A hallmark of chronic and inflammatory diseases is the formation of a fibrotic and stiff extracellular matrix (ECM), typically associated with abnormal, leaky microvascular capillaries. Mechanisms explaining how the microvasculature responds to ECM alterations remain unknown. Here, we used a microphysiological model of capillaries on a chip mimicking the characteristics of healthy or fibrotic collagen to test the hypothesis that perivascular cells mediate the response of vascular capillaries to mechanical and structural changes in the human ECM. Capillaries engineered in altered fibrotic collagen had abnormal migration of perivascular cells, reduced pericyte differentiation, increased leakage, and higher regulation of inflammatory/remodeling genes, all regulated via NOTCH3 , a known mediator of endothelial-perivascular cell communication. Capillaries engineered either with endothelial cells alone or with perivascular cells silenced for NOTCH3 expression showed a minimal response to ECM alterations. These findings reveal a previously unknown mechanism of vascular response to changes in the ECM in health and disease.

Head and neck cancers (HNCs) rank as the sixth most common cancer globally and result in over 450 000 deaths annually. Despite considerable advancements in diagnostics and treatment, the 5-year survival rate for most types of HNCs remains below 50%. Poor prognoses are often attributed to tumor heterogeneity, drug resistance, and immunosuppression. These characteristics are difficult to replicate using in vitro or in vivo models, culminating in few effective approaches for early detection and therapeutic drug development. Organs-on-a-chip offer a promising avenue for studying HNCs, serving as microphysiological models that closely recapitulate the complexities of biological tissues within highly controllable microfluidic platforms. Such systems have gained interest as advanced experimental tools to investigate human pathophysiology and assess therapeutic efficacy, providing a deeper understanding of cancer pathophysiology. This review outlines current challenges and opportunities in replicating HNCs within microphysiological systems, focusing on mimicking the soft, glandular, and hard tissues of the head and neck. We further delve into the major applications of organ-on-a-chip models for HNCs, including fundamental research, drug discovery, translational approaches, and personalized medicine. This review emphasizes the integration of organs-on-a-chip into the repertoire of biological model systems available to researchers. This integration enables the exploration of unique aspects of HNCs, thereby accelerating discoveries with the potential to improve outcomes for HNC patients.

After bleaching, enamel surfaces are damaged, contributing to erosion and tooth sensitivity. Although fluoride is used after bleaching to try and revert alterations, it is not capable of repairing tooth structure. This study compared the effect of a self-assembly peptide (P₁₁-4), with and without fluoride, and sodium fluoride (NaF 2%) on the Knoop microhardness (KHN) and surface roughness (Ra (μm)) of bleached enamel with an in-office bleaching regimen. Enamel blocks of bovine teeth (5 × 5 × 2 mm) with standardized surface hardness were bleached with 35% carbamide peroxide, following the manufacturer’s instructions. The teeth were randomly divided into the following groups (n = 7) according to post-bleaching treatment: no treatment (negative control) (C-); 2% NaF (NaF); Curodont™ Repair (Repair); and Curodont™ Protect (Protect). Specimens were stored in artificial saliva at 37 °C. To evaluate the effect of the post-bleaching treatments, KHN and Ra were measured before bleaching (baseline) and 24 h and 7 days after bleaching. Data were submitted to repeated measures ANOVA and Bonferroni tests (α = 0.05). There were significant interactions between the study factors (p = 0.001). After 7 days, Repair (572.50 ± 79.04) and Protect (583.00 ± 74.76) specimens showed increased surface KHN, with values higher than the NaF (465.50 ± 41.50) and C- (475.22 ± 58.95) baseline values. There was no significant difference in KHN at 24 h among groups (p = 0.587). At 24 h after bleaching, Repair was significantly different from all groups (p < 0.05). Repair showed the lowest Ra (μm) values (0.133 ± 0.035). After seven days, there was no significant difference in Ra values among groups when compared to the baseline. The use of P₁₁-4-based materials after bleaching resulted in the fastest recovery to baseline enamel properties.