Mechanics of biomimetic 4D printed structures.

Recent progress in additive manufacturing and materials engineering has led to a surge of interest in shape-changing plate and shell-like structures. Such structures are typically printed in a planar configuration and, when exposed to an ambient stimulus such as heat or humidity, swell into a desired three-dimensional geometry. Viewed through the lens of differential geometry and elasticity, the application of the physical stimulus can be understood as a local change in the metric of a two dimensional surface embedded in three dimensions. To relieve the resulting elastic frustration, the structure will generally bend and buckle out-of-plane. Here, we propose a numerical approach to convert the discrete geometry of filament bilayers, associated with print paths of inks with given material properties, into continuous plates with inhomogeneous growth patterns and thicknesses. When subject to prescribed growth anisotropies, we can then follow the evolution of the shapes into their final form. We show that our results provide a good correspondence between experiments and simulations, and lead to a framework for the prediction and design of shape-changing structures.

Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing.

3D hydrogel scaffolds are widely used in cellular microcultures and tissue engineering. Using direct ink writing, microperiodic poly(2-hydroxyethyl-methacrylate) (pHEMA) scaffolds are created that are then printed, cured, and modified by absorbing 30 kDa protein poly-l-lysine (PLL) to render them biocompliant in model NIH/3T3 fibroblast and MC3T3-E1 preosteoblast cell cultures. Spatial light interference microscopy (SLIM) live cell imaging studies are carried out to quantify cellular motilities for each cell type, substrate, and surface treatment of interest. 3D scaffold mechanics is investigated using atomic force microscopy (AFM), while their absorption kinetics are determined by confocal fluorescence microscopy (CFM) for a series of hydrated hydrogel films prepared from prepolymers with different homopolymer-to-monomer (Mr ) ratios. The observations reveal that the inks with higher Mr values yield relatively more open-mesh gels due to a lower degree of entanglement. The biocompatibility of printed hydrogel scaffolds can be controlled by both PLL content and hydrogel mesh properties.

Biomimetic 4D printing.

Shape-morphing systems can be found in many areas, including smart textiles, autonomous robotics, biomedical devices, drug delivery and tissue engineering. The natural analogues of such systems are exemplified by nastic plant motions, where a variety of organs such as tendrils, bracts, leaves and flowers respond to environmental stimuli (such as humidity, light or touch) by varying internal turgor, which leads to dynamic conformations governed by the tissue composition and microstructural anisotropy of cell walls. Inspired by these botanical systems, we printed composite hydrogel architectures that are encoded with localized, anisotropic swelling behaviour controlled by the alignment of cellulose fibrils along prescribed four-dimensional printing pathways. When combined with a minimal theoretical framework that allows us to solve the inverse problem of designing the alignment patterns for prescribed target shapes, we can programmably fabricate plant-inspired architectures that change shape on immersion in water, yielding complex three-dimensional morphologies.

Autonomic healing of acrylic bone cement.

Self-healing in orthopedic bone cement is demonstrated with a novel thermoplastic solvent-bonding approach. Low toxicity solvent-filled microcapsules, embedded in a commercial acrylic bone cement matrix, enable recovery of up to 80% of the virgin fracture toughness of the cement at room and body temperature conditions without external stimuli or human intervention.

3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs.

A new bioprinting method is reported for fabricating 3D tissue constructs replete with vasculature, multiple types of cells, and extracellular matrix. These intricate, heterogeneous structures are created by precisely co-printing multiple materials, known as bioinks, in three dimensions. These 3D micro-engineered environments open new -avenues for drug screening and fundamental studies of wound healing, angiogenesis, and stem-cell niches.

Infrared thermographic SAR measurements of interstitial hyperthermia applicators: errors due to thermal conduction and convection.

Thermal conduction and convection were examined as sources of error in thermographically measured SAR patterns of an interstitial microwave hyperthermia applicator. Measurements were performed in a layered block of muscle-equivalent phantom material using an infrared thermographic technique with varying heating duration. There was a 52.7% reduction in maximum SAR and 75.5% increase in 50% iso-SAR contour area for a 60-s heating duration relative to a 10-s heating duration. A finite element model of heat transfer in an homogeneous medium was used to model conductive and convective heat transfer during the thermographic measurement. Thermal conduction artefacts were found to significantly distort thermographically measured SAR patterns. Convective cooling, which occurs when phantom layers are exposed for thermal image acquisition, was found to significantly affect the magnitude, but not the spatial distribution, of thermographically measured SAR patterns. Results from this investigation suggest that the thermal diffusion artefacts can be minimized if the duration of the applied power pulse is restricted to 10 s or less.

Interstitial microwave thermal therapy for prostate cancer: method of treatment and results of a phase I/II trial.

PURPOSE: Interstitial microwave thermal therapy is experimental treatment for prostate cancer with the goal of curing disease, while causing fewer complications than standard treatment options. We present a method for delivering interstitial microwave thermal therapy using microwave radiating helical antennae inserted percutaneously under transrectal ultrasound guidance. We report the results of a trial of this method in 25 patients in whom primary external beam radiation therapy had previously failed. This patient group currently has limited curative options that are associated with a high complication rate. However, these recurrent tumors often remain localized to the prostate, and so they may be amenable to localized therapy. MATERIALS AND METHODS: Patients with proved prostatic adenocarcinoma were candidates for treatment when prostate specific antigen (PSA) was 15 ng./ml. or less and prostate volume was 50 cc. or less. Followup included PSA measurement, digital rectal examination, urinalysis, and documentation of adverse events at 4, 8, 12 and 24 weeks. Sextant biopsy was performed at week 24. The procedure involved the insertion of 5 antennae percutaneously through a modified brachytherapy template. The antenna arrangement was determined based on computer simulated predictions of temperature throughout the prostate. The prostate was dissected away from the rectum by an injection of sterile saline to provide a thermal barrier that protected the rectum from thermal damage. Temperatures were monitored using interstitial mapping thermistor probes that were also inserted through the template. A minimum peripheral target temperature of 55C but less than 70C was maintained for 15 to 20 minutes, while the urethra, rectum and hydrodissection space remained below 42C. The urethra and rectum were actively cooled in addition to hydrodissection. RESULTS: Peripheral target temperatures of 55C were achieved. The urethra and rectum remained at a safe temperature. The procedure, including setup and treatment, required approximately 2.5 hours of operating room time. At 24 weeks the PSA nadir was 0.5 ng./ml. or less in 52% of patients and 0.51 to 4 ng./ml. was achieved in an additional 40%. The negative biopsy rate at 24 weeks was 64%, assuming that 3 patients lost to followup would have had positive results. No major complications were observed and in most cases minor complications resolved within 3 months. CONCLUSIONS: Interstitial microwave thermal therapy for prostate cancer was developed to heat the prostate safely to a cytotoxic temperature. Experience with 25 patients in whom external beam radiation therapy for prostate cancer had failed indicates that the treatment is safe. Although our series indicates that this therapy may be effective, further studies and longer followup are required in larger patient groups to confirm the potential role of this therapy as an option for recurrent and primary prostate cancer.

Helical antenna arrays for interstitial microwave thermal therapy for prostate cancer: tissue phantom testing and simulations for treatment.

Interstitial microwave therapy is an experimental treatment for prostate cancer. The objective of this work was to measure the power deposition (specific absorption rate, SAR) patterns of helical microwave antennae both individually and in array patterns that would be useful for clinical treatment protocols. Commercial helical antenna 3D SAR patterns were measured in muscle equivalent phantoms using a thermographic technique. Two array patterns were tested: a 'square' and a 'crescent' array, both surrounding the urethra. To assess the feasibility of pre-treatment planning, the measured SAR patterns were input to a treatment planning computer simulation program based on a series of trans-rectal ultrasound images from a prostate cancer patient. The simulation solved the Pennes linear bioheat heat transfer equation in prostate tissue, with the aim of achieving a target of 55 degrees C at the prostate periphery while not allowing normal surrounding tissues (bladder, urethra, rectum) to rise above 42 C. These criteria could not be met with the square array but they could be met with the crescent array, provided that the prostate was first dissected away from the rectum. This can be done with a procedure such as 'hydrodissection', where sterile saline is injected to separate the prostate and rectum. The results of these SAR measurements and heat transfer simulations indicate that arrays of helical antennae could be used for safe and effective thermal therapy for prostate cancer.

Strategies for assessing pain and pain exaggeration: controlled studies.

OBJECTIVE: To compare structured with intuitive methods of detecting exaggerated pain, in 2 randomized studies, with masked observers, and to compare properties of measures of relative tenderness, as surrogates for measures of pain. METHODS: Pairs of experienced rheumatologists assessed tenderness and behavior in subjects who were either giving honest responses (Not Acting) or exaggerating their tenderness while hiding the deception (Acting). In Study 1 (20 subjects) the assessments of behavior were descriptive only; for Study 2 (25 subjects) a prestructured format was developed. The challenge to the examiners was to detect Acting. The challenge to the analyst was to develop, from the recorded data, an algorithm that described or bettered the examiners' performance. RESULTS: By exaggerating, nontender patients could meet formal ACR criteria for fibromyalgia. The addition of a prestructured pain behavior assessment in Study 2 was associated with improvement in the observers' ability to detect Acting, with improvement of sensitivity from 60 to 90% (p = 0.0003, Study 2 compared with Study 1). False positive diagnoses of Acting by the observers were uniformly uncommon, with specificity of 85 and 86% in the 2 studies. CONCLUSION: Formal numerical techniques are required and feasible for separately assessing the structural and psychogenic components of chronic pain.

Magnetic resonance imaging of temperature changes during interstitial microwave heating: a phantom study.

Changes in magnetic resonance (MR) signals during interstitial microwave heating are reported, and correlated with simultaneously acquired temperature readings from three fiber-optic probes implanted in a polyacrylamide gel phantom. The heating by a MR-compatible microwave antenna did not interfere with simultaneous MR image data acquisition. MR phase-difference images were obtained using a fast two-dimensional-gradient echo sequence. From these images the temperature-sensitive resonant frequency of the 1H nuclei was found to decrease approximately by 0.008 ppm/ degree C. The method and results presented here demonstrate that noninvasive MR-temperature imaging can be performed simultaneously with interstitial microwave thermal treatment.

Relation between fibrositic and control site tenderness; effects of dolorimeter scale length and footplate size.

Recent data have suggested a correlation between the tenderness measured at tender and control sites, differing from earlier studies indicating site specific tenderness. In our study, the "constant control" model is tested against the "correlated control" model, in which control site tenderness varies with fibrositic site tenderness. Our study also addresses relevant technical issues in dolorimetry. We measured threshold of tenderness at 4 sites (2 fibrositic and 2 control) on 21 subjects, using dolorimeters with a 17 kg scale limit, and 3 different footplates, 0.7, 1.4 and 2.0 cm in diameter. To measure observer variation, we used multiple replications by multiple observers, obtaining in all 1,416 observations. There was a strong relationship between control and fibrositic site tenderness with control thresholds twice as high (half as tender). Scale length and dolorimeter footplate size each had important effects. The site specific approach is valuable diagnostically, but more broadly operative mechanisms should be the focus of research and therapy.