Challenging applicability of ISO 10993-5 for calcium phosphate biomaterials evaluation: Towards more accurate in vitro cytotoxicity assessment.

Research on biomaterials typically starts with cytocompatibility evaluation, using the ISO 10993-5 standard as a reference that relies on extract tests to determine whether the material is safe (cell metabolic activity should exceed 70 %). However, the generalized approach within the standard may not accurately reflect the material's behavior in direct contact with cells, raising concerns about its effectiveness. Calcium phosphates (CaPs) are a group of materials that, despite being highly biocompatible and promoting bone formation, still exhibit inconsistencies in basic cytotoxicity evaluations. Hence, in order to test the cytocompatibility dependence on different experimental setups and material-cell interactions, we used amorphous calcium phosphate, α-tricalcium phosphate, hydroxyapatite, and octacalcium phosphate (0.1 mg/mL to 5 mg/mL) with core cell lines of bone microenvironment: mesenchymal stem cells, osteoblast-like and endothelial cells. All materials have been characterized for their physicochemical properties before and after cellular contact and once in vitro assays were finalized, groups identified as 'cytotoxic' were further analyzed using a modified Annexin V apoptosis assay to accurately determine cell death. The obtained results showed that indirect contact following ISO standards had no sensitivity of tested cells to the materials, but direct contact tests at physiological concentrations revealed decreased metabolic activity and viability. In summary, our findings offer valuable guidelines for handling biomaterials, especially in powder form, to better evaluate their biological properties and avoid false negatives commonly associated with the traditional standard approach.

Pre-Registration Assessment of Bone-Filling Products.

The use of bone-filling material to repair bone defects and fix implanted bone grafts is a developing area in medicine. Investigators can evaluate bone-filling materials through use of several indices to make comparisons and to determine suitability for application in humans1 . However, it is quite difficult to transform their discovery into practical use, because the viability of the studied material might require examination of all aspects of properties. In addition, for a material to become a product, a complete procedure involving a declaration, registration, and approval is necessary. This article introduces the technical indices that the investigators and reporters should provide in their declaration and registration data to meet the relevant standards in China. The indices include physical and chemical properties, biocompatibility, biosecurity, pre-clinical animal model tests, sterilization and disinfection, product duration, and packaging. Full consideration of all possible indices is crucial to realize the transformation from a designed product to a commercial medical device, which requires effective interaction between clinicians and engineers.

Current Methods Applied to Biomaterials - Characterization Approaches, Safety Assessment and Biological International Standards.

Safety and biocompatibility assessment of biomaterials are themes of constant concern as advanced materials enter the market as well as products manufactured by new techniques emerge. Within this context, this review provides an up-to-date approach on current methods for the characterization and safety assessment of biomaterials and biomedical devices from a physical-chemical to a biological perspective, including a description of the alternative methods in accordance with current and established international standards.

Computational Fluid Dynamics Assessment Associated with Transcatheter Heart Valve Prostheses: A Position Paper of the ISO Working Group.

The governing international standard for the development of prosthetic heart valves is International Organization for Standardization (ISO) 5840. This standard requires the assessment of the thrombus potential of transcatheter heart valve substitutes using an integrated thrombus evaluation. Besides experimental flow field assessment and ex vivo flow testing, computational fluid dynamics is a critical component of this integrated approach. This position paper is intended to provide and discuss best practices for the setup of a computational model, numerical solving, post-processing, data evaluation and reporting, as it relates to transcatheter heart valve substitutes. This paper is not intended to be a review of current computational technology; instead, it represents the position of the ISO working group consisting of experts from academia and industry with regards to considerations for computational fluid dynamic assessment of transcatheter heart valve substitutes.

Experimental Assessment of Flow Fields Associated with Heart Valve Prostheses Using Particle Image Velocimetry (PIV): Recommendations for Best Practices.

Experimental flow field characterization is a critical component of the assessment of the hemolytic and thrombogenic potential of heart valve substitutes, thus it is important to identify best practices for these experimental techniques. This paper presents a brief review of commonly used flow assessment techniques such as Particle image velocimetry (PIV), Laser doppler velocimetry, and Phase contrast magnetic resonance imaging and a comparison of these methodologies. In particular, recommendations for setting up planar PIV experiments such as recommended imaging instrumentation, acquisition and data processing are discussed in the context of heart valve flows. Multiple metrics such as residence time, local velocity and shear stress that have been identified in the literature as being relevant to hemolysis and thrombosis in heart valves are discussed. Additionally, a framework for uncertainty analysis and data reporting for PIV studies of heart valves is presented in this paper. It is anticipated that this paper will provide useful information for heart valve device manufacturers and researchers to assess heart valve flow fields for the potential for hemolysis and thrombosis.

Utilization of recycled asphalt concrete with warm mix asphalt and cost-benefit analysis.

The asphalt paving industries are faced with two major problems. These two important challenges are generated with an increase in demand for environmentally friendly paving mixtures and the problem of rapidly rising raw materials. Recycling of reclaimed asphalt pavement (RAP) is a critical necessity to save precious aggregates and reduce the use of costly bitumen. Warm Mix Asphalt (WMA) technology provides not only the option of recycling asphalt pavement at a lower temperature than the temperature maintained in hot mixtures but also encourages the utilization of RAP and therefore saves energy and money. This paper describes the feasibility of utilizing three different WMA additives (organic, chemical and water containing) at recommended contents with different percentages of RAP. The mechanical properties and cost-benefit analysis of WMA containing RAP have been performed and compared with WMA without RAP. The results indicated that, 30%, 10% and 20% can be accepted as an optimum RAP addition related to organic, chemical and water containing additives respectively and organic additive with 30% RAP content has an appreciable increase in tensile strength over the control mix. It was also concluded that the RAP with WMA technology is the ability to reduce final cost compared to HMA and WMA mixtures.

Characterisation factors for life cycle impact assessment of sound emissions.

Noise is a serious stressor affecting the health of millions of citizens. It has been suggested that disturbance by noise is responsible for a substantial part of the damage to human health. However, no recommended approach to address noise impacts was proposed by the handbook for life cycle assessment (LCA) of the European Commission, nor are characterisation factors (CFs) and appropriate inventory data available in commonly used databases. This contribution provides CFs to allow for the quantification of noise impacts on human health in the LCA framework. Noise propagation standards and international reports on acoustics and noise impacts were used to define the model parameters. Spatial data was used to calculate spatially-defined CFs in the form of 10-by-10-km maps. The results of this analysis were combined with data from the literature to select input data for representative archetypal situations of emission (e.g. urban day with a frequency of 63 Hz, rural night at 8000 Hz, etc.). A total of 32 spatial and 216 archetypal CFs were produced to evaluate noise impacts at a European level (i.e. EU27). The possibility of a user-defined characterisation factor was added to support the possibility of portraying the situation of full availability of information, as well as a highly-localised impact analysis. A Monte Carlo-based quantitative global sensitivity analysis method was applied to evaluate the importance of the input factors in determining the variance of the output. The factors produced are ready to be implemented in the available LCA databases and software. The spatial approach and archetypal approach may be combined and selected according to the amount of information available and the life cycle under study. The framework proposed and used for calculations is flexible enough to be expanded to account for impacts on target subjects other than humans and to continents other than Europe.

A preliminary biomechanical assessment of a polymer composite hip implant using an infrared thermography technique validated by strain gage measurements.

With the resurgence of composite materials in orthopaedic applications, a rigorous assessment of stress is needed to predict any failure of bone-implant systems. For current biomechanics research, strain gage measurements are employed to experimentally validate finite element models, which then characterize stress in the bone and implant. Our preliminary study experimentally validates a relatively new nondestructive testing technique for orthopaedic implants. Lock-in infrared (IR) thermography validated with strain gage measurements was used to investigate the stress and strain patterns in a novel composite hip implant made of carbon fiber reinforced polyamide 12 (CF/PA12). The hip implant was instrumented with strain gages and mechanically tested using average axial cyclic forces of 840 N, 1500 N, and 2100 N with the implant at an adduction angle of 15 deg to simulate the single-legged stance phase of walking gait. Three-dimensional surface stress maps were also obtained using an IR thermography camera. Results showed almost perfect agreement of IR thermography versus strain gage data with a Pearson correlation of R(2) = 0.96 and a slope = 1.01 for the line of best fit. IR thermography detected hip implant peak stresses on the inferior-medial side just distal to the neck region of 31.14 MPa (at 840 N), 72.16 MPa (at 1500 N), and 119.86 MPa (at 2100 N). There was strong correlation between IR thermography-measured stresses and force application level at key locations on the implant along the medial (R(2) = 0.99) and lateral (R(2) = 0.83 to 0.99) surface, as well as at the peak stress point (R(2) = 0.81 to 0.97). This is the first study to experimentally validate and demonstrate the use of lock-in IR thermography to obtain three-dimensional stress fields of an orthopaedic device manufactured from a composite material.

Inference and sample size calculation in the fit assessment of filtering facepiece respirators.

Filtering facepiece respirators have recently been cleared by the U.S. Food and Drug Administration (FDA) for use by the general public in public health medical emergencies such as pandemic influenza. In the fit assessment of these devices it is important to distinguish between the two sources of variability: population heterogeneity and random fluctuations over repeated donnings. The FDA Special Controls Guidance Document (SCGD) which describes these devices and their evaluation, recommends that the fit performance of a filtering facepiece respirator be evaluated in terms of the proportion of users who will receive a specified level of protection 95% of the time. A point estimator of this proportion is easily obtained under an analysis of variance model, and the SCGD suggests bootstrap as one possible approach to interval estimation. This paper describes a closed-form procedure to obtain confidence intervals and provides sample size formulas. Simulation results suggest that the proposed procedure performs well in realistic settings and compares favorably to two simple bootstrap procedures.

Preparation and assessment of glutaraldehyde-crosslinked collagen-chitosan hydrogels for adipose tissue engineering.

A portfolio of crosslinked chitosan:collagen blends was prepared, and their microarchitecture and water binding capacity were studied to investigate their application for adipose tissue engineering. Glutaraldehyde (GA) concentration had little effect on scaffold morphology or water binding capacity. However, the processing freezing temperature prior to lyophilization affected both. In vitro cytocompatibility of pre-adipocytes (PAs) was assessed for a candidate collagen:chitosan blend using two assays. Results confirm the viability of PAs on GA-crosslinked collagen:chitosan scaffolds. A rat subcutaneous pocket assay was employed to assess PA-seeded scaffolds in vivo. Animal tests proved that PA-seeded scaffolds were biocompatible, could induce vascularization, and form adipose tissue.

Product quality-based eco-efficiency applied to digital cameras.

When calculating eco-efficiency, there are considerable confusion and controversy about what the product value is and how it should be quantified. We have proposed here a quantification method for eco-efficiency that derives the ratio of the multiplication value of the product quality and the life span of a product to its whole environmental impact based on Life Cycle Assessment (LCA). In this study, product quality was used as the product value and quantified by the following three steps: (1) normalization based on a value function, (2) determination of the subjective weighting factors of the attributes, and (3) calculation of product quality of the chosen products. The applicability of the proposed method to an actual product was evaluated using digital cameras. The results show that the eco-efficiency values of products equipped with rechargeable batteries were higher than those products that use alkaline batteries, because of higher quality values and lower environmental impacts. The sensitivity analysis shows that the proposed method was superior to the existing methods, because it enables to identify the quality level of the chosen products by considering all products that have the same functions in the market and because, when adding a new product, the calculated quality values in the proposed method do not have to be changed.

The European standard for sun-protective clothing: EN 13758.

Clothing is considered one of the most important tools for sun protection. Contrary to popular opinion, however, some summer fabrics provide insufficient ultraviolet (UV) protection. The European Committee for Standardization (CEN), has developed a new standard on requirements for test methods and labelling of sun-protective garments. This document has now been completed and is published. Within CEN, a working group, CEN/TC 248 WG14 'UV protective clothing', was set up with the mission to produce standards on the UV-protective properties of textile materials. This working group started its activities in 1998 and included 30 experts (dermatologists, physicists, textile technologists, fabric manufacturers and retailers of apparel textiles) from 11 European member states. Within this working group, all medical, ethical, technical and economical aspects of standardization of UV-protective clothing were discussed on the basis of the expertise of each member and in consideration of the relevant literature in this field. Decisions were made in consensus. The first part of the standard (EN 13758-1) deals with all details of test methods (e.g. spectrophotometric measurements) for textile materials and part 2 (EN 13758-2) covers classification and marking of apparel textiles. UV-protective cloths for which compliance with this standard is claimed must fulfill all stringent instructions of testing, classification and marking, including a UV protection factor (UPF) larger than 40 (UPF 40+), average UVA transmission lower than 5%, and design requirements as specified in part 2 of the standard. A pictogram, which is marked with the number of the standard EN 13758-2 and the UPF of 40+, shall be attached to the garment if it is in compliance with the standard. The dermatology community should take cognizance of this new standard document. Garment manufacturers and retailers may now follow these official guidelines for testing and labelling of UV-protective summer clothes, and the sun-aware consumer can easily recognize garments that definitely provide sufficient UV protection.

Medical devices; patient examination and surgeons' gloves; test procedures and acceptance criteria. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule to improve the barrier quality of medical gloves marketed in the United States. The rule will accomplish this by reducing the current acceptable quality levels (AQLs) for leaks and visual defects observed during FDA testing of medical gloves. By reducing the AQLs for medical gloves, FDA will also harmonize its AQLs with consensus standards developed by the International Organization for Standardization (ISO) and ASTM International (ASTM).

New trends in biological evaluation of medical devices.

More extensive material characterisation and increased determination of toxicological risks are now required when evaluating new medical devices. The new requirements together with other changes in the ISO 10993 series described here suggest how companies can adjust their approach.

Benchmark studies of induced radioactivity produced in LHC materials, Part I: Specific activities.

Samples of materials which will be used in the LHC machine for shielding and construction components were irradiated in the stray radiation field of the CERN-EU high-energy reference field facility. After irradiation, the specific activities induced in the various samples were analysed with a high-precision gamma spectrometer at various cooling times, allowing identification of isotopes with a wide range of half-lives. Furthermore, the irradiation experiment was simulated in detail with the FLUKA Monte Carlo code. A comparison of measured and calculated specific activities shows good agreement, supporting the use of FLUKA for estimating the level of induced activity in the LHC.

Benchmark studies of induced radioactivity produced in LHC materials, Part II: Remanent dose rates.

A new method to estimate remanent dose rates, to be used with the Monte Carlo code FLUKA, was benchmarked against measurements from an experiment that was performed at the CERN-EU high-energy reference field facility. An extensive collection of samples of different materials were placed downstream of, and laterally to, a copper target, intercepting a positively charged mixed hadron beam with a momentum of 120 GeV c(-1). Emphasis was put on the reduction of uncertainties by taking measures such as careful monitoring of the irradiation parameters, using different instruments to measure dose rates, adopting detailed elemental analyses of the irradiated materials and making detailed simulations of the irradiation experiment. The measured and calculated dose rates are in good agreement.