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Biomaterial-associated infections (BAIs) are an increasing problem where antibiotic therapies are often ineffective. The design of novel strategies to prevent or combat infection requires a better understanding of how an implanted foreign body prevents the immune system from eradicating surface-colonizing pathogens. The objective of this review is to chart factors resulting in sub-optimal clearance of Staphylococcus aureus bacteria involved in BAIs. To this end, we first describe three categories of bacterial mechanisms to counter the host immune system around foreign bodies: direct interaction with host cells, modulation of intercellular communication, and evasion of the immune system. These mechanisms take place in a time frame that differentiates sterile foreign body reactions, BAIs, and soft tissue infections. In addition, we identify experimental interventions in S. aureus BAI that may impact infectious mechanisms. Most experimental treatments modulate the host response to infection or alter the course of BAI through implant surface modulation. In conclusion, the first week after implantation and infection is crucial for the establishment of an S. aureus biofilm that resists the local immune reaction and antibiotic treatment. Although established and chronic S. aureus BAI is still treatable and manageable, the focus of interventions should lie on this first period.

Implantable insulin infusion systems using the intra-peritoneal route have dramatically changed the management of diabetes paving the way toward the realization of the potential "holy grail" of a fully implantable artificial pancreas. However, the wear duration of delivery catheters is compromised by the foreign body-mediated immune response. Both occlusion material present at the distal catheter tip end and fibrotic encapsulation surrounding the catheters influence the controlled and precise delivery of insulin, which eventually leads to the need for surgical intervention. The novel part of the current work is the investigation of the roles of implant physical properties (catheter size and tip configuration), as well as local inflammation control (through utilization of an anti-inflammatory agent) on the host fibrotic response using a previously developed animal model. The cellular and molecular response, the medication delivery efficacy as well as the ability to flush the catheters were examined and further compared among the different mitigation strategies. Reduction in catheter size as well as tuning the tip configuration from a cone shape to a round shape showed delayed host recognition and delayed propagation of the fibrotic response. However, the round shaped tips had an increased occurrence of lumen occlusion as a result of flow change. It became apparent that changing the physical properties of the catheters was not a long-term solution to catheter obstructions caused by the foreign body reaction. In comparison, control of the local inflammatory response through the use of an anti-inflammatory agent demonstrated a promising strategy for maintenance of catheter functionality without any type of obstructions. These finding will have a large impact toward the development of long-term use catheters for continuous intraperitoneal insulin infusion., (Copyright © 2021 Elsevier B.V. All rights reserved.)