3D Printed Models of Trochlear Dysplasia and Trochleoplasty Simulation for Trainee Education.

Trochlear dysplasia is a major contributor to patellofemoral instability and subsequent failure of isolated soft tissue reconstruction procedures in the treatment of recurrent patellar dislocation and/or subluxation. Trochleoplasty procedures aim to address abnormal osseous trochlear morphologic factors that contribute to patellar maltracking. However, teaching these techniques is limited by the lack of reliable training models for trochlear dysplasia and trochleoplasty simulation. Although a cadaveric knee model of trochlear dysplasia for trochleoplasty simulation has been recently described, cadaveric knees are less amenable for use in trochleoplasty planning and surgeon training because of the absence of reliable, natural dysplastic anatomic relationships, such as suprapatellar spurs due to the rarity of dysplastic cadavers and the high cost of cadaveric specimens. Furthermore, readily available sawbone models represent "normal" osseous trochlear morphology and are difficult to modify and bend due to their material composition. Given this, we have developed a cost-effective, reliable, and anatomically accurate three-dimensional (3D) knee model of trochlear dysplasia for trochleoplasty simulation and trainee education.

Three-dimensional printing accuracy analysis for medical applications across a wide variety of printers.

Purpose: Three-dimensional (3D) printing has had a significant impact on patient care. However, there is a lack of standardization in quality assurance (QA) to ensure printing accuracy and precision given multiple printing technologies, variability across vendors, and inter-printer reliability issues. We investigated printing accuracy on a diverse selection of 3D printers commonly used in the medical field. Approach: A specially designed 3D printing QA phantom was periodically printed on 16 printers used in our practice, covering five distinct printing technologies and eight different vendors. Longitudinal data were acquired over six months by printing the QA phantom monthly on each printer. Qualitative assessment and quantitative measurements were obtained for each printed phantom. Accuracy and precision were assessed by comparing quantitative measurements with reference values of the phantom. Data were then compared among printer models, vendors, and printing technologies; longitudinal trends were also analyzed. Results: Differences in 3D printing accuracy across printers were observed. Material jetting and vat photopolymerization printers were found to be the most accurate. Printers using the same 3D printing technology but from different vendors also showed differences in accuracy, most notably between vat photopolymerization printers from two different vendors. Furthermore, differences in accuracy were found between printers from the same vendor using the same printing technology, but different models/generations. Conclusions: These results show how factors such as printing technology, vendor, and printer model can impact 3D printing accuracy, which should be appropriately considered in practice to avoid potential medical or surgical errors.

An international collaborative study to assign value for Total Factor XIII-B Subunit Antigen to the WHO 1st International Standard for Factor XIII Plasma, (02/206): Communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen.

BACKGROUND: Factor XIII (FXIII)-B subunit measurements are required for the diagnosis and characterization of the type of FXIII deficiency. Furthermore, therapy for FXIII-A deficiency with recombinant FXIII (rFXIII-A) relies on available FXIII-B. OBJECTIVE: To carry out a collaborative study to calibrate and assign value to the current WHO 1st International Standard (IS) FXIII Plasma for Total FXIII-B subunit, relative to locally collected normal plasma pools. METHODS: Laboratories were instructed to use a validated method (specific ELISA antibodies provided) for assessment of Total FXIII-B subunit antigen potency. All laboratories used this method with one laboratory using an additional in-house method. Nine data sets were received from seven laboratories (37 assays in total), which provided a total of 35 valid estimates for this new assignment. Total FXIII-B subunit estimates were calculated relative to locally collected normal plasma pools, using an arbitrary value of 1.00 unit of Total FXIII-B subunit per ml, for each pool. RESULTS: Combination of results produced an overall mean of 0.98 units/mL with an inter-laboratory variability (geometric coefficients of variation - GCV%) of 18.3% [95% confidence interval: 0.86-1.11]. Real-time and bench stability studies indicated good stability and preservation of the FXIII-B subunit analyte in the WHO 1st IS FXIII Plasma (02/206). CONCLUSION: Following agreement by study participants, ISTH/SSC Experts, WHO-ISTH Liaison Group and the SSC Board, the WHO/ECBS established the current WHO 1st IS Factor XIII plasma (NIBSC code 02/206) by additionally assigning it with a Total FXIII-B subunit antigen value of 0.98 IU/ampoule, in October 2019.

Characterisation and application of recombinant FVIII-neutralising antibodies from haemophilia A inhibitor patients.

The development of anti-drug antibodies (ADAs) is a serious outcome of treatment strategies involving biological medicines. Coagulation factor VIII (FVIII) is used to treat haemophilia A patients, but its immunogenicity precludes a third of severe haemophiliac patients from receiving this treatment. The availability of patient-derived anti-drug antibodies can help us better understand drug immunogenicity and identify ways to overcome it. Thus, there were two aims to this work: (i) to develop and characterise a panel of recombinant, patient-derived, monoclonal antibodies covering a range of FVIII epitopes with varying potencies, kinetics and mechanism of action, and (ii) to demonstrate their applicability to assay development, evaluation of FVIII molecules and basic research. For the first objective we used recombinant antibodies to develop a rapid, sensitive, flexible and reproducible ex vivo assay that recapitulates inhibitor patient blood using blood from healthy volunteers. We also demonstrate how the panel can provide important information about the efficacy of FVIII products and reagents without the need for patient or animal material. These materials can be used as experimental exemplars or controls, as well as tools for rational, hypothesis-driven research and assay development in relation to FVIII immunogenicity and FVIII-related products.

Impact of controlled vacuum induced surface freezing on the freeze drying of human plasma.

During the freezing step of a typical freeze drying process, the temperature at which nucleation is induced is generally stochastically distributed, resulting in undesired within-batch heterogeneity. Controlled nucleation techniques have been developed to address this problem; these make it possible to trigger the formation of ice crystals at the same time and temperature in all the batch. Here, the controlled nucleation technique known as vacuum induced surface freezing is compared to spontaneous freezing for the freeze drying of human plasma, a highly concentrated system commonly stored in a dried state. The potency of Factor VIII (FVIII), a sensitive, labile protein present in plasma, and the reconstitution time of the dried cakes are evaluated immediately after freeze drying, and after 1, 3, 6 or 9 months storage at different degradation temperatures. We show that the application of controlled nucleation significantly reduces the reconstitution time and in addition helps to improve FVIII stability.