Modulus Of Tissue Research Articles

Increased tissue modulus and hardness in the TallyHO mouse model of early onset type 2 diabetes mellitus.

Individuals with type 2 diabetes mellitus (T2DM) have a higher fracture risk compared to those without T2DM despite having higher bone mineral density (BMD). Thus, T2DM may alter other aspects of resistance to fracture beyond BMD such as bone geometry, microarchitecture, and tissue material properties. We characterized the skeletal phenotype and assessed the effects of hyperglycemia on bone tissue mechanical and compositional properties in the TallyHO mouse model of early-onset T2DM using nanoindentation and Raman spectroscopy. Femurs and tibias were harvested from male TallyHO and C57Bl/6J mice at 26 weeks of age. The minimum moment of inertia assessed by micro-computed tomography was smaller (-26%) and cortical porosity was greater (+490%) in TallyHO femora compared to controls. In three-point bending tests to failure, the femoral ultimate moment and stiffness did not differ but post-yield displacement was lower (-35%) in the TallyHO mice relative to that in C57Bl/6J age-matched controls after adjusting for body mass. The cortical bone in the tibia of TallyHO mice was stiffer and harder, as indicated by greater mean tissue nanoindentation modulus (+22%) and hardness (+22%) compared to controls. Raman spectroscopic mineral:matrix ratio and crystallinity were greater in TallyHO tibiae than in C57Bl/6J tibiae (mineral:matrix +10%, p < 0.05; crystallinity +0.41%, p < 0.10). Our regression model indicated that greater values of crystallinity and collagen maturity were associated with reduced ductility observed in the femora of the TallyHO mice. The maintenance of structural stiffness and strength of TallyHO mouse femora despite reduced geometric resistance to bending could potentially be explained by increased tissue modulus and hardness, as observed at the tibia. Finally, with worsening glycemic control, tissue hardness and crystallinity increased, and bone ductility decreased in TallyHO mice. Our study suggests that these material factors may be sentinels of bone embrittlement in adolescents with T2DM.

Variation in enamel and dentine mineral concentration and density in primate molars

ObjectiveVariation in enamel and dentine mineral concentration and total effective density can be reliably collected using Micro-CT scans. Both variables are suggested to reflect mechanical properties such as hardness and elastic modulus in dental tissues, meaning Micro-CT methods allow relative composition and mechanical properties to be collected non-destructively. Design16 lower molars from 16 Catarrhine primates were Micro-CT scanned alongside hydroxyapatite phantoms using standardized settings and methods to calculate mineral concentration and total effective density. Mineral concentration, total effective density and thickness of dentine and enamel were calculated for four cusps, representing each 'corner' of the tooth and four lateral crown positions (i.e., mesial, buccal, lingual and distal). ResultsThe results show mean mineral concentration and total effective density values were higher in areas of thicker enamel, while the opposite was observed for dentine. Buccal positions had significantly higher mineral concentration and total effective density values than lingual areas. Cuspal positions had higher mean values than lateral enamel, for both dentine (mineral concentration cuspal: 1.26 g/cm3; lateral: 1.20 g/cm3) and enamel (mineral concentration cuspal: 2.31 g/cm3; lateral: 2.25 g/cm3). Mesial enamel had significantly lower values than other locations. ConclusionsThese common patterns across Catarrhine taxa may be linked to functional adaptations related to optimization of mastication and tooth protection. Variation in mineral concentration and total effective density may also be associated with wear and fracture patterns, and can be used as baseline information to investigate the effect of diet, pathological changes and aging on teeth through time.

Limitations of Curl and Directional Filters in Elastography

In the approaches to elastography, two mathematical operations have been frequently applied to improve the final estimate of shear wave speed and shear modulus of tissues. The vector curl operator can separate out the transverse component of a complicated displacement field, and directional filters can separate distinct orientations of wave propagation. However, there are practical limitations that can prevent the intended improvement in elastography estimates. Some simple configurations of wavefields relevant to elastography are examined against theoretical models within the semi-infinite elastic medium and guided waves in a bounded medium. The Miller–Pursey solutions in simplified form are examined for the semi-infinite medium and the Lamb wave symmetric form is considered for the guided wave structure. In both cases, we examine simple but practical wave combinations that can prevent the curl and directional filter operations from directly providing an improved measure of shear wave speed and shear modulus. Additional factors including signal-to-noise and the support of filters also restrict the applicability of these strategies for improving elastographic measures. Thus, some implementations of shear wave excitations applied to the body and to bounded structures within the body are shown to involve waves that are not easily resolved by the vector curl operator and directional filters. These limitations may be overcome by more advanced strategies or simple improvements in baseline parameters including the size of the region of interest and the number of shear waves propagated within.

Studying trabecular bone samples demonstrates a power law relation between deteriorated structure and mechanical properties -a study combining 3D printing with the finite element method.

The bone volume fraction (BV/TV) significantly contributes to the mechanical properties of trabecular bone. However, when studies compare normal trabeculae against osteoporotic trabeculae (in terms of BV/TV decrease), only an "average" mechanical result has been determined because of the limitation that no two trabecular structures are the same and that each unique trabecular structure can be mechanically tested only once. The mathematic relation between individual structural deterioration and mechanical properties during aging or the osteoporosis process has yet to be further clarified. Three-dimensional (3D) printing and micro-CT-based finite element method (μFEM) can assist in overcoming this issue. In this study, we 3D printed structural-identical but BV/TV value-attenuated trabecular bones (scaled up ×20) from the distal femur of healthy and ovariectomized rats and performed compression mechanical tests. Corresponding μFEM models were also established for simulations. The tissue modulus and strength of 3D printed trabecular bones as well as the effective tissue modulus (denoted as Ez) derived from μFEM models were finally corrected by the side-artifact correction factor. The results showed that the tissue modulus corrected, strength corrected and Ez corrected exhibited a significant power law function of BV/TV in structural-identical but BV/TV value-attenuated trabecular samples. Using 3D printed bones, this study confirms the long-known relationship measured in trabecular tissue with varying volume fractions. In the future, 3D printing may help us attain better bone strength evaluations and even personal fracture risk assessments for patients who suffer from osteoporosis.

Development of a bioreactor for in-vitro compression cycling of tissue engineered meniscal implants

Injuries to the meniscus are common and can impair physical activities. Bioprinted meniscal tissue offers an attractive alternative to donor tissue for meniscal repair but achieving the strength of native tissue is a challenge. Here we report the development of a tissue engineering bioreactor designed to apply repetitive force which may lead to an increase in the compressive modulus and durability of bioprinted meniscal tissues. The modular bioreactor system is composed of a sterilizable tissue culture vessel together with a dock that applies and measures mechanical force. The culture vessel allows for simultaneous compression cycling of two anatomically sized menisci. Using a hybrid linear actuator with a stepper motor, the dock can apply up to 300 N of force at speeds up to 20 mm/s, corresponding to the upper limits of anatomical force and motion in the knee. An interchangeable 22 N load cell was mated between the culture vessel and the dock to log changes in force. Both the culture vessel and dock are maintained in a standard cell culture incubator to provide heat and CO2, while the dock is powered and controlled externally using a step motor drive and customized software.

Acoustic Radiation Force Impulse (ARFI) Elastography in Evaluation of Supraspinatus Tendinopathy.

The most common etiology of shoulder pain in adults is rotator cuff tear. Elastography is an imaging method that can report the strain and elastic modulus of the biological tissue. We think acoustic radiation force impulse (ARFI) elastography can effectively assess rotator cuff tendinopathy. This study aimed to investigate the usefulness of ARFI elastography in evaluating supraspinatus tendinopathy. We included 44 patients (22 men, 22 women, median age, 47 years; range, 20-69 years) with unilateral supraspinatus tendinopathy diagnosed with magnetic resonance imaging (MRI) in this prospective study. The normal tendons and tendinopathies, including supraspinatus tendinosis, partial-thickness, and full-thickness supraspinatus tears, were evaluated with ultrasound and ARFI elastography. The ARFI elastography values were compared between healthy and tendinopathy groups, and the gender was compared between elastography values of the normal tendons and tendinopathies using the Mann-Whitney U test. The values of ARFI elastography correlated with tendinopathy. (P = 0.001). The gender differed between the elastography values of the normal tendons (P = 0.002) and tendinopathies (P = 0.001). ARFI elastography is a non-invasive and feasible method for quantitatively assessing supraspinatus tendinopathy. It can be an alternative method to MRI in diagnosing supraspinatus tendinopathy.

Biological Tissue-Inspired Ultrasoft, Ultrathin, and Mechanically Enhanced Microfiber Composite Hydrogel for Flexible Bioelectronics

HighlightsA novel strategy was developed to construct ultrathin microfiber composite hydrogel films (< 5 μm) by embedding an electrospun fiber network into a hydrogel.The microfiber composite hydrogel offers tunable modulus in a broad range (from ~ 5 kPa to tens of MPa), which matches the modulus of most biological tissues and organs.The ultrathin configuration and ultrasoft nature allow the microfiber composite hydrogel seamlessly attaching to various rough surfaces.

Viscoelastic behavior of oral mucosa. A rheological study using small-amplitude oscillatory shear tests

The purpose of this work was to determine the viscoelastic behavior of porcine and human oral mucosa under physiological conditions of temperature, hydration and chewing. The linear elastic and viscous shear moduli of these soft tissues were determined by small-amplitude oscillatory shear (SAOS) tests at masticatory frequency using a stress-controlled rheometer equipped with an immersion cell on punched biopsies 8 mm in diameter. Non physiological conditions of temperature were also used to access other parameters such as the denaturation temperature of collagen.First, the different parameters such as normal force, frequency and maximal strain were adjusted to obtain reliable data on porcine mucosa. The optimal normal force was 0.1N and the linear viscoelastic limit was found for a strain amplitude of 0.5% for both 0.1 and 1 Hz. The storage moduli of porcine mucosa, ranging from 5 to 16 kPa, were in the same range as cutaneous tissues determined by SAOS at equivalent frequencies. The storage modulus, superior to the loss modulus G″, indicates a predominant elastic contribution to shear stress in chewing conditions.Second, this protocol evidenced an influence of the anatomic site of the mouth on the viscoelastic behavior of porcine mucosa, mandibular biopsies having higher storage moduli than maxillary biopsies. Temperature scans showed the mechanical manifestation of collagen denaturation in the 60–70 °C range as previous calorimetric analyses. Finally, this mechanical protocol was successfully adapted to characterize human mucosa in an elderly population. It was shown that the elastic modulus is impacted by local inflammation (gingivitis), decreasing significantly from 6 ± 1.4 kPa to 2.5 ± 0.3 kPa.

Stretchable ultrasonic arrays for the three-dimensional mapping of the modulus of deep tissue.

Serial assessment of the biomechanical properties of tissues can be used to aid the early detection and management of pathophysiological conditions, to track the evolution of lesions and to evaluate the progress of rehabilitation. However, current methods are invasive, can be used only for short-term measurements, or have insufficient penetration depth or spatial resolution. Here we describe a stretchable ultrasonic array for performing serial non-invasive elastographic measurements of tissues up to 4 cm beneath the skin at a spatial resolution of 0.5 mm. The array conforms to human skin and acoustically couples with it, allowing for accurate elastographic imaging, which we validated via magnetic resonance elastography. We used the device to map three-dimensional distributions of the Young's modulus of tissues ex vivo, to detect microstructural damage in the muscles of volunteers before the onset of soreness and to monitor the dynamic recovery process of muscle injuries during physiotherapies. The technology may facilitate the diagnosis and treatment of diseases affecting tissue biomechanics.

The Corneal Ectasia Model of Rabbit: A Validity and Stability Study.

Keratoconus is a bilateral progressive degenerative corneal disease characterized by localized corneal thinning and dilatation. The pathogenesis of keratoconus is not fully elucidated. To gain a better understanding of the pathophysiology of this disease and to explore potential treatments, animal models are essential for basic research. Several attempts have been made to establish animal models of corneal ectasia by using collagenase. However, continuous changes of the cornea have not been well-tracked for the model. In this study, corneal morphology and biomechanical behavior in vivo were determined before and after collagenase Ⅱ treatment at 2, 4, and 8 weeks. The elastic modulus and histology of cornea tissues ex vivo were measured at 8 weeks postoperatively. The results showed that the posterior corneal curvature (Km B) increased and central corneal thickness (CCT) decreased after collagenase treatment. The mechanical properties of ectatic corneas weakened significantly and the collagen fiber interval in the stromal layer was increased and disorganized. This study provides insights into the changes of corneal morphology and biomechanical properties in a rabbit model of corneal ectasia. Changes observed at 8 weeks indicated that the cornea was still undergoing remodeling.

Characterizing viscoelastic properties of human melanoma tissue using Prony series.

Melanoma is the most invasive and deadly skin cancer, which causes most of the deaths from skin cancer. It has been demonstrated that the mechanical properties of tumor tissue are significantly altered. However, data about characterizing the mechanical properties of in vivo melanoma tissue are extremely scarce. In addition, the viscoelastic or viscous properties of melanoma tissue are rarely reported. In this study, we measured and quantitated the viscoelastic properties of human melanoma tissues based on the stress relaxation test, using the indentation-based mechanical analyzer that we developed previously. The melanoma tissues from eight patients of different ages (57-95), genders (male and female patients), races (White and Asian), and sites (nose, arm, shoulder, and chest) were excised and tested. The results showed that the elastic property (i.e., shear modulus) of melanoma tissue was elevated compared to normal tissue, while the viscous property (i.e., relaxation time) was reduced. Moreover, the tissue thickness had a significant impact on the viscoelastic properties, probably due to the amount of the adipose layer. Our findings provide new insights into the role of the viscous and elastic properties of melanoma cell mechanics, which may be implicated in the disease state and progression.

Effect of cell size distribution on mechanical properties of strawberry fruit tissue

Strawberry fruit are high value, but also perishable products, because of their soft texture. Better insight on the strawberry mechanics are requested for understanding postharvest decay due to bruising. To gain data on the volumetric cell size distribution of strawberry tissue capturing the volume of 10 * 5 * 5 mm, fruit cells were suspended in 0.3 M mannitol solution. Cell size of 'Flair', 'Malwina', and 'Sonata' strawberry fruit, each in three commercially marketed ripeness stages (N = 135), was measured with particle size analyzer based on laser light scattering density analysis (LSD). The strawberry cell size distribution showed a wide range from 30–500 µm with frequency peak between 200 and 240 µm. The cell size of 'Flair' and 'Malwina' was smaller compared to 'Sonata' strawberry fruit. The volumetric cell size distribution obtained by LSD was correlated to microscopy results (R2 = 0.97–0.99) obtained on single cells (N = 1215), indicating that LSD can be used for measuring the percentages of different cell size ranges of volumetric fruit sample. The three ripeness stages were classified with Gaussian Naïve Bayes approach considering absorption coefficient of anthocyanins at 405 nm (GNBa) and percentage frequency of peak cell size (GNBc). For GNBa classes, ripening stage showed no interaction with failure stress, strain, and elastic modulus. Considering GNBc classes, the failure stress and elastic modulus of strawberry tissue increased with enhanced percentage frequency of peak cell size for all three cultivars. An enhanced percentage frequency of large cells resulted in increased susceptibility of the strawberry tissue. Overall, this study showed that LSD cell size distribution data from a volumetric tissue sample are related to fruit tissue mechanics, which is conducive to a better analysis of the actual stress and damage problems of strawberry fruit tissue specimens during compression in supply chain processes.

Elastographic measurements on soft biological tissues using holographic imaging by Rayleigh wave tracing

Tissue elasticity is one of the significant diagnostic parameters to study disease progression in biological tissues. Elastography measurements hold strong potential for determining the mechanical properties of malignant tissues in clinical practice. Optical methods for quantifying the elastic properties have received the attention of both research and medical community. In the current work, we calculate the elastic modulus of tissue-mimicking phantoms and ex-vivo biological tissue using holographic imaging by tracing Rayleigh wave propagation on the tissue surface. Rayleigh waves produced by the electromechanical actuator over a set of excitation frequencies are imaged by an ultrafast camera. The phase map reconstruction of the Rayleigh wave is carried out using a phase-shifting algorithm and the distance-time slope method is analyzed to compute Rayleigh wave velocities. The elastic modulus calculated by holographic imaging is validated against the gold standard mechanical compressional testing data. The quantitative results obtained from this current optical system combining holographic imaging and Rayleigh wave tracing are highly effective in ex-vivo and in-vivo tissue characterization and carry high potential as a promising tool in clinical translations and commercial adaptations.

Mind the mechanical strength: tailoring a 3D matrix to encapsulate isolated human preantral follicles.

Would a hydrogel with similar mechanical properties to the human ovarian cortex support preantral follicle development? Yes, our tailored PEGylated fibrin hydrogel was shown to significantly improve follicle growth in vitro. One of the main challenges in developing an engineered ovary is to provide a 3D matrix that supports the follicle architecture and the interaction between granulosa cells and the oocyte as they are essential for folliculogenesis. Thanks to its biocompatibility and bioactivity, fibrin has been employed to fabricate a 3D matrix to encapsulate ovarian follicles. However, follicles lose their physical support within a few days owing to rapid fibrin degradation. Therefore, different strategies, including physical and chemical modifications, have been developed to enhance the stability of fibrin. By developing a matrix made of a synthetic (polyethylene glycol: PEG) and natural polymer (fibrin), we aimed to overcome fibrin degradation by the chemical reaction of PEGylation and tailor a PEGylated fibrin hydrogel formulation with mechanical strength similar to the ovarian cortex in women of reproductive age. To this end, response surface methodology was employed to obtain a tailored formulation of PEGylated fibrin. This hydrogel was then tested to encapsulate and support isolated human preantral follicles in vitro. A PEGylated fibrin formulation was tailored using mathematical modeling software to mimic the mechanical properties of human ovarian tissue at reproductive age. Human preantral follicles were isolated from 11 patients of reproductive age and encapsulated in the tailored hydrogels, which were cultured in vitro for 4 or 7 days. Follicle survival and diameter were assessed on Days 1 and 7. Furthermore, the follicles were subjected to confocal microscopy to evaluate their growth (Ki67 staining) on Day 7 and analyze cell-cell communication (connexin 43 and transzonal projection staining) on Day 4. In this study, mathematical modeling was applied to achieve the biomechanically tailored PEGylated fibrin formulation by targeting the specific goal of 3178 ± 245 Pascal, Young's modulus of ovarian cortical tissue in reproductive-age women. Our results demonstrated that the PEGylated fibrin hydrogel consisting of 39.06 mg/ml of PEGylated fibrinogen and 50.36 IU/ml of thrombin was the optimum condition with the desirability of 97.5%. This tailored hydrogel yielded a high follicle survival rate (83%) after 7 days of in vitro culture and supported its development up to the secondary stage. Follicle growth was confirmed by the presence of Ki67-positive granulosa cells on Day 7. Additionally, connexin 43 and Phalloidin staining indicated the retention of connections between granulosa cells and the oocyte. N/A. In this study, our tailored hydrogel was only tested in vitro, which is not the same as the physiological environment. It is crucial to conduct a study assessing the follicles following their encapsulation in the tailored hydrogel and transplantation, which will be the next step of our investigation. The findings from this study introduced a suitable biomaterial similar to the ovarian cortex in reproductive-age women in terms of biomechanical properties for encapsulating human preantral follicles. This biomaterial allowed the radial growth of follicles and preserved their viability. Furthermore, PEGylation improved the stability of fibrin and the physical support of follicles. This study was supported by grants from the Fondation Louvain (PhD scholarship awarded to S.M., as part of a legacy from Mr Frans Heyes, and PhD scholarship awarded to A.D. as part of a legacy from Mrs Ilse Schirmer). The authors declare no competing interests.

MR elastography of soft porous tissue phantoms with varying macrostructure and pore pressure

Tissue porosity pressure mechanics play a vital role in the physiological workings and anatomical structures of soft tissue. Further understanding relationships between the pressurized state of the tissue and its function by noninvasive measurements may lead to new diagnostic methods for identifying early stages of disease pathology. The purpose of this study was to investigate the ability of Magnetic Resonance Elastography (MRE) to identify mechanics related to different pressurized states of porous soft tissue-like media. Phantoms with variations in stiffness and porous network geometries are scanned with MRE at 9.4 Tesla while pore pressure is quasi-statically loaded with 0, 50, 100, 150 mmHg gauge using air and liquid pressure. The MRE-derived shear modulus of tissue around isolated pores correlates with pore pressure. However, this was not observed for interconnected porous systems, in which the shear wavelength is much larger than the distance between neighboring pore branches. In these systems, the presented experimental results highlight the importance of a compressibility marker derived from 3D MRE acquisitions, which may be sensitive to pore pressure and pore network geometry.

Self-Closing Stretchable Cuff Electrodes for Peripheral Nerve Stimulation and Electromyographic Signal Recording

The cuff electrode can be wrapped in the columnar or tubular biological tissue for physiological signal detection or stimulation regulation. The reliable and non-excessive interfaces between the electrode and complex tissue are critical. Here, we propose a self-closing stretchable cuff electrode, which is able to self-close onto the bundles of tissues after dropping water. The curliness is realized by the mechanical stress mismatch between different layers of the elastic substrate. The material of the substrate can be selected to match the modulus of the target tissue to achieve minimal constraint on the tissue. Moreover, the self-closing structure keeps the cuff electrode free from any extra mechanical locking structure. For in vivo testing, both sciatic nerve stimulation to drive muscles and electromyographic signal monitoring around a rat's extensor digitorum longus for 1 month prove that our proposed electrode conforms well to the curved surface of biological tissue.

Experimental extraction of Young’s modulus of MCF-7 tissue using atomic force microscopy and the spherical contact models

The study of mechanical properties of tissues can be considered as biomarkers for early detection of cancer and help in new treatments. In this study, the Young's modulus of MCF-7 breast cancer tissue was extracted using atomic force microscopy (AFM) by measuring the interaction force of the sample and performing a simulation. The force-indentation depth diagram was plotted by averaging the experimental results. In this paper, the modulus of elasticity of breast cancer tissue has been extracted with complex models such as DMT, MD, BCP, and SUN. By comparing the experimental and theoretical results and by changing the amount of hypothetical Young's modulus in the spherical contact models, the Young's modulus of the cancer tissue is considered to be between 300 and 400Pa. The geometry of the cell was also assumed to be spherical according to the images obtained by atomic force microscopy.

Time-lapse mechanical imaging of neural tube closure in live embryo using Brillouin microscopy

Neural tube closure (NTC) is a complex process of embryonic development involving molecular, cellular, and biomechanical mechanisms. While the genetic factors and biochemical signaling have been extensively investigated, the role of tissue biomechanics remains mostly unexplored due to the lack of tools. Here, we developed an optical modality that can conduct time-lapse mechanical imaging of neural plate tissue as the embryo is experiencing neurulation. This technique is based on the combination of a confocal Brillouin microscope and a modified ex ovo culturing of chick embryo with an on-stage incubator. With this technique, for the first time, we captured the mechanical evolution of the neural plate tissue with live embryos. Specifically, we observed the continuous increase in tissue modulus of the neural plate during NTC for ex ovo cultured embryos, which is consistent with the data of in ovo culture as well as previous studies. Beyond that, we found that the increase in tissue modulus was highly correlated with the tissue thickening and bending. We foresee this non-contact and label-free technique opening new opportunities to understand the biomechanical mechanisms in embryonic development.

Linear and nonlinear rheology of liberase-treated breast cancer tumors.

Extracellular matrix (ECM) rigidity has been shown to increase the invasive properties of breast cancer cells, promoting transformation and metastasis through mechanotransduction. Reducing ECM stiffness via enzymatic digestion could be a promising approach to slowing breast cancer development by de-differentiation of breast cancer cells to less aggressive phenotypes and enhancing the effectiveness of existing chemotherapeutics via improved drug penetrance throughout the tumor. In this study, we examine the effects of injectable liberase (a blend of collagenase and thermolysin enzymes) treatments on the linear and nonlinear rheology of allograft 4T1 mouse mammary tumors. We perform two sets of in vivo mouse studies, in which either one or multiple treatment injections occur before the tumors are harvested for rheological analysis. The treatment groups in each study consist of a buffer control, free liberase enzyme in buffer, a thermoresponsive copolymer called LiquoGel (LQG) in buffer, and a combined, localized injection of LQG and liberase. All tumor samples exhibit gel-like linear rheological behavior with the elastic modulus significantly larger than the viscous modulus and both independent of frequency. Tumors that receive a single injection of localized liberase have significantly lower tumor volumes and lower tissue moduli at both the center and edge compared to buffer- and free liberase-injected control tumors, while tissue viscoelasticity remains relatively unaffected. Tumors injected multiple times with LQG and liberase also have lower tissue volumes but possess higher tissue moduli and lower viscoelasticities compared to the other treatment groups. We propose that a mechanotransductive mechanism could cause the formation of smaller but stiffer tumors after repeated, localized liberase injections. Large amplitude oscillatory shear (LAOS) experiments are also performed on tissues from the multiple injection study and the results are analyzed using MITlaos. LAOS analysis reveals that all 4T1 tumors from the multiple injection study exhibit nonlinear rheological behavior at high strains and strain rates. Examination of the Lissajous-Bowditch curves, Chebyshev coefficient ratios, elastic moduli, and dynamic viscosities demonstrate that the onset and type of nonlinear behavior is independent of treatment type and elastic modulus, suggesting that multiple liberase injections do not affect the nonlinear viscoelasticity of 4T1 tumors.

Biomechanical Properties of Repair Cartilage Tissue Are Superior Following Microdrilling Compared to Microfracturing in Critical Size Cartilage Defects.

Common surgical treatment options for large focal chondral defects (FCDs) in the knee include microfracturing (MFX) and microdrilling (DRL). Despite numerous studies addressing MFX and DRL of FDCs, no in vivo study has focused on biomechanical analysis of repair cartilage tissue in critical size FCDs with different amounts of holes and penetration depths. Two round FCDs (d=6 mm) were created on the medial femoral condyle in 33 adult merino sheep. All 66 defects were randomly assigned to 1 control or 4 different study groups: 1) MFX1, 3 holes, 2 mm depth; 2) MFX2, 3 holes, 4 mm depth; 3) DRL1, 3 holes, 4 mm depth; and 4) DRL2, 6 holes, 4 mm depth. Animals were followed up for 1 year. Following euthanasia, quantitative optical analysis of defect filling was performed. Biomechanical properties were analysed with microindentation and calculation of the elastic modulus. Quantitative assessment of defect filling showed significantly better results in all treatment groups compared to untreated FCDs in the control group (p<0.001), with the best results for DRL2 (84.2% filling). The elastic modulus of repair cartilage tissue in the DRL1 and DRL2 groups was comparable to the adjacent native hyaline cartilage, while significantly inferior results were identified in both MFX groups (MFX1: p=0.002; MFX2: p<0.001). More defect filling and better biomechanical properties of the repair cartilage tissue were identified for DRL compared to MFX, with the best results for 6 holes and 4 mm of penetration depth. These findings are in contrast to the current clinical practice with MFX as the gold standard and suggest a clinical return to DRL.