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Single polypropylene microfibers plasma-coated with polymers of different surface charge [N,N-dimethylaminoethyl methacrylate (NN) (positive charge), methacrylic acid (MA) (negative charge), and hexafluoropropylene (HF) (neutral)] were implanted in the subcutaneous dorsum of Sprague-Dawley rats for 5-week intervals. Thee groups of fiber diameters were used: (I) 1.0 to 5.9 μm; (II) 6.0 to 10.9 μm; and (III) 11.0 to 15.9 μm. Fibrous capsule thickness and blood-vessel density (number of vessels within 100 μm of the fiber) were assessed in tissue sections in the planes of microfiber cross-sections. Results from a multifactorial analysis of variance demonstrated statistically significant main effects (p < 0.05) for microfiber diameter but not for surface-charge coating. The mean differences in capsule thickness among the microfiber diameter groups were: between groups II and I: 5.4 μm; between groups III and I: 10.2 μm; and between groups III and II: 4.7 μm. The mean differences in capsule thickness among surface-charge coatings were: between MA and NN: 0.7 μm; between MA and HF: 1.4 μm; and between NN and HF: 0.7 μm. Many of the 1.0 to 5.9 μm-in-diameter fibers had no capsule and no sign of a foreign-body reaction. For the vessel density analysis, neither microfiber diameter nor surface-charge coating had a statistically significant effect. Thus the geometric feature of microfiber diameter was more important than was surface charge relative to fibrous capsule formation but not relative to local vessel density. This ranking of the relative influence of design features in relation to tissue response provides useful information for prioritization in biomaterial design. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 462–467, 2003 [ABSTRACT FROM AUTHOR]