Biology subjects

Hast, M. W.

Publications and source records attributed to Hast, M. W..

9 recordsLinked to original sources

bioRxiv2024

Learning on a Limb: An outreach module to engage high school students in orthopaedics

Orthopaedic researchers need new strategies for engaging diverse students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb, an orthopaedic research outreach module to teach diverse high school students about orthopaedic research. During the 4-hr module, students completed hands-on activities to learn how biomechanical testing, microcomputed tomography, cell culture, and histology are used in orthopaedic research. Over three years, we recruited 32 high school students from the Greater Philadelphia Area to participate in Learning on a Limb. Most participants identified as racial/ethnic or gender minorities in orthopaedic research. Using pre/post-tests, we found that students experienced significant learning gains of 51 percentage points from completing Learning on a Limb. In addition to teaching students about orthopaedic research, post-survey data demonstrated that participating in Learning on a Limb strongly influenced students interest in orthopaedic research. Several students acted on this interest by completing summer research experiences in the McKay Orthopaedic Research Laboratory at the University of Pennsylvania. Learning on a Limb instructors also benefited by having the opportunity to "pay it forward" to the next generation of students and build community within their department. Empowering institutions to host modules like Learning on a Limb would synergistically inspire diverse high school students and strengthen community within orthopaedic departments to ultimately enhance orthopaedic research innovations.

scientific communication and education↗

bioRxiv2022

Anti-Inflammatory Tension-Activated Repair Patches Improve Repair After Intervertebral Disc Herniation

Conventional treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus (AF), resulting in a high incidence of recurrent herniation and persistent disfunction. The lack of repair and the acute inflammation that arise after injury further compromises the disc and can result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annular repair and the local delivery of bioactive anti-inflammatory factors. TARPs transmit physiologic strains to mechanically-activated microcapsules (MAMCs) embedded within, which activate and release encapsulated biomolecules in response to physiologic loading. Here, we demonstrate that the TARP design modulates implant biomechanical properties and regulates MAMC mechano-activation. Next, the FDA-approved anti-inflammatory molecule, interleukin 1 receptor antagonist, Anakinra, was loaded in TARPs and the effects of TARP-mediated annular repair and Anakinra delivery was evaluated in a model of annular injury in the goat cervical spine. TARPs showed robust integration with the native tissue and provided structural reinforcement at the injury site that prevented disc-wide aberrant remodeling resulting from AF detensioning. The delivery of Anakinra via TARP implantation improved the retention of disc biochemical composition through increased matrix deposition and retention at the site of annular injury. Anakinra delivery additionally attenuated the inflammatory response associated by scaffold implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the AF. These results demonstrate the translational and therapeutic potential of this novel TARP system for the treatment of intervertebral disc herniations. One Sentence SummaryTension-activated repair patches delivering bioactive anti-inflammatory factors improve healing in an in vivo goat cervical disc injury model.

bioengineering↗

bioRxiv2022

Glisson's capsule structure and function is altered in cirrhotic patients irrespective of etiology

Background and AimsGlissons capsule is the interstitial connective tissue that surrounds the liver. As part of its normal physiology, it withstands significant daily changes in liver size. The pathophysiology of the capsule in disease is not well understood. The aim of this study was to characterize the changes in capsule matrix, cellular composition, and mechanical properties that occur in liver disease and to determine whether these correlate with disease severity or etiology. Methods10 control, 6 steatotic, 7 moderately fibrotic and 37 cirrhotic patient samples were collected from autopsies, intraoperative biopsies and liver explants. Matrix proteins and cell markers were assessed by staining and second harmonic generation imaging. Mechanical tensile testing was performed on a test frame. ResultsCapsule thickness was significantly increased in cirrhotic samples compared to normal controls irrespective of disease etiology (69.62 {+/-} 9.99 and 171.269 {+/-} 16.65 {micro}m respectively), whereas steatosis and moderate fibrosis had no effect on thickness (62.15 {+/-} 4.97 {micro}m). Changes in cirrhosis included an increase in cell number (fibroblasts, vascular cells, infiltrating immune cells and biliary epithelial cells). Key matrix components (collagens 1 and 3, hyaluronan, versican and elastin) were all deposited in the lower capsule although only the relative amounts per area of hyaluronan and versican were increased. Organizational features including crimping and alignment of collagen fibers were also altered in cirrhosis. Unexpectedly, capsules from cirrhotic livers had decreased resistance to loading in comparison to controls. ConclusionsThe liver capsule, like the parenchyma, is an active site of disease, demonstrating changes in matrix and cell composition as well as mechanical properties. Lay summaryWe assessed the changes in composition and response to stretching of the liver outer sheath, the capsule, in human liver disease. We find an increase in key structural components and numbers of cells as well as a change in matrix organization of the capsule in the later stages of disease. This allows the diseased capsule to stretch more under any given force, suggesting it is less stiff than healthy tissue. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/505570v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@10a9b60org.highwire.dtl.DTLVardef@15eea52org.highwire.dtl.DTLVardef@69b874org.highwire.dtl.DTLVardef@cccd03_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe capsule is an active site of disease: thickness and cellularity increase markedly in cirrhosis C_LIO_LIExtracellular matrix composition and organization change in cirrhosis C_LIO_LIThe cirrhotic capsule stretches more and is less stiff C_LI

physiology↗

bioRxiv2019

Ultrasound Echogenicity is Associated with Achilles Tendon Fatigue Damage in a Cadaveric Loading Model

Achilles tendon disorders are among the most difficult sports-related injuries to predict with current diagnostic tools. The purpose of this study was to identify a clinically useful marker for early tendon damage. We hypothesized that alterations in mean echogenicity are linked with changes in vitro tendon mechanics. To test our hypothesis, we harvested Achilles tendons from 10 fresh-frozen cadaveric feet and cyclically fatigued them using a universal test frame while we continuously acquired ultrasound images. Throughout this fatigue protocol, we applied 2 stress tests every 500 loading cycles to quantify changes in ultrasound imaging echogenicity. We continued this fatigue protocol until each tendon either failed completely or survived 150,000 cycles. Tendons that failed during the fatigue loading (6/10) underwent greater changes in mean echogenicity compared to tendons that did not fail (P = 0.031). These tendons that failed during fatigue loading demonstrated greater changes in mean echogenicity that surpassed 1.0%; whereas survivor tendons exhibited less than 0.5% changes in mean echogenicity. We found that changes in mean echogenicity measured with ultrasound increased proportionally with increased tendon damage. The magnitude of these changes was relatively small (<1.5% change in mean echogenicity) but may be an effective predictor of tendon failure. Mean echogenicity is a promising marker for quantifying fatigue damage in cadaveric Achilles tendons during a stress test. Although these changes cannot be detected with the naked eye, computer-based predictive models may effectively assess risk of tendon damage in physically active adults. Level of evidenceControlled laboratory experiment

bioengineering↗

bioRxiv2018

Plantarflexor fiber length and tendon slack length are the strongest determinates of simulated single-leg heel raise function

AbstractAchilles tendon ruptures lead to reduced ankle function and often limits recreational activity. Single-leg heel raises are often used clinically to characterize patient function. However, it is unclear how the structure of the Achilles tendon and plantarflexor muscles affects single-leg heel raise function. Therefore, the purpose of this study was to develop a musculoskeletal model in order to simulate the effects of muscle-tendon unit (MTU) parameters on peak plantarflexion during this clinically-relevant task. The ankle joint was plantarflexed by two MTUs that represented the soleus and gastrocnemius muscles. The optimal fiber length, maximal muscle force, muscle pennation, tendon stiffness, and resting ankle angle - a surrogate measure of tendon slack length - were iteratively adjusted to test the combined effects of each of these MTU parameters. Single-leg heel raises were simulated by maximally exciting the two plantarflexor MTUs for each model configuration (N = 161,051 simulations). Optimal muscle fiber and tendon slack lengths had the greatest effect on peak plantarflexion during simulated single-leg heel raises. Simulations that were unable to produce at least 30 degrees of plantarflexion had muscle fibers that were shorter than healthy muscle and longer tendon slack lengths. These findings highlight the importance of preserving muscle fascicle and tendon length following Achilles tendon injuries.\n\nFunding no funding has been provided for this research\n\nAcknowledgements the Authors have no acknowledgements\n\nConflict of interest the Authors have no conflicts of interest that are relevant to this work

bioengineering↗

bioRxiv2018

Parameterization of Proximal Humerus Locking Plate Impingement with In Vitro, In Silico, and In Vivo Techniques

BackgroundLocked plating of displaced proximal humerus fractures is common, but rates of subacromial impingement remain high. Computational predictions of implant impingement have yet to be sufficiently explored in proximal humerus fixation. The goal of this study was to utilize a multidisciplinary approach to elucidate the relationships between common surgical parameters, anatomical variability, and the likelihood of plate impingement.\n\nMethodsThe experiment was completed in three phases. First, a controlled in vitro experiment was conducted to simulate impingement. Second, a dynamic in silico musculoskeletal model was developed to simulate changes to implant geometry, surgical techniques, and acromial anatomy, where a collision detection algorithm was used to simulate contact between the plate and acromion. Finally, in vivo shoulder kinematics were recorded for nine activities of daily living and motions that created a high likelihood of impingement were identified.\n\nResultsImpingement was measured at 73.3{+/-}14.5{degrees} abduction in the cadaveric model and 92.0{degrees}{+/-}34.0{degrees} with computational simulations. Impingement events were limited to ranges of motion between 10-40{degrees} of cross-body adduction. Activities of daily living, such as combing ones hair, lifting and object overhead, and reaching behind ones head are likely to cause impingement.\n\nDiscussion and ConclusionThis multidisciplinary experiment quantified key preoperative factors to assist with implantation decisions. Results demonstrated that proximal implant placement, superior translation of the humeral center of rotation, increases in plate thickness, and increases in acromial tilt all increase the likelihood of impingement. Careful preoperative planning that includes these factors could help guide operative decision making and improve clinical outcomes.\n\nLevel of Evidence: V

bioengineering↗

bioRxiv2018

Mechanical and Microstructural Properties of Pediatric Anterior Cruciate Ligaments and Autograft Tendons used for Reconstruction

BackgroundOver the last several decades there has been a steady increase in pediatric ACL tears, particularly in young female basketball and soccer players. Because allograft tissue for pediatric ACL reconstruction (ACLR) has shown high rates of failure, autograft tissue may be the best option for ACLR in this population. However, the differences in structure and mechanical behavior of these tissues are not clear.\n\nPurposeThis study sought to characterize mechanical and microstructural properties in pediatric ACLs and autograft tissues using a rare cadaveric cohort (mean age 9.2 years).\n\nStudy DesignDescriptive laboratory study.\n\nMethodsACLs, patellar tendons, quadriceps tendons, semitendinosus tendons, and iliotibial bands (ITBs) were harvested from five fresh-frozen pediatric knee specimens (3M, 2F) and subjected to a tensile loading protocol. A subset of contralateral tissues were analyzed using brightfield, polarized light, and transmission electron microscopy.\n\nResultsPatellar tendons exhibited values for ultimate stress (5.2{+/-}3.1 MPa), ultimate strain (35.3{+/-}12.5%), and Youngs Modulus (27.0{+/-}8.0 MPa) that were most similar to the ACL (5.2{+/-}2.2 MPa; 31.4{+/-}9.9%; 23.6{+/-}15.5 MPa). Semitendinosus tendons and ITBs were stronger but less compliant than the quadriceps or patellar tendons. ITBs exhibited crimp wavelengths (24.3{+/-}3.1 um) and collagen fibril diameters (67.5{+/-}19.5 nm) that were most similar to the ACL (24.4{+/-}3.2 um; 69.7{+/-}20.3 nm).\n\nConclusionThe mechanical properties of the patellar tendon were almost identical to that of the ACL. The ITB exhibited increased strength and similar microstructure to the native ACL. These findings are not entirely congruent to studies examining adult tissues.\n\nClinical RelevanceResults suggest that ITB tissue may be the preferable choice as an autograft tissue in pediatric ACL reconstructions.\n\nKey TermsPediatric, ACL reconstruction, mechanical properties, microstructural properties, patella tendon grafts, quadriceps tendon grafts, hamstring grafts\n\nWhat is Known about the SubjectDue to the extreme rarity of pediatric cadaveric specimens, very little is known about these tissues.\n\nWhat this Study Adds to Existing KnowledgeThis suite of data can be used to further optimize the design and selection of grafts for reconstruction and may provide insight into the development of constitutive musculoskeletal models.

bioengineering↗

bioRxiv2018

Tendon slack length is the primary determinant of plantarflexor muscle-tendon function in computational simulations of gait

1Background: Locomotion is partly dictated by plantarflexor function and structure. Computational simulations are powerful tools capable of testing the isolated effects of muscle-tendon structure on gait function. Research Question: The purpose of this study was to characterize the sensitivity of plantarflexor muscle function based on muscle-tendon unit (MTU) parameters. We hypothesized that plantarflexor metabolics and shortening dynamics would be sensitive to MTU parameters. Methods: Stance phase of gait was simulated using a musculoskeletal model and computed muscle control algorithm. Optimal muscle fiber length, tendon slack length, and tendon stiffness parameters were systematically changed to test the effects on plantarflexor metabolics and shortening dynamics. Results and Significance: Plantarflexor metabolic demands were 8 and 28 times more sensitive to muscle fiber and tendon slack lengths, respectively, compared to the effect of tendon stiffness. Shortened tendon slack lengths induced a large passive plantarflexion moment during early stance, which required non-physiologic dorsiflexor contractions. Conversely, longer muscle fiber and tendon slack lengths increased the shortening demands of the plantarflexors to account for the added length of the MTU. These findings highlight the importance of carefully selecting MTU parameters when modeling gait with musculoskeletal models, especially in pathologic or high-performance athlete populations.

bioengineering↗

bioRxiv2018

Simulating Contact Using the Elastic Foundation Algorithm in OpenSim

Modeling joint contact is necessary to test many questions using simulation paradigms, but this portion of OpenSim is not well understood. The purpose of this study was to provide a guide for implementing a validated elastic foundation contact model in OpenSim. First, the load-displacement properties of a stainless steel ball bearing and ultra high molecular weight polyethylene (UHMWPE) slab were recorded during a controlled physical experiment. These geometries were imported and into OpenSim and contact mechanics were modeled with the on-board elastic foundation algorithm. Particle swarm optimization was performed to determine the elastic foundation model stiffness (2.14x1011 {+/-} 6.81x109 N/m) and dissipation constants (0.999 {+/-} 0.003). Estimations of contact forces compared favorably with blinded experimental data (root mean square error: 87.58 {+/-} 1.57 N). Last, total knee replacement geometry was used to perform a sensitivity analysis of material stiffness and mesh density with regard to penetration depth and computational time. These simulations demonstrated that material stiffnesses between 1011 and 1012 N/m resulted in realistic penetrations (< 0.15mm) when subjected to 981N loads. Material stiffnesses between 1013 and 1015 N/m increased computation time by factors of 12-23. This study shows the utility of performing a simple physical experiment to tune model parameters when physical components of orthopaedic implants are not available to the researcher. It also demonstrates the efficacy of employing the on-board elastic foundation algorithm to create realistic simulations of contact between orthopaedic implants.

bioengineering↗