Subgingival delivery of oral debriding agents: a proof of concept.

OBJECTIVE: This study is a proof of concept to determine the efficacy of a custom-fabricated tray in placing antimicrobial and debriding agents in the periodontal pockets of persons with active gingival infections. Localized subgingival delivery of antimicrobial and antibiotic agents is routinely employed as adjunctive therapy for the treatment and management ofperiopathogens associated with periodontal disease. Because these delivery techniques often face time constraints and impose temporary restrictions on patient brushing and flossing, a custom-formed prescription dental tray can be used to deliver and maintain medications in periodontal pockets between office visits and without brushing or flossing restrictions. The ability of this tray to maintain sufficient concentrations of medication in the periodontal pockets to have a therapeutic effect is evaluated here with theoretical modeling and practical application. METHODS: Hydrogen peroxide is an oral debriding agent and oral wound cleanser with antimicrobial properties. The debriding effect of 1.7% hydrogen peroxide gel was tested in vitro on Streptococcus mutans biofilm using glass carriers for collection. Diffusion modeling tested the potential of the customized tray to place hydrogen peroxide gel into the sulcus in the presence of crevicular fluid flow. Changes in periodontal microflora with scanning electron microscopy analysis of in vivo paper point site sampling were analyzed before and after a thin ribbon of 1.7% hydrogen peroxide gel (approximately 0.7 gm) and a subtherapeutic dose (three drops) of Vibramycin (50 mg/5 ml) were placed via Perio Trays into periodontal pockets, ranging from 4-8 mm at daily prescribed intervals for two to five weeks. RESULTS: In vitro results indicate that 1.7% hydrogen peroxide gel breaks down the exopolysaccharide slime and cell walls ofS. mutans, and begins to debride the cells from glass carriers within 10 minutes. Diffusion modeling indicates that hydrogen peroxide can penetrate into the deeper pockets (9 mm), but also its concentration in these deep pockets will increase over wearing time in the absence of degradation by peroxidases and catalase. Site sampling data confirm diffusion modeling results, with evidence that medication delivered with the prescription tray reduced subgingival bacterial loads and enhanced healing of corresponding oral tissues. CONCLUSION: The prescription Perio Tray effectively placed medication in the gingival sulcus. Mathematical modeling indicated Perio Tray placement of hydrogen peroxide gel in periodontal pockets with depths up to 9 mm over 15 minutes treatment time was theoretically possible. Pathology reports reveal reductions in subgingival bacterial loads and improvements in pretreatment pocket depths of up to 8 mm after 1.7% hydrogen peroxide and Vibramycin Syrup were prescribed for use with the Perio Tray. The in vitro analysis indicating that hydrogen peroxide is the active and effective oral debriding agent needs to be confirmed with additional studies.

Isokinetic resistance training increases tibial bending stiffness in young women.

Bone mineral content (BMC) and bone mineral density (BMD) are common but imperfect surrogate measures of bone strength. The mechanical response tissue analyzer is a device that measures long bone bending stiffness (EI), which strongly predicts bone breaking strength. We hypothesized that isokinetic resistance training of the knee flexor and extensor muscles would increase tibial EI, BMC, and BMD in young women. Fifty-two women, aged 18-26 years, performed concentric (CON, n = 30) or eccentric (ECC, n = 22) isokinetic resistance training with the nondominant leg three times per week for 20 weeks. Before and after the training period, subjects were tested for CON and ECC peak torque of the knee flexor and extensor muscles with isokinetic dynamometry, tibial BMC and BMD using dual-energy X-ray absorptiometry, and tibial EI using mechanical response tissue analysis. Both training groups increased CON (15-21%) and ECC (17-31%) peak torque vs. the untrained leg. Tibial EI increased in the entire cohort (26%) and in each training group (CON 34%, ECC 16%) vs. the untrained tibia. Tibial BMC and BMD increased in the trained and untrained tibiae, with no significant differences between limbs. No differential tibial EI or bone mineral outcomes were observed between the CON and ECC training groups. In summary, CON and ECC isokinetic resistance training increased tibial EI, but not BMC or BMD, in young women.

Lower rotational inertia and larger leg muscles indicate more rapid turns in tyrannosaurids than in other large theropods.

SYNOPSIS: Tyrannosaurid dinosaurs had large preserved leg muscle attachments and low rotational inertia relative to their body mass, indicating that they could turn more quickly than other large theropods. METHODS: To compare turning capability in theropods, we regressed agility estimates against body mass, incorporating superellipse-based modeled mass, centers of mass, and rotational inertia (mass moment of inertia). Muscle force relative to body mass is a direct correlate of agility in humans, and torque gives potential angular acceleration. Agility scores therefore include rotational inertia values divided by proxies for (1) muscle force (ilium area and estimates of m. caudofemoralis longus cross-section), and (2) musculoskeletal torque. Phylogenetic ANCOVA (phylANCOVA) allow assessment of differences in agility between tyrannosaurids and non-tyrannosaurid theropods (accounting for both ontogeny and phylogeny). We applied conditional error probabilities a(p) to stringently test the null hypothesis of equal agility. RESULTS: Tyrannosaurids consistently have agility index magnitudes twice those of allosauroids and some other theropods of equivalent mass, turning the body with both legs planted or pivoting over a stance leg. PhylANCOVA demonstrates definitively greater agilities in tyrannosaurids, and phylogeny explains nearly all covariance. Mass property results are consistent with those of other studies based on skeletal mounts, and between different figure-based methods (our main mathematical slicing procedures, lofted 3D computer models, and simplified graphical double integration). IMPLICATIONS: The capacity for relatively rapid turns in tyrannosaurids is ecologically intriguing in light of their monopolization of large (>400 kg), toothed dinosaurian predator niches in their habitats.

Isokinetic training increases ulnar bending stiffness and bone mineral in young women.

Numerous studies have investigated the effects of physical activity on bone health; however, little is known about the effects of isokinetic strength training on bone. While bone mineral density (BMD) is widely used to assess bone health and fracture risk, there are several limitations of this measure that warrant new technology development to measure bone strength. The mechanical response tissue analyzer (MRTA) assesses bone strength by measuring maximal bending stiffness (EI). We hypothesized that isokinetic strength training of the elbow flexors and extensors would increase ulnar EI, BMD, and bone mineral content (BMC) in young women. Fifty-four women trained the nondominant arm 3 times per week for 20 weeks; 32 trained concentrically (CON) and 22 trained eccentrically (ECC). Subjects were assessed for the following variables pre- and post-training: CON and ECC peak torque of the elbow flexors and extensors with isokinetic dynamometry, ulnar mineral content and density using dual-energy X-ray absorptiometry, and ulnar EI using MRTA. Isokinetic training increased CON (17%) and ECC (17%) peak torque, even when controlling for changes in the untrained arm. Eccentric training increased CON and ECC peak torque while CON training improved CON peak torque only. Isokinetic training increased ulnar EI 28%, which was statistically greater than the untrained arm. Ulnar EI increased 25% with CON training and 32% with ECC training. Both training modes resulted in greater EI gains compared to the untrained limb. Isokinetic training increased ulnar BMC (2.7%) and BMD (2.3%), even when controlling for untrained ulna changes. Both training modalities resulted in BMC and BMD increases; however, only CON training yielded gains when controlling for changes in the untrained limb. In conclusion, isokinetic strength training increases ulnar EI, BMC, and BMD in young women; no statistical differences were noted between CON and ECC training modes.

Mechanical analysis of percutaneous sacroplasty using CT image based finite element models.

Sacral insufficiency fractures are an under-diagnosed source of acute lower back pain. A polymethylmethacrylate (PMMA) cement injection procedure called sacroplasty has recently been utilized as a treatment for sacral insufficiency fractures. It is believed that injection of cement reduces fracture micromotion, thus relieving pain. In this study, finite element models were used to examine the mechanical effects of sacroplasty. Finite element models were constructed from CT images of two cadavers on which sacroplasties were performed. The images were used to create the mesh geometry, and to apply non-homogeneous material properties to the models. Models were created representing the case with and without cement, thus simulating the pre- and post-sacroplasty situation. The results indicate that the sacrum has a 3D multi-axial state of strain. While compressive strains were the largest, tensile and shear strains were significant as well. Cement in the sacrum reduced strains 40-60% locally around the cement. However, overall model stiffness only increased 1-4%. This indicates that the effects of sacroplasty are primarily local.

Analysis of creep strain during tensile fatigue of cortical bone.

During fatigue tests of cortical bone specimens, at the unload portion of the cycle (zero stress) non-zero strains occur and progressively accumulate as the test progresses. This non-zero strain is hypothesised to be mostly, if not entirely, describable as creep. This work examines the rate of accumulation of this strain and quantifies its stress dependency. A published relationship determined from creep tests of cortical bone (Journal of Biomechanics 21 (1988) 623) is combined with knowledge of the stress history during fatigue testing to derive an expression for the amount of creep strain in fatigue tests. Fatigue tests on 31 bone samples from four individuals showed strong correlations between creep strain rate and both stress and "normalised stress" (sigma/E) during tensile fatigue testing (0-T). Combined results were good (r(2)=0.78) and differences between the various individuals, in particular, vanished when effects were examined against normalised stress values. Constants of the regression showed equivalence to constants derived in creep tests. The universality of the results, with respect to four different individuals of both sexes, shows great promise for use in computational models of fatigue in bone structures.

Simulation of creep in non-homogenous samples of human cortical bone.

Characterising the mechanisms causing viscoelastic mechanical properties of human cortical bone, as well as understanding sources of variation, is important in predicting response of the bone to creep and fatigue loads. Any better understanding, when incorporated into simulations including finite element analysis, would assist bioengineers, clinicians and biomedical scientists. In this study, we used an empirically verified model of creep strain accumulation, in a simulation of 10 non-homogeneous samples, which were created from micro-CT scans of human cortical bone of the femur midshaft obtained from a 74-year-old female cadaver. These non-homogeneous samples incorporate the presence of Haversian canals and resorption cavities. The influence of inhomogeneity on the response and variation in the samples in both creep and stress relaxation tests are examined. The relationship between steady-state creep rate, applied loads (stress relaxation and creep tests) and microstructure, that is bone apparent porosity, is obtained. These relations may provide insight into damage accumulation of whole human bones and be relevant to studies on osteoporosis.

A finite element analysis of sacroiliac joint ligaments in response to different loading conditions.

STUDY DESIGN: A finite element analysis of the sacroiliac joint (SIJ) and its associated ligaments utilizing a three-dimensional model constructed from computed tomography scans. OBJECTIVE: To characterize the sacroiliac ligament strains in response to flexion, extension, and axial rotation loads and quantify the changes in SIJ stress and angular displacement in response to changes in ligament stiffness. SUMMARY OF BACKGROUND DATA: The SIJ may be a major contributor to low back pain in up to 13% to 30% of patients. States of ligament laxity are often associated with hypermobility and possibly pain of SIJ origin. The mechanism by which the SIJ generates pain is both controversial and poorly understood. METHODS: A finite element model of the human pelvis, SIJs, and sacroiliac ligaments was constructed from computed tomography scans. Ligament stiffnesses were altered and the SIJ stresses were compared with the original case. For simulated flexion, extension, and axial rotation scenarios, sacroiliac ligament strains were characterized and compared. RESULTS: Sacroiliac joint stress and angular motion increases as ligament stiffness decreases. Periarticular intraligamentous strains vary depending on the magnitude and direction of the applied loads. Maximum ligamentous strains occur at the interosseous sacroiliac ligament. CONCLUSION: The sacroiliac ligaments function to constrain the SIJ and decrease stress across the SIJ for different load scenarios. Decreasing sacroiliac ligament stiffness leads to both increased joint motion and stress.

A virtual hair cell, II: evaluation of mechanoelectric transduction parameters.

The virtual hair cell we have proposed utilizes a set of parameters related to its mechanoelectric transduction. In this work, we observed the effect of such channel gating parameters as the gating threshold, critical tension, resting tension, and Ca(2+) concentration. The gating threshold is the difference between the resting and channel opening tension exerted by the tip link assembly on the channel. The critical tension is the tension in the tip link assembly over which the channel cannot close despite Ca(2+) binding. Our results show that 1), the gating threshold dominated the initial sensitivity of the hair cell; 2), the critical tension minimally affects the peak response, (I), but considerably affects the time course of response, I(t), and the force-displacement, F-X, relationship; and 3), higher intracellular [Ca(2+)] resulted in a smaller fast adaptation time constant. Based on the simulation results we suggest a role of the resting tension: to help overcome the viscous drag of the hair bundle during the oscillatory movement of the bundle. Also we observed the three-dimensional bundle effect on the hair cell response by varying the number of cilia forced. These varying forcing conditions affected the hair cell response.

A virtual hair cell, I: addition of gating spring theory into a 3-D bundle mechanical model.

We have developed a virtual hair cell that simulates hair cell mechanoelectrical transduction in the turtle utricle. This study combines a full three-dimensional hair bundle mechanical model with a gating spring theory. Previous mathematical models represent the hair bundle with a single degree of freedom system which, we have argued, cannot fully explain hair bundle mechanics. In our computer model, the tip link tension and fast adaptation modulator kinetics determine the opening and closing of each channel independently. We observed the response of individual transduction channels with our presented model. The simulated results showed three features of hair cells in vitro. First, a transient rebound of the bundle tip appeared when fast adaptation dominated the dynamics. Second, the dynamic stiffness of the bundle was minimized when the response-displacement (I-X) curve was steepest. Third, the hair cell showed "polarity", i.e., activation decreased from a peak to zero as the forcing direction rotated from the excitatory to the inhibitory direction.

Mechanical properties and consequences of stereocilia and extracellular links in vestibular hair bundles.

Although knowledge of the fine structure of vestibular hair bundles is increasing, the mechanical properties and functional significance of those structures remain unclear. In 2004, Bashtanov and colleagues reported the contribution of different extracellular links to bundle stiffness. We simulated Bashtanov's experimental protocol using a three-dimensional finite element bundle model with geometry measured from a typical striolar hair cell. Unlike any previous models, we separately consider two types of horizontal links: shaft links and upper lateral links. Our most important results are as follows. First, we identified the material properties required to match Bashtanov's experiment: stereocilia Young's modulus of 0.74 GPa, tip link assembly (gating spring) stiffness of 5,300 pN/microm, and the combined stiffness of shaft links binding two adjacent stereocilia of 750 approximately 2,250 pN/microm. Second, we conclude that upper lateral links are likely to have nonlinear mechanical properties: they have minimal stiffness during small bundle deformations but stiffen as the bundle deflects further. Third, we estimated the stiffness of the gating spring based on our realistic three-dimensional bundle model rather than a conventional model relying on the parallel arrangement assumption. Our predicted stiffness of the gating spring was greater than the previous estimation.

Damage rate is a predictor of fatigue life and creep strain rate in tensile fatigue of human cortical bone samples.

We present results on the growth of damage in 29 fatigue tests of human femoral cortical bone from four individuals, aged 53-79. In these tests we examine the interdependency of stress, cycles to failure, rate of creep strain, and rate of modulus loss. The behavior of creep rates has been reported recently for the same donors as an effect of stress and cycles. In the present paper we first examine how the evolution of damage (drop in modulus per cycle) is associated with the stress level or the "normalized stress" level (stress divided by specimen modulus), and results show the rate of modulus loss fits better as a function of normalized stress. However, we find here that even better correlations can be established between either the cycles to failure or creep rates versus rates of damage than any of these three measures versus normalized stress. The data indicate that damage rates can be excellent predictors of fatigue life and creep strain rates in tensile fatigue of human cortical bone for use in practical problems and computer simulations.