Multiplexed cytokine detection of interstitial fluid collected from polymeric hollow tube implants—A feasibility study

Abstract

Cytokines are important cellular signaling proteins involved in inflammation, wound healing and are thought to direct the foreign body response to implanted materials. In this work, polyurethane tubes (25 mm length, 1.02 mm i.d., and 1.65 mm o.d.) were implanted into subcutaneous tissue of male Sprague-Dawley rats. The tubes served as the biomaterial and a means to collect the interstitial fluid that would be exchanged within the tube lumen and the surrounding tissue. After three and seven days, the tubes were explanted and cytokines in the fluid were quantified with a multiplexed cytokine immunoassay. Six cytokines, interleukin-1β. (IL-1β), IL-4, IL-6, IL-10, macrophage chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α), were simultaneously quantified. All cytokine concentrations with the exception of IL-4 and TNF-α ranged between low pg/mL to mid ng/mL levels. Neither TNF-α nor IL-4 was detected from any sample. These results illustrate the potential of using the tube materials combined with bead-based immunoassays as a direct method for in vivo collection of multiple cytokines in low microliter sample volumes for fixed day biomaterial implant studies.

Macrophage differentiation and polarization on a decellularized pericardial biomaterial

“…Two studies have investigated the physiological levels of cytokines present within an implanted hollow biomaterial tube [44,45]. Unfortunately, the outcomes obtained in those in vivo studies were constrained by the protocol employed: the subcutaneous implantation of the tube resulted (not surprisingly) in encapsulation.…”

Serum profile of pro- and anti-inflammatory cytokines in rats following implantation of low-temperature plasma-modified titanium plates

“…To examine the response of the body after implantation of biomaterials, the in vivo determination of different cytokines has recently been used in several studies [8][9][10][11]. Furthermore, a recent study which found that variations in the genes of cytokines including IL-2 and IL-6 influence the severity of osteolysis in patients with total hip arthroplasty demonstrates the potential relevance of cytokines for implant-associated complications [12].…”

In vitro and in vivo affinity microdialysis sampling of cytokines using heparin-immobilized microspheres

“…In our experience with sampling cytokines, it is rare to achieve a steady-state concentration. Cytokine concentrations can be quite variable, and for implanted objects, the concentrations can be in the low 10- to 100-pg/mL range [39-42], which, combined with microdialysis sampling extraction efficiencies, will lead to non-quantifiable concentrations. To obtain more consistent cytokine concentrations, we chose to use LPS to induce cytokine production, as previously demonstrated in mice [43].…”