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Cartilage defect treatment strategies are dependent on the lesion size and severity. Osteochondral explants models are a platform to test cartilage repair strategies ex vivo. Current models lack in mimicking the variety of clinically relevant defect scenarios. In this controlled laboratory study, an automated device (artificial tissue cutter, ARTcut®) was implemented to reproducible create cartilage defects with controlled depth. In a pilot study, the effect of cartilage defect depth and oxygen tension on cartilage repair was investigated. Osteochondral explants were isolated from porcine condyles. 4 mm chondral and full thickness defects were treated with either porcine chondrocytes (CHON) or co-culture of 20 % CHON and 80 % MSC (MIX) embedded in collagen hydrogel. Explants were cultured with tissue specific media (without TGF-β) under normoxia (20 % O2) and physiological hypoxia (2 % O2). After 28 days, immune-histological stainings (Collagen II and X, Aggrecan) were scored (modified Bern-score, 3 independent scorer) to quantitatively compare treatments outcome. ARTcut® represents a software-controlled device for creation of uniform cartilage defects. Comparing the scoring results of the MIX and the CHON treatment, a positive relation between oxygen tension and defect depth was observed. Low oxygen tension stimulated cartilaginous matrix deposition in MIX group in chondral defects and CHON treatment in full thickness defects. ARTcut® has proved a powerful tool to create cartilage defects and thus opens a wide range of novel applications of the osteochondral model, including the relation between oxygen tension and defect depth on cartilage repair.

Abstract Objective High failure rates of (trauma induced) knee injuries highlight the need to improve current treatment strategies aiming to decrease the number of secondary osteoarthritis developed by patients in later stage [1-3]. In this controlled laboratory study the stimulative effect of mesenchymal stromal cells (MSC) on chondrocyte (CHON) extracellular matrix production was investigated in an ex vivo cartilage defect model (chondral vs. full thickness defects) cultured under normoxic (20 % O2) and physioxic (2 % O2) conditions. Design Porcine CHON or co-culture of 20 % CHON and 80 % MSC (MIX) were embedded in collagen type I hydrogel, implanted into 4 mm diameter cartilage defects of osteochondral explants and cultured with tissue specific media without addition of TGF-β under normoxia and physioxia. Chondral defects were induced automatically, while full thickness defects were created with biopsy punch. After 28 days of culture, samples were histologically processed, and treatments outcome was evaluated using international cartilage repair society (ICRS)-II scoring. Results Under physioxic conditions, cartilage repair scoring results of the MIX treatment (chondral 8.67 ± 2.42, full thickness 5.67 ± 1.21) were close to those of CHON treatment (chondral 8.17 ± 0.75, full thickness 7.33 ± 1.21). Overall, scoring results were higher in physioxia compared to normoxia conditions in chondral defects, but less or no prevalent for full thickness defects. Conclusion Co-culture of CHON with MSC represents a promising approach to stimulate chondrogenic repair and tissue formation in our ex vivo model and reduces total amount of CHON needed for cell-based treatment. Competing Interest Statement The authors have declared no competing interest. Footnotes * Andrea Schwab University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland E-Mail: andrea.schwabataofoundation.org * Alexa Buß University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, Roentgenring 11, 97070 Wuerzburg, Germany, Klinikum Würzburg Mitte gGmbH, Juliusspital, Juliuspromenade 19, 97070 Wuerzburg, Germany, E-Mail: alexa.bussatkwm-klinikum.de * Oliver Pullig University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine, Roentgenring 11, 97070 Wuerzburg, Germany, Fraunhofer Institute for Silicate Research ISC, Translational Center Regenerative Therapies, Roentgenring 11, 97070 Wuerzburg, Germany, E-Mail: oliver.pulligatisc.fraunhofer.de

Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were < 21 weeks at enrollment, between 2013 and 2015. CM was measured via the Childhood Trauma Questionnaire (CTQ) and participants above the moderate/severe cut-off for any of the five childhood abuse and neglect scales were assigned to the CM-exposed group. Common CM-associated health (obesity, depressive symptoms, hypertensive disorders) and behavioral (substance use) sequelae were obtained from standardized questionnaires and medical records. The main outcomes included PTB (gestational age < 37 weeks at birth) and SGA (birthweight < 10%ile for gestational age) abstracted from the medical record. Multivariable logisitic regression was used to test associations between CM, sequeale, and birth outcomes, and both moderation and mediation by CM-related sequelae were tested. Data were available for 657/744 participants. Any CM exposure was reported by 32% of participants. Risk for SGA birth was 61% higher among those in the CM group compared to the non-CM group (14.1% vs. 7.6%), and each subsequent form of CM that an individual was exposed to corresponded with a 27% increased risk for SGA (aOR 1.27, 95% CI 1.05, 1.53). There was no significant association between CM and PTB (9.3% vs. 13.0%, aOR 1.07, 95% CI 0.58, 1.97). Of these sequelae only hypertensive disorders were associated with both CM and SGA and hypertensive disorders of pregnancy did not mediate the association between CM and SGA. Our findings indicate that maternal CM exposure is associated with increased risk for SGA birth and highlight the importance of investigating the mechanisms whereby childhood adversity sets the trajectory for long-term and intergenerational health issues.

Several app-based studies share similar characteristics of a light touch approach that recruit, enroll, and onboard via a smartphone app and attempt to minimize burden through low-friction active study tasks while emphasizing the collection of passive data with minimal human contact. However, engagement is a common challenge across these studies, reporting low retention and adherence. This study aims to describe an alternative to a light touch digital health study that involved a participant-centric design including high friction app-based assessments, semicontinuous passive data from wearable sensors, and a digital engagement strategy centered on providing knowledge and support to participants. The Stress and Recovery in Frontline COVID-19 Health Care Workers Study included US frontline health care workers followed between May and November 2020. The study comprised 3 main components: (1) active and passive assessments of stress and symptoms from a smartphone app, (2) objective measured assessments of acute stress from wearable sensors, and (3) a participant codriven engagement strategy that centered on providing knowledge and support to participants. The daily participant time commitment was an average of 10 to 15 minutes. Retention and adherence are described both quantitatively and qualitatively. A total of 365 participants enrolled and started the study, and 81.0% (n=297) of them completed the study for a total study duration of 4 months. Average wearable sensor use was 90.6% days of total study duration. App-based daily, weekly, and every other week surveys were completed on average 69.18%, 68.37%, and 72.86% of the time, respectively. This study found evidence for the feasibility and acceptability of a participant-centric digital health study approach that involved building trust with participants and providing support through regular phone check-ins. In addition to high retention and adherence, the collection of large volumes of objective measured data alongside contextual self-reported subjective data was able to be collected, which is often missing from light touch digital health studies. ClinicalTrials.gov NCT04713111; https://clinicaltrials.gov/ct2/show/NCT04713111.