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Bacterial products primarily mediate fibroblast inhibition in biomaterial infection
P K Henke1, T M Bergamini, A L Watson
1Department of Surgery, University of Louisville School of Medicine, Kentucky 40292, USA.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Infected perigraft fluid (PGF) significantly inhibits fibroblast growth, crucial for healing. This inhibition is primarily due to bacterial products, not the biomaterial or host factors, impacting graft infection outcomes.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Wound Healing Research
Background:
- Fibroblast growth is vital for biomaterial integration and tissue repair.
- Infection-associated proinflammatory mediators in perigraft fluid (PGF) may impede fibroblast proliferation.
- Understanding factors influencing fibroblast response in infected grafts is critical for improving healing outcomes.
Purpose of the Study:
- To investigate whether infected PGF inhibits fibroblast growth.
- To determine if this inhibition is dependent on the biomaterial, bacteria, or host response.
- To elucidate the mechanisms underlying fibroblast inhibition in infected biomaterial environments.
Main Methods:
- Implantation of Dacron or ePTFE grafts infected with Staphylococcus epidermidis in mice.
- Harvesting of PGF at 7 and 28 days post-implantation.
- In vitro fibroblast proliferation assay using PGF treated with antibodies, heat, or trypsin.
Main Results:
- Infected PGF significantly inhibited fibroblast growth compared to sterile PGF at both 7 and 28 days.
- Inhibition was independent of bacterial slime production or viability.
- Sterile ePTFE grafts stimulated fibroblast growth, while Dacron did not significantly inhibit it.
Conclusions:
- Biomaterial infection leads to fibroblast inhibition primarily driven by bacterial products.
- Host factors and the biomaterial itself are not the main drivers of this inhibition.
- Effective treatment strategies for graft infections must address both bacterial clearance and impaired healing.