Development of 3D Bioartificial Human Tissue Models of Periprosthetic Shoulder Joint Infection
Abstract
Periprosthetic joint infection (PJI) is a devastating and costly post-surgical complication that is not well understood due to the scarcity of physiologically representative experimental models. This thesis outlines the development of two 3D bioartificial human tissue models designed to study the cellular and biochemical interactions between primary fibroblasts from the shoulder capsule (SC) and infectious microorganisms. Using the Fibroblast-Bacteria Co-culture in 3D Collagen model, we demonstrated a global gene repression of metabolic and homeostatic processes in SC fibroblasts following 48 hours of co-culture with Cutibacterium acnes – the most common microbial cause of PJI in the shoulder. These cellular changes coincided with an increase in pro-inflammatory signaling. The Shoulder-Joint Implant Mimetic (S-JIM) model generated a range of oxygen levels (< 0.3% to 21% O2) that accurately represents the different microenvironments present across connective tissue layers in a shoulder joint. Electron microscopy images confirmed that the hypoxic conditions generated in the core of the S-JIM supported the anaerobic proliferation of C. acnes, but this microbial expansion resulted in the death of adjacent SC fibroblasts after 96 hours of co-culture. Using the S-JIM, we demonstrated the bactericidal effectiveness of direct vancomycin prophylaxis against C. acnes and confirmed the possibility of differentiating between healthy host tissues and C. acnes-infected tissues using mass spectrometry.