Alex K. Roth

Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects

Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated. We start this review with basic background information on cartilage structure, its intrinsic repair, and an overview of the cartilage repair treatments from a historical perspective. Next, we thoroughly discuss polymer construct components and their current use in commercially available constructs. Finally, we provide an in-depth discussion about construct considerations such as degradation rates, cell sources, mechanical properties, joint homeostasis, and non-degradable/hybrid resurfacing techniques. As future prospects in cartilage repair, we foresee developments in three areas: first, further optimization of degradable scaffolds towards more biomimetic grafts and improved joint environment. Second, we predict that patient-specific non-degradable resurfacing implants will become increasingly applied and will provide a feasible treatment for older patients or failed regenerative treatments. Third, we foresee an increase of interest in hybrid construct, which combines degradable with non-degradable materials.

Large animal models in fusionless scoliosis correction research: a literature review

BACKGROUND CONTEXT Numerous prenatal, systemic, or local procedures have been described that have created an experimental scoliosis within different animal species. Compression-based fusionless scoliosis correction devices have been used to induce scoliosis (inverse approach) as an indication for their potential corrective efficacy in large animals. Deformities that most closely approximate the three-dimensional nature of an idiopathic-like scoliosis have been created in large animals using a posterior spinal tether. Fusionless scoliosis correction devices have subsequently been tested in these models. PURPOSE To provide an overview of large animal models used for preclinical testing of fusionless scoliosis correction devices and to describe recent advances in the creation of an idiopathic-like scoliosis large animal model. STUDY DESIGN Literature review of large animal models in fusionless scoliosis correction research. METHODS MEDLINE electronic database was searched for studies in which large animal models for spinal or vertebral growth modulation or the creation of an experimental scoliosis were described. The literature search was limited to articles written in the English language. RESULTS The pig appears to be the most suitable animal species for preclinical testing of fusionless scoliosis correction devices because of its large growth potential and the possibility for early weaning. With the inverse approach, it is difficult to gain insight into the possible corrective efficacy of the tested device, and therefore, a two-step approach is preferred. Using a posterior spinal tether, persistent spinal deformities are attained when the deformity has approximately doubled in comparison to the postoperative measure in a time span of approximately 12 weeks. Sufficient tether midline offset is required to render rib procedures unnecessary. CONCLUSIONS An idiopathic-like scoliosis animal model can be created using a posterior spinal tether in a fully reversible procedure. Experimental results will need to be reproduced to establish a standard idiopathic-like scoliosis large animal model.

Synthesis and characterization of a new vertebroplasty cement based on gold-containing PMMA microspheres

There are a number of drawbacks to incorporating large concentrations of barium sulfate (BaSO4) as the radiopacifier in PMMA-based bone cements for percutaneous vertebroplasty. These include adverse effects on injectability, viscosity profile, setting time, mechanical properties of the cement and bone resorption. We have synthesized a novel cement that is designed to address some of these drawbacks. Its powder includes PMMA microspheres in which gold particles are embedded and its monomer is the same as that used in commercial cements for vertebroplasty. In comparison to one such commercial cement brand, VertaPlex™, the new cement has longer doughing time, longer injection time, higher compressive strength, higher compressive modulus, and is superior in terms of cytotoxicity. For augmentation of fractured fresh-frozen cadaveric vertebral bodies (T6-L5) using simulated vertebroplasty, results for compressive strength and compressive stiffness of the construct and the percentage of the volume of the vertebral body filled by the cement were comparable for the two cements although the radiopacity of the new cement was significantly lower than that for VertaPlex™. The present results indicate that the new cement warrants further study.

Range of motion in segmental versus nonsegmental ultrahigh molecular weight polyethylene sublaminar wire growth guidance type constructs for early onset scoliosis correction

Study Design. An in vitro biomechanical study in porcine thoracic spine segments comparing range of motion (ROM) in segmental versus multiple nonsegmental ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wire constructs. Objective. To determine the effect of varying instrumentation (wire) density in an UHMWPE sublaminar wire construct for patients with early-onset scoliosis (EOS) to find an optimal wire density, which allows maximum growth whereas still providing adequate correction and fixation. Summary of Background Data. UHMWPE sublaminar wires in a segmental construct did not negatively affect longitudinal spinal growth during a 24-week period in an ovine model; application in growth guidance system for EOS may therefore be feasible. To avoid ectopic bone formation as much as possible, a reduction of instrumented levels, without affecting spinal stabilization, is desirable. Methods. ROM of 9 porcine thoracic spines (T6–T14) was determined in flexion/extension (FE), lateral bending (LB), and axial rotation up to ± 4 Nm. Tests were performed for the uninstrumented spine in a segmental construct with UHMWPE sublaminar wires and dual pedicle screws at the most caudal level, and in four nonsegmental constructs that were attained by stepwise removal of the most caudal wire. Results. Segmental instrumentation led to a decrease in total ROM by approximately 70% for both FE and LB. A stepwise increase in ROM with decreasing number of consecutively instrumented levels was most clearly observed in LB. However, consistent significant but also relevant substantial differences in ROM for both FE and LB were noted only when comparing two and one consecutively instrumented end levels (P < 0.05). Conclusion. A construct with two consecutive end levels instrumented with UHMWPE sublaminar wires seems to provide the best balance between spinal stabilization and minimizing the number of instrumented levels and thereby surgical exposure, which is crucial for allowing longitudinal growth. Level of Evidence: N/A

Novel radiopaque ultrahigh molecular weight polyethylene sublaminar wires in a growth-guidance system for the treatment of early-onset scoliosis: feasibility in a large animal study.

Study Design. In vivo analysis in an ovine model. Objective. To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. Summary of Background Data. Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. Methods. Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. Results. No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5–T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. Conclusion. This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. Level of Evidence: N/ASTUDY DESIGN In vivo analysis in an ovine model. OBJECTIVE To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. SUMMARY OF BACKGROUND DATA Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. METHODS Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. RESULTS No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. CONCLUSION This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. LEVEL OF EVIDENCE N/A.

The Development of a Representative Porcine Early-Onset Scoliosis Model With a Standalone Posterior Spinal Tether

STUDY DESIGN In vivo analysis in a porcine model. OBJECTIVES To develop a porcine experimental scoliosis model representative of early-onset scoliosis (EOS) with the use of a radiopaque ultra-high molecular weight polyethylene (UHMWPE) posterior spinal tether. Large animal experimental scoliosis models with substantial growth potential are needed to test new fusionless scoliosis correction techniques. Previously described scoliosis models involve rib procedures, which violate the thoracic cage and affect subsequent corrective procedures. Models omitting these rib procedures have experienced difficulties in producing persistent three-dimensional structural deformities representative of EOS. METHODS Scoliosis was induced in 14 immature pigs using an asymmetric posterior radiopaque UHMWPE spinal tether fixated to an offset device at lumbar and thoracic levels. Radiographs were taken at 2-week intervals, and frontal and sagittal Cobb angles were measured. A tether release was performed at the 10-week follow-up, and the animals were observed for another 10 weeks. RESULTS Four animals had complications (infections and/or screw breakout) and were excluded from the study. Eight animals developed progressive curves with a mean frontal Cobb angle of 62°. A thoracic lordosis (34°) and a thoracolumbar kyphosis (22°) formed. CT analysis, acquired prior to tether release, showed a mean vertebral rotation of 37° at the apex with a mean vertebral wedge angle of 10°. After tether release, the frontal Cobb angles decreased to 46° at the 20-week follow-up. Sagittal curvature was not substantially affected after tether release. CONCLUSIONS We describe a large animal scoliosis model, which exhibits a substantial deformity in three planes without the use of rib procedures additional to a posterior spinal tether. The created deformities showed persistence after tether release. With the management of infection and enhancement of instrumentation stability, the creation of a valid model for testing new devices in fusionless scoliosis surgery seems feasible. LEVEL OF EVIDENCE Level V.

Reduction of intradiscal pressure by the use of polycarbonate-urethane rods as compared to titanium rods in posterior thoracolumbar spinal fixation

Loss of sagittal alignment and balance in adult spinal deformity can cause severe pain, disability and progressive neurological deficit. When conservative treatment has failed, spinal fusion using rigid instrumentation is currently the salvage treatment to stop further curve progression. However, fusion surgery is associated with high revision rates due to instrumentation failure and proximal junctional failure, especially if patients also suffer from osteoporosis. To address these drawbacks, a less rigid rod construct is proposed, which is hypothesized to provide a more gradual transition of force and load distribution over spinal segments in comparison to stiff titanium rods. In this study, the effect of variation in rod stiffness on the intradiscal pressure (IDP) of fixed spinal segments during flexion-compression loading was assessed. An ex vivo multisegment (porcine) flexion-compression spine test comparing rigid titanium rods with more flexible polycarbonate-urethane (PCU) rods was used. An increase in peak IDP was found for both the titanium and PCU instrumentation groups as compared to the uninstrumented controls. The peak IDP for the spines instrumented with the PCU rods was significantly lower in comparison to the titanium instrumentation group. These results demonstrated the differences in mechanical load transfer characteristics between PCU and titanium rod constructs when subjected to flexion-compression loading. The concept of stabilization with a less rigid rod may be an alternative to fusion with rigid instrumentation, with the aim of decreasing mechanical stress on the instrumented segments and the possible benefit of a decrease in the incidence of screw pullout.Graphical abstract

Novel Radiopaque Ultrahigh Molecular Weight Polyethylene Sublaminar Wires in a Growth-Guidance System for the Treatment of Early-Onset Scoliosis

Study Design. In vivo analysis in an ovine model. Objective. To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. Summary of Background Data. Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. Methods. Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. Results. No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5–T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. Conclusion. This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. Level of Evidence: N/ASTUDY DESIGN In vivo analysis in an ovine model. OBJECTIVE To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. SUMMARY OF BACKGROUND DATA Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. METHODS Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. RESULTS No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. CONCLUSION This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. LEVEL OF EVIDENCE N/A.