Ring Constructs Research Articles

Technical Trick: T-Bar External Fixator for Definitive Management of Periarticular and Metadiaphyseal Tibial Fractures

Purpose: Tibia fractures with soft tissue compromise present are challenging to manage. For fractures with significant swelling or open injury not amenable to internal stabilization, external fixators provide sufficient stability for bony healing. Ring fixators and hybrid constructs provide adequate stability for healing but are costly, and challenging to apply and maintain. We present the “T-bar” external fixator, a novel construct that can be maintained until bony union and allows for range of motion of adjacent joints. We also report the demographics, clinical, and radiographic outcomes of 34 patients treated definitively with this construct. Materials and Methods: The T-bar external fixator uses standard pins and bars in a novel arrangement. It can be applied for Arbeitsgemeinshaft fur Osteosynthesefragen/Orthopaedic Trauma Association-type 41/42/43 type injuries, with or without supplemental fixation for intra-articular patterns. Results: Between 2008 and 2015, 34 patients were treated for tibia fracture with T-bar external fixation, with intention to treat in a definitive manner. Twenty-nine were male, and average age was 44.3 years. Thirty-one sustained high energy mechanisms of injury. Twenty were Gustilo-type 2 or 3 fractures. Of 14 closed fractures, 12 were Tscherne-type 2 or 3. Conclusions: The T-bar external fixator offers an alternative to ring and hybrid external fixator constructs in treatment of tibia fractures with significant soft tissue compromise. Of 28 patients with complete follow up, only 1 case of osteomyelitis was reported. All patients were managed without amputation. Three required revision for nonunion, all Arbeitsgemeinshaft fur Osteosynthesefragen/Orthopaedic Trauma Association-type 43.

Influence of dual-mobility acetabular implants on revision and survivorship of cup and Kerboull-type reinforcement ring constructs in aseptic acetabular loosening

IntroductionDual-mobility (DM) acetabular implants have been used in revision total hip arthroplasty (THA) to prevent postoperative instability, with excellent mid-term survivorship. However, few comparative studies assessed the long-term outcomes of DM implants used in Kerboull-type reinforcement ring constructs for acetabular revision. The present study aimed to compare long-term survivorship, dislocation rates and clinical outcome between DM acetabular implants and conventional single-bearing (SB) implants when cemented in a reinforcement ring. HypothesisDual-mobility implants are associated with equivalent survivorship and lower dislocation rates than SB implants. Material and methodsA retrospective study included 60 revision THAs for aseptic loosening using a Kerboull-type reinforcement ring, and finally included 2 groups of 23 patients with either DM or SB cemented acetabular implants after matching for age, gender, BMI and preoperative Harris hip score. Mean follow-up was 10 years (range, 6–14 years). Acetabular implant survivorship, dislocation rate and radiographic failure incidence (>5mm migration, progressive radiolucency, graft non-integration, reinforcement ring breakage) were compared between the two groups. Clinical outcomes used the Harris hip score, the Postel-Merle d’Aubigné score and the Parker score. ResultsSurvivorship free of aseptic acetabular re-revision was 89% at 10 years, with no significant difference between DM and SB (91% and 86%, respectively; p=0.54). Single-bearing implants showed a hazard ratio for dislocation of 6.7 (95% CI, 1.5–29.6; p=0.01) compared to DM implants. There were no significant differences in radiologic failure (10-year survivorship 72% and 64%, respectively; p=0.88) or functional scores. DiscussionThe present study confirmed the impact of dual-mobility implants in reducing long-term dislocation risk when used in Kerboull-type reinforcement ring constructs for acetabular aseptic revision, with no increased risk of re-revision compared to conventional single-bearing implants. Level of evidenceIII, comparative retrospective study.

Pulsed electromagnetic field (PEMF) transiently stimulates the rate of mineralization in a 3-dimensional ring culture model of osteogenesis.

Pulsed Electromagnetic Field (PEMF) has shown efficacy in bone repair and yet the optimum characteristics of this modality and its molecular mechanism remain unclear. To determine the effects of timing of PEMF treatment, we present a novel three-dimensional culture model of osteogenesis that demonstrates strong de novo generation of collagen and mineral matrix and exhibits stimulation by PEMF in multiple stages over 62 days of culture. Mouse postnatal day 2 calvarial pre-osteoblasts were cast within and around Teflon rings by polymerization of fibrinogen and cultured suspended without contact with tissue culture plastic. Ring constructs were exposed to PEMF for 4h/day for the entire culture (Daily), or just during Day1-Day10, Day11-Day 27, or Day28-Day63 and cultured without PEMF for the preceding or remaining days, and compared to no-PEMF controls. PEMF was conducted as HF Physio, 40.85 kHz frequency with a 67 ms burst period and an amplitude of 1.19 mT. Osteogenesis was kinetically monitored by repeated fluorescence measurements of continuously present Alizarin Red S (ARS) and periodically confirmed by micro-CT. PEMF treatment induced early-onset and statistically significant transient stimulation (~4-fold) of the mineralization rate when PEMF was applied Daily, or during D1-D10 and D11-D27. Stimulation was apparent but not significant between D28-D63 by ARS but was significant at D63 by micro-CT. PEMF also shifted the micro-CT density profiles to higher densities in each PEMF treatment group. Ring culture generated tissue with a mineral:matrix ratio of 2.0 by thermogravimetric analysis (80% of the calvaria control), and the deposited crystal structure was 50% hydroxyapatite by X-ray diffraction (63% of the calvaria and femur controls), independent of PEMF. These results were consistent with backscatter, secondary electron, and elemental analysis by scanning electron microscopy. Thus, in a defined, strong osteogenic environment, PEMF applied at different times was capable of further stimulation of osteogenesis with the potential to enhance bone repair.

A Novel Plate-Based System (UNIMAX) for Posterior Instrumented Spinal Fusion.

IntroductionThe polyaxial head pedicle screw-rod system is a commonly used spinal instrumentation technique to achieve stabilization, deformity correction, and bony fusion. We present a novel plate-based pedicle screw system (UNIMAXTM) that can be used for multi-level instrumentation with potential advantages for selected applications.MethodsBilateral titanium monoaxial pedicle screws are linked at each level by robust transversely oriented cross plates forming ring constructs capable of rigid triangulation at each level. The cross plates are then interconnected by sagittally oriented rigid plates situated medial to the screw heads. Biomechanically, the construct was tested for quasi-static torsion and fatigue in axial compression. The system is approved by the Food and Drug Administration (FDA). The system and case examples are presented showing its potential advantages.ResultsThe quasi-static torsion, the mean for the angular displacement, torsional stiffness, and torsional ultimate strength was 2.5 degrees (SD ± 0.8), 5.3 N-m/mm (SD ± 0.7), and 21.6 N-m (SD ± 4.4). For the fatigue in axial compression, the closed ring construct failed when the applied load and bending moment were ≥ 1500 N and ≥ 60 N.m. This system maximizes the construct rigidity, allows easy extension to adjacent levels, and can be incorporated intuitively into practice. The ring construct with triangulation at each level, together with its biomechanical robustness, predicts a high pullout resistance. It requires an open posterior approach incompatible with minimally invasive techniques.ConclusionThis system may have advantages over the screw-rod systems in carefully selected situations requiring extra rigidity and high pull-out strength for complex reconstructions, sagittal and/or coronal correction, patients with poor bone quality, revisions, and/or extension to adjacent levels.

Multicomponent bioprinting of heterogeneous hydrogel constructs based on microfluidic printheads.

Multimaterial bioprinting provides a promising strategy to recapitulate complex heterogeneous architectures of native tissues in artificial tissue analogs in a controlled manner. However, most of the existing multimaterial bioprinting techniques relying on multiple printing nozzles and complicate control program make it difficult to flexibly change the material composition during the printing process. Here, we developed a multicomponent bioprinting strategy to produce heterogeneous constructs using a microfluidic printhead with multiple inlets and one outlet. The composition of the printed filaments can be flexibly changed by adjusting volumetric flow rate ratio. Heterogeneous hydrogel constructs were successfully printed to have predefined spatial gradients of inks or microparticles. A rotary microfluidic printhead was used to maintain the heterogeneous morphology of the printed filaments as the printing path direction changed. Multicellular concentric ring constructs with two kinds of cell types distribution in the printed filaments were fabricated by utilizing coaxial microfluidic printhead and rotary collecting substrate, which significantly improves the printing efficiency for multicomponent concentric structures. The presented approach is simple and promising to potentially print multicomponent heterogeneous constructs for the fabrication of artificial multicellular tissues.

Non-invasive functional molecular phenotyping of human smooth muscle cells utilized in cardiovascular tissue engineering

Smooth muscle cell (SMC) diversity and plasticity are limiting factors in their characterization and application in cardiovascular tissue engineering. This work aimed to evaluate the potential of Raman microspectroscopy and Raman imaging to distinguish SMCs of different tissue origins and phenotypes. Cultured human SMCs isolated from different vascular and non-vascular tissues as well as fixed human SMC-containing tissues were analyzed. In addition, Raman spectra and images of tissue-engineered SMC constructs were acquired. Routine techniques such as qPCR, histochemistry, histological and immunocytological staining were performed for comparative gene and protein expression analysis. We identified that SMCs of different tissue origins exhibited unique spectral information that allowed a separation of all groups of origin by multivariate data analysis (MVA). We were further able to non-invasively monitor phenotypic switching in cultured SMCs and assess the impact of different culture conditions on extracellular matrix remodeling in the tissue-engineered ring constructs. Interestingly, we identified that the Raman signature of the human SMC-based ring constructs was similar to the one obtained from native aortic tissue.We conclude that Raman microspectroscopic methods are promising tools to characterize cells and define cellular and extracellular matrix components on a molecular level. In this study, in situ measurements were marker-independent, fast, and identified cellular differences that were not detectable by established routine techniques. Perspectively, Raman microspectroscopy and MVA in combination with artificial intelligence can be suitable for automated quality monitoring of (stem) cell and cell-based tissue engineering products. Statement of SignificanceThe accessibility of autologous blood vessels for surgery is limited. Tissue engineering (TE) aims to develop functional vascular replacements; however, no commercially available TE vascular graft (TEVG) exists to date. One limiting factor is the availability of a well-characterized and safe cell source. Smooth muscle cells (SMCs) are generally used for TEVGs. To engineer a TEVG, proliferating SMCs of the synthesizing phenotype are essential, whereas functional, sustainable TEVGs require SMCs of the contractile phenotype. SMC diversity and plasticity are therefore limiting factors, also for their quality monitoring and application in TE. In this study, Raman microspectroscopy and imaging combined with machine learning tools allowed the non-destructive, marker-independent characterization of SMCs, smooth muscle tissues and TE SMC-constructs. The spectral information was specific enough to distinguish for the first time the phenotypic switching in SMCs in real-time, and monitor the impact of culture conditions on ECM remodeling in the TE SMC-constructs.

Synthesis and characterization of two novel bimetallic macrocyclic complexes generated from 1,2,4-triazole-containing semi-rigid ligands and M(NO3)2 units (M = Ni and Zn).

Bimetallic macrocyclic complexes have attracted the attention of chemists and various organic ligands have been used as molecular building blocks, but supramolecular complexes based on semi-rigid organic ligands containing 1,2,4-triazole have remained rare until recently. It is easier to obtain novel topologies by making use of asymmetric semi-rigid ligands in the self-assembly process than by making use of rigid ligands. A new semi-rigid ligand, 3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine (L), has been synthesized and used to generate two novel bimetallic macrocycle complexes, namely bis{μ-3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine}bis[(methanol-κO)(nitrato-κ(2)O,O')nickel(II)] dinitrate, [Ni2(NO3)2(C17H14N6S)2(CH3OH)2](NO3)2, (I), and bis{μ-3-[(pyridin-4-ylmethyl)sulfanyl]-5-(quinolin-2-yl)-4H-1,2,4-triazol-4-amine}bis[(methanol-κO)(nitrato-κ(2)O,O')zinc(II)] dinitrate, [Zn2(NO3)2(C17H14N6S)2(CH3OH)2](NO3)2, (II), by solution reactions with the inorganic salts M(NO3)2 (M = Ni and Zn, respectively) in mixed solvents. In (I), two Ni(II) cations with the same coordination environment are linked by L ligands through Ni-N bonds to form a bimetallic ring. Compound (I) is extended into a two-dimensional network in the crystallographic ac plane via N-H...O, O-H...N and O-H...O hydrogen bonds, and neighbouring two-dimensional planes are parallel and form a three-dimensional structure via π-π stacking. Compound (II) contains two bimetallic rings with the same coordination environment of the Zn(II) cations. The Zn(II) cations are bridged by L ligands through Zn-N bonds to form the bimetallic rings. One type of bimetallic ring constructs a one-dimensional nanotube via O-H...O and N-H...O hydrogen bonds along the crystallographic a direction, and the other constructs zero-dimensional molecular cages via O-H...O and N-H...O hydrogen bonds. They are interlinked into a two-dimensional network in the ac plane through extensive N-H...O hydrogen bonds, and a three-dimensional supramolecular architecture is formed via π-π interactions between the centroids of the benzene rings of the quinoline ring systems.

Abstract LB-103: Structural characterization of SPRY2-Cbl interactions

Abstract Sprouty 2 (SPRY2) is a feedback modulator of receptor tyrosine kinase (RTK)-ERK signaling, and a potential tumor suppressor. Cbl, an E3 ubiquitin ligase and scaffold protein, binds SPRY2 with high affinity, and sequesters or targets it for degradation. Cbl also binds several growth factor receptors. Hence SPRY2, Cbl and receptors are in a dynamic equilibrium. Truncation and site-mutagenesis studies previously mapped SPRY2-Cbl interactions to two discrete domains, TKB and RING. A pY binding pocket in the TKB SH2 region is critical for binding, but the role(s) of other TKB regions and/or RING are undefined. Interactions of three Cbl recombinant proteins (P47-G351 (TKBD), and two phosphomimetic RING active-conformation constructs, P47-D435 Y371D/E) with three SPRY2 peptides (P1: Q36-N53, a putative RING binder; P2: Q36-T60 (pY55), TKB binder; and P3: 54-60(pY55), a truncated TKB binder) were characterized by computational simulation, surface plasmon resonance spectroscopy (SPR), fluorescence polarization (FP), and X-ray crystallography. In silico modeling suggested possible low-affinity binding of P1 in the groove between TKBD SH2 and 4-helix (4H) regions and near the RING, but this was not confirmed by FP, SPR, or crystallography. Apo and P2 ligand-bound structures agreed with prior published data; three previously unknown 4H interaction sites were also identified. Data on the effects of site-specific 4H mutants on P2 binding affinities are pending. Binding affinities for P2 with the TKBD, Y371E, and Y371D constructs were 160±5, 92±9, and 45±3 nM, respectively, by SPR; FP results were similar. Direct interactions with the RING were not confirmed, but the higher P2 binding affinities observed with RING constructs suggest that this domain indirectly facilitates SPRY2 binding. Binding of P2 induced 16.9° rotation of the SH2 region and formation of new H-bonds to 4H, compressing the TKBD. Importantly, P4 induced identical conformational changes as P2, but had no direct contact with 4H. These observations are consistent with a refined model of SPRY2-Cbl interaction, where ligand docking at the pY SH2 site is sufficient to globally change TKB architecture, facilitating SPRY2 binding at previously unrecognized sites in the 4H region (Support: KU COBRE-PSF (NIH/RR017708, NIH/GM103420), KU Cancer Center, Kansas Bioscience Authority, and the George & Floriene Lieberman Endowment). Citation Format: Na Zhang, Xuan Zhang, Laurie Washington, Asokan Anbanandam, Kevin Battaile, Philip Gao, Aaron Smalter Hall, Scott Lovell, Anuradha Roy, Robert Hanzlik, Raymond Perez. Structural characterization of SPRY2-Cbl interactions. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-103. doi:10.1158/1538-7445.AM2015-LB-103

Design of broadband microstrip‐to‐CPW transition

A broadband microstrip-to-CPW transition is presented. In the proposed structure, the upper microstrip ring is vertically coupled to the central conductor of the lower circular CPW via electromagnetic coupling. To obtain a wide bandwidth of operation, a short-ended stub is introduced. The introduced short-ended stub combined with the open-ended microstrip ring constructs a quarter-wavelength resonator. A sample transition has been designed and measured. Experimental results indicate that over 129% bandwidth with better than 10 dB return loss and below 1.7 dB insertion loss can be obtained.

Axial stiffness and ring deformation of complete and incomplete single ring circular external skeletal fixator constructs

To compare the axial stiffness, maximum axial displacement, and ring deformation during axial loading of single complete and incomplete circular (ring) external skeletal fixator constructs. 32 groups of single ring constructs (5 constructs/group). Single ring constructs assembled with 2 divergent 1.6-mm-diameter Kirschner wires were used to stabilize a 60-mm-long segment of 16-mm-diameter acetyl resin rod. Construct variables included ring type (complete or incomplete), ring diameter (50, 66, 84, or 118 mm), and fixation wire tension (0, 30, 60, or 90 kg). Axial loading was performed with a materials testing system. Construct secant stiffness and maximum displacement were calculated from the load-displacement curves generated for each construct. Ring deformation was calculated by comparing ring diameter during and after construct loading to ring diameter prior to testing. Complete ring constructs had greater axial stiffness than did the 66-, 84-, and 118-mm-diameter incomplete ring constructs. As fixation wire tension increased, construct stiffness increased in the 66-, 84-, and 118-mm-diameter incomplete ring constructs. Maximum axial displacement decreased with increasing fixation wire tension, and complete ring constructs allowed less displacement than did incomplete ring constructs. Incomplete rings were deformed by wire tensioning and construct loading. Mechanical performance of the 66-, 84-, and 118-mm-diameter incomplete ring constructs improved when wire tension was applied, but these constructs were not as stiff as and allowed greater displacement than did complete ring constructs of comparable diameter. For clinical practice, tensioning the wires placed on 84- and 118-mm-diameter incomplete rings to 60 kg is recommended.

Current concepts of leg lengthening.

Any lower limb discrepancy may be equalised by conservative means (insoles, prosthesis and orthosis). However, their long-term acceptance is low in regard to function, costs, expenditure and appearance. Timely epiphysiodesis is the best option in uniplanar deformities with adequate remaining growth and for patients whose predicted final body height is above the 50th percentile. However, many patients present late or with multi-planar deformities, which warrant more sophisticated operative approaches. The history of surgical bone lengthening comprises 100 exciting years of struggling, development and ongoing learning. The initial strategy of acute or rapid incremental distraction had lasted almost half a century until Ilizarov recognised the benefits of biological periosteum-preserving osteotomies and incremental lengthening at slow rates (1mm/day) at a 4×0.25-mm daily rhythm, well appreciated as callotasis. In parallel, ring and wire constructs made complex three-dimensional axial, translational and rotational bone moulding possible. Taylor Spatial Frames-built on hexapod strut-linked platform technology as known from flight simulators-took limb correction to a more reliable, more precise and aesthetical level, all the more that the whole process became web-based. It represents state-of-the-art methodology and technology for complex, multi-plane deformities. Due to the significant risk of secondary malalignment, indications for lengthening by unilateral fixation have shrunken to moderate amounts of length disparity and uni- to bi-planar deformities in patients with still open physes. Mechanical or motorised, minimally invasively placed nails prevent muscle fixation and, therefore, ease rehabilitation, increase patient comfort and potentially shorten the overall time of sick leave and refrain from sports activities. Hence, they offer a valuable alternative for low-grade complexity situations. It remains to be proved if the significantly higher implant costs are compensated by lower treatment costs. Overall, limb lengthening, particularly in combination with multi-planar deformity correction, can still be an arduous endeavour. In any case, wise judgement of the patient's deformity, medical and biological situation, psychosocial environment, selection of the appropriate method and hardware, as well as meticulous operating technique by an experienced surgeon are the cornerstones of successful outcomes.

Surgical implantation of a bioengineered internal anal sphincter

Purpose Fecal incontinence is a common disorder that can have devastating social and psychologic consequences. However, there are no long-term ideal solutions for such patients. Although loss of continence is multifactorial, the integrity of the internal anal sphincter (IAS) has particular significance. We previously described the development of 3-dimensional bioengineered constructs using isolated smooth muscle tissue from donor C57BL/6 IAS. We hypothesized that the bioengineered ring constructs would retain cellular viability and promote neovascularization upon implantation into a recipient mouse. Methods Internal anal sphincter ring constructs were surgically implanted into the subcutaneous tissue of syngeneic C57BL/6 mice and treated with either fibroblastic growth factor 2 (0.26 μg daily) or saline controls using a microosmotic pump. Internal anal sphincter constructs were harvested after 25 days (range, 23-26 days) and assessed morphologically and for tissue viability. Result Gross morphology showed that there was no rejection. Rings showed muscle attachment to the back of the mouse with no sign of inflammation. Fibroblastic growth factor 2 infusion resulted in a significantly improved histologic score and muscle viability compared with the control group. Conclusions Three-dimensional bioengineered IAS rings can be successfully implanted into the subcutaneous tissue of recipient mice. The addition of fibroblastic growth factor 2 led to improved muscle viability, vascularity, and survival. This approach may become a feasible option for patients with fecal incontinence.

Axial Characteristics of Circular External Skeletal Fixator Single Ring Constructs

Evaluate the effects of varying ring diameter, wire tension, and wire-divergence angle on the axial stiffness characteristics of circular external skeletal fixator single-ring constructs. Study Design-Biomechanical evaluation using circular fixator components and a Delrin cylinder bone model. Single ring constructs using two 1.6 mm diameter Kirschner wires to secure a 19 mm Delrin cylinder centered within the ring were examined. Component variables evaluated were ring diameter (50 mm, 66 mm, 84 mm, and 118 mm), wire-divergence angle (30 degrees, 60 degrees, and 90 degrees ), and wire tension (0 kg, 30 kg, 60 kg, and 90 kg). A total of 48 constructs were examined. Rings were rigidly mounted on a universal testing system and the cylinder loaded in axial compression (7.4 N/s) to 220 N. Load/displacement curves were analyzed to determine the following: the displacement (mm) that occurred before the slope of each load/displacement curve became linear, the stiffness (N/mm) of the linear portion of each load/deformation curve, and the total displacement (mm) produced at maximal load. Least-squares linear regression was used to model response variables as linear functions of ring diameter, wire divergence angle, and wire tension. Three-way interactions and 2-way interactions among independent component variables were evaluated first in the modeling process and included in a best model if response variables were found to have statistically significant regression coefficients. The regression coefficients and corresponding standard errors and covariances were used to estimate the maximal effect and standard error attributable to wire divergency angle (change from 30 degrees to 90 degrees ) and wire tension (change from 0 to 90 kg) for each ring diameter. All load/deformation curves had an initial exponential increase in stiffness, with the slope becoming linear at higher loads. The exponential phase was more pronounced in larger-diameter ring constructs and was mitigated by tensioning the wires. Ring diameter had the greatest influence on displacement that occurred before the curve became linear (semipartial r(2) [sp-r2] = .89), stiffness (sp-r2 = .94), and total displacement (sp-r2 = .93). Wire tension exerted a smaller influence on displacement that occurred before the curve became linear (sp-r2 =.06), stiffness (sp-r2 = .03), and total displacement (sp-r2 = .05). Wire divergence angle had a nominal effect on displacement that occurred before the curve became linear (sp-r2 = .0001), on stiffness (sp-r2 = .004), and on total displacement (sp-r2 =.003). Ring diameter had a profound effect on the axial stiffness characteristic of single ring constructs. Tensioning of the fixation wires can improve the axial stiffness characteristics of these constructs, particularly in larger diameter ring constructs, by mitigating the initial exponential phase of the load/deformation curve. Wire divergence angle had only a nominal differential effect on axial stability. Understanding how individual component variables and their interactions influence bone segment stability should help surgeons to optimize interfragmentary strain. Tensioning fixation wires is probably unnecessary in 50 mm diameter ring constructs, but assumes greater importance as ring diameter increases.

Effects of ring diameter and wire tension on the axial biomechanics of four-ring circular external skeletal fixator constructs.

To determine relative effects of ring diameter and wire tension on axial biomechanical properties of 4-ring circular external skeletal fixator constructs. 4-ring circular external skeletal fixator constructs and artificial bone models. 4-ring constructs were assembled, using 50-, 66-, 84-, or 118-mm-diameter rings. Two 1.6-mm-diameter fixation wires were attached to opposing surfaces of each ring at intersection angles of 90 degrees and placed through a gap-fracture bone model. Three examples of each construct were loaded in axial compression at 7 N/s to a maximum load of 400 N at each of 4 wire tensions (0, 30, 60, and 90 kg). Response variables were determined from resulting load-displacement curves (construct stiffness, load at 1 mm of displacement, displacement at 400 N). Ring diameter and wire tension had a significant effect on all response variables and had a significant interaction for construct stiffness and displacement at 400 N. Significant differences within all response variables were seen among all 4 ring diameters and all 4 wire tensions. As ring diameter increased, effect of increasing wire tension on gap stiffness and gap displacement at 400 N decreased. Ring diameter had a greater effect than wire tension on all response variables. Although effects of wire tension decrease as ring diameter increases, placing tension on wires in larger ring constructs is important because these constructs are inherently less stiff. The differential contribution of ring diameter, wire tension, and their interactions must be considered when using circular external skeletal fixators.

Stereoselective Synthesis of the Taxane Ring System via the Tandem Diels-Alder Cycloaddition.

The application of the tandem Diels-Alder cycloaddition to the stereoselective synthesis of the tricyclic ring system of the taxane diterpenes is described. The exceedingly direct, two-step synthesis of the B/C cis-fused taxane nucleus in 50% overall yield from the reaction of two readily available acyclic precursors underscores the efficiency of this approach. A critical feature of the second, intramolecular Diels-Alder cyclcoaddition is the transmission of stereochemical information across the taxane framework, i.e., from the C ring to the A ring. The cycloaddition of both cis- and trans-disubstituted C ring constructs leads to the establishment of the requisite C-1/C-3 relative stereochemistry for the synthesis of taxanes. A computational model is presented to account for the high levels of asymmetric induction observed in these reactions.