Mechanical Behavior and Failure Analysis of Prosthetic Retaining Screws after Long‐term Use In Vivo. Part 3: Preload and Tensile Fracture Load Testing

Purpose: The aim of this study was to determine the preload and tensile fracture load values of prosthetic retaining screws after long‐term use in vivo compared to unused screws (controls). Additionally, the investigation addressed whether the preload and fracture load values of prosthetic retaining screws reported by the manufacturer become altered after long‐term use in vivo. Materials and Methods: For preload testing, 10 new screws (controls) from Nobel Biocare (NB) and 73 used retaining screws [58 from NB and 15 from Sterngold (SG)] were subjected to preload testing. For tensile testing, eight controls from NB and 58 used retaining screws (46 from NB and 12 from SG) were subjected to tensile testing. Used screws for both tests were in service for 18–120 months. A custom load frame, load cell, and torque wrench setup were used for preload testing. All 83 prosthetic screws were torqued once to 10 Ncm, and the produced preload value was recorded (N) using an X–Y plotter. Tensile testing was performed on a universal testing machine and the resulting tensile fracture load value was recorded (N). Preload and tensile fracture load values were analyzed with 2‐way ANOVA and Tukey post‐hoc tests. Results: There was a significant difference between preload values for screws from NB and screws from SG (p \u3c 0.001). The preload values for gold alloy screws from NB decreased as the number of years in service increased. There was a significant difference between tensile fracture values for the three groups (gold alloy screws from NB and SG and palladium alloy screws from NB) at p \u3c 0.001. The tensile fracture values for gold alloy screws from NB and SG decreased as the number of years in service increased. Conclusions: In fixed detachable hybrid prostheses, perhaps as a result of galling, the intended preload values of prosthetic retaining screws may decrease with increased in‐service time. The reduction of the fracture load value may be related to the increase of in‐service time; however, the actual determination of this relationship is not possible from this study alone

Mechanical Behavior and Failure Analysis of Prosthetic Retaining Screws after Long‐term Use in vivo. Part 4: Failure Analysis of 10 Fractured Retaining Screws Retrieved from Three Patients

Purpose: The aim of this study was to perform a failure analysis on fractured prosthetic retaining screws after long‐term use in vivo. Additionally, the study addresses the commonly asked question regarding whether complex repeated functional occlusal forces initiate fatigue‐type cracks in prosthetic retaining screws. Materials and Methods: Ten fractured prosthetic retaining screws retrieved from three patients treated with fixed detachable hybrid prostheses were subjected to a failure analysis. In patients 1 and 2, the middle three retaining screws of the prostheses were found fractured at retrieval time after they had been in service for 20 and 19 months, respectively. In patient 3, the middle three and one of the posterior retaining screws were found to be fractured at retrieval after they had been in service for 18 months. Low power stereomicroscopy and high‐power scanning electron microscopy (SEM) were performed to analyze the fractured surfaces of the retaining screws examining fatigue cracks in greater detail. Results: Typical fatigue failure characterized by ratchet mark formation was revealed by light microscopy and SEM for all examined screws. Using low magnification light microscopy, ratchet marks were visible on the fracture surfaces of only two screws. SEM examination revealed all three classical stages of fatigue failure, and it was possible to see the ratchet marks on the fracture surfaces of all specimens, indicating a fatigue zone. The final catastrophic overload fracture appeared fibrous, indicating ductile fracture. The final overload ductile fracture surfaces showed equiaxed dimples, suggesting tensile overload in all examined screws except in two specimens that showed an elongated dimple pattern indicating shear/tearing overload forces. Conclusions: Fracture of prosthetic retaining screws in hybrid prostheses occurs mainly through a typical fatigue mode involving mostly the middle anterior three screws. Fatigue cracks can grow in more than one prosthetic retaining screw, leading to fracture before the patient or clinician determines that any problem exists

Mechanical Behavior and Failure Analysis of Prosthetic Retaining Screws after Long‐Term Use In Vivo. Part 2: Metallurgical and Microhardness Analysis

Abstract Purpose: This study involved testing and analyzing multiple retrieved prosthetic retaining screws after long‐term use in vivo to: (1) detect manufacturing defects that could affect in‐service behavior; (2) characterize the microstructure and alloy composition; and (3) further characterize the wear mechanism of the screw threads. Materials and Methods: Two new (control) screws from Nobel Biocare (NB) and 18 used (in service 18–120 months) retaining screws [12 from NB and 6 from Sterngold (SG)] were: (1) metallographically examined by light microscopy and scanning electron microscopy (SEM) to determine the microstructure; (2) analyzed by energy dispersive X‐ray (EDX) microanalysis to determine the qualitative and semiquantitative average alloy and individual phase compositions; and (3) tested for Vickers microhardness. Results: Examination of polished longitudinal sections of the screws using light microscopy revealed a significant defect in only one Group 4 screw. No significant defects in any other screws were observed. The defect was considered a “seam” originating as a “hot tear” during original casting solidification of the alloy. Additionally, the examination of longitudinal sections of the screws revealed a uniform homogeneous microstructure in some groups, while in other groups the sections exhibited rows of second phase particles. The screws for some groups demonstrated severe deformation of the lower threads and the bottom part of the screw leading to the formation of crevices and grooves. Some NB screws were comprised of Au‐based alloy with Pt, Cu, and Ag as alloy elements, while others (Groups 4 and 19) were Pd‐based with Ga, Cu, and Au alloy elements. The microstructure was homogeneous with fine or equiaxed grains for all groups except Group 4, which appeared inhomogeneous with anomalous grains. SG screws demonstrated a typical dendritic structure and were Au‐based alloy with Cu and Ag alloy elements. There were differences in the microhardness of gold alloy screws from NB and SG as well as palladium alloy screws from NB. Conclusions: Significant differences within NB retaining screws and between NB and SG screws were found for microstructure, major alloy constituents, and microhardness

Mechanical Behavior and Failure Analysis of Prosthetic Retaining Screws after Long‐term Use In Vivo. Part 1: Characterization of Adhesive Wear and Structure of Retaining Screws

Purpose: The general aim of this study and those presented in Parts 2–4 of this series was to characterize the structure, properties, wear, and fracture of prosthetic retaining screws in fixed detachable hybrid prostheses after long‐term use in vivo. This part of the overall investigation addresses whether there are differences in thread wear between the screws closest to the fulcrum and those that are farthest from the fulcrum in fixed detachable hybrid prostheses. Materials and Methods: The total number of prosthetic retaining screws used in this study was 100 (10 new and 90 used). New screws (controls) from Nobel Biocare (NB) were divided into Group 1 (slotted) and Group 2 (hexed). Ninety used screws (in service 18–120 months) were retrieved from fixed detachable hybrid prostheses in 18 patients (5 screws from each patient, 60 from NB and 30 from Sterngold). The used screws were divided into 18 groups. Additionally, each group was subdivided into A and B categories. Category A contained the middle three prosthetic screws, which were considered the farthest screws from the fulcrum line. Category B contained the most posterior two screws, which were considered the screws closest to the fulcrum line. All 100 screws were subjected to thorough, nondestructive testing. Results: Light and scanning electron microscopic examination of all used screws for each group revealed surface deterioration of the active profile of the screw threads consistent with adhesive wear. The observed thread profile deterioration ranged from mild to severe. The wear was aggressive enough to cause galling, which led to thinning of the threads and, in severe cases, to knife‐edges at thread crests. In ten groups, the most anterior three screws exhibited more wear than the most posterior two screws. In addition to thread wear, severe plastic deformation was detected on the bottom part of each screw for three groups, and a long external longitudinal crack was detected in one screw of Group 2. Conclusions: The findings of this study and those presented in Parts 2–4 demonstrate that different retaining screws from the same manufacturer and/or from different manufacturers have different geometrical design, microstructures, major alloy constituents, and microhardness, and that these differences influence their preload and fractured load values. In this part of the overall investigation, the occurrence of galling as a result of wear involving prosthetic retaining screws appears to be an inevitable and unavoidable consequence of long‐term use in vivo in fixed detachable hybrid prostheses regardless of the intended/original preload value. The galling rate is greater on the middle three screws compared to the most posterior two screws in fixed detachable hybrid prostheses. The wear pattern is consistent with an adhesive wear mechanism; however, this study does not provide enough data to support a definitive analysis

Adjusting the Course of Youth Ministry

The purpose of this project is to explore how youth ministry at Sequim Community Church (hereafter, SCC) can counter systemic abandonment of adolescents by instituting a church-wide holistic praxis of adoption. Part One of this project defines the “youth” of youth ministry. It discusses the current youth culture and the psychosocial development of adolescents, and it provides a baseline for understanding the youth of Sequim, Washington. This is the context in which this project tries to define a ministry method that can be implemented cross-culturally and cross-generationally to counter what adolescents experience as abandonment. Part Two presents a theological exercise regarding how to counter systemic abandonment with the redemptive power of adoption, addressing the “ministry” of youth ministry. An ecclesiology of the local church as a family of families is explained. Churches have the ability to adopt young people into the church family with the hope of adoption into God’s eternal family. Adoption is associated with particular ministries and calls the Church to focus on the whole family. The hope of adoption when associated with the stages of discipleship outlines a new model for ministry that can guide SCC and other youth ministries into a more holistic praxis of ministry. A strategy for SCC is developed in Part Three. The youth ministry at SCC was critiqued using an evaluation tool specifically designed to see if, as a ministry, it is providing movement towards abandonment or adoption. Adaptive problems require everyone in leadership to participate in finding solutions together; therefore, a plan for creating holding environments of discussability concerning a new model of ministry is planned for SCC. Potential changes for SCC are offered with the knowledge that community input might shift the final outcome. Theological Mentor: Kurt Fredrickson, Ph

Bioresorbable Polylactide Interbody Implants in an Ovine Anterior Cervical Discectomy and Fusion Model: Three-Year Results

Study Design. In vivo study of anterior discectomy and fusion using a bioresorbable 70:30 poly(l-lactide-co-d,l-lactide) interbody implant in an ovine model. Objective. To evaluate the efficacy of the polylactide implant to function as an interbody fusion device, and to assess the tissue reaction to the material during the resorption process. Summary of Background Data. The use of polylactide as a cervical interbody implant has several potential advantages when compared with traditional materials. Having an elastic modulus very similar to bone minimizes the potential for stress shielding, and as the material resorbs additional loading is transferred to the developing fusion mass. Although preclinical and clinical studies have demonstrated the suitability of polylactide implants for lumbar interbody fusion, detailed information on cervical anterior cervical discectomy and fusion (ACDF) with polylactide devices is desirable. Methods. Single level ACDF was performed in 8 skeletally mature ewes. Bioresorbable 70:30 poly (l-lactide-co-d,l-lactide) interbody implants packed with autograft were used with single-level metallic plates. Radiographs were made every 3 months up to 1 year, and yearly thereafter. The animals were killed at 6 months (3 animals), 12 months (3 animals), and 36 months (2 animals). In addition to the serial plain radiographs, the specimens were evaluated by nondestructive biomechanical testing and undecalcified histologic analysis. Results. The bioresorbable polylactide implants were effective in achieving interbody fusion. The 6-month animals appeared fused radiographically and biomechanically, whereas histologic sections demonstrated partial fusion (in 3 of 3 animals). Radiographic fusion was confirmed histologically and biomechanically at 12 months (3 of 3 animals) and 36 months (2 of 2 animals). A mild chronic inflammatory response to the resorbing polylactide implant was observed at both 6 months and 12 months. At 36 months, the operative levels were solidly fused and the implants were completely resorbed. No adverse tissue response was observed in any animal at any time period. Conclusion. Interbody fusion was achieved using bioresorbable polylactide implants, with no evidence of implant collapse, extrusion, or adverse tissue response to the material. The use of polylactide as a cervical interbody device appears both safe and effective based on these ACDF animal model results

Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. Methods: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1·) or 0.90 mg (7·). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. Results: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1· and the 7· rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-tomarked resorption at the 7·-dose level and less resorption at the 1·-dose level. Both dose (p \u3c 0.0007) and time (p \u3c 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. Conclusions: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. Clinical Relevance: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption

Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways

Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall.Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogen activated protein kinase (MAPK) activation, though the molecular mechanisms of this process are poorly understood. Here we report that tribbles-1, a recently described modulator of MAPK activation controls vascular smooth muscle cell proliferation and chemotaxis via the Jun Kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whilst the activation and the expression of MKK4/SEK1 is not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries compared to non-atherosclerotic controls, suggesting that this protein may pay a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology

Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke.

Nitrones (e.g. α-phenyl-N-tert-butyl nitrone; PBN) are cerebroprotective in experimental stroke. Free radical trapping is their proposed mechanism. As PBN has low radical trapping potency, we tested Sgk1 induction as another possible mechanism. PBN was injected (100 mg/kg, i.p.) into adult male rats and mice. Sgk1 was quantified in cerebral tissue by microarray, quantitative RT-PCR and western analyses. Sgk1+/+ and Sgk1-/- mice were randomized to receive PBN or saline immediately following transient (60 min) occlusion of the middle cerebral artery. Neurological deficit was measured at 24 h and 48 h and infarct volume at 48 h post-occlusion. Following systemic PBN administration, rapid induction of Sgk1 was detected by microarray (at 4 h) and confirmed by RT-PCR and phosphorylation of the Sgk1-specific substrate NDRG1 (at 6 h). PBN-treated Sgk1+/+ mice had lower neurological deficit ( p < 0.01) and infarct volume ( p < 0.01) than saline-treated Sgk1+/+ mice. PBN-treated Sgk1-/- mice did not differ from saline-treated Sgk1-/- mice. Saline-treated Sgk1-/- and Sgk1+/+ mice did not differ. Brain Sgk3:Sgk1 mRNA ratio was 1.0:10.6 in Sgk1+/+ mice. Sgk3 was not augmented in Sgk1-/- mice. We conclude that acute systemic treatment with PBN induces Sgk1 in brain tissue. Sgk1 may play a part in PBN-dependent actions in acute brain ischemia

Engineering novel complement activity into a pulmonary surfactant protein

Complement neutralizes invading pathogens, stimulates inflammatory and adaptive immune responses, and targets non- or altered-self structures for clearance. In the classical and lectin activation pathways, it is initiated when complexes composed of separate recognition and activation subcomponents bind to a pathogen surface. Despite its apparent complexity, recognition-mediated activation has evolved independently in three separate protein families, C1q, mannose-binding lectins (MBLs), and serum ficolins. Although unrelated, all have bouquet-like architectures and associate with complement-specific serine proteases: MBLs and ficolins with MBL-associated serine protease-2 (MASP-2) and C1q with C1r and C1s. To examine the structural requirements for complement activation, we have created a number of novel recombinant rat MBLs in which the position and orientation of the MASP-binding sites have been changed. We have also engineered MASP binding into a pulmonary surfactant protein (SP-A), which has the same domain structure and architecture as MBL but lacks any intrinsic complement activity. The data reveal that complement activity is remarkably tolerant to changes in the size and orientation of the collagenous stalks of MBL, implying considerable rotational and conformational flexibility in unbound MBL. Furthermore, novel complement activity is introduced concurrently with MASP binding in SP-A but is uncontrolled and occurs even in the absence of a carbohydrate target. Thus, the active rather than the zymogen state is default in lectin·MASP complexes and must be inhibited through additional regions in circulating MBLs until triggered by pathogen recognition