Biology subjects

Ghezzi, C. E.

Publications and source records attributed to Ghezzi, C. E..

5 recordsLinked to original sources

bioRxiv2026

Electrophysiological and neuroimmune responses of a cortical tissue model to chronic gamma radiation exposure

Exposure to chronic space radiation is a major health concern for long-duration missions beyond low Earth orbit. While most experimental studies simulate mission-relevant doses using acute irradiation, astronauts will experience persistent low-dose-rate exposure over months. Here, we used engineered three-dimensional (3D) mouse cortical tissue models and two-dimensional (2D) primary cortical cultures to investigate the effects of radiation dose rate on neuroglial function, inflammatory responses, and neuronal network activity. Cultures were exposed to a cumulative 0.5 Gy dose of {gamma}-radiation delivered either acutely (1 h) or chronically (166 h), with or without pretreatment using the radioprotective agent amifostine. In 3D cortical tissue models, we quantified DNA damage, astrocyte and microglia reactivity, neuronal survival, neurite morphology, and secretion of pro-inflammatory cytokines. In parallel, microelectrode array recordings were used to assess electrophysiological function in 2D neuronal networks following {gamma}-radiation or treatment with the radiomimetic drug bleomycin. Acute gamma radiation induced modest astrocyte activation, whereas chronic exposure caused limited neuroimmune alterations. Neither exposure paradigm impaired neuronal network activity, despite measurable DNA damage responses. Together, these findings indicate that neuronal function is preserved following low-dose-rate gamma irradiation while glial populations display selective sensitivity to radiation exposure.

bioengineering↗

bioRxiv2026

Profiling Gingival Inflammation in a 3D Oral Tissue Model Reveals Early Features of Disease Progression

Gingival health depends on a balanced interplay among the gingival epithelium, immune system, and oral microbiome. Disruption of this equilibrium through sustained biofilm accumulation and host inflammatory responses leads to gingivitis, a highly prevalent yet reversible condition which if left untreated could progress into more severe and irreversible condition called periodontitis. The early onset of gingivitis remains poorly defined due to subtle clinical presentation and pronounced interindividual variability. Current diagnostic approaches rely largely on clinical assessment and endpoint biomarkers, limiting insight into the early host-microbiome interactions that drive disease initiation. Here, we employ a previously validated, physiologically relevant oral tissue model (OTM) to longitudinally investigate epithelial-microbiome interactions following inoculation with patient-derived dysbiotic microbiomes from early-stage gingivitis. The OTM maintained host tissue integrity and microbial viability over a seven-day period, preserving epithelial barrier function, dynamic inflammatory responses, and disease-associated microbial signatures. Notably, we establish, for the first time in an in vitro platform, clinical calibration against gingival crevicular fluid (GCF), demonstrating that OTM responses recapitulate inoculum-dependent inflammatory signatures, increased microbial dissimilarity under dysbiotic conditions, and coordinated host-microbiome metabolic interactions. While pro-inflammatory responses were most pronounced at early time points, subsequent modulation toward anti-inflammatory states highlights the temporal complexity of host responses and suggests that longer culture durations may further resolve disease trajectories. Collectively, these findings validate the OTM as a robust, physiologically relevant platform that captures key features of periodontal health and inflammation. By integrating host viability, microbial ecology, and clinical benchmarking, this system enables mechanistic interrogation of early disease-driving processes and provides a translational framework for advancing predictive diagnostics and preventive therapeutic strategies in periodontal disease.

microbiology↗

bioRxiv2024

Sustaining healthy long-term host-microbiome interactions in a physiologically relevant dynamic gingival tissue model

Host-oral microbiome interactions are known to be critical in maintaining local and systemic health of the human body, although they are difficult to study in both clinical and in vitro applications. Despite efforts, recapitulation of gingival architecture and physiological characteristics of the periodontal niche cannot be achieved by traditional tissue engineering strategies. Here, we advanced our humanized three-dimensional gingival model by co-culturing it with a healthy patient-derived microbiomes for seven days within an oral bioreactor that mimics native salivary dynamics. Our results indicated long-term host and microbiome viability, host barrier integrity and physiological response, and preservation of healthy microbial populations and interbacterial dialogues. The model has proven useful in successfully mimicking tissue homeostasis at the interface of the periodontal niche and suitable for the introduction of immune cells. Future studies will focus on using the model as a comparator of periodontal inflammation and identifying biomarkers associated with eubiotic/dysbiotic profiles. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/577629v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1bc808aorg.highwire.dtl.DTLVardef@9b0ef8org.highwire.dtl.DTLVardef@1f3fbb1org.highwire.dtl.DTLVardef@11135f5_HPS_FORMAT_FIGEXP M_FIG Created partially in biorender.com. C_FIG

bioengineering↗

bioRxiv2023

A 3D in vitro cortical tissue model based on dense collagen to study the effects of gamma radiation on neuronal function

Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, we have developed a physiologically relevant 3D collagen-based cortical tissue model (CTM) for studying the functional response of human iPSC derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). We quantified cytotoxicity, DNA damage, morphology, and extracellular electrophysiology. We reported that 5 Gy exposure significantly increased cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreased neurite length and neuronal network activity. Additionally, we found that clinically deployed radioprotectant amifostine ameliorated the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which GR affects human cortical tissue and to screen prospective radioprotectant compounds.

bioengineering↗

bioRxiv2022

Three-dimensional humanized gingival tissue model to study oral microbiome

The oral cavity contains different microenvironments, as the non-shedding surface of the teeth and the epithelial mucosa, where oral barriers and microbial communities coexist. The interactions and balances between these two communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium is the first necessary step towards chronic inflammation and permanent tissue damage in the case of chronic periodontitis. There are currently no experimental models able to mimic the structural, physical, and metabolic conditions present in the oral gingival tissue to support the long-term investigation of host-pathogens unbalances. Herein, we report a 3D anatomical gingival in vitro model based on human primary culture that recapitulates the native tissue organization, and a native oxygen gradient within the gingival pocket to support human microbiome persistence with a physiologically relevant level of microbial diversity as well as native spatial organization. The modulation of inflammatory markers in the presence of oral microbiome suggested the humanized functional response of this model. The model will be used in future studies to investigate host-pathogen unbalances in gingivitis and periodontal disease.

bioengineering↗