Harnessing potential of avian eggshell membrane derived collagen hydrolysate for bone tissue regeneration.

BACKGROUND: Natural bone grafts are the highly preferred materials for restoring the lost bone, while being constrained of donor availability and risk of disease transmission. As a result, tissue engineering is emerging as an efficacious and competitive technique for bone repair. Bone tissue engineering (TE) scaffolds to support bone regeneration and devoid of aforesaid limitations are being vastly explored and among these the avian eggshell membrane has drawn attention for TE owing to its low immunogenicity, similarity with the extracellular matrix, and easy availability. METHODOLOGY AND RESULTS: In this study, the development of bone ingrowth support system from avian eggshell membrane derived collagen hydrolysates (Col-h) is reported. The hydrolysate, cross-linked with glutaraldehyde, was developed into hydrogels with poly-(vinyl alcohol) (PVA) by freeze-thawing and further characterized with ATR-FTIR, XRD, FESEM. The biodegradability, swelling, mechanical, anti-microbial, and biocompatibility evaluation were performed further for the suitability in bone regeneration. The presence of amide I, amide III, and -OH functional groups at 1639 cm- 1,1264 cm- 1, and 3308 cm- 1 respectively and broad peak between 16°-21° (2θ) in XRD data reinstated the composition and form. CONCLUSIONS: The maximum ratio of Col-h/PVA that produced well defined hydrogels was 50:50. Though all the hydrogel matrices alluded towards their competitive attributes and applicability towards restorative bone repair, the hydrogel with 40:60 ratios showed better mechanical strength and cell proliferation than its counterparts. The prominent E. coli growth inhibition by the hydrogel matrices was also observed, along with excellent biocompatibility with MG-63 osteoblasts. The findings indicate strongly the promising application of avian eggshell-derived Col-h in supporting bone regeneration.

Thermo-Chemical Cues-Mediated Strategy to Control Peptide Self-Assembly and Charge Transfer Complexation.

Peptide amphiphiles (PAs) are known for their remarkable ability to undergo molecular self-assembly, a process that is highly responsive to the local microenvironment. Herein, we design a pyrene tethered peptide amphiphile Py-VFFAKK, 1 that exhibits pathway-driven self-assembly from metastable nanoparticles to kinetically controlled nanofibers and thermodynamically stable twisted bundles upon modulations in pH, temperature, and chemical cues. The presence of the pyrene moiety ensures donation of the electron to an electron acceptor, namely, 7,7,8,8-tetracyanoquinodimethane (TCNQ), to form a supramolecular charge transfer complex in aqueous solution that was studied in detail with microscopic and spectroscopic techniques. Excitation of the donor species in its excimer state facilitates electron donation to the acceptor moiety, paving away a long-lived charge-separated state that persists for over a nanosecond, as ascertained through transient absorption spectroscopy. Finally, the self-assembled charge transfer complex is explored toward antimicrobial properties with Escherichia coli while maintaining biocompatibility toward L929 mice fibroblast cells.

Thermoresponsive Injectable Hydrogel To Mimic the Heat- and Strain-Stiffening Behavior of Biopolymers toward Muscle Cell Proliferation.

Injectable hydrogels with nonlinear mechanical attributes to emulate natural biopolymers hold paramount significance in tissue engineering, offering the potential to create scaffolds that seamlessly mimic the biomechanical intricacies of living tissues. Herein, we unveil a synthetic design strategy employing Schiff base chemistry to furnish a peptide-polymer hierarchical contractile injectable hydrogel network. This innovative design demonstrates cross-linking of supramolecular peptide nanostructures such as nanofibers, 1NF, and twisted bundles, 1TB, with a thermosensitive aldehyde-functionalized polymer, PCHO. These networks exhibit interesting nonlinear mechanical stiffening responses to temperature and external stress. Furthermore, the hydrogels transform into a gel state at physiological temperature to exhibit injectable behavior and demonstrate compression load-bearing capabilities. Finally, the hydrogel network exhibits excellent biocompatibility and cell proliferation toward fibroblast, L929, and myoblast, C2C12, to validate their use as potential extracellular matrix mimetic injectable scaffolds.

Orthogonal chain collapse in stimuli-responsive di-block polymers leading to self-sorted nanostructures.

We design amphiphilic di-block copolymers (P-b-F and P-b-C) tethered with stimuli-responsive ferrocene and coumarin hydrophobic pendants that exhibit chain collapse behaviour in response to light, redox and chemical cues, with subsequent transformation of the vesicles into micelles. Interestingly, the co-assembled vesicles of the polymer blend under orthogonal stimuli furnish self-sorted micelles and vesicles.

Clinical potential and neuroplastic effect of targeted virtual reality based intervention for distal upper limb in post-stroke rehabilitation: a pilot observational study.

PURPOSE: A library of Virtual Reality (VR) tasks has been developed for targeted post-stroke rehabilitation of distal upper extremities. The objective of this pilot study was to evaluate the clinical potential of the targeted VR-based therapeutic intervention in a small cohort of patients specifically with chronic stroke. Furthermore, our aim was to explore the possible neuronal reorganizations in corticospinal pathways in response to the distal upper limb targeted VR-intervention. METHODOLOGY: Five patients with chronic stroke were enrolled in this study and were given VR-intervention of 20 sessions of 45 min each. Clinical Scales, cortical-excitability measures (using Transcranial Magnetic Stimulation): Resting Motor Threshold (RMT), and Motor Evoked Potential (MEP) amplitude, task-specific performance metrics i.e., Time taken to complete the task (TCT), smoothness of trajectory, relative % error were evaluated pre- and post-intervention to evaluate the intervention-induced improvements. RESULTS: Pre-to post-intervention improvements were observed in Fugl-Meyer Assessment (both total and wrist/hand component), Modified Barthel Index, Stroke Impact Scale, Motor Assessment Scale, active range of motion at wrist, and task-specific outcome metrics. Pre-to post-intervention ipsilesional RMT reduced (mean ∼9%) and MEP amplitude increased (mean ∼29µV), indicating increased cortical excitability at post-intervention. CONCLUSION: VR-training exhibited improved motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes observed in terms of improved cortical-excitability might be a consequence of plastic reorganization induced by VR-intervention.IMPLICATIONS FOR REHABILITATIONPost-stroke rehabilitation of distal upper extremities is crucial and needs targeted intervention to rehabilitate in the chronic phase of recovery.Virtual reality (VR) has emerged as a supplemental approach in post-stroke rehabilitation. However, its customization as per clinical need is still under research.This pilot study provides preliminary evidence of the clinical utility of the developed VR tasks targeted for distal upper extremities.

Post-Stroke Rehabilitation of Distal Upper Limb with New Perspective Technologies: Virtual Reality and Repetitive Transcranial Magnetic Stimulation-A Mini Review.

Upper extremity motor impairment is the most common sequelae in patients with stroke. Moreover, its continual nature limits the optimal functioning of patients in the activities of daily living. Because of the intrinsic limitations in the conventional form of rehabilitation, the rehabilitation applications have been expanded to technology-driven solutions, such as Virtual Reality and Repetitive Transcranial Magnetic Stimulation (rTMS). The motor relearning processes are influenced by variables, such as task specificity, motivation, and feedback provision, and a VR environment in the form of interactive games could provide novel and motivating customized training solutions for better post-stroke upper limb motor improvement. rTMS being a precise non-invasive brain stimulation method with good control of stimulation parameters, has the potential to facilitate neuroplasticity and hence a good recovery. Although several studies have discussed these forms of approaches and their underlying mechanisms, only a few of them have specifically summarized the synergistic applications of these paradigms. To bridge the gaps, this mini review presents recent research and focuses precisely on the applications of VR and rTMS in distal upper limb rehabilitation. It is anticipated that this article will provide a better representation of the role of VR and rTMS in distal joint upper limb rehabilitation in patients with stroke.

Modeling and Characterization of Surface Discharges in Insulating Material for Spacers: Electrode Shape, Discharge Mode, and Revision of the Creepage Concept.

In the design of MV AC and DC spacers, the predominant factors are surface and interface conditions. Design is generally carried out on specifications and standards which are based on long-term experience and lab testing. However, the diffusion of power electronics with a trend to increase electric field, switching frequency, and rise time to achieve higher power density calls for an innovative, global approach to optimized insulation system design. A new methodology, based on field simulation, discharge modeling, and partial discharge inception measurements, called the three-leg approach, can form the basis to optimize insulation design for any type of supply voltage waveform. This paper focuses on the influence of the type of electrode on the inception and phenomenology of surface discharges and, as a consequence, on the interpretation of the results used for application of the three-leg approach. It is demonstrated that a typical electrode system used for insulating material testing can generate both gas and surface discharges at the triple point, when the electrodes have a smooth profile that is used to avoid corona or flashover. Hence, testing partial discharge may not provide a straightforward indication of the surface discharge inception and, thus, be partially misleading for insulation design. Another takeover is that such analysis must benefit from PD testing tools endowed with analytics able to provide automatic identification of the type of defect generating PD, i.e., internal, surface, and corona, since design and remedy actions can be taken, and adequate insulating materials developed, only knowing the type of source generating PD. Hence, testing partial discharge may not provide a straightforward indication of surface discharge inception and, thus, be partially misleading for insulation design. In addition to the importance of the three-leg approach to favor reliable and optimized design of insulation systems, there is a clear need to have a PD testing tool endowed with analytics. It should preferably be able to provide automatic identification of the type of defect generating PD, i.e., internal, surface, and corona.

Stimuli-Responsive Self-Assembly Disassembly in Peptide Amphiphiles to Endow Block-co-Fibers and Tunable Piezoelectric Response.

Supramolecular assemblies with well-defined structural attenuation toward varied functional implications are an emerging area in mimicking natural biomaterials. In that regard, the redox stimuli-responsive ferrocene moiety can reversibly change between a nonpolar ferrocenyl and polar ferrocenium cation that endows interesting modular features to the building blocks with respect to self-assembly/disassembly. We design a series of ferrocene anchored peptide fragment NVFFAKKC using hydrophobic alkyl spacers of different chain lengths. Increasing the spacer length between the redox-responsive and self-assembling motifs increases the propensity to form robust nanofibers, which can be physically cross-linked to form hydrogels. The controlled redox response of the ferrocene moiety tandem with pH control provides access to structural control over the peptide nanostructures and tunable mechanical strengths. Further, such redox-sequestered dormant states hinder the spontaneous nucleation process that we exploit toward seeded supramolecular polymerization to form block cofibers composed of redox-responsive periphery and nonresponsive cores. Finally, such redox sequestration of peptide self-assembly renders an on-off piezoelectric response for potential utilization in peptide bioelectronics.

Insulating Material Development for the Design of Standoff Insulators Fed by Hybrid Voltage.

Innovative electrical assets are being developed in transmission and distribution, as well as in electrified transportation, from ships to aerospace. In general, power electronics have to master the whole power supply, being the driver of high specific power, low weight and volume components, in addition to enabling flexible and highly variable power flow. In these conditions, electrical and electronic insulation systems will have to withstand new types and levels of electric stresses, while still maintaining its reliability throughout its whole design life. This paper presents a study on the interrelation between insulating material properties and surface field of standoff insulators. The aim is mainly to provide indications on material properties which can be tailored to provide a robust, reliable and optimised insulator design that will hold for any type of electrical stress the insulation will have to withstand during operation. Specifically, we focus on ac and dc supply, including voltage transients, which could feed the same insulator depending on operation, according to a hybrid asset paradigm. The challenge is, indeed, to establish a pattern to material and insulation system design which takes into account the differences between the types of electrical stress profile and magnitude when insulators are supplied either in a dc or in ac, in order to infer which type of material characteristics would be more appropriate for the sake of life and reliability. The main contribution of this paper is to show that engineering the values of bulk and surface conductivity (which can be done selecting appropriate materials or modifying them, e.g., by nano-structuration) and modelling surface discharge inception would allow the electric field profile to be stabilised whatever the shape of the applied waveform. This will enable us to reach a reliability target that not only accounts for macroscopic phenomena, but also for the likelihood of extrinsic accelerated aging mechanism occurrence as partial discharges. In such a way, optimization of conditions to improve life, reliability, design and creepage and clearance characteristics can be achieved.

Natural Occurrence of Carbon Dots during In Vitro Nonenzymatic Glycosylation of Hemoglobin A0.

Carbon dots, the nanostructures of carbon, have excellent optical and chemical properties and find a range of applications in various fields of biology and medicine. In the current study, carbon dots are synthesized using in vitro nonenzymatic glycosylation at 37 °C, which is the conventional method for the synthesis of Advanced Glycosylation End products. While comparing the physicochemical properties using a series of physical and chemical analyses including light absorption, fluorescence, photoluminescence, chemical composition, functional group analysis, and in vitro imaging, striking similarities are found among Carbon dots and Advanced Glycosylation End products. Based on the evident resemblance between the two, we propose either the presence of a common structural backbone or the coexistence of the two individual chemical entities. Thus, the formation of carbon dots at physiological temperatures raises health concerns as nonenzymatic glycosylation is a physiological process in humans and the rate of which is elevated during diabetes. The Advanced Glycosylation End products are known to have a detrimental effect in diabetic patients, and the chemical similarity between the two questions the widely studied biocompatibility of carbon dots.

Design and Validation of Virtual Reality Task for Neuro-Rehabilitation of Distal Upper Extremities.

Stroke, affecting approximately 15 million people worldwide, has long been a global cause of death and disability. Virtual Reality (VR) has shown its potential as an assistive tool for post-stroke rehabilitation. The objective of this pilot study was to define the task-specific performance metrics of VR tasks to assess the performance level of healthy subjects and patients quantitatively and to obtain their feedback for improving the developed framework. A pilot prospective study was designed. We tested the designed VR tasks on forty healthy right-handed subjects to evaluate its potential. Qualitative trajectory plots and three quantitative performance metrics-time taken to complete the task, percentage relative error, and trajectory smoothness-were computed from the recorded data of forty healthy subjects. Two patients with stroke were also enrolled to compare their performance with healthy subjects. Each participant received one VR session of 90 min. No adverse effects were noticed throughout the study. Performance metrics obtained from healthy subjects were used as a reference for patients. Relatively higher values of task completion time and trajectory smoothness and lower values of relative % error was observed for the affected hands w.r.t the unaffected hands of both the patients. For the unaffected hands of both the patients, the performance levels were found objectively closer to that of healthy subjects. A library of VR tasks for wrist and fingers were designed, and task-specific performance metrics were defined in this study. The evaluation of the VR exercises using these performance metrics will help the clinicians to assess the patient's progress quantitatively and to design the rehabilitation framework for a future clinical study.

Clinical Effectiveness of Non-Immersive Virtual Reality Tasks for Post-Stroke Neuro-Rehabilitation of Distal Upper-Extremities: A Case Report.

A library of non-immersive Virtual Reality (VR) tasks were developed for post-stroke rehabilitation of distal upper extremities. The objective was to evaluate the rehabilitation impact of the developed VR-tasks on a patient with chronic stroke. The study involved a 50-year-old male patient with chronic (13 month) stroke. Twenty VR therapy sessions of 45 min each were given. Clinical scales, cortical-excitability measures, functional MRI (fMRI), and diffusion tensor imaging (DTI) data were acquired pre-and post-therapy to evaluate the motor recovery. Increase in Fugl-Meyer Assessment (wrist/hand) by 2 units, Barthel Index by 5 units, Brunnstrom Stage by 1 unit, Addenbrooke's Cognitive Examination by 3 units, Wrist Active Range of Motion by 5° and decrease in Modified Ashworth Scale by 1 unit were observed. Ipsilesional Motor Evoked Potential (MEP) amplitude (obtained using Transcranial Magnetic Stimulation) was increased by 60.9µV with a decrease in Resting Motor Threshold (RMT) by 7%, and contralesional MEP amplitude was increased by 56.2µV with a decrease in RMT by 7%. The fMRI-derived Laterality Index of Sensorimotor Cortex increased in precentral-gyrus (from 0.28 to 0.33) and in postcentral-gyrus (from 0.07 to 0.3). The DTI-derived FA-asymmetry decreased in precentral-gyrus (from 0.029 to 0.024) and in postcentral-gyrus (from 0.027 to 0.017). Relative reduction in task-specific performance metrics, i.e., time taken to complete the task (31.6%), smoothness of trajectory (76.7%), and relative percentage error (80.7%), were observed from day 1 to day 20 of the VR therapy. VR therapy resulted in improvement in clinical outcomes in a patient with chronic stroke. The research also gives insights to further improve the overall system of rehabilitation.