Biology subjects

Ghezzi, C. E.

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

3 recordsLinked to original sources

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↗