A study assessing the viability of using Fused Filament Fabrication (FFF) Additive Manufacturing (AM) technology to manufacture customised Class I medical devices

Additive manufacturing (AM) is becoming an increasingly common manufacturing method for medical devices due to the benefits of advanced customisation, improved fit and opportunities for innovation. However, many AM medical devices remain inaccessible due to high costs of hardware and consumables, and the large infrastructural requirements required for operation. Fused filament fabrication (FFF) is a highly accessible AM technique due to its open-source nature, which has led to an extensive market of affordable desktop 3D printers. In this work FFF has been demonstrated as a potentially viable technique to fabricate low-risk medical devices in two case studies presented in this thesis: a customised daily living aid and a range of medical devices in response to the COVID-19 pandemic. Although the potential of the technology has been demonstrated, research around the practical suitability of FFF for medical applications remained limited, with much of the research in the field focussing on proof-of-concept applications, which did not explore the necessary requirements for the integration of the technology into daily clinical practices. This thesis investigates the fundamental requirements of the FFF AM technique for it to be used for Class I medical device applications in three identified use cases: non-specialist, research and industrial use. In keeping with the ambition for FFF to provide accessible solutions, mid-range hardware aimed at professional printing applications was selected to carry out this work, which encompasses the activities present in each of the three identified use cases. A methodology was presented to determine the repeatability and reproducibility of FFF across three potential use cases, which revealed varying process capability between the X-, Y- and Z- printing directions for individual machines, and significant variation between multiple machines of the same make and model. The repeatability and reproducibility of the FFF technique was identified as a key limitation for the widespread adoption of FFF technology for specialist and industrial use. The smallest tolerance achieved from a professional desktop FFF printer was 0.3mm in both the X- and Y- directions, and 0.4mm in the Z-direction. Additional variable factors were studied, including the condition of filament with respect to its storage environment and duration of storage, the influence of different colours and pigments present in filament and the use of an air management add-on unit intended to enhance the hardware. The glass transition temperature of Tough PLA remained largely unaffected from variable storage conditions, which when submerged in water decreased by around 1.4ºC from that of ambiently stored filament. The mechanical properties of printed parts were influenced by filament colour, with white filament producing parts with increased elongation and tensile strength than other colours studied. Dimensional accuracy in the Z-printing direction was affected by air management, where samples produced with air management were measured higher than the nominal value, and without air management lower than the nominal value. This thesis is the first known work to explore the suitability of FFF technology for Class I medical devices, from the perspective of both specialist and non-specialist users. The key barriers to widespread adoption were identified as the repeatability and reproducibility of the technique, and the influence of variable factors on the process and part performance. The exploration of these continually referenced medical device regulations, whilst consideration was given to how the experimental work can be applied to real-world Class I medical device manufacturing applications

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC