Nguyen, Kianna

ABSTRACT Encapsulation of human pluripotent stem cells (hPSC) has high relevance for biomedical applications ranging from tissue engineering to drug screening and cellular therapies. Microcapsules serve a multitude of purposes—from promoting hPSC organization into spheroids to enabling scalable differentiation in vitro and providing immunoisolation in vivo. While multiple encapsulation strategies have been reported, there is typically a tradeoff between the structural complexity of capsules and throughput of their generation. Our paper describes a novel 3D printed microfluidic encapsulation device for fabricating structurally complex microcapsules with a hydrogel shell and aqueous core at rates of up to 1825 Hz. The use of 3D printing allowed to dramatically decrease device footprint when compared to standard soft lithography‐based microfluidic encapsulation devices. Leveraging decreased footprint and the ability to arrange fluidic networks in a 3D space, we fabricated a 10‐nozzle microencapsulation device that generated microcapsules at a rate 10‐times that of the single‐nozzle device. The novel microfluidic device was used to encapsulate hPSCs, human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPSCs). Hydrogel microcapsules with aqueous core promoted hPSCs aggregation into spheroids or embryoid bodies, which maintained high levels of pluripotency. Our technology enables safe and effective encapsulation of hPSCs on a scale (billions of cells) required to treat patients.

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.