Biology subjects

Cidonio, G.

Publications and source records attributed to Cidonio, G..

3 recordsLinked to original sources

bioRxiv2024

Chronic mycobacteria infection triggers macrophage senescence

Chronic infections with intracellular pathogens such as Mycobacterium abscessus (Mab) pose significant health challenges due to their capacity to persist within host cells and evade immune responses. This study investigates the cellular responses to chronic Mab infection in macrophages, particularly focusing on cellular senescence. Using an in vitro model of chronic infection in murine alveolar-like macrophages, we found that Mab induces a senescent phenotype characterised by decreased proliferation, altered morphology, DNA damage signalling activation, and upregulation of senescence markers such as p21 and SA-{beta}-galactosidase. Intriguingly, senescent macrophages secreted pro-inflammatory cytokines, consistent with a senescence-associated secretory phenotype (SASP), which promoted secondary senescence in neighbouring uninfected cells. This paracrine transmission of senescence underscores a potentially deleterious effect of Mab-induced SASP on tissue microenvironments, fostering a pro-inflammatory niche that may contribute to pathogen persistence. These findings highlight Mab-induced senescence as a key factor in chronic infection pathology, suggesting that targeting senescent cells and SASP-related pathways could enhance treatment outcomes in chronic bacterial infections.

microbiology↗

bioRxiv2023

Human bone tissue-derived ECM hydrogels: Controlling physicochemical, biochemical, and biological properties through processing parameters

Decellularized tissues offer significant potential as biological materials for tissue regeneration due to their ability to preserve the complex compositions and architecture of the native extracellular matrix (ECM). While the use of decellularized ECM hydrogels from bovine and porcine bone tissues has been extensively studied, the evaluation and derivation of decellularized matrices from human bone tissue remain largely unexplored. The objective of this study was to investigate how the physiochemical and biological properties of ECM hydrogels derived from human bone ECM could be controlled by manipulating bone powder size (45-250 m, 250-1000 m, and 1000-2000 m) and ECM composition through modulation of digestion time (3, 5, and 7 days). The current studies demonstrate that a reduction in material bone powder size and an increase in ECM digestion time resulted in enhanced protein concentrations in the ECM hydrogels, accompanied by the presence of a diverse array of proteins. Furthermore, these adjustments in the physicochemical properties generated improved gelation strength of the hydrogels. The evaluation of human bone marrow-derived stromal cells (HBMSCs) cultured on ECM hydrogels derived from 45-250 m bone powder, treated for 7 days, demonstrated enhanced osteogenic differentiation compared to hydrogels derived from both larger bone powders and collagen gels. In conclusion, this study highlights the significant promise of human bone ECM hydrogels as biologically active materials for bone regeneration. The ability to manipulate digestion time and bone powder size enables the generation of hydrogels with enhanced release of ECM proteins and appropriate gelation and rheological properties, offering new opportunities for application in bone tissue engineering.

bioengineering↗

bioRxiv2023

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair but can fail to provide a long-term clinical resolution, emphasising the need for a functional biomimetic tissue engineering alternative. An attractive sustainable opportunity for tissue regeneration would be the application of human bone waste tissue for the synthesis of a material ink for 3D bioprinting of skeletal tissue. The use of human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate micro-environment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. Extrusion-based deposition was mediated by the blending of human bone-ECM (B) with nanoclay (L, Laponite(R)) and alginate (A) polymer, to engineer a novel material ink (LAB). The inclusion of nanofiller and polymeric material increased the rheological, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularisation following implantation in an ex vivo chick chorioallantoic membrane (CAM) model. Addition of bone morphogenetic protein-2 (BMP-2) with HBMSCs further enhanced vascularisation together with mineralisation after only 7 days. The current study demonstrates the synergistic combination of nanoclay with biomimetic materials, (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalised skeletal tissue repair. Graphical AbstractEngineering nanoclay-based bone ECM novel bioink for bone regeneration. Human bone trabecular tissue was demineralised, decellularised and blended with nanoclay (Laponite(R)) and alginate after digestion. The resulting ink was investigated for printability following rheological and filament fusion investigation. The microstructural arrangement of the blends was examined together with viability and functionality of bioprinted HBMSCs. Finally, the ability of the novel blend to support drug release ex vivo in a CAM model was determined confirming the potential of the bone ECM ink to support bone formation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/536074v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@b9dc13org.highwire.dtl.DTLVardef@1f6f0dorg.highwire.dtl.DTLVardef@1b3c098org.highwire.dtl.DTLVardef@295192_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗