The role of Porphyromonas gingivalis (P. gingivalis) or its virulence factors, including lipopolysaccharide (LPS) not only has been related with periodontitis but also with endothelial dysfunction, a key mechanism involved in the genesis of atherosclerosis and hypertension that involving systemic inflammatory markers as angiotensin II (Ang II) and cytokines. This study compares the effect of repeated and unique exposures of P. gingivalis W83 LPS and live bacteria on the production and expression of inflammatory mediators and vasoconstrictor molecules with Ang II. Human coronary artery endothelial cells (HCAEC) were stimulated with purified LPS of P. gingivalis (1.0, 3.5 or 7.0 μg/mL) or serial dilutions of live bacteria (MOI 1: 100 - 1:0,1) at a single or repeated exposure for a time of 24 h. mRNA expression levels of AGTR1, AGTR2, IL-8, IL-1β and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1β and GM-CSF levels were measured by flow cytometry, ELISA determined Ang II levels. Live bacteria in a single dose increased mRNA levels of AGTR1, and repeated doses increased mRNA levels of IL-8 and IL-1β (p < 0.05). Repeated exposure of live-P. gingivalis induced significant production IL-6, MCP-1 and GM-CSF (p < 0.05). Moreover, these MCP-1, IL-6 and GM-CSF levels were greater than in cells treated with single exposure (p < 0.05), The expression of AGTR1 and production of Ang II induced by live-P. gingivalis W83 showed a vasomotor effect of whole bacteria in HCAEC more than LPS. In conclusion, the findings of this study suggest that repeated exposure of P. gingivalis in HCAEC induces the activation of proinflammatory and vasoconstrictor molecules that lead to endothelial dysfunction being a key mechanism of the onset and progression of arterial hypertension and atherosclerosis.

Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O₂), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, oxygen nanobubbles (OnB), an emerging versatile oxygen delivery platform, offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.

Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allows in vivo formation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5–28.8 ± 0.8 °C), low viscosity (133 ± 1.4–188 ± 16 cP), low force requirements for injectability (17 ± 0.3–39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4–332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably, in vivo subcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.

Hypoxia and nutrient-deprived microenvironments pose significant challenges to the survival of transplanted human umbilical cord mesenchymal stem cells (UC-MSCs), necessitating the development of controllable oxygen delivery strategies. In this study, we engineered fluorosurfactant-coated oxygen nanobubbles (Tivida^®-stabilized; TONBs) and assessed their cytoprotective effects in a two-dimensional (2D) ischemia-mimetic model (1% O₂ and 1% FBS). The TONBs were characterized by nanoparticle tracking analysis and zeta potential, while dissolved oxygen (DO) release was quantified in DMEM culture media. TONBs formed stable sub-200 nm populations with high colloidal stability (−58 mV) and demonstrated elevated DO levels up to ~18 ppm, compared to DMEM control (~ 8 ppm). Under hypoxic stress, TONB treatment preserved metabolic activity and viability, reduced mitochondrial ROS levels by ~20% and resulted in an ~8–9 fold downregulation of HIF-1α expression relative to untreated hypoxic controls. These results indicate that TONBs provide oxygen buffering to mitigate hypoxia-driven metabolic stress, supporting their potential as an oxygen delivery adjunct for regenerative medicine applications and tissue engineering applications.