Abstract
Osteomyelitis is an inflammatory bone infection that is caused most commonly by the opportunistic pathogen Staphylococcus aureus. Research into staphylococcal induced bone infection is typically conducted using traditional 2D in vitro culture settings, which is not fully representative of the dynamic in vivo environment. In this study we utilised a collagen glycosaminoglycan scaffold, previously developed for bone tissue engineering, as a representative 3D model of infection. The scaffold resisted degradation and retained its pore structure, which is important for cellular function and survival, when seeded with both cells and bacteria. Using this model, we showed that in the presence of S. aureus, osteoblast proliferation was reduced over 21 days. Interestingly however these cells were more metabolically active compared to the uninfected cells and demonstrated increased mineralisation. Protein A (SpA) is a virulence factor found on the surface of S. aureus and has been shown to interact with osteoblasts. When SpA was removed from the surface of S. aureus, the osteoblasts show comparable activity with the uninfected cells—demonstrating the importance of SpA in the interaction between bone cells and S. aureus. Our results suggest that infected osteoblasts are capable of over-compensating for bone loss and bone destruction by increasing mineralisation in a 3D environment, key elements required for ensuring bone strength. It also reinforces our previously established result that S. aureus SpA is a critical mediator in osteomyelitis and might be a potential novel drug target to treat osteomyelitis by preventing the interaction between S. aureus and osteoblasts.
Highlights
Osteomyelitis is characterised by the presence of an infection in the typically sterile bone marrow, in particular cortical bone and periosteum
Achieving this we developed a 3D model of bone infection, using a collagen glycosaminoglycan biomaterial, which better represents the physiological bone microenvironment, in which bone cells, osteoblasts, are found
Scaffolds crosslinked with dehydrothermal treatment (DHT) and Ethyl-3-dimethyl aminopropyl carbodiimide (EDAC) resists collagen degradation when co-cultured with both osteoblasts and Staphylococcus aureus
Summary
Osteomyelitis is characterised by the presence of an infection in the typically sterile bone marrow, in particular cortical bone and periosteum It is characterised by severe non-resolving inflammation coupled with progressive bone loss and bone destruction [1, 2]. Bones are highly vascularised where arterial blood travels through the endosteal cavity to the marrow sinusoids before exiting through small vessels in the cortex [4] These bacteria in the blood (bacteraemia) can migrate through the vascular endothelial bed into the bone space initiating what is termed haematogenous osteomyelitis. Contiguous-focus osteomyelitis without vascular insufficiency can form from contaminated wounds or infected sites of implanted prosthetic material. A contiguous-focus osteomyelitis with vascular insufficiency typically arises from foot ulcers due to diabetes, where a non- resolving wound becomes infected, and often polymicrobial in nature, predominated by Staphylococci [7]. Regardless of the source of the contiguous-focus osteomyelitis, the opportunistic bacteria are in close proximity with bone to which they can attach, triggering bone loss and destruction
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