Osteoarthritis (OA), or degenerative joint disease, burdens approximately 40 million people in th... 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.
Journal of biomedical materials research. Part B, Applied biomaterials, Aug 15, 2016
Two complete unicondylar surface replacement scaffold designs to support tissue-engineered cartil... 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...
Purpose: Develop, validate and apply noninvasive ultrasoundelasticityimaging (UEI) of the human p... 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.
Pre- and poststudy motion and gait analyses of eight size-matched male greyhounds confirmed unifo... 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.
Tendinopathies and tendon tears heal slowly because tendons have a limited blood supply. Intense ... 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 o... 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...
Osteoarthritis (OA), or degenerative joint disease, burdens approximately 40 million people in th... 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.
Journal of biomedical materials research. Part B, Applied biomaterials, Aug 15, 2016
Two complete unicondylar surface replacement scaffold designs to support tissue-engineered cartil... 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...
Purpose: Develop, validate and apply noninvasive ultrasoundelasticityimaging (UEI) of the human p... 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.
Pre- and poststudy motion and gait analyses of eight size-matched male greyhounds confirmed unifo... 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.
Tendinopathies and tendon tears heal slowly because tendons have a limited blood supply. Intense ... 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 o... 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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Papers by John Szivek