Tissue reactions to biomaterials

University dissertation from Inst. fysiologi och neurovetenskap, avd. neuroendokrin cellbiologi, EA-blocket, 5:e vån., Universitetssjukhuset, 221 85 Lund

Abstract: The biological response to different implanted biomaterials vary. The relative importance of factors in the material and host for this variation are at present incompletely known. The variation in the cellular response to specific proteins and the rapid adsorption of proteins to surfaces exposed to biological environments has created the hypothesis that the cellular interactions with biomaterials are influenced by the accumulated plasma proteins. These initial reactions have been suggested to determine the subsequent wound healing process and the long term stability of an implant. The main purpose of the present thesis was to study the distribution of selected proteins and to quantify the macrophage subpopulations, in the soft tissue adjacent to implants with different characteristics and at different localization. A technique was developed for light and electron microscopical studies on the localization of accumulated proteins in the relatively inaccessible zone between implant and soft tissue. A procedure including mild chemical fixation, cryosubstitution and electrochemical removal of the metallic implant allowed immunohistochemical localization of selected proteins. Implants of commercially pure (c.p.) titanium and polytetrafluoroethylene (PTFE) were inserted in rat abdominal wall for 1-12 weeks. Differences in the distribution pattern of the individual proteins (albumin, fibrinogen, fibronectin, IgG and collagen I) were revealed. The distribution also varied over time and differed to some extent between the two materials. Macrophage-specific antibodies were used for identification of newly recruited macrophages (ED1) and of mature tissue macrophages (ED2) in the soft tissue adjacent to titanium implants which penetrated or did not penetrate, respectively, the peritoneal membrane of rat for 3-30 days. The penetrating implants induced a more pronounced inflammatory response at 30 days but not at earlier time points. PTFE and c.p. titanium, which have widely different material properties, were compared with respect to the number of macrophage subpopulations and total cells during a 12 weeks follow-up period. PTFE induced a larger accumulation of cells and a thicker capsule formation at 12 weeks insertion. However, no significant differences were seen in the macrophage subset response between the two implants. Variation in surface topography on polyethylene implants induced small but significant differences in the soft tissue response when examined after 1-12 weeks. The smoother surface induced the thickest capsule formation at all time points, and at 1 week it also recruited the largest number of macrophages and total cells as compared to the coarser surfaces. In summary, significant differences in the biological response to implanted biomaterials due to localization, material characteristics and surface topography were seen, particularly after relatively long implantation times.

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