John Szivek
University of Arizona, Orthopaedic surgery, Faculty Member
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Osteoarthritis (OA), or degenerative joint disease, burdens approximately 40 million people in the US and is one of the most disabling conditions in developed nations. Recent studies have shown that surgical interventions such as... more
Osteoarthritis (OA), or degenerative joint disease, burdens approximately 40 million people in the US and is one of the most disabling conditions in developed nations. Recent studies have shown that surgical interventions such as autologous chondrocyte implantation and osteochondral cylinder transplantation (mosaicplasty) have been successful in reducing the pain caused by OA; however, with autologus chondrocyte implantation the defect ultimately is filled with fibrocartilage rather than the native hyaline articulating cartilage. Furthermore, with mosaicplasty, a number of patients often complain of painful disturbances at the graft site due to the donor site morbidity associated with larger defects (Horas et al 2003, Hangody et al 2003). The potential use of an engineered articular cartilage grown in cell culture to resurface the defect caused by OA is the ideal treatment when compared with filling the defect with a mechanically unfit form of cartilage or causing damage to an otherwise healthy donor site. As better techniques to stratify and orient engineered cartilaginous tissue layers become available it will be valuable to use a high resolution, nondestructive imaging technique to monitor growth and therapeutic effectiveness of the engineered construct. Optical coherence tomography (OCT) has shown potential as a method of high resolution (4-15 μm), non-invasive intraarticular cartilage imaging (Drexler et al 2001, Herrmann et al 1999). OCT is analogous to ultrasound in that it measures the intensity of back-reflected light rather than sound waves. We used OCT to characterize the femoral articulating cartilage of canines obtained post-limb amputation. After OCT imaging, the articulating surfaces were sectioned and stained for a histological evaluation. The OCT images were then compared to their corresponding histology, using non-polarized and polarized light microscopy, in order to evaluate the usefulness and structural clarity of the images. In the OCT images we were able to identify the superficial layer of the articular cartilage, the cartilage-bone interface, and the cartilage thickness. We conclude that OCT does in fact provide enough structural information to monitor growth and therapeutic effectiveness of an engineered cartilage model. In the future we hope to use polarization sensitive OCT to further characterize articular cartilage and identify the middle and deep layers. Once characterization of native cartilage is complete this technique will be implemented on engineered cartilaginous cells and tissue grown in culture to determine whether layer formation occurs.
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Two complete unicondylar surface replacement scaffold designs to support tissue-engineered cartilage growth that utilized adult endogenous stem cells were 3D printed and tested in a dog stifle model. Integrated rosette strain gauges were... more
Two complete unicondylar surface replacement scaffold designs to support tissue-engineered cartilage growth that utilized adult endogenous stem cells were 3D printed and tested in a dog stifle model. Integrated rosette strain gauges were calibrated and used to determine shear loading within stifle joints for up to 12 months. An activity index that compared extent of daily activity with tissue formation showed differences in the extent and quality of new tissue with the most active animal having the most new tissue formation. Shear loads were highest early and decreased with time indicating that cartilage tissue formation begins while tissues experience high shear loads and continues as the loads decrease toward normal physiological levels. Scaffolds with biomimetic support pegs facilitated the most rapid bone ingrowth and were noted to have more cartilage formation with better quality cartilage as measured using both indentation testing and histology. Comparison of implant placement...
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Purpose: Develop, validate and apply noninvasive ultrasoundelasticityimaging (UEI) of the human posterior tibial tendon (PTT) as a potential tool to diagnose different stages of PTT disorders and guide treatment of PTT dysfunction in the... more
Purpose: Develop, validate and apply noninvasive ultrasoundelasticityimaging (UEI) of the human posterior tibial tendon (PTT) as a potential tool to diagnose different stages of PTT disorders and guide treatment of PTT dysfunction in the clinic.Methods: We have developed ex vivo and in vivo platforms to develop UEI of the PTT. Healthy PTTs from four cadaveric feet were dissected at the proximal end and attached to a materials testingsystem (MTS) for controlled force/stroke production and measurement. Longitudinal ultrasoundimages of the tendon were collected at 80 Hz using a 14 MHz clinical ultrasound probe and scanner (Zonare MedicalSystems) during force production up to 60 kg. Displacement maps between successive ultrasound frames were obtained using 2D phase sensitive cross—correlation tracking. Mechanical properties of each tendon were estimated from both MTS and ultrasound measurements. This system complements our in vivo platform for UEI of the human PTT. Results: In the ultrasound movies, the PTT can be easily distinguished from superficial soft tissue and malleolus. Young's modulus of PTT was found to be similar across specimens and range of loads tested. The average Young's modulus was found to be 0.24 ± 0.05 GPa for the MTS and 0.62 ± 0.15 GPa for the ultrasound measurements. This difference was expected because the MTS measurement included properties of support material in series with the tendon. We have also extended our platform for in vivo and noninvasive ultrasound strain imaging of the PTT in human volunteers. Initial results suggest that this approach is a potentially powerful tool to diagnose and identify stages of PTTD for helping determine optimal treatment strategies. Conclusions: This study demonstrated the feasibility of using ultrasound to noninvasively track mechanical properties of the PTT. Further studies are needed to compare the elastic properties of diseased versus healthy tendon. Department of Radiology, University of Arizona; Department of Orthopaedic Surgery, University of Arizona.
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Pre- and poststudy motion and gait analyses of eight size-matched male greyhounds confirmed uniform loading of their femora. Subminiature strain gages implanted on the intact inferior and anterior aspects of the femoral neck in six... more
Pre- and poststudy motion and gait analyses of eight size-matched male greyhounds confirmed uniform loading of their femora. Subminiature strain gages implanted on the intact inferior and anterior aspects of the femoral neck in six greyhounds indicated in vivo strain variations among test animals. Motion and gait analyses confirmed uniform loading of femora following unilateral hemiarthroplasty with cobalt-chromium hip implants. In vivo strain measurements adjacent to the implants indicated large variations among test animals. A consistent direction of strain change relative to the intact femur was noted, even though strain changes varied in magnitude. Image analysis of microradiographs indicated insignificant differences in the cortical areas of implanted and intact femora. Extensive new trabecular bone formation was noted along the implant in the endosteal cavity and correlated with a combination of implant placement and exercise level. Most of the bone was formed with centrally placed implants in exercised dogs, and the least with stems on the medial neck surface in rested dogs. Iliac crest biopsies indicated that bone formation rates slowed in rested animals and remained constant throughout the study in exercised animals. All implanted femora had a thin (< 1 mm thick) aligned fibrous tissue layer separating the implant from bone. It varied in thickness as a function of the aspect of the implant. Exercised dogs had a larger proportion of fibrous tissue on the anterior and posterior aspects, while rested dogs had a larger proportion of fibrous tissue on the medial and lateral aspects.
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Tendinopathies and tendon tears heal slowly because tendons have a limited blood supply. Intense therapeutic ultrasound (ITU) is a treatment modality that creates very small, focal coagula in tissue, which can stimulate a healing... more
Tendinopathies and tendon tears heal slowly because tendons have a limited blood supply. Intense therapeutic ultrasound (ITU) is a treatment modality that creates very small, focal coagula in tissue, which can stimulate a healing response. This pilot study investigated the effects of ITU on rabbit and rat models of partial Achilles tendon rupture. The right Achilles tendons of 20 New Zealand White rabbits and 118 rats were partially transected. Twenty-four hours after surgery, ITU coagula were placed in the tendon and surrounding tissue, alternating right and left legs. At various time points, the following data were collected: ultrasound imaging, optical coherence tomography (OCT) imaging, mechanical testing, gene expression analysis, histology, and multiphoton microscopy (MPM) of sectioned tissue. Ultrasound visualized cuts and treatment lesions. OCT showed the effect of the interventions on birefringence banding caused by collagen organization. MPM showed inflammatory infiltrate,...
INTRODUCTION Spinal instrumentation with arthrodesis is commonly used in the surgical treatment of scoliosis because rigid fixation leads to higher fusion rates. However, stiff instrumentation causes device-related osteopenia due to... more
INTRODUCTION Spinal instrumentation with arthrodesis is commonly used in the surgical treatment of scoliosis because rigid fixation leads to higher fusion rates. However, stiff instrumentation causes device-related osteopenia due to "stress shielding." Earlier patient rehabilitation during which loading can be insured through monitoring, may be able prevent this problem. Currently no diagnostic technique is available to adequately assess when spine fusion has occurred. Fusion is judged using serial radiographs even though animal studies have shown that fusion occurs much earlier than is evident on radiographs. The aim of this study was to develop a technique to detect fusion in vivo in order to facilitate adequate bone loading during rehabilitation and an early return of patients to unrestricted activity. CPC coated strain gauges were implanted into a patient in conjunction with a subminiature radio transmitter to monitor bone strain changes which were measured during spec...
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Bioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were... more
Bioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were largely unexplored due to the lack of suitable tools. The musculoskeletal system is an understudied area where these new technologies can result in advanced capabilities. Bones as a sensor and stimulation location offer tremendous advantages for chronic biointerfaces because devices can be permanently bonded and provide stable optical, electromagnetic, and mechanical impedance over the course of years. Here we introduce a new class of wireless battery-free devices, named osseosurface electronics, which feature soft mechanics, ultra-thin form factor and miniaturized multimodal biointerfaces comprised of sensors and optoelectronics directly adhered to the surface of the bone. Potential of this fully implanted device class is demonstrated via real-time ...
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No current clinical treatments provide an ideal long-term solution for repair of long bone segment defects. Incomplete healing prevents patients from returning to preinjury activity and ultimately requires additional surgery to induce... more
No current clinical treatments provide an ideal long-term solution for repair of long bone segment defects. Incomplete healing prevents patients from returning to preinjury activity and ultimately requires additional surgery to induce healing. Obtaining autologous graft material is costly, incurs morbidity, requires surgical time, and quality material is finite. In this pilot study, 3D printed biomimetic scaffolds were used to facilitate rapid bone bridging in critical sized defects in a sheep model. An inverse trabecular pattern based on micro-CT scans of sheep trabecular bone was printed in polybutylene terephthalate. Scaffolds were coated with micron-sized tricalcium phosphate particles to induce osteoconductivity. Mesenchymal stem cells (MSCs) were isolated from sheep inguinal and tail fat, in one group of sheep and scaffolds were infiltrated with MSCs in a bioreactor. Controls did not undergo surgery for cell extraction. Scaffolds were implanted into two experimental and two co...
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Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a source of mesenchymal stem cells that have been shown to be beneficial in many regenerative medicine applications. ASCs are an attractive source... more
Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a source of mesenchymal stem cells that have been shown to be beneficial in many regenerative medicine applications. ASCs are an attractive source of stem cells in particular, due to their lack of immunogenicity. This study examines differences between mitochondrial bioenergetic profiles of ASCs isolated from adipose tissue of five peri-organ regions: pericardial, thymic, knee, shoulder, and abdomen. Flow cytometry showed that the majority of each ASC population isolated from the adipose tissue of 12 donors, with an n = 3 for each tissue type, were positive for MSC markers CD90, CD73, and CD105, and negative for hematopoietic markers CD34, CD11B, CD19, and CD45. Bioenergetic profiles were obtained for ASCs with an n = 4 for each tissue type and graphed together for comparison. Mitochondrial stress tests provided the following measurements: basal respiration rate (measured as oxygen consumption ...
Bone remodeling adjacent to orthopedic implants has been attributed to bone strain changes. Although many animal studies have assessed bone remodeling near implants, the altered bone strains and even the strains in the intact bone prior... more
Bone remodeling adjacent to orthopedic implants has been attributed to bone strain changes. Although many animal studies have assessed bone remodeling near implants, the altered bone strains and even the strains in the intact bone prior to implantation have not been mapped extensively. Instead, bone changes are often correlated with implant stiffnesses. In this study, a benchtop loading system was developed using measurements from in vivo strain analysis to simulate physiologic loading of a canine femur. The effect on bone strains of three different stiffness canine hip implants with the same anatomic shape were compared by taking measurements from the proximal greyhound femur during loading. Peak compressive and tensile strains of the order of 200 to 400 microstrain were measured in the intact and implanted femora. The measurements indicate that during simulated in vivo loading, none of the implants substantially alter the normal strain state of the bone. If initial axial strains significantly affect the remodeling response of bone, the similarity of measurements with the different implants in place suggests that the same remodeling response would be expected to both the stiffest and least stiff implant, as has been noted in animal studies adjacent to the intermediate stiffness implant. It also suggests that this implant shape and initial bone implant interface condition can compensate for strain reductions expected near stiff straight-stemmed implants.
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Bone remodeling resulting from implant insertion has been attributed to changes in the bone's strain state. Since remodeling takes several months, it was this study's purpose to develop a long-term in vivo... more
Bone remodeling resulting from implant insertion has been attributed to changes in the bone's strain state. Since remodeling takes several months, it was this study's purpose to develop a long-term in vivo strain sensor. Porous surfaced metal tabs were attached to a standard strain gauge. Two standard gauges and the porous tabbed gauge were attached to one femur and three standard gauges to the contralateral femur of a greyhound. Tissue ingrowth provided an attachment mechanism for the porous tabbed gauge in vivo. Gauge measurements were compared to those from the standard gauges. Post sacrifice testing allowed further comparisons. After histological preparation the femoral section shapes as well as the gauge locations were examined and photographed. The porous tabbed gauge remained bonded and sensed strain throughout the 8-week implantation period, while the standard gauges debonded and were unable to detect strain after 3 weeks. During testing, the measurements from the porous tabbed gauge were lower than those from the standard gauges. This was consistent with the histology which indicated that fibrous tissue had invaded the gauge's porous surface. Although the use of tissue ingrowth as an attachment mechanism seems to be worthwhile, a means of insuring bone ingrowth is necessary.
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Calcium phosphate ceramic (CPC)-coated strain gauges have been used for in vivo bone strain measurements for up to 18 weeks, but they require 6 to 9 weeks for sufficient bonding. Osteogenic protein-1 (OP-1), PepTite (a proprietary... more
Calcium phosphate ceramic (CPC)-coated strain gauges have been used for in vivo bone strain measurements for up to 18 weeks, but they require 6 to 9 weeks for sufficient bonding. Osteogenic protein-1 (OP-1), PepTite (a proprietary ligand), calcium sulfate dihydrate (CSD), transforming growth factor beta-1 (TGF-beta1 ), and an endothelial cell layer with and without TGF-beta1 were used as surface enhancements to accelerate bone-to-CPC bonding. Young male Sprague-Dawley rats were implanted with unenhanced and enhanced CPC-coated gauges. Animals were allowed normal activity for 3 weeks and then calcein labeled. Femurs were explanted following euthanasia. A gauge was attached with cyanoacrylate to the opposite femur in the same position as the CPC-coated gauge. Bones were cantilever-loaded to assess strain transfer. They were sectioned and stained with mineralized bone stain (MIBS) and examined with transmitted and ultraviolet light. Mechanical testing indicated increased sensing accuracy for TGF-beta1 and OP-1 enhancements to 105 +/- 14% and 92 +/- 12% versus 52 +/- 44% for the unenhanced gauges. The PepTite and the endothelial-cell-layer-enhanced gauges showed lower sensing accuracy, and histology revealed a vascular layer near CPC particles. TGF-beta1 increased bone formation when used prior to endothelial cell sodding. CSD prevented strain transfer to the femur. TGF-beta1 and OP-1 surface enhancements produced accurate in vivo strain sensing on the rat femur after 3 weeks.
Research Interests: Biomedical Engineering, Kinetics, Bone Morphogenetic Proteins, Ceramics, Biomedical Materials, and 15 moreFemur, Animals, Male, Calcium Phosphates, Follow-up studies, Mechanical Stress, Rats, Surface Properties, Transforming Growth Factor Beta, ENDOTHELIUM, Materials Testing, Biocompatible Materials, Ligands, Calcium Sulfate, and Strain Gauge
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Subminiature single element and rosette strain gauges used for deformation measurement were prepared for surgical implantation using a technique published previously (Szivek JA, Magee FP. J Invest Surg. 1989; 2: 195-206). During surgery,... more
Subminiature single element and rosette strain gauges used for deformation measurement were prepared for surgical implantation using a technique published previously (Szivek JA, Magee FP. J Invest Surg. 1989; 2: 195-206). During surgery, gauges were placed on the ...
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Bone remodeling resulting from implant insertion has been attributed to changes in the bone's strain state. Since remodeling takes several months, it was this study's purpose to develop a long-term in vivo... more
Bone remodeling resulting from implant insertion has been attributed to changes in the bone's strain state. Since remodeling takes several months, it was this study's purpose to develop a long-term in vivo strain sensor. Porous surfaced metal tabs were attached to a standard strain gauge. Two standard gauges and the porous tabbed gauge were attached to one femur and three standard gauges to the contralateral femur of a greyhound. Tissue ingrowth provided an attachment mechanism for the porous tabbed gauge in vivo. Gauge measurements were compared to those from the standard gauges. Post sacrifice testing allowed further comparisons. After histological preparation the femoral section shapes as well as the gauge locations were examined and photographed. The porous tabbed gauge remained bonded and sensed strain throughout the 8-week implantation period, while the standard gauges debonded and were unable to detect strain after 3 weeks. During testing, the measurements from the porous tabbed gauge were lower than those from the standard gauges. This was consistent with the histology which indicated that fibrous tissue had invaded the gauge's porous surface. Although the use of tissue ingrowth as an attachment mechanism seems to be worthwhile, a means of insuring bone ingrowth is necessary.