Analysis of osteomyelitis development in a translational 3D tissue model: Skin-Bone-Endothelium integration and bacterial inoculation for the optimization of clinical treatment approaches

Status:

ongoing

Aims:

The project aims to develop a novel human 3D osteomyelitis model integrating bone, endothelial, and skin tissue. This vascularised and subsequently infected construct will mimic infection processes in human bone more realistically than two-dimensional cell cultures, enabling improved understanding of underlying mechanisms and to identify potential therapeutic approaches.

Activities/Methods:

The model is generated through a multi-step tissue engineering workflow. Human osteoblasts first synthesise a mineralised extracellular bone matrix, which is subsequently decellularised using a modified chemical protocol and recellularised with osteogenic and osteoclastic progenitor cells. Co-culture with human endothelial cells induces the formation of angiogenesis-like microvascular structures. This vascularised bone construct is then integrated with an organotypic 3D skin equivalent. Following full tissue differentiation, the system is inoculated with biofilm-forming Staphylococcus aureus laboratory strains as well as clinical wild-type isolates. Infection and biofilm progression are analysed by cytokine profiling, histological and immunofluorescent characterisation, viability and permeability assays, and quantitative as well as imaging-based biofilm assessment techniques.

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