The Effects of Postural Loading, Sacral Orientation, and Age on Sex Differences in Lumbar Functional Morphology and Health

Thesis (Ph.D.)--University of Washington, 2016-06

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

Biomechanical performance of polycaprolactone (PCL)-based scaffold with rhBMP-2 in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. Resulting spine deformities include progressive coronal curvature, hypokyphosis, or frank lordosis in the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Problems with bone graft harvest site morbidity as well as limited bone availability have led to the search for bone graft substitutes. Recently, a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone (PCL) has been developed for bone regeneration at load bearing sites. Combined with recombinant human bone morphogenic protein–2 (rhBMP-2), this has been shown to be successful in acting as a bone graft substitute in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft. This in vivo sheep study intends to evaluate the suitability of a custom designed medical grade PCL scaffold in combination with rhBMP-2 as a bone graft substitute in the setting of mini–thoracotomy surgery as a platform for ongoing research to benefit patients with adolescent idiopathic scoliosis.

Histomorphometric and Radiographical Changes After Lumbar Implantation of the PEEK Nonfusion Interspinous Device in the BB.4S Rat Model

Study Design. An experimental animal study. Objective. To investigate histomorphometric and radiographical changes in the BB.4S rat model after PEEK (polyetheretherketone) nonfusion interspinous device implantation. Summary of Background Data. Clinical effectiveness of the PEEK nonfusion spine implant Wallis (Abbott, Bordeaux, France; now Zimmer, Warsaw, IN) is well documented. However, there is a lack of evidence on the long-term effects of this implant on bone, in particular its influence on structural changes of bone elements of the lumbar spine. Methods. Twenty-four male BB.4S rats aged 11 weeks underwent surgery for implantation of a PEEK nonfusion interspinous device or for a sham procedure in 3 groups of 8 animals each: 1) implantation at level L4–L5; 2) implantation at level L5–L6; and 3) sham surgery. Eleven weeks postoperatively osteolyses at the implant-bone interface were measured via radiograph, bone mineral density of vertebral bodies was analyzed using osteodensitometry, and bone mineral content as well as resorption of the spinous processes were examined by histomorphometry. Results. Resorption of the spinous processes at the site of the interspinous implant was found in all treated segments. There was no significant difference in either bone density of vertebral bodies or histomorphometric structure of the spinous processes between adjacent vertebral bodies, between treated and untreated segments and between groups. Conclusion. These findings indicate that resorption of spinous processes because of a result of implant loosening, inhibit the targeted load redistribution through the PEEK nonfusion interspinous device in the lumbar spinal segment of the rat. This leads to reduced long-term stability of the implant in the animal model. These results suggest that PEEK nonfusion interspinous devices like the Wallis implants may have time-limited effects and should only be used for specified indications.

Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery

A bioactive and bioresorbable scaffold fabricated from medical grade poly (epsilon-caprolactone) and incorporating 20% beta-tricalcium phosphate (mPCL–TCP) was recently developed for bone regeneration at load bearing sites. In the present study, we aimed to evaluate bone ingrowth into mPCL–TCP in a large animal model of lumbar interbody fusion. Six pigs underwent a 2-level (L3/4; L5/6) anterior lumbar interbody fusion (ALIF) implanted with mPCL–TCP þ 0.6 mg rhBMP-2 as treatment group while four other pigs implanted with autogenous bone graft served as control. Computed tomographic scanning and histology revealed complete defect bridging in all (100%) specimen from the treatment group as early as 3 months. Histological evidence of continuing bone remodeling and maturation was observed at 6 months. In the control group, only partial bridging was observed at 3 months and only 50% of segments in this group showed complete defect bridging at 6 months. Furthermore, 25% of segments in the control group showed evidence of graft fracture, resorption and pseudoarthrosis. In contrast, no evidence of graft fractures, pseudoarthrosis or foreign body reaction was observed in the treatment group. These results reveal that mPCL–TCP scaffolds could act as bone graft substitutes by providing a suitable environment for bone regeneration in a dynamic load bearing setting such as in a porcine model of interbody spine fusion.

Establishment and characterisation of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model

Background A large animal model is required for assessment of minimally invasive, tissue engineering based approaches to thoracic spine fusion, with relevance to deformity correction surgery for human adolescent idiopathic scoliosis. Here we develop a novel open mini–thoracotomy approach in an ovine model of thoracic interbody fusion which allows assessment of various fusion constructs, with a focus on novel, tissue engineering based interventions. Methods The open mini-thoracotomy surgical approach was developed through a series of mock surgeries, and then applied in a live sheep study. Customized scaffolds were manufactured to conform with intervertebral disc space clearances required of the study. Twelve male Merino sheep aged 4 to 6 years and weighing 35 – 45 kg underwent the abovementioned procedure and were divided into two groups of six sheep at survival timelines of 6 and 12 months. Each sheep underwent a 3-level discectomy (T6/7, T8/9 and T10/11) with randomly allocated implantation of a different graft substitute at each of the three levels; (i) polycaprolactone (PCL) based scaffold plus 0.54μg rhBMP-2, (ii) PCL-based scaffold alone or (iii) autograft. The sheep were closely monitored post- operatively for signs of pain (i.e. gait abnormalities/ teeth gnawing/ social isolation). Fusion assessments were conducted post-sacrifice using Computed Tomography and hard-tissue histology. All scientific work was undertaken in accordance with the study protocol has been approved by the Institute's committee on animal research. Results. All twelve sheep were successfully operated on and reached the allotted survival timelines, thereby demonstrating the feasibility of the surgical procedure and post-operative care. There were no significant complications and during the post-operative period the animals did not exhibit marked signs of distress according to the described assessment criteria. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluation of the respective groups. Conclusion. This novel open mini-thoracotomy surgical approach to the ovine thoracic spine represents a safe surgical method which can reproducibly form the platform for research into various spine tissue engineered constructs (TEC) and their fusion promoting properties.

Comparative effectiveness research across two spine registries

Comparative effectiveness research in spine surgery is still a rarity. In this study, pain alleviation and quality of life (QoL) improvement after lumbar total disc arthroplasty (TDA) and anterior lumbar interbody fusion (ALIF) were anonymously compared by surgeon and implant.

Cordectomía por sustracción pedicular en la columna dorsal y lumbar en fracturas traumáticas: experiencia en el hospital universitario mayor Mederi y revisión sistemática de la literatura

Objetivo: Presentar la experiencia con la técnica de corpectomia por sustracción pedicular en fracturas traumática a nivel de la columna dorsal y Lumbar en el Hospital Universitario Mayor en Bogotá y hacer una revisión sistemática de la literatura de esta técnica quirúrgica. Material y métodos: Se realizó un análisis retrospectivo de las historias clínicas de pacientes que consultaron al servicio de neurocirugía entre los años 2013 y 2015 con fracturas traumáticas a nivel de la columna dorsal y lumbosacra. Se realizó un análisis de déficit neurológico pre y posoperatorio por medio de la Clasificación neurológica estándar de lesión medular (ASIA), al igual que tiempos de cirugía, sangrado intraoperatorio y complicaciones. A su vez se realiza una revisión sistemática de la literatura sobre esta técnica quirúrgica. Resultados: El total de pacientes que se sometieron a cirugía fue de 32, de los cuales el tiempo quirúrgico promedio fue de 396 min, se obtuvo un ASIA prequirúrgico B: 50% C: 47% y E: 3%. El ASIA post operatorio fue de B: 9% C: 47% D: 38% E: 6%. Se obtuvo una mejoría del déficit neurológico en el 75% los pacientes intervenidos. El promedio de sangrado fue de 1,223 cc. Se tuvieron 4 complicaciones, 2 hematomas en lecho quirúrgico que requirió re intervención y dos fistulas de líquido cefalorraquídeo las cuales se manejaron con vendaje compresivo y reposo absoluto. Conclusiones: La corpectomia por sustracción pedicular requiere de un adecuado entrenamiento y un grupo multidisciplinario dentro de los que se incluye neuroanestesiologo, a su vez de neurocirujanos entrenados en columna. Este abordaje presenta grandes beneficios como disminución de tiempos quirúrgicos, disminución de sangrado intraoperatorio y disminución de morbilidad entre otras.

Factores asociados a transfusión sanguínea en el manejo quirúrgico del canal lumbar estrecho en la Fundación Santa Fe de Bogotá 2003 - 2013

Introduccion: El canal lumbar estrecho es un motivo de consulta frecuente en el servicio de columna de la Fundación Santa Fe de Bogotá. Derivado del tratamiento quirurgico se pueden generar múltiples complicaciones, entre las que se encuentra la transfusión sanguínea. Objetivo: Identificar los factores sociodemográficos, antecedentes personales y factores quirúrgicos asociados a transfusión sanguínea en cirugía canal lumbar estrecho en la Fundación Santa Fe de Bogotá 2003- 2013. Materiales y métodos: Se aplicó en diseño de estudio observacional analítico transversal. Se incluyeron 367 pacientes sometidos a cirugía de canal lumbar estrecho a quienes se les analizaron variables de antecedentes personales, características sociodemograficas y factores quirúrgicos. Resultados: La mediana de la edad fue de 57 años y la mayoría de pacientes fueron mujeres (55,6%). La mediana del Índice de Masa Corporal (IMC) fue de 24,9 clasificado como normal. Entre los antecedentes patológicos, la hipertensión arterial fue el más común (37,3%). La mayoría de pacientes (59,1%) presentaron clasificación ASA de II. El tipo de cirugía más prevalente fue el de descompresión (55,6%). En el 79,8% de los pacientes se intervinieron 2 niveles. Se realizó transfusión de glóbulos rojos en 26 pacientes correspondiente a 7,1% del total. En la mayoría de procedimientos quirúrgicos (42,5%) el sangrado fue clasificado como moderado (50-500 ml). En el modelo explicativo transfusión sanguínea en cirugía de canal lumbar estrecho se incluyen: antecedente de cardiopatía (OR 4,68, P 0,034, IC 1,12 – 19,44), Sangrado intraoperatorio >500ml (OR 6,74, p 0,001, 2,09 – 21,74) y >2 niveles intervenidos (OR 3,97, p 0,023, IC 1,20 – 13,09). Conclusión: Como factores asociados a la transfusión sanguínea en el manejo quirúrgico del canal lumbar estrecho a partir de la experiencia de 10 años en la Fundación Santa Fe de Bogotá se encontraron: enfermedad cardiaca, sangrado intraoperatorio mayor de 500ml y más de dos niveles intervenidos.