Assessment of bone ingrowth around beaded coated tibial implant for total ankle replacement using mechanoregulatory algorithm.

The long-term performance of porous coated tibial implants for total ankle replacement (TAR) primarily depends on the extent of bone ingrowth at the bone-implant interface. Although attempts were made for primary fixation for immediate post-operative stability, no investigation was conducted on secondary fixation. The aim of this study is to assess bone ingrowth around the porous beaded coated tibial implant for TAR using a mechanoregulatory algorithm. A realistic macroscale finite element (FE) model of the implanted tibia was developed based on computer tomography (CT) data to assess implant-bone micromotions and coupled with microscale FE models of the implant-bone interface to predict bone ingrowth around tibial implant for TAR. The macroscale FE model was subjected to three near physiological loading conditions to evaluate the site-specific implant-bone micromotion, which were then incorporated into the corresponding microscale model to mimic the near physiological loading conditions. Results of the study demonstrated that the implant experienced tangential micromotion ranged from 0 to 71 µm with a mean of 3.871 µm. Tissue differentiation results revealed that bone ingrowth across the implant ranged from 44 to 96 %, with a mean of around 70 %. The average Young's modulus of the inter-bead tissue layer varied from 1444 to 4180 MPa around the different regions of the implant. The analysis postulates that when peak micromotion touches 30 µm around different regions of the implant, it leads to pronounced fibrous tissues on the implant surface. The highest amount of bone ingrowth was observed in the central regions, and poor bone ingrowth was seen in the anterior parts of the implant, which indicate improper osseointegration around this region. This macro-micro mechanical FE framework can be extended to improve the implant design to enhance the bone ingrowth and in future to develop porous lattice-structured implants to predict and enhance osseointegration around the implant.

Automation Opportunities in Pharmacovigilance: An Industry Survey.

BACKGROUND: TransCelerate's Intelligent Automation Opportunities (IAO) in Pharmacovigilance initiative has been working to evaluate various pharmacovigilance processes to facilitate systematic innovation with intelligent automation across the entire area. The individual case safety report (ICSR) process was the first process selected for evaluation because of its resource-intensive nature, risk of errors, and operational inefficiencies. OBJECTIVES: TransCelerate's IAO in Pharmacovigilance initiative initially worked to articulate an end-to-end ICSR process that would generically apply to various pharmacovigilance organizations, despite organizational variations in specific ICSR process steps. This paper aims to address the need for a systematic review framework for automation of the ICSR process from the value, impact, perceived risk, and opportunity point of view. METHODS: The generic ICSR process, which starts with receipt of an adverse event report, was grouped into three process blocks: case intake, case processing, and case reporting. Each of these was then further detailed in individual process steps. A total of 19 TransCelerate member companies were invited to complete a survey designed to facilitate understanding of automation opportunities across the ICSR process. Heat maps of the current level of effort, expected benefit of automation, and perceived risk of automation were compiled from responses to identify intelligent automation opportunities for specific ICSR process steps. Relevant experts on the TransCelerate evaluation team analyzed and interpreted the anonymized and aggregated results. RESULTS: In total, 15 TransCelerate member companies responded to the survey and indicated that ICSR process steps with current high effort, expected high automation benefit, low or manageable automation risk, and low levels of current automation present the best opportunities for future automation. Such steps include language translations, case verification, in-line quality control, prioritization/triage, data entry, alerts for cases of interest, workflow management, and monitoring. Some steps (e.g., submission) have been automated for a number of years and appear on the heat map as having low potential for further automation. The survey responses implied that, despite successful use of intelligent automation technologies in other areas, adoption within pharmacovigilance and the ICSR process in particular remains limited. The perceived high risk to patient safety is expected to decrease with additional successful applications in pharmacovigilance. CONCLUSIONS: Our results highlight the areas of greatest opportunity for intelligent automation based on the potential benefits of applying intelligent automation and the perceived risks associated with each ICSR process step. Responding TransCelerate member companies already automate many steps to varying degrees. However, a significant opportunity remains for automation to penetrate further. Additionally, the pharmacovigilance industry culture needs to change in order to reduce the perceived risk of automation and to encourage a more progressive approach to intelligent automation. Increased automation is crucial to empower agile and efficient pharmacovigilance.

Monte Carlo Type Simulations of Mineralized Collagen Fibril Based on Two Scale Asymptotic Homogenization.

A multiscale model for mineralized collagen fibril (MCF) is proposed by taking into account the uncertainties associated with the geometrical properties of the mineral phase and its distribution in the organic matrix. The asymptotic homogenization approach along with periodic boundary conditions has been used to derive the effective elastic moduli of bone's nanostructure at two hierarchical length scales, namely: microfibril (MF) and MCF. The uncertainties associated with the mineral plates have been directly included in the finite element mesh by randomly varying their sizes and structural arrangements. A total of 100 realizations for the MCF model with random distribution have been generated using an in-house MATLAB code, and Monte Carlo type of simulations have been performed under tension load to obtain the statistical equivalent modulus. The deformation response has been studied in both small (≤10%) and large (≥10%) strain regimes. The stress transformation mechanism has also been explored in MF which showed stress relaxation in the organic phase upon different stages of mineralization. The elastic moduli for MF under small and large strains have been obtained as 1.88 and 6.102 GPa, respectively, and have been used as an input for the upper scale homogenization procedure. Finally, the characteristic longitudinal moduli of the MCF in the small and large strain regimes are obtained as 4.08 ± 0.062 and 12.93 ± 0.148 GPa, respectively. All the results are in good agreement to those obtained from previous experiments and molecular dynamics (MD) simulations in the literature with a significant reduction in the computational cost.

Assessment of failure of cemented polyethylene acetabular component due to bone remodeling: A finite element study.

The aim of the study is to determine failure of the cemented polyethylene acetabular component, which might occur due to excessive bone resorption, cement-bone interface debonding and fatigue failure of the cement mantle. Three-dimensional finite element models of intact and implanted pelvic bone were developed and bone remodeling algorithm was implemented for present analysis. Soderberg fatigue failure diagram was used for fatigue assessment of the cement mantle. Hoffman failure criterion was considered for prediction of cement-bone interface debonding. Results indicate fatigue failure of the cement mantle and implant-bone interface debonding might not occur due to bone remodeling.