Abstract
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.