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The goal of this research study was to create an artificial annulus fibrosus similar to that of the natural intervertebral disc, as well as find preliminary results for vertebral endplate connection and nucleus pulposus internal pressure, for the correction of disc degeneration in the spine. The three-part composite samples needed to demonstrate good shock absorption and load distribution while maintaining strength and flexibility, and removing the need for metal in the body, something of which no current total disc replacement or spinal fusion surgery can offer. For this study, the spinal disc was separated into its three different components, the annulus fibrosus, the nucleus pulposus, and the vertebral endplates, each playing a vital role in the function of the disc. Two low-cost materials were selected, a Covestro polyurethane and cellulose nanocrystals, for the purpose of creating a polymer composite spinal disc implant. A methodology was established for creating the cast composite material for use as an annulus fibrosus, while also investigating its mechanical properties. The same composite material was used to acquire preliminary results for vertebral endplate connection to the synthesized annulus, however no additional material was used to determine or mimic the mechanical properties of these endplates, due to time constraints. Also because of time constraints, the nucleus used in this study was only comprised of water with no other additives for preliminary testing since the natural nucleus is comprised of about 80-90% water. These properties were then compared to the mechanical properties of the natural disc, so that they could be finely tuned to emulate the natural disc. It is shown in this study that the composite material, when swelled in water, was able to mimic the annulus fibrosus in tensile strength and modulus, however showed higher compressive strength and modulus than ideal. The samples also did not undergo any permanent deformation within the realm of force actually introduced to the natural disc. The vertebral endplates showed decent adhesion to the synthesized annulus, however there were slight defects that became failure concentrators during compression testing. The nucleus showed promising results maintaining good internal pressure to the system causing better compressive load distribution, with barreling of the samples. / Master of Science / Spinal disc degeneration is a very prevalent problem in today’s society, effecting anywhere from 12% to 35% of a given population. It usually occurs in the lumbar section of the spine, and when severe enough, can cause bulging and herniation of the intervertebral disc itself. This can cause immense lower back pain in individual’s stricken with this disease, and in the US, medical costs associated with lower back pain to exceed $100 billion. Current solutions to this problem include multiple different treatment options of which, spinal fusion surgery and total disc replacement (TDR) are among the most common. Although these treatments cause pain relief for the majority of patients, there are multiple challenges that come with these options. For example, spinal fusion surgery severely limits the mobility of its patients by fusing two vertebrae together, disallowing any individual movement, and TDR can cause hypermobility in among the vertebrae and offer little to no shock absorption of loads. Therefore, a better treatment option is needed to relieve the pain of the patients, as well as maintain equal motion, shock absorption, and load cushioning to that of the normal intervertebral disc and remaining biocompatible. The goal of this research study was to create a three-component system, like that of the natural intervertebral disc, for the use of spinal disc replacement and to replace current options. The fabricated system was comprised of the three components found in the natural intervertebral disc; the annulus fibrosus, the nucleus pulposus, and the vertebral endplates. Because the system will need to go in-body, the materials used were all characterized as biocompatible materials; the polyurethane currently being used in medical devices and implants, and the cellulose nanocrystals (CNCs) coming from natural cellulose in sources such as wood and plants. The results determined that the mechanical properties of the system can be fine-tuned in order to mimic the natural strength and cushioning capabilities of the natural disc, based on CNC content added to the polyurethane, and when all three components of the system are added together, the compressive stress-strain is most similar to the natural disc in compression. However, the system did show failure in the connection between the annulus fibrosus and vertebral endplates, causing herniation of the nucleus similar to the initial problem attempting to be solved. For this, more ideal fabrication methods should be researched in the future including 3D printing techniques, injection molding, and roll milling. As well as alternate fabrication techniques, cell grow and viability should be determined to show that cells don’t die once the system in implanted.

Yes / Objective: To better understand the pathogenesis of DISH, identifying early or pre-DISH lesions in the spine and investigating the relationship between spinal and extra-spinal manifestations of DISH. Material: 44 skeletonized individuals with DISH from the WM Bass Donated Skeletal Collection. Methods: For each vertebra, location, extension, point of origin and appearance of vertebral outgrowths were recorded. The size of the enthesophytes at the olecranon process, patella and calcaneal tuberosity was measured with digital callipers. Results: At either end of the DISH-ankylosed segment, isolated vertical outgrowths arising from the central third of the anterior aspect of the vertebral body can usually be observed. These bone outgrowths show a well-organized external cortical layer, an internal structure of trabecular bone and usually are unaccompanied by or show minimal associated endplate degeneration. Analysis of the relationship between spinal and extra-spinal manifestations (ESM) suggests great inter-individual variability. No correlation between any ESM and the stage of spinal DISH was found. Conclusions: Small isolated outgrowths represent the earliest stages of the spinal manifestations of DISH. The use of ESM as an indicator of DISH should be undertaken with great caution until the relationship between these two features is understood. Significance: Improved accuracy of paleopathological diagnostic criteria of DISH. Limitations: Small sample comprised of only individuals with DISH. Future research: micro-CT analysis to investigate the internal structure of the spinal lesions. Analysis of extra-spinal enthesophytes in individuals with and without DISH to understand their pathogenesis and association with the spinal lesions in individuals with DISH. / Institute of Life Sciences Research Studentship awarded by the University of Bradford, Bradford, UK.

Bakgrund: Spinalanestesi är en metod där bedövning läggs intratekalt i ryggraden för att bedöva nedre delen av kroppen i syfte att kunna utföra kirurgiska operationer. Metoden anses kunna sänka vårdkostnader samt minska riskerna för komplikationer jämfört med generell anestesi. Syftet: var att beskriva patienternas perioperativa erfarenheter av spinalanestesi. Metod: En integrativ litteraturstudie med systematisk litteratursökning där 16 artiklar har analyserats enligt Whittmore & Knafl. Resultat: Fyra kategorier identifieras, en känsla av oro och rädsla, upplevelser av förlorad kontroll och sårbarhet, information och stödjande strategier och känslan när allt är över. Patienter beskriver erfarenheter av oro och rädsla i den perioperativa processen samt faktorer som kan upplevas obehagliga och exponerande. Patienter berättar också om hur musik, information och vårdpersonalens bemötande spelar en betydande roll för deras erfarenheter. Slutsats: Patienter beskriver olika erfarenheter av spinalanestesi. Studien betonar vikten av att anestesisjuksköterskan arbetar personcentrerat för att bemöta patienters olika behov och önskemål. / Background: Spinal anaesthesia is a method in which anaesthesia is administrated intrathecally in to the spinal cord. The purpose is to anesthetize the lower body to perform surgery. The method is considered to potentially reduce the cost of healthcare and at the same time decrease the risk of complication when compared with general anaesthesia. Purpose: The aim of the study was to describe patient’s experience of spinal anaesthesia under the perioperative process. Method: An integrative literature review with a systematic search, where 16 articles are analysed according to Whittmore and Knafl. Results: Four categories where identified, feeling of anxiety and fear, experiences of lost control and vulnerability, information and supportive strategies and the feeling when everything is over. Patients describe anxiety and fear in the perioperative process and factors that can contribute to discomfort and exposure. Music, information, and the approach of healthcare staff is considered to play a significant role in the experiences of the patients. Conclusion: Patients describe different experiences of spinal anaesthesia. Studies emphasize the nurse anaesthetist role and the importance of person-centred care in meeting the needs and request of patients.

Thesis advisor: Mary E. Duffy / Ten people with tetraplegic spinal cord injuries participated in a nurse-coached exercise intervention/single subject design study over a period of six months. Four pieces of exercise equipment were used: the RT300S Functional Electrical Stimulation Bike, the VIta Glide, the NuStep TRS 4000, and the Easy Stand Evolv Glider. Measurement of variables of the Manual Muscle Test (MMT), Catz-Itzkovich Spinal Cord Independence Measures (CI-SCIM), and Moorong Self-Efficacy Scale (MSES) were collected at baseline, at three months into the exercise intervention, and at six months (at the conclusion of the intervention). Results were determined by visual analysis of graphs, in keeping with single subject design methods, and statistical analysis of combined data. Of those muscles that demonstrated some strength at baseline, 75% experienced increased strength at three and/or six months into the intervention. Of those muscles that demonstrated no strength at baseline and that were adjacent to muscles that demonstrated some strength at baseline, 66% were found to have increased strength at three and/or six months. Nine of ten participants experienced upward trends in CI-SCIM scores overall (p<.0001). The results of the subscales of Self-Care (p<.0001) and Mobility (p<.0001) indicated statistically significant changes over time. The subscale Respiratory and Sphincter Management was not statistically significant (p>.05). Visual analysis of graphs demonstrated that each of ten participants experienced strong improvements in self-efficacy scores from baseline to three months and from three months to six months into the intervention. R-ANOVA (p<.0001) confirmed statistical significance across ten participants. The Sheehy Spinal Cord Injury Functional Improvement Via Exercise (SCI-FIVE) Model was constructed prior to the study and validated throughout the course of the study. The results of the study validated all components of the Model and demonstrated increased muscle strength, increased self-efficacy, and improved quality of life for the ten study participants who participated in a nurse-coached exercise intervention for people with tetraplegic spinal cord injuries. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

Chondroitin sulfate proteoglycans (CSPGs) are one major class of axon growth inhibitors that are upregulated and accumulated around the lesion site after spinal cord injury (SCI), and result in regenerative failure. To overcome CSPG-mediated inhibition, digestion of CSPGs with chondroitinase ABC (chABC) has been explored and it has shown promising results. chABC digests glycosaminoglycan chains on CSPGs and can thereby enhance axonal regeneration and promote functional recovery when delivered at the site of injury. However, chABC has a crucial limitation; it is thermally unstable and loses its enzymatic activity rapidly at 37 ºC. Therefore, it necessitates the use of repeated injections or local infusions with a pump for days to weeks to provide fresh chABC to retain its enzymatic activity. Maintaining these infusion systems is invasive and clinically problematic. In this dissertation, three studies are reported that demonstrate our strategy to overcome current limitations of using chABC and develop a delivery system for facilitating chABC treatment after SCI: First, we enhanced the thermostability of chABC by adding trehalose, a protein stabilizer, and developed a system for its sustained local delivery in vivo. Enzymatic activity was assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and dimethylmethylene blue (DMMB), and conformational change of the enzyme was measured via circular dichroism (CD) with and without trehalose. When stabilized with trehalose, chABC remained enzymatically active at 37 ºC for up to 4 weeks in vitro. We developed a lipid microtube-agarose hydrogel delivery system for a sustained release and showed that chABC released from the delivery system is still functionally active and slowly released over 2 weeks in vitro. Second, the hydrogel-microtube system was used to locally deliver chABC over two weeks at the lesion site following a dorsal over hemisection injury at T10. The scaffold consisting of hydrogel and chABC loaded lipid microtubes was implanted at the top of the lesion site immediately following injury. To determine effectiveness of topical delivery of thermostabilized chABC, animal groups treated with single injection or gel scaffold implantation of chABC and penicillinase (P'ase) were included as controls. Two weeks after surgery, the functionality of released chABC and the cellular responses were examined by immunohistological analysis with 3B3, CS-56, GFAP and Wisteria floribunda agglutinin (WFA). The results demonstrated that thermostabilized chABC was successfully delivered slowly and locally without the need for an indwelling catheter by using the hydrogel-microtube delivery system in vivo. The results demonstrated that released chABC from the gel scaffold effectively digested CSPGs, and therefore, there were significant differences in CSPG digestion at the lesion site between groups treated with chABC loaded microtube-hydrogel scaffolds and controls. Third, a long term in vivo study (45 days) was conducted to examine axonal sprouting/regeneration and functional recovery with both a single treatment each of microtube loaded chABC or Neurotrophin-3 (NT-3), and a combination of them by using the hydrogel-microtube delivery system. Over the long term study period, the treated animals showed significant improvement in locomotor function and more sprouting of cholera toxin B subunit (CTB)-positive ascending dorsal column fibers and 5-HT serotonergic fibers around the lesion site. We demonstrated that this significant improvement of chABC thermostability facilitates the development of a minimally invasive method for sustained, local delivery of chABC that is potentially a useful and effective approach for treating SCI. In addition to that, we demonstrated that combinatorial therapy with chABC and neurotrophic factors could provide a synergistic effect on axonal regrowth and functional recovery after SCI.

published_or_final_version / Psychiatry / Master / Master of Philosophy