Henke P K, Bergamini T M, Watson A L, Brittian K R, Powell D W, Peyton J C
Department of Surgery, University of Louisville School of Medicine, Kentucky 40292, USA.
J Surg Res. 1998 Jan;74(1):17-22. doi: 10.1006/jsre.1997.5210.
The stimulation of fibroblast growth is essential for the normal healing and tissue integration of biomaterials. The local elevation of proinflammatory mediators in infected perigraft fluid (PGF) may inhibit this growth. We sought to determine whether infected PGF inhibited fibroblast growth, and, if so, whether this was primarily dependent on the biomaterial, bacteria, or host.
In vivo Dacron or expandable polytetra-fluoroethylene (ePTFE) grafts, sterile or colonized with slime-producing (RP-62A, viable or formalin-killed) or nonslime-producing (RP-62NA) Staphylococcus epidermidis (1 x 10(7) CFU/cm2), were implanted in Swiss Webster mice, and the PGF was harvested at 7 and 28 days. Antibodies to tumor necrosis factor alpha, interleukin 1 alpha, interferon gamma (7 micrograms/day), and indomethacin (50 micrograms/day) were administered by microinfusion pumps for 7 days and the PGF was harvested. Inhibition of the proinflammatory mediators was confirmed by enzyme-linked immunosorbant assay. The nontreated, heat-treated, or trypsin-digested in vivo PGF was incubated with an in vitro [3H]thymidine murine fibroblast (ATCC CCL-12) proliferation assay.
Fibroblast inhibition was significant at 7 and 28 days with infected PGF incubation compared with sterile and was not dependent on bacterial slime production or viability. Dacron sterile PGF did not significantly inhibit fibroblasts compared with control, whereas sterile ePTFE stimulated (P < 0.05) fibroblasts. Treatment of the PGF with proinflammatory cytokines, heat, and trypsin failed to reverse fibroblast inhibition in the infected state.
Biomaterial infection is associated with fibroblast inhibition that is dependent primarily on bacterial products and not the host or biomaterial. Conservative intervention strategies for graft infection need to address the problem of poor healing as well as bacterial clearance.
成纤维细胞生长的刺激对于生物材料的正常愈合和组织整合至关重要。感染性移植物周围液（PGF）中促炎介质的局部升高可能会抑制这种生长。我们试图确定感染性PGF是否会抑制成纤维细胞生长，如果是，这是否主要取决于生物材料、细菌或宿主。
将体内植入的涤纶或可扩张聚四氟乙烯（ePTFE）移植物，无菌的或定植有产黏液（RP - 62A，活的或福尔马林灭活的）或不产黏液（RP - 62NA）的表皮葡萄球菌（1×10⁷CFU/cm²），植入瑞士韦伯斯特小鼠体内，并在第7天和第28天收集PGF。通过微量输注泵给予肿瘤坏死因子α、白细胞介素1α、干扰素γ（7微克/天）和吲哚美辛（50微克/天）的抗体7天，并收集PGF。通过酶联免疫吸附测定法确认促炎介质的抑制作用。将未经处理、热处理或胰蛋白酶消化的体内PGF与体外[³H]胸腺嘧啶核苷小鼠成纤维细胞（ATCC CCL - 12）增殖测定法一起孵育。
与无菌PGF相比，感染性PGF孵育在第7天和第28天对成纤维细胞的抑制作用显著，且不依赖于细菌黏液的产生或活力。与对照相比，涤纶无菌PGF对成纤维细胞的抑制作用不显著，而无菌ePTFE刺激（P < 0.05）成纤维细胞。用促炎细胞因子、加热和胰蛋白酶处理PGF未能逆转感染状态下对成纤维细胞的抑制作用。
生物材料感染与成纤维细胞抑制有关，这主要取决于细菌产物而非宿主或生物材料。移植物感染的保守干预策略需要解决愈合不良以及细菌清除的问题。
