The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials

Abstract

The inflammatory and fibrous responses in a subcutaneous rat model were evaluated around degradable polyurethane urea (PUUR; Artelon), with titanium and tissue culture polystyrene (PS) discs having different surface chemical properties but similar surface topography. Cytokines, viability, cellular response, differentiation of cells and fibrous capsule formation and vascularization was investigated after 1, 7 and 21 days of implantation. The exudates retrieved from the pockets were analysed with respect to the total cell numbers, the proportions of cell types, the differentiation of monocytes/macrophages (ED1, ED2), the DNA content and the viability (LD, Trypan blue). Tumour necrosis factor alpha ((h)TNF-alpha) and interleukin-10 ((h)IL-10) were quantified by ELISA. The number of blood vessels, blood vessel luminal area, blood vessel distribution and the fibrous capsule thickness were analysed. The highest number of cells in the exudates around all implants was detected during the early phase of healing (1-7 days). The proportion of ED2-positive cells in the exudates increased from 2-8% at 1 day to 43-56% at 21 days. The levels of TNF-alpha were low with a decrease at 7 days. After 21 days high amounts of IL-10 in the exudates were detected, in particular around PUUR. This study shows that the transition from inflammation to repair (1-21 days) around PUUR, Ti and PS materials was characterized by a decrease in inflammatory cell influx, an increasing proportion of ED2-expressing macrophages, a biphasic TNF-alpha secretion, an increase of IL-10 and a fibrous capsule formation similar to all materials tested.

The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

“…Foreign body giant cells are formed by fusion of macrophages (Anderson, 2000) and are considered a hallmark of the foreign body response (Jay et al, 2010). The presence of macrophages up to 28 days after foreign body implantation is in accord with a previous report by Gretzer et al (2006) who showed increasing proportions of ED2 + mature macrophages over time in exudates surrounding subcutaneous implants in rats. However in our experience, the peritoneal foreign body response is more rapid in rats than mice.…”

“…However despite attempts to identify non-immunogenic implant materials, or to mask surface properties of the implant material with biocompatible coatings (Quinn et al, 1995;Shive & Anderson, 1997;Draye et al, 1998;Paradossi et al, 2003), the inflammatory response cannot be completely avoided (Cao et al, 2008). This is thought to be due to the adsorption of proteins such as fibrinogen, complement and antibodies to the material immediately after implantation (Kao et al, 1999;Hu et al, 2001;Gretzer et al, 2006). Thus as outlined by Wisniewski et al (2001), the key to long-term functionality of implanted devices such as glucose sensors is modulation of the tissue response.…”

Foreign body reaction to biomaterials

“…[120] IL-1α, IL-1β, TNF-α, and IL-10 were quantified at biomaterial implant sites by enzyme linked immunosorbent assay (ELISA). [3,131] We have recently started using high throughput immunoassays to quantify a multitude of cytokines/chemokines at biomaterial implant sites (unpublished results).…”

“…[1][2][3][4] In the very early process of implantation, blood/material interactions occur with protein adsorption to the biomaterial surface and development of a blood-based transient provisional matrix that forms on and around the biomaterial. The provisional matrix is the initial thrombus/blood clot at the tissue/material interface.…”

Interfacing with the nervous system: a review of current bioelectric technologies

“…Following implantation of any bioelectronic device, the host foreign body response will result in rapid protein adsorption onto the material surface, resulting in a cascade of inflammatory events mediated by cytokines, chemoattractants, and growth factors released by neutrophils, monocytes, and lymphocytes [2,45]. The acute polymorphonuclear cell-mediated inflammatory phase transcends into a chronic inflammatory phase mediated by monocytes and lymphocytes.…”