Anand K. Agarwal

Microwave assisted preparation of magnesium phosphate cement (MPC) for orthopedic applications: A novel solution to the exothermicity problem

There are two interesting features of this paper. First, we report herein a novel microwave assisted technique to prepare phosphate based orthopedic cements, which do not generate any exothermicity during setting. The exothermic reactions during the setting of phosphate cements can cause tissue damage during the administration of injectable compositions and hence a solution to the problem is sought via microwave processing. This solution through microwave exposure is based on a phenomenon that microwave irradiation can remove all water molecules from the alkaline earth phosphate cement paste to temporarily stop the setting reaction while preserving the active precursor phase in the formulation. The setting reaction can be initiated a second time by adding aqueous medium, but without any exothermicity. Second, a special emphasis is placed on using this technique to synthesize magnesium phosphate cements for orthopedic applications with their enhanced mechanical properties and possible uses as drug and protein delivery vehicles. The as-synthesized cements were evaluated for the occurrences of exothermic reactions, setting times, presence of Mg-phosphate phases, compressive strength levels, microstructural features before and after soaking in (simulated body fluid) SBF, and in vitro cytocompatibility responses. The major results show that exposure to microwaves solves the exothermicity problem, while simultaneously improving the mechanical performance of hardened cements and reducing the setting times. As expected, the cements are also found to be cytocompatible. Finally, it is observed that this process can be applied to calcium phosphate cements system (CPCs) as well. Based on the results, this microwave exposure provides a novel technique for the processing of injectable phosphate bone cement compositions.

Smaller Interval Distractions May Reduce Chances of Growth Rod Breakage Without Impeding Desired Spinal Growth: A Finite Element Study

BACKGROUND Growth rods allow regular distraction of the spine to compensate for growth. Traditionally such distractions are performed every 6 months via open surgery. However with the advent of minimally invasive techniques like magnetically controlled growing rods, the distractions can be performed non-surgically. This also implies that the interval of distraction could be changed or customized based on individual patients need. HYPOTHESIS In this study we have hypothesized that the distraction at shorter intervals reduces the stresses on the rods which in turn reduces the chance of rod failure. OBJECTIVE A finite element model of a juvenile spine was instrumented with growth rods and distractions were applied at different frequencies (2 months, 3 months, 6 months, and 12 months) for a period of two years to study the effects of frequency of distraction on maximum von Mises stresses on the rods for different loading conditions were studied. RESULTS The stresses on the rods were highest for 12-month distraction (2 distractions in 2 years) and lowest for 2-months distraction (12 distractions in 2 years). CONCLUSION It was found that the shorter intervals of distraction led to reduction of stresses on the rod for same spinal height gain in two years.

Biomechanical Evaluation of an Endplate-Conformed Polycaprolactone-Hydroxyapatite Intervertebral Fusion Graft and Its Comparison With a Typical Nonconformed Cortical Graft

In the thoracolumbar region, between 7% and 30% of spinal fusion failures are at risk for pseudarthrosis. From a biomechanical perspective, the nonconformity of the intervertebral graft to the endplate surface could contribute to pseudarthrosis, given suboptimal stress distributions. The objective of this study was to quantify the effect of endplate-graft conformation on endplate stress distribution, maximum Von Mises stress development, and stability. The study design used an experimentally validated finite element (FE) model of the L4-L5 functional spinal unit to simulate two types of interbody grafts (cortical bone and polycaprolactone (PCL)-hydroxyapatite (HA) graft), with and without endplate-conformed surfaces. Two case studies were completed. In Case Study I, the endplate-conformed grafts and nonconformed grafts were compared under without posterior instrumentation condition, while in Case Study II, the endplate-conformed and nonconformed grafts were compared with posterior instrumentation. In both case studies, the results suggested that the increased endplate-graft conformity reduced the maximum stress on the endplate, created uniform stress distribution on endplate surfaces, and reduced the range of motion of L4-L5 segments by increasing the contact surface area between the graft and the endplate. The stress distributions in the endplate suggest that the load sharing is greater with the endplate-conformed PCL-HA graft, which might reduce the graft subsidence possibility.

Development of monetite–nanosilica bone cement: A preliminary study

In this paper, we reported the results of our efforts in developing DCPA/nanosilica composite orthopedic cement. It is motivated by the significances of DCPA and silicon in bone physiological activities. More specifically, this paper examined the effects of various experimental parameters on the properties of such composite cements. In this work, DCPA cement powders were synthesized using a microwave synthesis technique. Mixing colloidal nanosilica directly with synthesized DCPA cement powders can significantly reduce the washout resistance of DCPA cement. In contrast, a DCPA-nanosilica cement powder prepared by reacting Ca(OH)2 , H3 PO4 and nanosilica together showed good washout resistance. The incorporation of nanosilica in DCPA can improve compressive strength, accelerate cement solidification, and intensify surface bioactivity. In addition, it was observed that by controlling the content of NaHCO3 during cement preparation, the resulting composite cement properties could be modified. Allowing for the development of different setting times, mechanical performance and crystal features. It is suggested that DCPA-nanosilica composite cement can be a potential candidate for bone healing applications.

Distraction magnitude and frequency affects the outcome in juvenile idiopathic patients with growth rods: finite element study using a representative scoliotic spine model

BACKGROUND CONTEXT Growth rods are used to limit the progression of scoliosis without restraining the opportunity for the spine to grow. However, major complications like rod breakage, screw loosening, and altered sagittal contour have been encountered. OBJECTIVE To analyse the effect of the magnitude of distraction forces on the T1-S1 growth, maximum von Mises stresses on the rods, sagittal contours, and load at the pedicle screw-bone interface and quantify the maximum stresses on the rod for a period of 24 months using different frequencies of distraction in a representative scoliotic spine model. STUDY DESIGN A representative finite element model of a juvenile scoliotic spine was used to study the effect of magnitude and frequency of distraction on growth rods. METHODS A representative scoliotic model was developed and instrumented using proximal foundation, distal foundation, and rods. Part 1: simulation steps comprised 6 months of growth under various distraction forces to analyze effects of distraction force on the biomechanics of the spine and instrument. Part 2: simulation steps comprised 24 months of growth under various intervals of distraction to analyze effects of distraction interval on the propensity of rod fracture. RESULTS Part 1: an optimal distraction force exists for which the growth is sustained with minimum stress on the rod, lower loads at screw-bone interface, and unaltered sagittal contours. Part 2: the stresses on the rods were highest for 12-month distraction (2 distractions in 2 years) and lowest for 2-month distraction (12 distractions in 2 years). CONCLUSIONS The data and trend suggest that as the distraction forces vary so do the effects on spinal growth. The results of this study also signify the importance of shorter distraction period in reducing the stresses on the rods.

Sustained release of small molecules from carbon nanotube-reinforced monetite calcium phosphate cement

The interest in developing calcium phosphate cement (CPC) as a drug delivery system has risen because of its capability to achieve local and controlled treatment to the site of the bone disease. The purpose of this study was to investigate the release pattern of drug-carrying carboxylic acid-functionalized multi-walled carbon nanotube (MWCNT)-reinforced monetite (DCPA, CaHPO4)-based CPC. Z-Leu-Leu-Leu-al (MG132), a small peptide molecule inhibiting NF-κB-mediated osteoclastic resorption, was used as a model drug. MG132 was added into the cement during setting and released into the medium used to culture indicator cells. Significant cell death was observed in osteoblast MC3T3-E1 cells cultured in the medium incubated with MG132-loaded CPC; however, with the presence of MWCNTs in the cement, the toxic effect was not detectable. NF-κB activation was quantified using a NF-κB promoter-driving luciferase reporter in human embryonic kidney 293 cells. The medium collected after incubation with drug-incorporated CPC with or without MWCNT inhibited TNFα-induced NF-κB activation indicating that the effective amount of MG132 was released. CPC/drug complex showed a rapid release within 24h whereas incorporation of MWCNTs attenuated this burst release effect. In addition, suppression of TNFα-induced osteoclast differentiation in RAW 264.7 cell culture also confirmed the sustained release of MWCNT/CPC/drug. Our data demonstrated the drug delivery capability of this cement composite, which can potentially be used to carry therapeutic molecules to improve bone regeneration in conjunction with its fracture stabilizing function. Furthermore, it suggested a novel approach to lessen the burst release effect of the CPC-based drug delivery system by incorporating functionalized MWCNTs.

Development of nanosilica bonded monetite cement from egg shells

This work represents further effort from our group in developing monetite based calcium phosphate cements (CPC). These cements start with a calcium phosphate powder (MW-CPC) that is manufactured using microwave irradiation. Due to the robustness of the cement production process, we report that the starting materials can be derived from egg shells, a waste product from the poultry industry. The CPC were prepared with MW-CPC and aqueous setting solution. Results showed that the CPC hardened after mixing powdered cement with water for about 12.5±1 min. The compressive strength after 24h of incubation was approximately 8.45±1.29 MPa. In addition, adding colloidal nanosilica to CPC can accelerate the cement hardening (10±1 min) process by about 2.5 min and improve compressive strength (20.16±4.39 MPa), which is more than double the original strength. The interaction between nanosilica and CPC was monitored using an environmental scanning electron microscope (ESEM). While hardening, nanosilica can bond to the CPC crystal network for stabilization. The physical and biological studies performed on both cements suggest that they can potentially be used in orthopedics.

Outcomes of Optimal Distraction Forces and Frequencies in Growth Rod Surgery for Different Types of Scoliotic Curves: An In Silico and In vitro Study

OBJECTIVE Analyze the effects of the distraction forces and frequencies on multiple representative scoliotic curves and to establish a relationship between high distraction forces and screw loosening. STUDY DESIGN Multiple representative finite-element models of a juvenile scoliotic spine were used to study the effects of the magnitude and frequency of distraction on growth rods. METHODS Simulation of 6 months of growth under various distraction forces to analyze the effects of distraction forces on the biomechanics of the scoliotic spine and growth rod instrumentation; simulation of 24 months of growth under various intervals of distraction to analyze the effects of the distraction interval on the propensity for rod fracture; in vitro study to assess screw loosening after 6 months. RESULTS For all scoliotic spine model instrumented with growth rods, an optimal distraction force existed at which normal T1-S1 growth was sustained, along with minimum stresses on the rods, the lowest load at the screw-bone interface, and the least alteration in the sagittal contour. The results followed similar trends for each model, with the numerical values of optimal distraction forces in proximity for all representative scoliotic spine models. The in vitro study proved that the pullout strength of pedicle screws reduced significantly after 6 months of fatigue at higher distraction forces (in comparison with optimal distraction forces). This corroborated the finite-element findings for lower loads at the screw-bone interface with optimal distraction forces. CONCLUSIONS This study concludes that the optimal distraction forces exists for all types of scoliotic curves that have been instrumented with growth rods, which exhibits reduction of stresses on the rods with frequent distractions. This study also links the second most common complication, screw loosening, with high distraction forces. Therefore, optimizing the biomechanical environment of the dual growth rods could drastically reduce the biomechanical complications associated with growth rods.

Adjacent-Level Hypermobility and Instrumented-Level Fatigue Loosening With Titanium and PEEK Rods for a Pedicle Screw System: An In Vitro Study

Adjacent-level disease is a common iatrogenic complication seen among patients undergoing spinal fusion for low back pain. This is attributed to the postsurgical differences in stiffness between the spinal levels, which result in abnormal forces, stress shielding, and hypermobility at the adjacent levels. In addition, as most patients undergoing these surgeries are osteoporotic, screw loosening at the index level is a complication that commonly accompanies adjacent-level disease. Recent studies indicate that a rod with lower rigidity than that of titanium may help to overcome these detrimental effects at the adjacent level. The present study was conducted in vitro using 12 L1-S1 specimens divided into groups of six, with each group instrumented with either titanium rods or PEEK (polyetheretherketone) rods. The test protocol included subjecting intact specimens to pure moments of 10 Nm in extension and flexion using an FS20 Biomechanical Spine Test System (Applied Test Systems) followed by hybrid moments on the instrumented specimens to achieve the same L1-S1 motion as that of the intact specimens. During the protocols later phase, the L4-L5 units from each specimen were segmented for cyclic loading followed by postfatigue kinematic analysis to highlight the differences in motion pre- and postfatigue. The objectives included the in vitro comparison of (1) the adjacent-level motion before and after instrumentation with PEEK and titanium rods and (2) the pre- and postfatigue motion at the instrumented level with PEEK and titanium rods. The results showed that the adjacent levels above the instrumentation caused increased flexion and extension with both PEEK and titanium rods. The postfatigue kinematic data showed that the motion at the instrumented level (L4-L5) increased significantly in both flexion and extension compared to prefatigue motion in titanium groups. However, there was no significant difference in motion between the pre- and postfatigue data in the PEEK group.

Prediction of clinically relevant initiation and progression of tears within annulus fibrosus.

Internal disc disruption and annular tears are some of the causes of back and leg pain. It is difficult to observe location of internal damage and its distribution and propagation in cadaveric experiments or via imaging in clinical scenarios. Finite element analysis is useful for understanding the effects of different loading conditions on the location of initiation and propagation of tears in the annulus. In this study, a hyperelastic anisotropic material model in conjunction with biaxial properties was used for modelling annulus fibrosus material under a variety of loading conditions. The loading conditions considered included compression, flexion, extension, and their combinations. Tsai‐Wu criterion was used to evaluate the damage, considering strength anisotropy and asymmetry. Damage predictions based on this criterion are in better agreement with available experimental studies and clinical observations, as compared to other approaches. Therefore, the use of Tsai‐Wu criterion is suggested as an appropriate mechanical parameter to quantify damage, its initiation locations, and its distribution in annulus fibrosus under different loading conditions.