Metal-free functionalization of tyrosine residues in short peptides and study of the morphological alterations.

An efficient functionalization of tyrosine residues in phenolic regions is achieved under metal-free conditions. The strategy involves the conversion of a tyrosine residue to 4-amino phenylalanine or 4-amino-3-methoxy phenylalanine in short peptides through a controlled oxidative dearomatization. This transformation is achieved in one pot with good yields and excellent regioselectivity. Consequently, the self-assembly of the peptide compounds has been studied at the nanoscopic level before and after functionalization. The results suggest that the peptide derivatives comprising amide groups promote intermolecular H-bonding interactions and the difference in -OH and -NH2 functional groups is found to be responsible for the morphological changes. Morphological transitions from 1D nanowires to 2D nanosheets were observed during functional group modification.

Design and manufacturing of patient-specific Ti6Al4V implants with inhomogeneous porosity.

Stress shielding remains a challenge in orthopaedic implants, including total hip arthroplasty. Recent development in printable porous implants offers improved patient-specific solutions by providing adequate stability and reducing stress shielding possibilities. This work presents an approach for designing patient-specific implants with inhomogeneous porosity. A novel group of orthotropic auxetic structures is introduced, and their mechanical properties are computed. These auxetic structure units were distributed at different locations on the implant along with optimized pore distribution to achieve optimum performance. A computer tomography (CT) based finite element (FE) model was used to evaluate the performance of the proposed implant. The optimized implant and the auxetic structures were manufactured using laser powder bed-based laser metal additive manufacturing. Validation was done by comparing FE results with experimentally measured directional stiffness and Poisson's ratio of the auxetic structures and strain on the optimized implant. The correlation coefficient for the strain values was within a range of 0.9633-0.9844. Stress shielding was mainly observed in Gruen zones 1, 2, 6, and 7. The average stress shielding on the solid implant model was 56%, reduced to 18% when the optimized implant was used. This significant reduction in stress shielding can decrease the risk of implant loosening and create an osseointegration-friendly mechanical environment on the surrounding bone. The proposed approach can be effectively applied to the design of other orthopaedic implants to minimize stress shielding.

Effects of Microwave 10 GHz Radiation Exposure in the Skin of Rats: An Insight on Molecular Responses.

Microwave (MW) radiation poses the risk of potential hazards on human health. The present study investigated the effects of MW 10 GHz exposure for 3 h/day for 30 days at power densities of 5.23 ± 0.25 and 10.01 ± 0.15 mW/cm2 in the skin of rats. The animals exposed to 10 mW/cm2 (corresponded to twice the ICNIRP-2020 occupational reference level of MW exposure for humans) exhibited significant biophysical, biochemical, molecular and histological alterations compared to sham-irradiated animals. Infrared thermography revealed an increase in average skin surface temperature by 1.8°C and standard deviation of 0.3°C after 30 days of 10 mW/cm2 MW exposure compared to the sham-irradiated animals. MW exposure also led to oxidative stress (ROS, 4-HNE, LPO, AOPP), inflammatory responses (NFkB, iNOS/NOS2, COX-2) and metabolic alterations [hexokinase (HK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6-phospahte dehydrogenase (G6PD)] in 10 mW/cm2 irradiated rat skin. A significant alteration in expression of markers associated with cell survival (Akt/PKB) and HSP27/p38MAPK-related stress-response signaling cascade was observed in 10 mW/cm2 irradiated rat skin compared to sham-irradiated rat skin. However, MW-irradiated groups did not show apoptosis, evident by unchanged caspase-3 levels. Histopathological analysis revealed a mild cytoarchitectural alteration in epidermal layer and slight aggregation of leukocytes in 10 mW/cm2 irradiated rat skin. Altogether, the present findings demonstrated that 10 GHz exposure in continuous-wave mode at 10 mW/cm2 (3 h/day, 30 days) led to significant alterations in molecular markers associated with adaptive stress-response in rat skin. Furthermore, systematic scientific studies on more prevalent pulsed-mode of MW-radiation exposure for prolonged duration are warranted.

Design of patient specific bone stiffness mimicking scaffold.

The difference in stiffness of a patient's bone and bone implant causes stress shielding. Thus, implants which match the stiffness of bone of the patient result in better bone growth and osseointegration. Variation in porosity is one of the methods to obtain implants with different stiffness values. This study proposes a novel method to design biomimetic bone graft implant based on computed tomography (CT) scan data, that creates similar pre- and post-implant mechanical environment on peri-implant bone. The design methodology is demonstrated by taking three different sections of human femur bone, greater trochanter, diaphysis and epicondyle, with two different implant materials, Ti-6Al-4V and Ti-Mg. Bones from these three sections were replaced with porous implants of effective stiffness of replaced bone, as would have been required after a resection surgery. Models were simulated with physiological loading condition using finite element (FE) method. Variation of maximum von Mises stress and average strain on peri-prosthetic bone were found to be in the range of -6% to 10.7% and -7% to -17.9% for porous implants and 26% to 50% and -36% to -59% for solid implant respectively compared to natural bone. The results revealed that the porous implants, which have been designed based on CT scan data, can effectively produce mechanical response at peri-implant bone, which is very close to pre-implanted condition. Following this methodology, more osseointegration friendly mechanical environment can be achieved at peri-implant bone for any anatomical location independent of implant materials.

Design of Patient Specific Spinal Implant (Pedicle Screw Fixation) using FE Analysis and Soft Computing Techniques.

BACKGROUND: This work uses genetic algorithm (GA) for optimum design of patient specific spinal implants (pedicle screw) with varying implant diameter and bone condition. The optimum pedicle screw fixation in terms of implant diameter is on the basis of minimum strain difference from intact (natural) to implantation at peri-prosthetic bone for the considered six different peri-implant positions. METHODS: This design problem is expressed as an optimization problem using the desirability function, where the data generated by finite element analysis is converted into an artificial neural network (ANN) model. The finite element model is generated from CT scan data. Thereafter all the ANN predictions of the microstrain in six positions are converted to unitless desirability value varying between 0 and 1, which is then combined to form the composite desirability. Maximization of the composite desirability is done using GA where composite desirability should be made to go up as close as possible to 1. If the composite desirability is 1, then all 'strain difference values in 6 positions' are 0. RESULTS: The optimum solutions obtained can easily be used for making patient-specific spinal implants.

Measurement of strain in the rod for lumbar pedicle screw fixation: An experimental and finite element study.

Spinal fusion with pedicle-screw-rod is being used widely for treating spinal deformities diseases. Several biomechanical studies on screw rod based implant failure through screw pullout, bending, screw breakage have been performed. But few studies are available regarding the effect of strain for breakage of rod. So, the purpose of the present study is to observe strain at the rod connected with the pedicle screw for different loading condition. The strain in stainless steel (SS) connecting rods for pedicle screw fixation were measured using strain gauge. In order to investigate the bio-mechanical response of lumbar spine with reference to strain in the rod, a simple experimental setup was developed using a specimen of L1-S spine segment. SS rods were used for pedicle screw implant on prototyped lumbar Spine. Prior to testing with pedicle screw, the lumbar spine specimen was also compared with FE results. The strain measured using strain gauges at L3-L4 level on SS rod were within a range of 85 to 310 microstrain under 6, 8, 10 Nm flexion and extension, and for L4-L5 level, these values were within a range of 95 to 440 microstrain. It was found that FE result was higher than the strain gauge result and the error varied between 10.5% to 33% with average error of 22.8%. However similar stain behavior was observed by the FE analysis. The proposed method, as well as the qualitative data, might be helpful for the researchers to understand biomechanical behavior of pedicle-screw implanted spine.

Artificial Intervertebral Disc Replacement to Provide Dynamic Stability to the Lumbar Spine: A Finite Element Study.

Currently, intervertebral disc prostheses that are designed to restore mobility to a vertebral segment are possible for the lumbar spine. The ball-and-socket joint is a constrained design, wherein the rotational axis of the intervertebral joint is forced to pass through the center of the spherical surfaces that form the joint. One advantage of ball-and-socket joints versus unconstrained designs includes better shear stability, which results in sufficient flexibility. In this study, finite element analyses were performed in preimplanted and implanted (intervertebral disc replacement [IDR]) lumbar spine (L1-S) models to examine range of motion (ROM) and the resulting mechanical responses in the implant and the adjacent bones. Four physiological loading conditions including flexion, extension, and left and right lateral bending were analyzed to observe the effect on ROM under a 10-Newton meter moment. In terms of mechanical response, this study shows that disc replacement is an viable alternative to fusion surgery. The added advantage of IDR over fusion for degenerative discs is the reduced chance of disc degeneration at the adjacent segment of spinal vertebral column; with fusion surgery, chances of degeneration are increased.

Effect of two-level pedicle-screw fixation with different rod materials on lumbar spine: A finite element study.

BACKGROUND: Pedicle-screw-rod fixation system is very popular surgical remedy for degenerative disc disease. It is important to observe load vs. spinal motion characteristic for better understanding of clinical problems and treatment of spinal instability associated with low-back pain. OBJECTIVE: The objective of this study is to understand the effect [range of motion (ROM) and intervertebral foramen height] of pedicle-screw fixation with three rod materials on lumbar spine under three physiological loading conditions. METHOD: A three-dimensional finite element (FE) model of lumbar to sacrum (L1-S) vertebrae with pedicle-screw-rod fixation at L3-L5 level is developed. Three rod materials [titanium alloy (Ti6Al4V), ultra-high molecular weight poly ethylene (UHMWPE) and poly-ether-ether-ketone (PEEK)] are used for two-level fixation and the FE models are simulated for axial rotation, lateral bending and flexion-extension under ±10 Nm moment and 500 N compressive load and compared with the intact (natural) model. RESULT & DISCUSSION: For axial rotation, lateral bending and flexion, ROM increased 2.8, 4.5 and 1.83 times respectively for UHMWPE, and 3.7, 7.2 and 2.15 times respectively for PEEK in comparison to Ti6Al4V. As ROM is 49, 29 and 31% of the intact model during axial rotation, lateral bending and flexion respectively, PEEK rod produced better motion flexibility than Ti6Al4V and UHMWPE rod. Foramen height increased insignificantly by 2.21% for the PEEK rod with respect to the intact spine during flexion. For the PEEK rod, maximum stress of 40 MPa during axial rotation is much below the yield stress of 98 MPa. CONCLUSION: Ti6Al4V pedicle-screw-rod fixation system highly restricted the ROM of the spine, which is improved by using UHMWPE and PEEK, having lower stiffness. The foramen height did not vary significantly for any implant materials. In terms of ROM and maximum stress, PEEK rod may be considered for a better implant design to get better ROM and thus mobility.

Optimization of spinal implant screw for lower vertebra through finite element studies.

The increasing older population is suffering from an increase in age-related spinal degeneration that causes tremendous pain. Spine injury is mostly indicated at the lumbar spine (L3-L5) and corresponding intervertebral disks. Finite element analysis (FEA) is now one of the most efficient and accepted tools used to simulate these pathological conditions in computer-assisted design (CAD) models. In this study, L3-L5 spines were modeled, and FEA was performed to formulate optimal remedial measures. Three different loads (420, 490.5, and 588.6 N) based on three body weights (70, 90, and 120 kg) were applied at the top surface of the L3 vertebra, while the lower surface of the L5 vertebra remained fixed. Models of implants using stainless steel and titanium alloy (Ti6Al4V) pedicle screws and rods with three different diameters (4, 5, and 6 mm) were inserted into the spine models. The relative strengths of bone (very weak, weak, standard, strong, and very strong) were considered to determine the patient-specific effect. A total of 90 models were simulated, and von Mises stress and strain, shear stress, and strain intensity contour at the bone-implant interface were analyzed. Results of these analyses indicate that the 6-mm pedicle screw diameter is optimal for most cases. Experimental and clinical validation are needed to confirm these theoretical results.