Baseline features at the point of switching can independently predict outcomes.

Integrating Substrateless Electrospinning with Textile Technology for Creating Biodegradable Three-Dimensional Structures.

The present study describes a unique way of integrating substrateless electrospinning process with textile technology. We developed a new collector design that provided a pressure-driven, localized cotton-wool structure in free space from which continuous high strength yarns were drawn. An advantage of this integration was that the textile could be drug/dye loaded and be developed into a core-sheath architecture with greater functionality. This method could produce potential nanotextiles for various biomedical applications.

Sequential release of epigallocatechin gallate and paclitaxel from PLGA-casein core/shell nanoparticles sensitizes drug-resistant breast cancer cells.

Nanomedicines consisting of combinations of cytotoxic drugs and molecular targeted therapeutics which inhibit specific downstream signals are evolving as a novel paradigm for breast cancer therapy. This research addresses one such combination of Paclitaxel (Ptx), having several adversities related to the activation of NF-κB pathway, with Epigallocatechin gallate (EGCG), a multiple signaling inhibitor, encapsulated within a targeted core/shell PLGA-Casein nanoparticle. The sequential release of EGCG followed by Ptx from this core/shell nanocarrier sensitized Ptx resistant MDA-MB-231 cells to Ptx, induced their apoptosis, inhibited NF-κB activation and downregulated the key genes associated with angiogenesis, tumor metastasis and survival. More importantly, Ptx-induced expression of P-glycoprotein was repressed by the nanocombination both at the protein and gene levels. This combination also offered significant cytotoxic response on breast cancer primary cells, indicating its translational value. FROM THE CLINICAL EDITOR: Breast cancer is the most common cancer in women worldwide. As well as surgery, chemotherapy plays a major role in the treatment of breast cancer. The authors investigated in this article the combination use of a chemotherapeutic agent, Paclitaxel (Ptx), and an inhibitor of NF-?B pathway, packaged in a targeted nano-based delivery platform. The positive results provided a new pathway for future clinical use of combination chemotherapy in breast cancer.

ZnO nanoparticle incorporated nanostructured metallic titanium for increased mesenchymal stem cell response and antibacterial activity.

Recent trends in titanium implants are towards the development of nanoscale topographies that mimic the nanoscale properties of bone tissue. Although the nanosurface promotes the integration of osteoblast cells, infection related problems can also occur, leading to implant failure. Therefore it is imperative to reduce bacterial adhesion on an implant surface, either with or without the use of drugs/antibacterial agents. Herein, we have investigated two different aspects of Ti surfaces in inhibiting bacterial adhesion and concurrently promoting mammalian cell adhesion. These include (i) the type of nanoscale topography (Titania nanotube (TNT) and Titania nanoleaf (TNL)) and (ii) the presence of an antibacterial agent like zinc oxide nanoparticles (ZnOnp) on Ti nanosurfaces. To address this, periodically arranged TNT (80-120 nm) and non-periodically arranged TNL surfaces were generated by the anodization and hydrothermal techniques respectively, and incorporated with ZnOnp of different concentrations (375 µM, 750 µM, 1.125 mM and 1.5 mM). Interestingly, TNL surfaces decreased the adherence of staphylococcus aureus while increasing the adhesion and viability of human osteosarcoma MG63 cell line and human mesenchymal stem cells, even in the absence of ZnOnp. In contrast, TNT surfaces exhibited an increased bacterial and mammalian cell adhesion. The influence of ZnOnp on these surfaces in altering the bacterial and cell adhesion was found to be concentration dependent, with an optimal range of 375-750 µM. Above 750 µM, although bacterial adhesion was reduced, cellular viability was considerably affected. Thus our study helps us to infer that nanoscale topography by itself or its combination with an optimal concentration of antibacterial ZnOnp would provide a differential cell behavior and thereby a desirable biological response, facilitating the long term success of an implant.

Mn-doped zinc sulphide nanocrystals for immunofluorescent labeling of epidermal growth factor receptors on cells and clinical tumor tissues.

The field of molecular detection and targeted imaging has evolved considerably with the introduction of fluorescent semiconductor nanocrystals. Manganese-doped zinc sulphide nanocrystals (ZnS:Mn NCs), which are widely used in electroluminescent displays, have been explored for the first time for direct immunofluorescent (IF) labeling of clinical tumor tissues. ZnS:Mn NCs developed through a facile wet chemistry route were capped using amino acid cysteine, conjugated to streptavidin and thereafter coupled to biotinylated epidermal growth factor receptor (EGFR) antibody utilizing the streptavidin-biotin linkage. The overall conjugation yielded stable EGFR antibody conjugated ZnS:Mn NCs (EGFR ZnS:Mn NCs) with a hydrodynamic diameter of 65 ± 15 nm, and having an intense orange-red fluorescence emission at 598 nm. Specific labeling of EGF receptors on EGFR(+ve) A431 cells in a co-culture with EGFR(-ve) NIH3T3 cells was demonstrated using these nanoprobes. The primary antibody conjugated fluorescent NCs could also clearly delineate EGFR over-expressing cells on clinical tumor tissues processed by formalin fixation as well as cryopreservation with a specificity of 86% and accuracy of 88%, in comparison to immunohistochemistry. Tumor tissues labeled with EGFR ZnS:Mn NCs showed good fluorescence emission when imaged after storage even at 15 months. Thus, ZnS nanobioconjugates with dopant-dependent and stable fluorescence emission show promise as an efficient, target-specific fluorophore that would enable long term IF labeling of any antigen of interest on clinical tissues.

Injectable Tissue Adhesive Microgel Composite Containing Antifibrotic Drug for Vocal Fold Scarring.

Vocal fold (VF) scarring, a complex problem in laryngology, results from injury and inflammation of the layered architecture of the VFs. The resultant voice hoarseness, for which successful therapeutic options are currently limited, affects the patient's quality of life. A promising strategy to reverse this disorder is the use of antifibrotic drugs. The present study proposes a novel microbead-embedded injectable hydrogel that can sustain the release of the anti-fibrotic drug pirfenidone (PFD) for vocal fold scarring. Microbeads were developed using sodium alginate and gelatin, which were further embedded into a biomimetic and tissue adhesive gellan gum (GG) hydrogel. The microbead-embedded hydrogel exhibited improved injectability, viscoelasticity, tissue adhesiveness, degradability, and swelling compared to the hydrogel without beads. Additionally, the bead-embedded hydrogel could sustain the release of the PFD for a week. In vitro studies showed that the drug-loaded hydrogel could reduce the migration and proliferation of fibroblast cells in a dose-dependent manner. In summary, this study demonstrates the potential of a PFD-loaded injectable hydrogel with enhanced viscoelastic and tissue-adhesive properties for vocal fold scarring applications.

Nano-graphene oxide particles induce inheritable anomalies through altered gene expressions involved in oocyte maturation.

The inheritable impact of exposure to graphene oxide nanoparticles (GO NPs) on vertebrate germline during critical windows of gamete development remain undetermined to date. Here, we analyzed the transgenerational effects of exposure to nano-graphene oxide particles (nGO) synthesized in house with lateral dimensions 300-600 nm and surface charge of -36.8 mV on different developmental stages of germ cells (GCs): (1) during GCs undergoing early development and differentiation, and (2) during GCs undergoing gametogenesis and maturation in adulthood. Biocompatibility analyses in Japanese medaka embryos showed lethality above 1 µg/ml and also an aberrant increase in germ cell count of both males and females at doses below the lethal dose. However, no lethality or anomalies were evident in adults up to 45 µg/ml. Long term exposure of embryos and adults for 21 days resulted in reduced fecundity. This effect was transmitted to subsequent generations, F1 and F2. Importantly, the inheritable effects of nGO in adults were pronounced at a high dose of 10 µg/ml, while 1 µg/ml showed no impact on the germline indicating lower doses used in this study to be safe. Further, expressions of selected genes that adversely affected oocyte maturation were enhanced in F1 and F2 individuals. Interestingly, the inheritance patterns differed corresponding to the stage at which the fish received the exposure.

Poly-(ethylene glycol) modified gelatin nanoparticles for sustained delivery of the anti-inflammatory drug Ibuprofen-Sodium: an in vitro and in vivo analysis.

The limited bioavailability and rapid clearance of the anti-inflammatory drug Ibuprofen Sodium (IbS) necessitates repeated drug administration. To address this, injectable IbS loaded PEGylated gelatin nanoparticles (PIG NPs) of size ~200nm and entrapment efficiency ~70%, providing sustained release in vitro were prepared by a modified two-step desolvation process. The developed nanomedicine, containing a range of IbS concentrations up to 1mg/mL proved to be non-toxic, hemocompatible and non-immunogenic, when tested through various in vitro assays and was reaffirmed by in vivo cytokine analysis. HPLC analysis of intravenously administered PIG NPs showed a sustained release of IbS for ~4days with improved bioavailability and pharmacokinetics when compared to bare IbS and IbS-loaded non-PEGylated GNPs. Histological analysis of liver and kidney revealed tissue integrity as in the control, indicating biocompatibility of PIG NPs. The results demonstrate improved plasma half-life of IbS when encapsulated within nanogelatin, thereby aiding reduction in its frequency of administration. FROM THE CLINICAL EDITOR: In this preclinical study, improved plasma half-life of ibuprofen sodium was demonstrated when encapsulated within PEGylated gelatin nanoparticles of ~200 nm size, expected to lead to reduced frequency of administration in future clinical applications.

Human Adipose-Derived Mesenchymal Stem Cell-Secreted Extracellular Matrix Coating on a Woven Nanotextile Vascular Patch for Improved Endothelial Cell Response.

Biomedical implants possessing the structural and functional characteristics of extracellular matrix (ECM) are pivotal for vascular applications. This study investigated the potential of recreating a natural ECM-like structural and functional environment on the surface of biodegradable polymeric nanotextiles for vascular implants. Human adipose-derived mesenchymal stem cells (MSCs) were grown on a suitably engineered polycaprolactone (PCL) nanofibrous textile and were allowed to modify its surface through the deposition of MSC-specific ECM. This surface-modified nanotextile showed mechanical characteristics and functionality appropriate for vascular patch material. The uniformity of ECM coating significantly improved the viability, proliferation, and migration of human endothelial cells compared to bare and xenogeneic collagen-coated PCL nanotextile patches. Thus, a polymeric nanotextile, which is surface modified using MSC-driven ECM, provided a rapid and improved endothelialization, thereby suggesting its potential for vascular patch applications.

Hemocompatibility and macrophage response of pristine and functionalized graphene.

Graphene and its derivatives are being proposed for several important biomedical applications including drug delivery, gene delivery, contrast imaging, and anticancer therapy. Most of these applications demand intravenous injection of graphene and hence evaluation of its hemocompatibility is an essential prerequisite. Herein, both pristine and functionalized graphene are extensively characterized for their interactions with murine macrophage RAW 264.7 cells and human primary blood components. Detailed analyses of the potential uptake by macrophages, effects on its metabolic activity, membrane integrity, induction of reactive oxygen stress, hemolysis, platelet activation, platelet aggregation, coagulation cascade, cytokine induction, immune cell activation, and immune cell suppression are performed using optimized protocols for nanotoxicity evaluation. Electron microscopy, confocal Raman spectral mapping, and confocal fluorescence imaging studies show active interaction of both the graphene systems with macrophage cells, and the reactive oxygen species mediated toxicity effects of hydrophobic pristine samples are significantly reduced by surface functionalization. In the case of hemocompatibility, both types of graphene show excellent compatibility with red blood cells, platelets, and plasma coagulation pathways, and minimal alteration in the cytokine expression by human peripheral blood mononuclear cells. Further, both samples do not cause any premature immune cell activation or suppression up to a relatively high concentration of 75 µg mL(-1) after 72 h of incubation under in vitro conditions. This study clearly suggests that the observed toxicity effects of pristine graphene towards macrophage cells can be easily averted by surface functionalization and both the systems show excellent hemocompatibility.

Rationally designed aberrant kinase-targeted endogenous protein nanomedicine against oncogene mutated/amplified refractory chronic myeloid leukemia.

Deregulated protein kinases play a very critical role in tumorigenesis, metastasis, and drug resistance of cancer. Although molecularly targeted small molecule kinase inhibitors (SMI) are effective against many types of cancer, point mutations in the kinase domain impart drug resistance, a major challenge in the clinic. A classic example is chronic myeloid leukemia (CML) caused by BCR-ABL fusion protein, wherein a BCR-ABL kinase inhibitor, imatinib (IM), was highly successful in the early chronic phase of the disease, but failed in the advanced stages due to amplification of oncogene or point mutations in the drug-binding site of kinase domain. Here, by identifying critical molecular pathways responsible for the drug-resistance in refractory CML patient samples and a model cell line, we have rationally designed an endogenous protein nanomedicine targeted to both cell surface receptors and aberrantly activated secondary kinase in the oncogenic network. Molecular diagnosis revealed that, in addition to point mutations and amplification of oncogenic BCR-ABL kinase, relapsed/refractory patients exhibited significant activation of STAT5 signaling with correlative overexpression of transferrin receptors (TfR) on the cell membrane. Accordingly, we have developed a human serum albumin (HSA) based nanomedicine, loaded with STAT5 inhibitor (sorafenib), and surface conjugated the same with holo-transferrin (Tf) ligands for TfR specific delivery. This dual-targeted "transferrin conjugated albumin bound sorafenib" nanomedicine (Tf-nAlb-Soraf), prepared using aqueous nanoprecipitation method, displayed uniform spherical morphology with average size of ∼150 nm and drug encapsulation efficiency of ∼74%. TfR specific uptake and enhanced antileukemic activity of the nanomedicine was found maximum in the most drug resistant patient sample having the highest level of STAT5 and TfR expression, thereby confirming the accuracy of our rational design and potential of dual-targeting approach. The nanomedicine induced downregulation of key survival pathways such as pSTAT5 and antiapoptotic protein MCL-1 was demonstrated using immunoblotting. This study reveals that, by implementing molecular diagnosis, personalized nanomedicines can be rationally designed and nanoengineered by imparting therapeutic functionality to endogenous proteins to overcome clinically important challenges like molecular drug resistance.

Fibrin nanoconstructs: a novel processing method and their use as controlled delivery agents.

Fibrin nanoconstructs (FNCs) were prepared through a modified water-in-oil emulsification-diffusion route without the use of any surfactants, resulting in a high yield synthesis of fibrin nanotubes (FNTs) and fibrin nanoparticles (FNPs). The fibrin nanoconstructs formed an aligned structure with self-assembled nanotubes with closed heads that eventually formed spherical nanoparticles of size ~250 nm. The nanotubes were typically ~700 nm long and 150-300 nm in diameter, with a wall thickness of ~50 nm and pore diameter of about 150-250 nm. These constructs showed high stability against aggregation indicated by a zeta potential of -44 mV and an excellent temperature stability upto 200 °C. Furthermore, they were found to be enzymatically degradable, thereby precluding any long term toxicity effects. These unique fibrin nanostructures were analyzed for their ability to deliver tacrolimus, an immunosuppressive drug that is used widely to prevent the initial phase of tissue rejection during allogenic transplantation surgeries. Upon conjugation with tacrolimus, a drug encapsulation efficiency of 66% was achieved, with the in vitro release studies in PBS depicting a sustained and complete drug release over a period of one week at the physiological pH of 7.4. At a more acidic pH, the drug release was very slow, suggesting their potential for oral-intestinal drug administration as well. The in vivo drug absorption rates analyzed in Sprague Dawley rats further confirmed the sustained release pattern of tacrolimus for both oral and parenteral delivery routes. The novel fibrin nanoconstructs developed using a green chemistry approach thus proved to be excellent biodegradable nanocarriers for oral as well as parenteral administrations, with remarkable potential also for delivering specific growth factors in tissue engineering scaffolds.

Differential Drug Release Kinetics from Paclitaxel-Loaded Polydioxanone Membranes and Capsules.

BACKGROUND: Drug laden implantable systems can provide drug release over several hours to years, which eventually aid in the therapy of both acute and chronic diseases. The present study focuses on a fundamental evaluation of the influence of implant properties such as morphology, architecture, porosity, surface area, and wettability in regulating the drug release kinetics from drug-loaded polymeric matrices. METHODS: For this, Polydioxanone (PDS) was selected as the polymer and Paclitaxel (Ptx) as the model drug. Two different forms of the matrix implants, viz., reservoir type capsules developed by dip coating and matrix type membranes fabricated by phase inversion and electrospinning, were utilized for the study. Drug release from all the four different matrices prepared by simple techniques was evaluated in vitro in PBS and ex vivo in peritoneal wash fluid for ~4 weeks. The drug release profiles were thereafter correlated with the physicochemical parameters of the polymeric implants. RESULTS: Reservoir-type capsules followed a slow and steady zero-order kinetics, while matrix-type electrospun and phase inversion membranes displayed typical biphasic kinetics. CONCLUSION: It was inferred that the slow degradation rate of PDS polymer as well as the implant properties like porosity and wettability play an important role in controlling the drug release rates.

Inter-rater reliability for diagnosis of geographic atrophy using spectral domain OCT in age-related macular degeneration.

PURPOSE: To evaluate the inter-rater reliability for identification of complete retinal pigment epithelium and outer retinal atrophy (cRORA) on SD-OCT images as defined by the Classification of Atrophy Meetings (CAM) group. METHODS: Fifty images of anonymized SD-OCT line scans of eyes with cRORA due to AMD were selected. Each .tiff image was saved in both black-on-white (BW) and white-on-black (WB) format. Five retina-trained clinicians graded both sets of images twice for the diagnosis of cRORA based on the CAM group definition. Fleiss kappa statistic was calculated for inter-rater reliability and Cohen's kappa statistic for intra-grader and inter-grader reliability between any two graders. RESULTS: The inter-grader reliability varied from as low as 0.28 to 0.92 for WB images and 0.34 to 0.86 for BW images. However, the inter-grader and intra-grader agreement was ĸ WB 0.92; ĸ BW 0.86 and ĸ 0.92 respectively, for graders accustomed to the CAM criteria. Fleiss kappa was ĸ 0.49 (p value < 0.0001) for WB images and ĸ 0.34 (p value < 0.0001 for BW images. Overall, the agreement was better using WB images for all parameters except RPE attenuation/loss. CONCLUSION: There is significant variability in diagnosis of cRORA on SD-OCT by retina-trained ophthalmologists in the real world. The study highlights the need for training to recognise the different features of cRORA prior to its implementation in clinical practice.

Coupled benefits of nanotopography and titania surface chemistry in fostering endothelialization and reducing in-stent restenosis in coronary stents.

Recent advances in coronary stents have all been distinctively focused towards directing re-endothelialization with minimal in-stent restenosis, potentially via alterations in surface topographical cues, for augmenting the efficacy of vascular implants. This perspective was proven by our group utilizing a simple and easily scalable nanosurface modification strategy on metallic stents devoid of any drugs or polymers. In the present work, we explore the impact of surface characteristics in modulating this cell response in-vitro and in-vivo, using titania coated cobalt-chromium (CC) stents, with and without nanotopography, in comparison to commercial controls. Interestingly, titania nanotopography facilitated a preferential cell response in-vitro as against the titania coated and bare CC surfaces, which can be attributed to surface topography, hydrophilicity, and roughness. This in turn altered the cellular adhesion, proliferation and focal contact formations of endothelial and smooth muscle cells. We also demonstrate that titania nanotexturing plays a pivotal role in fostering rapid re-endothelialization with minimal neointimal hyperplasia, leading to excellent in-vivo patency of CC stents post 8 weeks implantation in rabbit iliac arteries, in comparison to bare CC, nano-less titania coated CC, and commercial drug-eluting stents (CC DES), without administering antiplatelet agents. This exciting result for the drug and polymer-free titania nanotextured stents, in the absence of platelet therapy, reveals the possibility of proposing an alternative to clinical DES for coronary stenting.

Functional clinical endpoints and their correlations in eyes with AMD with and without subretinal drusenoid deposits-a pilot study.

PURPOSE: To evaluate functional clinical endpoints and their structural correlations in AMD, with a focus on subretinal drusenoid deposits (SDD). METHODS: This prospective study enroled 50 participants (11 controls, 17 intermediate AMD (iAMD) with no SDD, 11 iAMD with SDD and 11 non-foveal atrophic AMD). Participants underwent best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), low luminance questionnaire (LLQ), scotopic thresholds, rod-intercept time (RIT), photopic flicker electroretinograms and multimodal imaging. Functional and structural relationships were assessed. RESULTS: Compared with healthy participants, BCVA, LLVA, scotopic thresholds were depressed, and RIT prolonged in iAMD patients with SDD (p = 0.028, p = 0.045, p = 0.014 and p < 0.0001 respectively). Patients with SDD also had reduced scotopic function and delayed RIT compared to iAMD without SDD (p = 0.005 and p < 0.0001). Eyes with SDD and non-foveal atrophy did not differ functionally. Nor did healthy subjects compared with iAMD without SDD. Functional parameters were significantly associated with scotopic thresholds (r = 0.39-0.64). BCVA, LLVA and scotopic thresholds correlated well with ONL volume, ONL thickness and choroidal thickness (r = 0.34-0.61). CONCLUSION: Eyes with SDD are surrogate markers of photoreceptor abnormalities comparable with non-central atrophy and should be sub-analysed in clinical trials evaluating potential prophylactic agents to decrease the progression of AMD and may even require different therapeutic interventions.

Nanocomposite fibrous scaffold mediated mandible reconstruction and dental rehabilitation: An experimental study in pig model.

Mandible reconstruction and dental rehabilitation after trauma or tumor resection represent a serious challenge for maxillofacial surgeons. This study aimed to investigate the bone formation potential of nanocomposite fibrous scaffold (silica-nanohydroxyapatite-gelatin reinforced with poly L-lactic acid yarns - CSF) for delayed Titanium (Ti) implantation, which was compared to autograft (AG) taken from the iliac crest. The grafts were placed in critical-sized mandibular defects in an adult pig model for 6 months followed by dental implant placement for another 3 months. There was complete union and vascularised lamellar bone formation within 6 months. Moreover, the biological processes associated with angiogenesis, bone maturation and remodelling were seen in CSF, which was comparable to AG. Later, when Ti dental implant was placed on newly formed bone, CSF group demonstrated better osseointegration. In short, nanocomposite fibrous scaffold promoted quality bone formation in mandible defect that leads to successful osseointegration, suggesting as a potential candidate for implant-based rehabilitation in clinics in future.