Scaffold-guided bone regeneration in large volume tibial segmental defects.

Large volume losses in weight bearing long bones are a major challenge in clinical practice. Despite multiple innovations over the last decades, significant limitations subsist in current clinical treatment options which is driving a strong clinical demand for clinically translatable treatment alternatives, including bone tissue engineering applications. Despite these shortcomings, preclinical large animal models of large volume segmental bone defects to investigate the regenerative capacity of bone tissue engineering strategies under clinically relevant conditions are rarely described in literature. We herein present a newly established preclinical ovine animal model for the treatment of XL volume (19 cm3) segmental tibial defects. In eight aged male Merino sheep (age > 6 years) a mid-diaphyseal tibial segmental defect was created and stabilized with a 5.6 mm Dynamic Compression Plate (DCP). We present short-term (3 months) and long-term (12-15 months) results of a pilot study using medical grade Polycaprolactone-Tricalciumphosphate (mPCL-TCP) scaffolds combined with a dose of 2 mg rhBMP-7 delivered in Platelet-Rich- Plasma (PRP). Furthermore, detailed analyses of the mechanical properties of the scaffolds as well as interfragmentary movement (IFM) and DCP-surface strain in vitro and a comprehensive description of the surgical and post-surgery protocol and post-mortem analysis is given.

Early mechanical stimulation only permits timely bone healing in sheep.

Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790-1796, 2018.

Risk Factors for Knee Injury in Golf: A Systematic Review.

BACKGROUND: Golf is commonly considered a low-impact sport that carries little risk of injury to the knee and is generally allowed following total knee arthroplasty (TKA). Kinematic and kinetic studies of the golf swing have reported results relevant to the knee, but consensus as to the loads experienced during a swing and how the biomechanics of an individual's technique may expose the knee to risk of injury is lacking. OBJECTIVES: Our objective was to establish (1) the prevalence of knee injury resulting from participation in golf and (2) the risk factors for knee injury from a biomechanical perspective, based on an improved understanding of the internal loading conditions and kinematics that occur in the knee from the time of addressing the ball to the end of the follow-through. METHODS: A systematic literature search was conducted to determine the injury rate, kinematic patterns, loading, and muscle activity of the knee during golf. RESULTS: A knee injury prevalence of 3-18% was established among both professional and amateur players, with no clear dependence on skill level or sex; however, older players appear at greater risk of injury. Studies reporting kinematics indicate that the lead knee is exposed to a complex series of motions involving rapid extension and large magnitudes of tibial internal rotation, conditions that may pose risks to the structures of a natural knee or TKA. To date, the loads experienced by the lead knee during a golf swing have been reported inconsistently in the literature. Compressive loads ranging from 100 to 440% bodyweight have been calculated and measured using methods including inverse dynamics analysis and instrumented knee implants. Additionally, the magnitude of loading appears to be independent of the club used. CONCLUSIONS: This review is the first to highlight the lack of consensus regarding knee loading during the golf swing and the associated risks of injury. Results from the literature suggest the lead knee is subject to a higher magnitude of stress and more demanding motions than the trail knee. Therefore, recommendations regarding return to golf following knee injury or surgical intervention should carefully consider the laterality of the injury.

A cadaveric biomechanical study comparing the ease of femoral nail insertion: 1.0- vs 1.5-m bow designs.

INTRODUCTION: Anatomic fit of intramedullary nails was suggested by previous studies to improve significantly when the nail radius of curvature (ROC) is closer to the average femoral anatomy. However, no attempt has been made to investigate the impact of different ROC designs on the nail insertion process. Therefore, this biomechanical study quantitatively compared the ease of insertion between femoral intramedullary nails with a 1.0-m and a 1.5-m bow radius. MATERIALS AND METHODS: Long TFN-ADVANCED™ (TFNA, 1.0 m ROC) and Proximal Femoral Nail Antirotation nails (PFNA, 1.5 m ROC) were implanted pairwise into seven paired cadaver femora. All bones were reamed 1.5 mm larger than the nail diameter. Using a material testing machine, intramedullary nailing was then performed stepwise with 20-mm steps and a 10-mm/s insertion rate, and force was measured. The nail deformation caused by the insertion was assessed through 3D computer models built from pre- and post-nailing CT scans. The ease of insertion between TFNA and PFNA nails was quantified in terms of insertion force, insertion energy and nail deformation. RESULTS: There was no significant difference in the peak force generated during nailing between TFNA and PFNA nails (P = 0.731). However, the force measured at the end of insertion (P = 0.002) was significantly smaller in TFNA nails compared to PFNA nails. After implantation, TFNA nails showed significantly smaller deformation when compared to PFNA nails (P = 0.005, both ends aligned). Furthermore, less energy was required to insert TFNA nails; however, the difference was not significant (P = 0.25). CONCLUSIONS: Compared to PFNA nails, a significant decrease in insertion force and nail deformation was found at the end of insertion for TFNA nails. Results suggest that TFNA having a 1.0-m ROC is easier to insert for the set of femora used in this study compared to PFNA with a 1.5-m ROC.

Mechanical testing of internal fixation devices: A theoretical and practical examination of current methods.

Successful healing of long bone fractures is dependent on the mechanical environment created within the fracture, which in turn is dependent on the fixation strategy. Recent literature reports have suggested that locked plating devices are too stiff to reliably promote healing. However, in vitro testing of these devices has been inconsistent in both method of constraint and reported outcomes, making comparisons between studies and the assessment of construct stiffness problematic. Each of the methods previously used in the literature were assessed for their effect on the bending of the sample and concordant stiffness. The choice of outcome measures used in in vitro fracture studies was also assessed. Mechanical testing was conducted on seven hole locked plated constructs in each method for comparison. Based on the assessment of each method the use of spherical bearings, ball joints or similar is suggested at both ends of the sample. The use of near and far cortex movement was found to be more comprehensive and more accurate than traditional centrally calculated interfragmentary movement values; stiffness was found to be highly susceptible to the accuracy of deformation measurements and constraint method, and should only be used as a within study comparison method. The reported stiffness values of locked plate constructs from in vitro mechanical testing is highly susceptible to testing constraints and output measures, with many standard techniques overestimating the stiffness of the construct. This raises the need for further investigation into the actual mechanical behaviour within the fracture gap of these devices.

Comparison of mechanical and ultrasound elastic modulus of ovine tibial cortical bone.

Finite element models of bones can be created by deriving geometry from an X-ray CT scan. Material properties such as the elastic modulus can then be applied using either a single or set of homogeneous values, or individual elements can have local values mapped onto them. Values for the elastic modulus can be derived from the CT density values using an elasticity versus density relationship. Many elasticity-density relationships have been reported in the literature for human bone. However, while ovine in vivo models are common in orthopaedic research, no work has been done to date on creating FE models of ovine bones. To create these models and apply relevant material properties, an ovine elasticity-density relationship needs to be determined. Using fresh frozen ovine tibias the apparent density of regions of interest was determined from a clinical CT scan. The bones were the sectioned into cuboid samples of cortical bone from the regions of interest. Ultrasound was used to determine the elastic modulus in each of three directions - longitudinally, radially and tangentially. Samples then underwent traditional compression testing in each direction. The relationships between apparent density and both ultrasound, and compression modulus in each direction were determined. Ultrasound testing was found to be a highly repeatable non-destructive method of calculating the elastic modulus, particularly suited to samples of this size. The elasticity-density relationships determined in the longitudinal direction were very similar between the compression and ultrasound data over the density range examined. A clear difference was seen in the elastic modulus between the longitudinal and transverse directions of the bone samples, and a transverse elasticity-density relationship is also reported.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae.

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with ß-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.