Biomechanical Characterization Research Articles

Biomechanical characterization of the small intestine to simulate gastrointestinal tract chyme propulsion

Regular intestinal motility is essential to guarantee complete digestive function. The coordinative action and integrity of the smooth muscle layers in the small intestine's wall are critical for mixing and propelling the luminal content. However, some patients present gastrointestinal limitations which may negatively impact the normal motility of the intestine. These patients have altered mechanical and muscle properties that likely impact chyme propulsion and may pose a daily scenario for long-term complications. To better understand how mechanics affect chyme propulsion, the propulsive capability of the small intestine was examined during a peristaltic wave along the distal direction of the tract. It was assumed that such a wave works as an activation signal, inducing peristaltic contractions in a transversely isotropic hyperelastic model. In this work, the effect on the propulsion mechanics, from an impairment on the muscle contractile ability, typical from patients with systemic sclerosis, and the presence of sores resultant from ulcers was evaluated. The passive properties of the constitutive model were obtained from uniaxial tensile tests from a porcine small intestine, along with both longitudinal and circumferential directions. Our experiments show decreased stiffness in the circumferential direction. Our simulations show decreased propulsion forces in patients in systemic sclerosis and ulcer patients. As these patients may likely need medical intervention, establishing action concerning the impaired propulsion can help to ease the evaluation and treatment of future complications.

Biomechanical characterization of isolated epineurial and perineurial membranes of rabbit sciatic nerve

Design of interface devices for effective, long-term integration into neural tissue is dependent on the biomechanical properties of the nerve membranes. Within the peripheral nerve, the two relevant connective tissue layers for interfacing are the epineurium and perineurium. Previous work has reported the forces needed to penetrate the whole nerve, but the mechanical differences between epineurium and perineurium were not reported. Design of intraneural electrodes that place electrodes within the nerve requires knowledge of the mechanics of individual tissues. This study quantified the Young’s moduli and ultimate strains of the perineurium and the epineurium separately. We also measured the forces necessary to penetrate each tissue in isolation. We used a custom-built microtensile testing device to measure the Young’s modulus values. The measured Young’s moduli of the epineurium and the perineurium was 0.4 ± 0.1 MPa and 3.0 ± 0.3 MPa, respectively. We also measured the force required for blunt and sharp stainless steel, 100 µm diameter probes to be inserted into isolated epineurial tissue and perineurial tissue at 2 mm/s. These data provide additional guidelines for selection of materials for long-term implants that best match the tissue properties. The results will guide neural interface design such that electrodes can be placed through either the epineurium alone or both the epineurium and perineurium.

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

Biomechanical Characterization of a New Acellular Dermal Matrix for Oral Soft Tissue Regeneration

Objectives Acellular dermal matrices (ADM) are a suitable alternative to autogenous soft tissue grafts (ASG). The aim of this study was to analyze the biomechanical properties and architectural features of ASG and ADM. Materials and methods ASG were harvested from the hard palate of fresh frozen body donors as connective tissue grafts and compared to ADM of porcine origin (NovoMatrix, NM; mucoderm, MD). Maximum load (ML, Newton [N]) and expansion (E, [mm]) were measured after rehydration in saline solution by tensile strength measurement. Light microscopy (LM) and scanning electron microscopy (SEM) were performed to analyze the architectural features of ASG and ADM in high resolution. Results ASG demonstrated a significantly decreased ML compared to NM and MD (p < 0.0001 and p = 0.019). NM showed a significantly increased ML compared to MD (p = 0.001). ASG demonstrated a non-significantly reduced E compared to NM (p = 0.13) and a significantly increased E compared to MD (p = 0.025). NM showed an increased E compared to MD (p < 0.0001). LM and SEM highlighted the surface characteristics and internal structures of ASG and ADM, such as the surface compact layer of MD and the densely packed, parallel running and ordered collagen fibers of NM and MD. Conclusions Significant differences concerning the biomechanical properties and architectural features of ASG, and ADM were found. Clinical relevance Information about the biomechanical properties and architectural features of ASG and ADM can contribute to a better understanding of the clinical performance and extend the application area.

Biomechanical Characterization of Scallop Shells Exposed to Ocean Acidification and Warming.

Increased carbon dioxide levels (CO2) in the atmosphere triggered a cascade of physical and chemical changes in the ocean surface. Marine organisms producing carbonate shells are regarded as vulnerable to these physical (warming), and chemical (acidification) changes occurring in the oceans. In the last decade, the aquaculture production of the bivalve scallop Argopecten purpuratus (AP) showed declined trends along the Chilean coast. These negative trends have been ascribed to ecophysiological and biomineralization constraints in shell carbonate production. This work experimentally characterizes the biomechanical response of AP scallop shells subjected to climate change scenarios (acidification and warming) via quasi-static tensile and bending tests. The experimental results indicate the adaptation of mechanical properties to hostile growth scenarios in terms of temperature and water acidification. In addition, the mechanical response of the AP subjected to control climate conditions was analyzed with finite element simulations including an anisotropic elastic constitutive model for a two-fold purpose: Firstly, to calibrate the material model parameters using the tensile test curves in two mutually perpendicular directions (representative of the mechanical behavior of the material). Secondly, to validate this characterization procedure in predicting the material’s behavior in two mechanical tests.

Biomechanical characterization and modeling of human mesenchymal stem cells under compression

The application of microelectromechanical systems (MEMS) in biomedical devices has expanded vastly over the last few decades, with MEMS devices being developed to measure different characteristics of cells. The study of cell mechanics offers valuable understanding of cell viability and functionality. Cell biomechanics approaches also facilitate the characterization of important cell and tissue behaviors. In particular, understanding of the biological response of cells to their biomechanical environment would enhance the knowledge of how cellular responses correlate to tissue level characteristics and how some diseases, such as cancer, grow in the body. This study focuses on viscoelastic modeling of the behavior of a single suspended human mesenchymal stem cell (hMSC). Mechanical properties of hMSC cells are particularly important in tissue engineering and research for the treatment of cardiovascular diseases. We evaluated the elastic and viscoelastic properties of hMSC cells using a miniaturized custom-made BioMEMS device. Our results were compared to the elastic and viscoelastic properties measured by other methods such as atomic force microscopy (AFM) and micropipette aspiration. Different approaches were applied to model the experimentally obtained force data, including elastic and Standard Linear Solid (SLS) constitutive models, and the corresponding constants were derived. These values were compared to the ones in literature that were based on micropipette aspiration and AFM methods. We then utilized a tensegrity approach to model major parts of the internal structure of the cell and treat the cell as a network of viscoelastic microtubules and microfilaments, as opposed to a simple spherical blob. The results predicted from the tensegrity model were similar to the recorded experimental data.

Biomechanical characterization and constitutive modeling of the layer-dissected residual strains and mechanical properties of abdominal porcine aorta

We analyze the residual stresses and mechanical properties of layer-dissected infrarenal abdominal aorta (IAA). We measured the axial pre-stretch and opening angle and performed uniaxial tests to study and compare the mechanical behavior of both intact and layer-dissected porcine IAA samples under physiological loads. Finally, some of the most popular anisotropic hyperelastic constitutive models (GOH and microfiber models) were proposed to estimate the mechanical properties of the abdominal aorta by least-square fitting of the recorded in-vitro uniaxial test results.The results show that the residual stresses are layer dependent. In all cases, we found that the OA in the media layer is lower than in the whole artery, the intima and the adventitia. For the axial pre-stretch, we found that the adventitia and the media were slightly stretched in the environment of the intact arterial strip, whereas the intima appears to be compressed. Regarding the mechanical properties, the media seems to be the softest layer over the whole deformation domain showing high anisotropy, while the intima and adventitia exhibit considerable stiffness and a lower anisotropy response. Finally, all the hyperelastic anisotropic models considered in this study provided a reasonable approximation of the experimental data. The GOH model showed the best fitting.

Comparison of bone formation mediated by bone morphogenetic protein delivered by nanoclay gels with clinical techniques (autograft and InductOs®) in an ovine bone model

Development of a growth factor delivery vehicle providing appropriate temporal-spatial release together with an appropriate preclinical large animal model to evaluate bone formation is critical in the development of delivery strategies for bone tissue regeneration. Smectite nanoclays such as LAPONITE™ possess unique thixotropic and protein retention properties offering promise for use in growth factor delivery in bone repair and regeneration. This study has examined bone formation mediated by a clinically approved growth factor delivery system (InductOs®) in combination with Laponite gel in an aged female ovine femoral condyle defect preclinical model (10 weeks). Two different designs, one containing a low volume of Laponite gel (LLG) in combination with the InductOs® absorbable collagen sponge (ACS), the other in which Laponite gel formed the implant (HLG), were compared against InductOs® alone and an autograft positive control. Thus, five groups: (i) empty defect, (ii) autograft, (iii) BMP2 + ACS, (iv) BMP2 + ACS + LLG and (v) BMP2 + HLG + ACS were examined in 9 mm × 12 mm defects performed bilaterally in the medial femoral condyles of 24 aged (>5 years) sheep. Bone formation within the defect was assessed using micro-computed tomography (micro-CT), digital volume correlation (DVC) for biomechanical characterisation as well as histology. The autograft and InductOs® mediated enhanced bone formation (p < 0001) compared to blank controls, while no significant differences were observed between the Laponite/Collagen/BMP delivery vehicles. However, the current study illustrated the excellent biocompatibility of Laponite and its ability to deliver localised active BMP-2, with the opportunity for improved efficacy with further optimisation. Interestingly, DVC-computed strain distributions indicated that the regenerated bone structure is mechanically adapted to bear external loads from the early remodelling stages of the bone reparation cascade. The current studies of selected nanoclay delivery platforms for BMP, assessed in a clinically relevant large animal model auger well for the development of bone fracture therapeutics for an ageing population.

Nonlinear Characterization of Tissue Viscoelasticity With Acoustoelastic Attenuation of Shear Waves.

Shear-wave elastography (SWE) measures shear-wave speed (SWS), which is related to the underlying shear modulus of soft tissue. SWS in soft tissue changes depending on the amount of external strain that soft tissue is subjected to due to the acoustoelastic (AE) phenomenon. In the literature, variations of SWS as a function of applied uniaxial strain were used for nonlinear characterization, assuming soft tissues to be elastic, although soft tissues are indeed viscoelastic in nature. Hence, nonlinear characterization using SWS alone is insufficient. In this work, we use SWS together with shear-wave attenuation (SWA) during incremental quasi-static compressions in order to derive biomechanical characterization based on the AE theory in terms of well-defined storage and loss moduli. As part of this study, we also quantify the effect of applied strain on measurements of SWS and SWA since such confounding effects need to be taken into account when using SWS and/or SWA, e.g., for staging a disease state, while such effects can also serve as an additional imaging biomarker. Our results from tissue-mimicking phantoms with varying oil percentages and ex vivo porcine liver experiments demonstrate the feasibility of our proposed methods. In both experiments, SWA was observed to decrease with applied strain. For 10% compression in ex vivo livers, shear-wave attenuation decreased, on average, by 28% (93 Np/m), while SWS increased, on average, by 20% (0.26 m/s).

Circulating Primitive Erythroblasts in the Murine Embryo Undergo Complex Proteomic and Metabolomic Changes during Terminal Maturation

Primitive erythropoiesis is a critical component of the fetal cardiovascular network and is essential for growth and survival of the mammalian embryo. The need to rapidly establish a functional cardiovascular system in the post-implantation murine embryo is met, in part, by the intravascular circulation of primitive erythroid precursors that mature as a single semi-synchronous cohort. To better understand the processes that regulate erythroid precursor maturation, we analyzed the proteome, metabolome and lipidome of primitive erythroblasts isolated from embryonic day (E)10.5 and E12.5 of mouse gestation, which represents their transition from basophilic erythroblast (BasoE) to orthochromatic erythroblast (OrthoE) stages of maturation. Previous transcriptional and biomechanical characterization of these precursors has highlighted a transition towards the expression of protein elements characteristic of mature red blood cell structure and function, including initial formation of a functional erythroid-specific cytoskeleton. Our analysis confirmed a loss of organelle-specific protein components - from mRNA maturation to translation, from metabolism to protein degradation - including ribosome, spliceosome, mitochondria and proteasomes. In parallel, we observed a metabolic rewiring towards the pentose phosphate pathway, glycolysis and the Rapoport-Luebering shunt, which is consistent with the progressively decreasing steady state levels of carboxylic acids, acylcarnitines and free fatty acids along with decreased mitochondrial content. In addition, activation of the pentose phosphate pathway in particular may stem from increases in the expression of mature red blood cell components including hemoglobin chains and band 3 that control oxygen-dependent metabolic modulation. Furthermore, this metabolic reprogamming may reflect increased control of oxidative stress in line with increased expression of several antioxidant enzymes, including catalase, peroxiredoxins and glutathione peroxidase 4. On the other hand, accumulation of oxylipins and cholesteryl esters in primitive OrthoE cells was paralleled by increased transcript levels of the p53-regulated cholesterol transporter (ABCA1) and decreased transcript levels of cholesterol synthetic enzymes including mevalonate kinase (MVK) and phosphomevalonate kinase (PVMK), highlighting transcriptional control of metabolic reprogramming during this developmental process. The present study characterizes the extensive metabolic rewiring that occurs in primary embryonic erythroid precursors as they prepare to enucleate and continue circulating without internal organelles. DisclosuresNemkov: Omix Thecnologies: Other: Co-founder. Hansen: Omix Technologies: Other: Co-founder; ScalmiBio: Membership on an entity's Board of Directors or advisory committees. Palis: Rubius Therapeutics: Consultancy. D'Alessandro: Omix Thecnologies: Other: Co-founder; Rubius Therapeutics: Consultancy; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Biomechanical characterization of the foot-ground interaction among Service members with unilateral transtibial limb loss performing unconstrained drop-landings: Effects of drop height and added mass

There exist limited data to guide the development of methodologies for evaluating impact resilience of prosthetic ankle–foot systems, particularly regarding human-device interaction in ecologically valid scenarios. The purpose of this study was to biomechanically characterize foot–ground interactions during drop-landings among Service members with and without unilateral transtibial limb loss. Seven males with, and seven males without, unilateral transtibial limb loss completed six drop-landing conditions consisting of all combinations of three heights (20 cm, 40 cm, 60 cm) and two loads (with and without a 22.2 kg weighted vest). Peak ground reaction forces (GRF), vertical GRF loading rate and impulse, as well as ankle–foot, knee, and hip joint negative (absorption) powers and work were compared across groups (i.e., contralateral side and prosthetic side vs. uninjured controls) by height and load conditions. Loading occurred primarily in the vertical direction, and increased with increasing drop height and/or with added load. Vertical GRFs were overall ~ 15% smaller on the prosthetic side (vs. controls) with similar loading rates across limbs/groups. From the most challenging condition (i.e., 60 cm with 22 kg load), ankle–foot absorption energies on the prosthetic side were 64.6 (7.2) J; corresponding values were 187.4 (8.9) J for the contralateral limb and 161.2 (6.7) J among uninjured controls. Better understanding biomechanical responses to drop-landings in ecological scenarios will help inform future iterations of mechanical testing methodologies for evaluating impact resilience of prosthetic ankle–foot systems (enhancing prescription criteria and return-to-activity considerations) as well as identifying and mitigating risk factors for long-term secondary complications within the contralateral limb (e.g., joint degeneration).

Biomechanics of Ophthalmic Crosslinking.

Crosslinking involves the formation of bonds between polymer chains, such as proteins. In biological tissues, these bonds tend to stiffen the tissue, making it more resistant to mechanical degradation and deformation. In ophthalmology, the crosslinking phenomenon is being increasingly harnessed and explored as a treatment strategy for treating corneal ectasias, keratitis, degenerative myopia, and glaucoma. This review surveys the multitude of exogenous crosslinking strategies reported in the literature, both “light” (involving light energy) and “dark” (involving non-photic chemical processes), and explores their mechanisms, cytotoxicity, and stage of translational development. The spectrum of ophthalmic applications described in the literature is then discussed, with particular attention to proposed therapeutic mechanisms in the cornea and sclera. The mechanical effects of crosslinking are then discussed in the context of their proposed site and scale of action. Biomechanical characterization of the crosslinking effect is needed to more thoroughly address knowledge gaps in this area, and a review of reported methods for biomechanical characterization is presented with an attempt to assess the sensitivity of each method to crosslinking-mediated changes using data from the experimental and clinical literature. Biomechanical measurement methods differ in spatial resolution, mechanical sensitivity, suitability for detecting crosslinking subtypes, and translational readiness and are central to the effort to understand the mechanistic link between crosslinking methods and clinical outcomes of candidate therapies. Data on differences in the biomechanical effect of different crosslinking protocols and their correspondence to clinical outcomes are reviewed, and strategies for leveraging measurement advances predicting clinical outcomes of crosslinking procedures are discussed.Advancing the understanding of ophthalmic crosslinking, its biomechanical underpinnings, and its applications supports the development of next-generation crosslinking procedures that optimize therapeutic effect while reducing complications.

Biomechanical characterization of the passive response of the thoracic aorta in chronic hypoxic newborn lambs using an evolutionary strategy

The present study involves experiments and modelling aimed at characterizing the passive structural mechanical behavior of the chronic hypoxic lamb thoracic aorta, whose gestation, birth and postnatal period were carried at high altitude (3600 masl). To this end, the mechanical response was studied via tensile and pressurization tests. The tensile and pressurization tests measurements were used simultaneously to calibrate the material parameters of the Gasser–Holzapfel–Ogden (GHO) hyperelasctic anisotropic constitutive model through an analytical-numerical optimization procedure solved with an evolutionary strategy that guarantees a stable response of the model. The model and procedure of calibration adequately adjust to the material behavior in a wide deformation range with an appropriate physical description. The results of this study predict the mechanical response of the lamb thoracic aorta under generalized loading states like those that can occur in physiological conditions and/or in systemic arterial hypertension. Finally, the novel use of the evolutionary strategy, together with the set of experiments and tools used in this study, provide a robust alternative to validate biomechanical characterizations.

Biomechanical analysis of wheelchair athletes with paraplegia during cross-training exercises

Context Extreme conditioning programs (ECPs), such as CrossFit®, are a relatively new method of fitness with rapid growth in individuals with paraplegia. However, it is unknown if wheelchair users are at an additional risk of musculoskeletal injury during these exercises. Biomechanical characterization is necessary to determine the safety and efficacy of ECPs as an exercise modality for wheelchair users with paraplegia. Objective To characterize the three-dimensional (3-D) thorax and upper extremity joint kinematics of paraplegic wheelchair athletes during exercises commonly prescribed as part of ECPs. Design Observational study Participants Three male wheelchair athletes, average age of 37.1 ± 4.6 years, with spinal cord injury levels of T8, L2, and T10, with varying exercise experience. Methods 3-D movement was acquired using motion capture during the performance of four exercises: battle ropes, sled pull, overhead press, and sledgehammer swing. A custom upper extremity inverse kinematics model was applied to compute 3-D joint angles. Outcome Measures 3-D peak thorax, glenohumeral, elbow, and wrist joint angles and ranges of motion (ROM), Visual Analog Scale (VAS), and Borg Scale of Perceived Exertion. Results Large joint motions were required for the exercises, at times demanding extreme shoulder and/or wrist flexion and extension, abduction, and external rotation, which are concerning for injury risk in wheelchair users. Participants, however, were able to perform the exercises pain free. Conclusion These quantitative findings highlight that wheelchair athletes may be exposed to potentially injurious positions during common ECP exercises. These findings provide insight that may lead to improved clinical guidelines for prescription and training of exercise regimens, particularly involving ECPs, for wheelchair users.

Mechanical characterization of fibrotic and mineralized tissue in Peyronie's disease.

Peyronie's disease affects penile mechanics, but published research lacks biomechanical characterization of affected tunica albuginea. This work aims to establish mechanical testing methodology and characterize pathological tissue mechanics of Peyronie's disease. Tunica albuginea was obtained from patients (n = 5) undergoing reconstructive surgery for Peyronie's disease, sectioned into test specimens (n = 12), stored frozen at -20 °C, and imaged with micro-computed tomography (µCT). A tensile testing protocol was developed based on similar soft tissues. Correlation of mechanical summary variables (force, displacement, stiffness, work, Young's modulus, ultimate tensile stress, strain at ultimate tensile stress, and toughness) and µCT features were assessed with linear regression. Specimens empirically grouped into hard or soft stress-strain behavior were compared using a Student's t-test. Surface strain and failure patterns were described qualitatively. Specimens displayed high inter- and intra-subject variability. Mineralization volume was not correlated with mechanical parameters. Empirically hard tissue had higher ultimate tensile stress. Failure mechanisms and strain patterns differed between mineralized and non-mineralized specimens. Size, shape, and quantity of mineralization may be more important in determining Peyronie's disease plaque behavior than presence of mineralization alone, and single summary variables like modulus may not fully describe mechanical behavior.

The Biomechanical Characterization of the Turning Phase during a 180° Change of Direction.

The aim of this study was to characterize the turning phase during a modified 505 test. Forty collegiate basketball students, divided into faster and slower performers and high-playing-level and low-playing-level groups, were evaluated for the force-time characteristics (braking and/or propulsive phase) of the penultimate foot contact (PFC), final foot contact (FFC), and first accelerating foot contact (AFC), and for completion time and approach velocity. Based on the composition of the AFC, trials were classified as braking/propulsive or only propulsive. Regression analysis for the prediction of completion time was performed. The AFC contributed to reacceleration through shorter contact times and step length, and lower braking force production (p < 0.05). Faster performers and the high-playing-level group demonstrated (p < 0.05): lower completion times, higher approach velocities, longer steps length in the PFC and FFC, greater braking forces and impulses in the PFC; greater braking and propulsive forces, braking impulses, lower contact times in the FFC; greater braking and propulsive horizontal forces, horizontal impulses, lower contact times and vertical impulses in the AFC. Kinetic variables from only the FFC and AFC and approach velocity predicted 75% (braking/propulsive trials) and 76.2% (only-propulsive trials) of completion times. The characterization of the turning phase demonstrated the specific contribution of each foot contact and the possible implications for training prescription.

Architecture-Promoted Biomechanical Performance-Tuning of Tissue-Engineered Constructs for Biological Intervertebral Disc Replacement.

Background: Biological approaches to intervertebral disc (IVD) restoration and/or regeneration have become of increasing interest. However, the IVD comprises a viscoelastic system whose biological replacement remains challenging. The present study sought to design load-sharing two-component model systems of circular, nested, concentric elements reflecting the nucleus pulposus and annulus fibrosus. Specifically, we wanted to investigate the effect of architectural design variations on (1) model system failure loads when testing the individual materials either separately or homogeneously mixed, and (2) also evaluate the potential of modulating other mechanical properties of the model systems. Methods: Two sets of softer and harder biomaterials, 0.5% and 5% agarose vs. 0.5% agarose and gelatin, were used for fabrication. Architectural design variations were realized by varying ring geometries and amounts while keeping the material composition across designs comparable. Results: Variations in the architectural design, such as lamellar width, number, and order, combined with choosing specific biomaterial properties, strongly influenced the biomechanical performance of IVD constructs. Biomechanical characterization revealed that the single most important parameter, in which the model systems vastly exceeded those of the individual materials, was failure load. The model system failure loads were 32.21- and 84.11-fold higher than those of the agarose materials and 55.03- and 2.14-fold higher than those of the agarose and gelatin materials used for system fabrication. The compressive strength, dynamic stiffness, and viscoelasticity of the model systems were always in the range of the individual materials. Conclusions: Relevant architecture-promoted biomechanical performance-tuning of tissue-engineered constructs for biological IVD replacement can be realized by slight modifications in the design of constructs while preserving the materials’ compositions. Minimal variations in the architectural design can be used to precisely control structure–function relations for IVD constructs rather than choosing different materials. These fundamental findings have important implications for efficient tissue-engineering of IVDs and other load-bearing tissues, as potential implants need to withstand high in situ loads.

Biomechanical, histological, and molecular characterization of a new posttraumatic model of arthrofibrosis in rats.

Experimental analyses of posttraumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel posttraumatic model of arthrofibrosis in rats. Forty eight rats were divided into two equal groups. An immobilization procedure was performed on the right hind limbs of experimental rats. One group was immobilized for 4 weeks and the other for 8 weeks. Both groups were remobilized for 4 weeks. Limbs were studied biomechanically via assessment of torque versus degree of extension, histologically via whole knee specimen, and molecularly via gene expression of posterior capsular tissues. Significant differences were observed between experimental and control limbs at 4 N-cm of torque in the 4-week (knee extension: 115° ± 8° vs. 169° ± 17°, respectively; p = 0.007) and 8-week immobilization groups (knee extension: 99° ± 12° vs. 174° ± 9°, respectively; p = 0.008). Histologically, in each group experimental limbs demonstrated increased posterior capsular thickness and total area of tissue when compared to control limbs (p < 0.05). Gene expression values evaluated in each group were comparable. This study presents a novel rat model of arthrofibrosis with severe and persistent knee contractures demonstrated biomechanically and histologically. Statement of clinical significance: Arthrofibrosis is a common complication following contemporary total knee arthroplasties. The proposed model is reproducible, cost-effective, and can be employed for translational investigations studying the pathogenesis of arthrofibrosis and efficacy of neoadjuvant pharmacologic agents.

Abstract No. 225 Venous large animal model for stenosis, thrombosis, and chronic occlusion: short-term results, with biomechanical analysis

Angiographic and biomechanical characterization of an ovine venous stenosis/occlusion model developed for studying translational interventions in venous occlusive disease. Unilateral iliac vein stenosis was created in six adult sheep using established endovenous radiofrequency (RF) ablation technique. Two sheep underwent short-segment RF ablation with the goal of creating chronic stenoses. Four sheep underwent long-segment RF ablation with the goal of inducing thrombosis/occlusion. Ultrasound and angiographic assessment was performed at baseline, immediately after venous stenosis creation, and prior to euthanasia at 2-week follow-up. Vein samples were immediately harvested for biomechanical assessment. Uniaxial longitudinal and circumferential tensile testing was performed with a custom mounting apparatus at a crosshead speed of 4 mm/min (MTS Criterion, Eden Prairie, MN). At 2-week follow-up venogram, the short-segment group (length: 11.5 ± 3.5 mm; stenosis: 64.0 ± 6.0%) showed stable stenosis without thrombosis in all animals. The long-segment group (length: 61.1 ± 12.2 mm; stenosis: 76.4 ± 3.3%) showed complete iliac occlusion/thrombosis with collateralization in all animals. Gross vein specimens showed thickened venous wall (0.28 ± 0.04 mm; contralateral normal control: 0.16 ± 0.02 mm; P< 0.05) and early scar tissue formation in all samples as well as soft non-adherent thrombi in the occlusion samples. Both stenotic and occlusive vein samples showed higher stiffness compared to the contralateral normal controls (P< 0.05), and higher stiffness in the longitudinal compared to the circumferential axis (P< 0.05). RF ablation can produce stable short-segment venous stenosis and long-segment thrombosis/occlusion in short-term survival. Tensile testing showed increased venous wall stiffness, replicating expected post-thrombotic biomechanical changes. Further studies are underway for biomechanical and histologic characterization of chronic fibrosis created in this large animal model. Once validated, this large animal model can be used for studying venous stenosis, thrombosis, chronic occlusion and their associated interventions.

Feasibility of Rib Kinematics and Intercostal-Space Biomechanical Characterization by Ultrasound in Adolescent Idiopathic Scoliosis

The aim of this work was to determine the feasibility of combined ultrasonography and elastography measurement to characterize the mechanical properties of the intercostal space during breathing. Eighteen asymptomatic participants (ages 13 ± 2 y) and six participants with adolescent idiopathic scoliosis (AIS) were included (Cobb angle 60° ± 12°). Ultrasonographic and elastographic clips were acquired of T8–T9 ribs and the intercostal space. The two adjacent ribs were tracked to infer the breathing cycle. Shear-wave speed (SWS) was measured in the intercostal space at different stages of the breathing cycle. SWS was symmetric in the control group, during both expiration and inspiration. In AIS, the SWS during inspiration was higher in the convex side than in the concave one (p = 0.02). Furthermore, SWS was higher during inspiration than expiration in the control group and in the AIS convex side, but not in the AIS concave side (p > 0.05). This new method combining echography and shear-wave elastography allowed measurement of the mechanical characteristics of the intercostal space at different phases of the breathing cycle and highlighted differences between the AIS and control groups. This approach opens the way to further analyses of the biomechanical characteristics of breathing in severe AIS.