Modulation of the tissue reaction to biomaterials. II. The function of T cells in the inflammatory reaction to crosslinked collagen implanted in T-cell-deficient rats

Abstract

Unwanted tissue reactions are often observed resulting in events such as early resorption of the biomaterial, loosening of the implant, or a chronic (immunologic) response. From immunologic studies it is known that inflammatory reactions can be modulated by use of (anti)-growth factors or anti-inflammatory drugs. Before this can be employed with respect to biomaterials, the role of individual factors (humoral and cellular) has to be studied. In this part of the investigation, the role of T cells was studied by use of T-cell-deficient (nude) rats and control (AO) rats. Hexamethylenediisocyanate-crosslinked dermal sheep collagen (HDSC) was selected as the test material. The results showed that T cells or T cell-related factors played a prominent role in the attraction of macrophages and the formation of giant cells, their antigen presentation, and their phagocytotic capacity. As a consequence, degradation of HDSC was strongly delayed. This study also showed that infiltration of fibroblasts and creation of stromal areas in HDSC was restricted to areas subjected to degradation. However, in time, absence of T cells resulted in increased formation and maturation of autologous rat collagen. Results obtained suggest that the inflammatory reaction to biomaterials might be modulated by controlling T-cell activation.

The in vivo assessment of a novel scaffold containing heparan sulfate for tissue engineering with human mesenchymal stem cells

“…In a normal immune response, T cells can signal to monocytes and activate the production of inflammatory cytokines such as IL-1b and TNF-a (Burger and Dayer 2002). However, T-cells are not necessary for the recruitment of macrophages, and NK cells have been suggested to take over the function of T-cells for macrophage activation in athymic rats in response to an implanted biomaterial (van Luyn et al 1998). We suspect this heightened innate immunity is most likely the cause of the loss of implanted hOPs observed in our study.…”

Tissue response to partially in vitro predegraded poly-L-lactide implants

“…What kind of immune reaction should trigger such an IFN g production or lack of production is not known. That T cells are important was demonstrated by the delayed degradation of dermal sheep collagen in T cell deficient (nude) rats [41]. Whether these reactions were related to the biological nature of the material implanted was not investigated.…”

An In Vivo Study of the Host Response to Starch‐Based Polymers and Composites Subcutaneously Implanted in Rats

“…[27,28] Lymphocytes have also been observed at the interface of some implants. [18,[29][30][31] These cells are able to secrete various mediators which, in turn, have functions in immunological and inflammatory responses. Although in the majority of the cases they are identified in low numbers, lymphocytes may secrete interleukin (IL)-4 [32] and interferon (IFN)-g [30] which can induce macrophage fusion and activation.…”

“…[18,[29][30][31] These cells are able to secrete various mediators which, in turn, have functions in immunological and inflammatory responses. Although in the majority of the cases they are identified in low numbers, lymphocytes may secrete interleukin (IL)-4 [32] and interferon (IFN)-g [30] which can induce macrophage fusion and activation. Studies with T-cell-deficient rats [30] have shown that T cells play a major role in the formation of giant cells and in the phagocytic activity of macrophages and giant cells during the tissue response to biomaterials.…”

“…Although in the majority of the cases they are identified in low numbers, lymphocytes may secrete interleukin (IL)-4 [32] and interferon (IFN)-g [30] which can induce macrophage fusion and activation. Studies with T-cell-deficient rats [30] have shown that T cells play a major role in the formation of giant cells and in the phagocytic activity of macrophages and giant cells during the tissue response to biomaterials. Serious complications have been demonstrated when lymphocytes were the main type of cell found in a retrieved cell suspension with a low number of mononuclear phagocytes, [29] which suggested a lymphocyte-mediated specific immunological reaction against the implant.…”