Modulation of the Foreign Body Reaction for Implants in the Subcutaneous Space: Microdialysis Probes as Localized Drug Delivery/Sampling Devices

Abstract

Modulation of the foreign body reaction is considered to be an important step toward creation of implanted sensors with reliable long-term performance. In this work, microdialysis probes were implanted into the subcutaneous space of Sprague-Dawley rats. The probe performance was evaluated by comparing collected endogenous glucose concentrations with internal standard calibration (2-deoxyglucose, antipyrine, and vitamin B12). Probes were tested until failure, which for this work was defined as loss of fluid flow. In order to determine the effect of fibrous capsule formation on probe function, monocyte chemoattractant protein-1/CC chemokine ligand 2 (MCP-1/CCL2) was delivered locally via the probe to increase capsule thickness and dexamethasone 21-phosphate was delivered to reduce capsule thickness. Probes delivering MCP-1 had a capsule that was twice the thickness (500-600 μm) of control probes (200-225 μm) and typically failed 2 days earlier than control probes. Probes delivering dexamethasone 21-phosphate had more fragile capsules and the probes typically failed 2 days later than controls. Unexpectedly, extraction efficiency and collected glucose concentrations exhibited minor differences between groups. This is an interesting result in that the foreign body capsule formation was related to the duration of probe function but did not consistently relate to probe calibration.

A review of the effects of FSCV and microdialysis measurements on dopamine release in the surrounding tissue

“…47 DXM has also been used to inhibit the immune response to microdialysis probes implanted subcutaneously. 48 As far as we know, we were the first to investigate the impact of DXM on tissue abnormalities associated with microdialysis probes in the brain. We performed microdialysis in the rat brain for 5 days with and without DXM in the perfusion fluid.…”

Drug delivery strategies to control macrophages for tissue repair and regeneration

“…35 Similarly, the continuous delivery of dexamethasone from microdialysis tubing reduced fibrous capsule thickness in subcutaneous tissue of rats. 36 However, somewhat contradictory results were shown when Stevens et al 37 delivered dexamethasone from a gelatin-based hydrogel implanted subcutaneously in mice. They found that the delivery of dexamethasone delayed but intensified the inflammatory response at day 7 postimplantation.…”

Localized delivery of dexamethasone-21-phosphate via microdialysis implants in rat induces M(GC) macrophage polarization and alters CCL2 concentrations

“…Since asolute concentration gradient exits between the perfusion fluid and the ECS, solutes diffuse into the membrane lumen and the resulting dialysate is collected and quantified [33]. This allows microdialysis to be used to simultaneously collect analytes from the ECS as well as deliver modulators to the ECS provided they are smaller than the MWCO of the membrane [34]. Dexamethasone-21-phosphate is a water-soluble derivative of the hydrophobic dexamethasone that is converted to dexamethasone in vivo by esterases [35].…”