Fu, Sai Chuen. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 173-195). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendixes includes Chinese.

Anterior cruciate ligament (ACL) rupture is a major clinical problem in sports medicine. The current mainstay of treatment is arthroscopic-assisted ACL reconstruction with a soft tissue tendon graft. However, the affected patients are required to abstain from any pivoting activity for at least six to nine months after the operation to protect the graft-host bone interface in order to allow the graft to heal. In this study, a method to accelerate the graft healing within the bone tunnel is proposed by using a local application of an osteoconductive bone cement (Strontium enriched calcium phosphate cement, Sr-CPC) at the graft-host bone interface. It is postulated that Sr-CPC can induce earlier new bone formation in the gap between the graft and host bone tunnel and hence can result in an accelerated healing of the graft within the bone tunnel in ACL reconstruction. Preparation of Sr-CPCs using the conventional setting method (a dissolution/precipitation process) leads to a delay in setting. This study adopted a new setting reaction, a chelate reaction, to manufacture a Sr-CPC system. The Sr-CPC system was fast-setting, injectable and cohesive, and it was suitable for use in minimally invasive orthopaedics surgeries (e.g. arthroscopic-assisted ACL reconstruction). In order to investigate the biocompatibility and osteoconductivity of the Sr-CPC, in vitro cell experiments and an in vivo animal study were carried out. The in vitro experiments showed that the Sr-CPC was biocompatible with no local toxicity. In addition, a higher proliferation rate of osteoblastic-like MG-63 cells, accompanying higher alkaline phosphatase activity, was found in the Sr-CPC group. The in vivo study using a rat femur metaphyseal bone defect model showed evidence of earlier endochondral ossification which was noted at 2 weeks post operation. Moreover, a higher peri-cement bone formation rate, accompanied by a higher cement resorption rate, was found in the Sr-CPC group at 32 weeks after the operation compared with the convention calcium phosphate cement group. To study the effect of the Sr-CPC on the graft healing within the bone tunnel, a one-stage bilateral ACL reconstruction using an Achilles tendon allograft was performed in 30 rabbits. One study (15 rabbits) was to investigate the effect of the Sr-CPC on the healing of a soft tissue tendon graft within the bone tunnel, and the other study (15 rabbits) was to study the difference between the Sr-CPC and the conventional CPC in the healing of a soft tissue tendon graft within the bone tunnel. The Sr-CPC treated graft showed an accelerated healing at all of the time points when compared with the non-treated graft; and at time points of 3 to 12 weeks when compared with the CPC treated graft. In conclusion, a strontium enriched calcium phosphate cement, which is suitable for the arthroscopic use, was manufactured. It is biocompatible, osteoconductive and degradable. It accelerates the graft healing within the bone tunnels in a rabbit ACL reconstruction model using an Achilles tendon allograft when compared with both of the non-treated group and the conventional CPC-treated group. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

The anterior cruciate ligament (ACL) is the most frequently injured ligament of the knee, with upwards of 100,000 ACL reconstructions performed annually. Current grafting techniques are limited by insufficient integration with subchondral bone and donor site morbidity issues related to graft harvest, potentially resulting in revision surgery and long-term joint pain. Therefore, significant demand exists for alternative grafting solutions that do not require additional surgery and can regenerate the native ACL-to-bone interface to promote biological fixation of the implanted ACL graft. To address this need, the ideal system must be able to withstand the functional demands of the native tissue by demonstrating physiologically equivalent mechanical properties, be comprised of compositionally varying phases in order to recapitulate the inherent heterogeneity of the native ligament to bone transition and be biodegradable such that it is gradually replaced by the regenerated tissue following implantation. It is hypothesized that a biomimetic, multi-phased scaffold comprised of optimized bone, interface and ligament regions coupled with controlled chemical and/or mechanical stimulation in vitro will guide phase-specific differentiation of mesenchymal stem cells (MSC) and result in a biologically integrated bone-ligament-bone complex in vivo. Mesenchymal stem cells are particularly attractive for this application as they can be routinely harvested from bone marrow, have been shown to respond to chemical, mechanical and structural cues, and are capable of differentiating towards the primary cell types (fibroblasts, osteoblasts and chondrocytes) found within ligament, bone and the ligament-to-bone interface. To this end, a nanofiber-based synthetic graft was designed with compositionally-varying phases to regenerate ligament, bone and interface tissues. The ligament phase was optimized in terms of nanofiber alignment, composition, mechanical stimulation and chemical stimulation. It was demonstrated that an aligned nanofiber substrate coupled with controlled mechanical stimulation was necessary to differentiate MSCs towards a fibroblastic phenotype. The bone phase was optimized in terms of ceramic content and it was shown that a threshold of mineral incorporation into nanofibers was necessary to differentiate MSCs towards an osteogenic phenotype. Lastly, a mechanoactive nanofiber collar was designed to induce interface formation. It was demonstrated that compressive stimulation applied via nanofiber collar contraction induced chondrogenic differentiation of MSCs. Subsequently, the three phases were incorporated to form a synthetic graft, for which graft architecture and cell seeding density were optimized. The resulting graft was cultured in vitro under the optimized parameters, demonstrating the formation of distinct and structurally continuous regions of bone, interface and ligament tissue. The graft was implanted in vivo where it was shown to be suitable for ACL reconstruction as it maintained knee stability and promoted ligament regeneration. In summary, this thesis focuses on the design of a biomimetic, nanofiber-based, integrated bone-ligament-bone construct, and elucidates chemical, mechanical and scaffold design-related parameters that can guide MSC differentiation towards desired tissue types. The impact of these studies extends beyond ligament reconstruction as they yield valuable scaffold design criteria, establish scaffold and culturing-related parameters to induce stem cell differentiation and can readily be applied to the formation of interfaces between soft-to-hard tissues as well as other complex tissues.

O autor estudou as propriedades biomecânicas dos tendões dos músculos tibial anterior e tibial posterior congelados a -20°C e a -86°C extraídos de cadáveres humanos frescos. Foram realizados ensaios mecânicos de tração até a ruptura e determinadas as seguintes propriedades: resistência máxima, coeficiente de rigidez, módulo de elasticidade e alongamento máximo relativo. Os dados obtidos foram comparados aos existentes na literatura relativos ao ligamento cruzado anterior, ligamento da patela e aos tendões dos músculos grácil e semitendíneo / The author studied the mechanical properties of the anterior and posterior tibialis muscle tendons frozen at -20°C and -86°C obtained from fresh-frozen human cadavers. The tendons were submitted to axial traction until failure and the following properties were determined: ultimate load, stiffness, modulus of elasticity and relative strain. Data obtained were compared to those from the literature related to the anterior cruciate ligament, patellar tendon, gracilis and semitendinous tendons

O autor estudou as propriedades biomecânicas dos tendões dos músculos tibial anterior e tibial posterior congelados a -20°C e a -86°C extraídos de cadáveres humanos frescos. Foram realizados ensaios mecânicos de tração até a ruptura e determinadas as seguintes propriedades: resistência máxima, coeficiente de rigidez, módulo de elasticidade e alongamento máximo relativo. Os dados obtidos foram comparados aos existentes na literatura relativos ao ligamento cruzado anterior, ligamento da patela e aos tendões dos músculos grácil e semitendíneo / The author studied the mechanical properties of the anterior and posterior tibialis muscle tendons frozen at -20°C and -86°C obtained from fresh-frozen human cadavers. The tendons were submitted to axial traction until failure and the following properties were determined: ultimate load, stiffness, modulus of elasticity and relative strain. Data obtained were compared to those from the literature related to the anterior cruciate ligament, patellar tendon, gracilis and semitendinous tendons

OBJETIVO: comparar a técnica de reconstrução convencional do LCA com enxerto patelar e feixe único com a técnica com enxerto patelar bipartido e quatro túneis ósseos, através de um estudo experimental biomecânico em joelhos de cadáveres com testes pareados, sem variação na quantidade de enxerto utilizada em ambas as técnicas. INTRODUÇÃO: As lesões do ligamento cruzado anterior (LCA) do joelho são comuns principalmente na prática esportiva, e o tratamento cirúrgico de reconstrução com o uso de enxertos autólogos, pelos bons resultados alcançados, um consenso na literatura mundial. As controvérsias ficam por conta das variações que podem apresentar a técnica deste procedimento, na busca constante pelo aperfeiçoamento da mesma. Uma delas encontra-se na troca da tradicional reconstrução de feixe único do LCA pela reconstrução dos dois feixes, visando uma maior semelhança com a anatomia do LCA original. Recentemente a tendência nesta técnica é pela passagem dos enxertos por dois túneis femorais e dois túneis tibiais. MÉTODOS: Nosso estudo foi realizado em joelhos de cadáveres (18 joelhos de 9 cadáveres), todos do sexo masculino, com idade variando entre 44 e 63 anos. Estas peças foram divididas aleatóriamente, sempre em pares, nos grupos A, de joelhos operados com a técnica de reconstrução do LCA com único feixe, e grupo B, de joelhos operados com a técnica de reconstrução com duplo feixe e quatro túneis ósseos. Cada espécime foi submetido a testes biomecânicos nas condições LCA íntegro, lesado e operado, com registro de dados de Deslocamento Anterior Máximo (DTAM), Rigidez Média (R) e Rotação Tibial Interna Passiva (RIT), sob força de 100N de deslocamento tibial horizontal, a 30°,60° e 90° de flexão dos joelhos. RESULTADOS: Não houve diferenças significativas, pelo método de Análise de Variância de grupos, entre as duas técnicas tanto para medidas de DTAM em 30°(p=0,47), 60°(p=0,59), 90°(p=0,27); como para R em 30° (p=0,93), 60° (p=0,97), 90° (p=0,45); e RIT em 30° (p= 0,59), 60° (p=0,67) e 90° (p=0,74). CONCLUSÕES: Em nosso estudo, a técnica de reconstrução dos dois feixes do LCA com enxerto patelar e quatro túneis tem comportamento biomecânico semelhante ao da reconstrução do LCA com enxerto patelar de feixe único, sob os aspectos de deslocamento anterior tibial, rigidez e rotação tibial passiva, durante o movimento de deslocamento anterior tibial com força constante / PURPOSES: Test an anatomical double bundle reconstruction technique with a longitudinally split bone-patellar tendon-bone graft through double femoral and tibial tunnels and biomechanically compare it to conventional single bundle reconstruction with the same total amount of bone-patelar tendon-bone graft in a paired experimental cadaver study. INTRODUCTION: Anterior Cruciate Ligament ruptures are frequent especially in sports practice. Surgical reconstruction with autologous grafts widely employed in international literature. Controversies remain in respect to technique variations as continuous research for improvement takes place. One these are the anatomical double bundle techniques instead of conventional single bundle (antero-medial bundle) technique. More recently there is a tendency of positioning of the two bundles through double tunnel technique in the femur and the tibia. METHODS: Nine pairs of male cadaver knees, age ranging from 44 to 63 years were randomized into 2 groups, (A) single bundle reconstruction and (B) anatomical double bundle reconstruction through double femoral and double tibial tunnels. Each knee was biomechanically tested in 3 conditions: intact ACL, sectioned ACL and reconstructed ACL. Maximum anterior dislocation, rigidity and passive internal tibia rotation were recorded with the knee submitted to a 100N horizontal anterior dislocation force applied to the tibia with the knee in 30º, 60º and 90º of flexion. RESULTS: There were no differences between the two techniques for any of the measurements. CONCLUSIONS: The technique of anatomical double bundle reconstruction of the anterior cruciate ligament with bone-patellar tendon-bone graft has a similar biomechanical behavior in regard to anterior tibial dislocation, rigidity and passive internal tibial rotation.

ACL injuries are ubiquitous and the literature surrounding ACL reconstructions is complex and difficult to comprehend. In summary, this paper provides a simple yet coherent overview of ACL injuries. Etiology, prevention, and the consequences of injury are discussed. The paper examines literature surrounding the decision to reconstruct the anterior cruciate ligament. An overwhelming quantity of literature is in favor of an ACL reconstruction in order to maintain an active lifestyle. ACL surgery has advanced exponentially in recent years and there is a multitude of fixation and tunneling methods. Graft choice for an ACL reconstruction is also complicated and multifactorial. In general, three types of grafts exist: autografts, allografts, and synthetic grafts. Autografts usually include the hamstring tendon (HT) and patella tendon (BTB), however, recent studies suggest the quadricep tendon (QT) may be a suitable graft. The BTB is often considered the “gold standard” due to its strength and stability. On the other hand, the HT is often used as it is less invasive and is associated with less antero-patellar knee pain. Common allografts include the patella tendon, Achilles tendon, and tibialis muscle group. Despite a higher cost, allografts are usually used in revision surgeries and leave patients with less donor-site morbidity. Lastly, synthetic grafts are growing in popularity, especially the LARS procedure, however, more research is needed. Lastly, this paper attempts to consolidate literature surrounding the QT graft. Only one meta-analysis focusing on the QT has been published, however, the last meta-analysis is from three years ago and several new studies have been published since. The recent literature suggests the QT is a viable option in terms of stability and functional outcomes. Specifically, when comparing the QT to BTB and HT, the QT grades similarity in KT-1000 scores, a common measure of knee laxity and stability. Additionally, IKDC scores, frequently used to assess functionality, show positive results. More literature is needed to fully understand the QT; however, preliminary research indicates the QT can be an esteemed option in ACL reconstruction surgery.

OBJETIVO: comparar a técnica de reconstrução convencional do LCA com enxerto patelar e feixe único com a técnica com enxerto patelar bipartido e quatro túneis ósseos, através de um estudo experimental biomecânico em joelhos de cadáveres com testes pareados, sem variação na quantidade de enxerto utilizada em ambas as técnicas. INTRODUÇÃO: As lesões do ligamento cruzado anterior (LCA) do joelho são comuns principalmente na prática esportiva, e o tratamento cirúrgico de reconstrução com o uso de enxertos autólogos, pelos bons resultados alcançados, um consenso na literatura mundial. As controvérsias ficam por conta das variações que podem apresentar a técnica deste procedimento, na busca constante pelo aperfeiçoamento da mesma. Uma delas encontra-se na troca da tradicional reconstrução de feixe único do LCA pela reconstrução dos dois feixes, visando uma maior semelhança com a anatomia do LCA original. Recentemente a tendência nesta técnica é pela passagem dos enxertos por dois túneis femorais e dois túneis tibiais. MÉTODOS: Nosso estudo foi realizado em joelhos de cadáveres (18 joelhos de 9 cadáveres), todos do sexo masculino, com idade variando entre 44 e 63 anos. Estas peças foram divididas aleatóriamente, sempre em pares, nos grupos A, de joelhos operados com a técnica de reconstrução do LCA com único feixe, e grupo B, de joelhos operados com a técnica de reconstrução com duplo feixe e quatro túneis ósseos. Cada espécime foi submetido a testes biomecânicos nas condições LCA íntegro, lesado e operado, com registro de dados de Deslocamento Anterior Máximo (DTAM), Rigidez Média (R) e Rotação Tibial Interna Passiva (RIT), sob força de 100N de deslocamento tibial horizontal, a 30°,60° e 90° de flexão dos joelhos. RESULTADOS: Não houve diferenças significativas, pelo método de Análise de Variância de grupos, entre as duas técnicas tanto para medidas de DTAM em 30°(p=0,47), 60°(p=0,59), 90°(p=0,27); como para R em 30° (p=0,93), 60° (p=0,97), 90° (p=0,45); e RIT em 30° (p= 0,59), 60° (p=0,67) e 90° (p=0,74). CONCLUSÕES: Em nosso estudo, a técnica de reconstrução dos dois feixes do LCA com enxerto patelar e quatro túneis tem comportamento biomecânico semelhante ao da reconstrução do LCA com enxerto patelar de feixe único, sob os aspectos de deslocamento anterior tibial, rigidez e rotação tibial passiva, durante o movimento de deslocamento anterior tibial com força constante / PURPOSES: Test an anatomical double bundle reconstruction technique with a longitudinally split bone-patellar tendon-bone graft through double femoral and tibial tunnels and biomechanically compare it to conventional single bundle reconstruction with the same total amount of bone-patelar tendon-bone graft in a paired experimental cadaver study. INTRODUCTION: Anterior Cruciate Ligament ruptures are frequent especially in sports practice. Surgical reconstruction with autologous grafts widely employed in international literature. Controversies remain in respect to technique variations as continuous research for improvement takes place. One these are the anatomical double bundle techniques instead of conventional single bundle (antero-medial bundle) technique. More recently there is a tendency of positioning of the two bundles through double tunnel technique in the femur and the tibia. METHODS: Nine pairs of male cadaver knees, age ranging from 44 to 63 years were randomized into 2 groups, (A) single bundle reconstruction and (B) anatomical double bundle reconstruction through double femoral and double tibial tunnels. Each knee was biomechanically tested in 3 conditions: intact ACL, sectioned ACL and reconstructed ACL. Maximum anterior dislocation, rigidity and passive internal tibia rotation were recorded with the knee submitted to a 100N horizontal anterior dislocation force applied to the tibia with the knee in 30º, 60º and 90º of flexion. RESULTS: There were no differences between the two techniques for any of the measurements. CONCLUSIONS: The technique of anatomical double bundle reconstruction of the anterior cruciate ligament with bone-patellar tendon-bone graft has a similar biomechanical behavior in regard to anterior tibial dislocation, rigidity and passive internal tibial rotation.

Osteoarthritis (OA) of the knee, a musculoskeletal disease characterized by degenerations in multiple joint tissues including the articular cartilage and subchondral bone, is a major clinical challenge worldwide that currently has no cure. Traumatic knee injuries such as anterior cruciate ligament (ACL) tear predispose subjects to early onset of post-traumatic OA (PTOA), necessitating the development of effective disease modifying therapies as total knee replacement surgeries have a limited lifetime. Significant knowledge gap remains in the pathogenesis of OA, while recent evidence suggests the important role of subchondral bone microstructure and mechanics in OA development. Subchondral bone is composed of the subchondral bone plate, a thin layer of cortical lamella, and the subchondral trabecular bone, composed of individual plate-like and rod-like trabeculae. These trabecular plates and rods determine the microstructure and mechanics of trabecular bone entirely and can be quantitatively analyzed using individual trabecula segmentation (ITS). Recent application of ITS showed that changes in the plate-and-rod microstructure of subchondral trabecular bone precede cartilage damage and are implicated to play a role in disease pathogenesis. Studies presented in this thesis aim to provide a deeper understanding of subchondral bone in knee OA scientifically and clinically, which may ultimately be used to improve diagnosis, prevention and treatment of this prevalent and disabling disease. In the first study, we comprehensively quantified microstructural and tissue biomechanical properties of the subchondral bone and articular cartilage in human knee specimens with advanced OA and control knees without OA. We found reduced tissue modulus in trabecular plates and rods in regions with moderate OA, where cartilage is still intact, that persisted in severe OA regions, where cartilage is severely damaged. These observations suggest that tissue biomechanical changes in the subchondral trabecular bone may precede cartilage damage in OA development. Furthermore, we found strong correlations between structural and mechanical parameters of the cartilage and subchondral bone in CT knees, suggesting cross-talk at the tissue level. This coupling persisted in moderate OA regions but disappeared in severe OA regions, suggesting that loss of tissue crosstalk may be an additional indicator of disease progression. In the second study, we quantified subchondral bone microstructural changes after ACL tear in vivo in human subjects using the second-generation high resolution peripheral quantitative computed tomography (HR-pQCT). We examined short-term longitudinal changes during the acute phase (~18 days to ~141 days) after injury, as well as long-term adaptations (~5 years post injury) in the injured knee relative to the contralateral knee in a cross-sectional cohort. We found subchondral bone loss within 1 month from injury that primarily targeted trabecular rods, especially at the distal femur. We also found increased spatial heterogeneity in subchondral trabecular microstructure within the injured knees compared to the contralateral knees in the long-term after injury. These findings indicate that ACL tear results in both short-term and long-term microstructural adaptations in the subchondral bone. ITS based on HR-pQCT knee scans may be a valuable tool to monitor disease progression in vivo. Finally, we quantified subchondral bone microstructural changes after ACL-transection in a canine model of PTOA and investigated the effects of bisphosphonate and NSAID treatment on subchondral bone changes and OA progression. Studies were conducted in skeletally-mature and juvenile animals to investigate the effect of injury age. We found that subchondral bone adaptations after surgery and treatment effects depended on skeletal maturity of animals. In mature animals, changes in the microstructure of trabecular plates and rods occurred 1-month post-op and persisted until 8-months post-op. Bisphosphonate treatment attenuated these microstructural changes and cartilage degeneration while NSAID treatment did not. In juvenile animals that have not reached skeletal maturity, transient changes in trabecular plate and rod microstructure occurred at 3-months post-op but disappeared by 9-months post-op. Neither bisphosphonate nor NSAID treatment attenuated bone microstructural changes or cartilage damages. These findings suggest that age and skeletal maturity at time of injury may need to be considered as additional factors in studying PTOA progression and developing preventative treatments. Taken together, these studies highlight the importance of microstructural and tissue biomechanical changes of subchondral bone in the development of OA. In vivo quantification of subchondral bone using advanced imaging modalities enable longitudinal monitoring of disease progression. Therapeutic agents targeting subchondral bone changes after traumatic injury may be effective preventative strategies for PTOA.

Thesis (MScPhysio (Physiotherapy))--University of Stellenbosch, 2010. / Patients’ knowledge about the effectiveness of interventions is now recognized as an important facilitator of the implementation of evidence in practice. Evidence-based, patient education programs aim to impart knowledge about the efficacy and effectiveness about interventions to individuals. However, there is currently a lack of structured evidence-based educational programs to educate patients about the evidence-base for interventions prescribed by the health professionals in the field of orthopaedics. OBJECTIVE: The main objective of this study was to develop and validate an Arabic version of an evidence-based educational program for patients who are scheduled to undergo ACL reconstruction surgery in UAE, based on available evidence collated through a systematic review process. METHODS: A systematic review was conducted to generate clinical recommendations which were used to develop the evidence-based educational program. The evidence-based information was derived from secondary research to determine which rehabilitation strategies were most effective in improving outcome measurements following ACL reconstruction surgery. A pre-final draft of the evidence-based educational program was prepared and forward and back translated from English into the Arabic language. Feedback groups of ACL patients and physiotherapists were used to determine the content and face validity of the program. The final draft was validated in a group of 40 ACL patients waiting to undergo ACL reconstruction surgery at Zayed Military hospital and Abu Dhabi Knee and Sports Medicine Centre in the UAE, using checklists. RESULTS: A total of 40 patients undergoing ACL reconstruction surgery consented to participate in this study. All the subjects were male. The age range was between 18 to 38 years old with mean age of 28.5 years (SD 5.75). Most of the patients (65%) underwent ACL reconstruction surgery to the right knee. Of the total sample (n=40), the majority of the subjects who participated in this study (90 %), had ACL surgery for the first time. Most of the responses to the evidence-based educational program checklist were positive. iv CONCLUSION: It can be recommended that the newly-developed evidence-based educational program is a valid tool which can be given to ACL patients prior to ACL reconstruction to prepare them for the rehabilitation postoperatively. By informing patients of their condition, the expected outcomes of their condition and the effect of doing exercises to improve their condition, the patients will be more encouraged to partake in rehabilitation, as they know it is for their own good. This will ultimately improve overall patient care and improve management of ACL patients.