Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue

Abstract

Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100 kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer’s solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives.

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

“…This procedure was performed every day for 3 days. At the end of the 3 rd day the animal was euthanized and the probes and tissue surrounding the probes were harvested as previously stated [40]. In some cases, the tissue surrounding the probe (~1–2 mm) was removed from the probe and stored in RNAlater for PCR analysis.…”

Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous microdialysis implants on macrophage activation in rats

“…The techniques for implanting microdialysis probes into the rats have been previously described [37, 40]. Two probes were implanted on opposite sides of the spine with approximately 2.5 cm separation between them.…”

“…Dexamethasone-21-phosphate was used as a derivative which is more water soluble than dexamethasone and is converted to dexamethasone by in vivo esterases [41]. Dextran-500 is an osmotic agent used to reduce fluid loss in high MWCO probes which has been shown to cause no additional inflammation at the implant site [40]. Bovine serum albumin (BSA) is used in the perfusion fluid to prevent non-specific binding to microdialysis materials [42].…”

“…For the final flush, Ringer’s or Ringer’s + 20 μg mL −1 Dex were used as perfusion fluids for the control and treatment, respectively. On the seventh day post implantation, the animal was euthanized and the probe as well as the tissue surrounding the probe were harvested as previously described [40]. The probe and tissue surrounding it were then stored in optimal cutting temperature (OCT) solution and flash frozen using liquid nitrogen for histological and immunohistochemical analyses or the tissue surrounding the membrane was removed and stored in RNAlater for qRT-PCR analyses.…”

Animal Study and Pre-clinical Trials of Biomaterials

“…The properties of biocompatibility can be analyzed by using various approach in order to know the local response as well as the systemic response and to know the short and long response after it implanted in animals model ( Table 2). The extracellular fluid in the surrounding implantation site is the sample example that can be taken to determine the local response with the application of microdialysis system (Keeler et al 2014). The sampling time of extracellular fluid can be done within a few days up to several months adjusted to the study design.…”