Cell culture systems for studying the combined effects of matrix proteins and mechanical forces on the behavior of soft tissue cells have not been well developed. Here, we describe a new biomimetic cell culture system that allows for the study of mixtures of matrix proteins while controlling mechanical stiffness in a range that is physiological for soft tissues. This system consists of layer-by-layer (LbL)-assembled films of native matrix proteins atop mechanically tunable soft supports. We used hepatic stellate cells, which differentiate to myofibroblasts in liver fibrosis, for proof-of-concept studies. By culturing cells on collagen and lumican LbL-modified hydrogels, we demonstrate that this system is noncytotoxic and offers a valid control substrate, that the hydrogel determines the overall system mechanics, and that the addition of lumican to collagen influences the stellate cell phenotype. LbL-modified hydrogels offer the potential to study the influence of complex environmental factors on soft-tissue cells in culture.

OBJECTIVE: To compare the incidence of hypertensive disorders of pregnancy among women living with human immunodeficiency virus (HIV) on combination antiretroviral therapy (ART) to women without HIV, and to evaluate the association of hypertensive disorders of pregnancy with ART regimens or timing of ART initiation. METHODS: We conducted a retrospective cohort study among two overlapping pregnancy cohorts using preexisting databases at a single tertiary care hospital: all pregnant women who delivered during years 2016–2018 (cohort 1) and all women living with HIV who delivered during years 2011–2018 (cohort 2). The primary outcome for both cohorts was any hypertensive disorder of pregnancy; gestational hypertension and preeclampsia were also examined separately. The primary exposure variables were HIV status for cohort 1 and ART regimen (integrase strand transfer inhibitor–containing, protease inhibitor–containing, or non-nucleoside reverse transcriptase inhibitor–containing) for cohort 2. For estimation of risk ratios (RRs), we used a modified Poisson regression with robust error variances. Multivariate models among the women living with HIV in cohort 2 were tested for a statistical interaction between ART regimen and timing of initiation. RESULTS: In cohort 1, among 80 women living with HIV compared with 3,464 women without HIV, there was no difference in the risk of hypertensive disorders of pregnancy (29% in women living with HIV vs 30% in women without HIV, adjusted RR 0.9, 95% CI 0.6–1.3). In cohort 2, among 265 women living with HIV, integrase strand transfer inhibitor–containing regimens were associated with an increased risk for any hypertensive disorder of pregnancy (25% among integrase strand transfer inhibitor vs 10% among protease inhibitor, adjusted RR 2.8, 95% CI 1.5–5.1) and gestational hypertension (20% among integrase strand transfer inhibitor vs 8% among protease inhibitor, adjusted RR 2.8, 95% CI 1.3–5.9) compared with protease inhibitor–containing regimens. Timing of ART initiation was not associated with hypertensive disorders of pregnancy, nor did it significantly alter the associations between ART regimen and hypertensive disorders of pregnancy outcomes. CONCLUSION: Overall the risk of hypertensive disorders of pregnancy was similar among women living with HIV on ART and women without HIV. With greater integrase strand transfer inhibitor use, the greater frequency of hypertensive disorders of pregnancy with these regimens compared with protease inhibitor–containing regimens warrants future evaluation using cohorts with greater sample size.