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Local Tumor Necrosis Factor Alpha Exposure Inhibits Posterolateral Fusion Rates in a Rat Model.

Mitchell K Ng1, John D Koerner2, Jonathan Dalton1

  • 1Department of Orthopaedic Surgery, Rothman Orthopaedic Institute, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

Spine
|April 3, 2026
PubMed
Summary

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Elevated tumor necrosis factor-alpha (TNF-α) levels after spine surgery significantly hinder bone fusion in rats. Controlling early TNF-α activity may improve spinal fusion outcomes, especially for patients with inflammation.

Area of Science:

  • Orthopedics
  • Spine Surgery
  • Regenerative Medicine

Background:

  • Elevated tumor necrosis factor-alpha (TNF-α) is implicated in spinal pathologies like pseudarthrosis and systemic inflammation.
  • The specific impact of localized TNF-α on posterolateral spinal fusion remains unclear.
  • Mesenchymal stem cell (MSC) differentiation is sensitive to inflammatory cytokines.

Purpose of the Study:

  • To investigate the effect of TNF-α on MSC osteogenic differentiation in vitro.
  • To evaluate the impact of localized TNF-α exposure on posterolateral spinal fusion in a rat model.

Main Methods:

  • In vitro assessment of MSCs with varying TNF-α concentrations.
  • Posterolateral spinal fusion (L4-L5) in 35 rats using demineralized bone matrix (DBM).
Keywords:
IL-1βMicro-CTTNF-αlumbar fusionrat

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  • Treatment group received localized TNF-α on a collagen sponge; controls received DBM only. Cytokine analysis (ELISA) and fusion assessment (palpation, microCT, histology) were performed.

    • Main Results:

    • TNF-α dose-dependently inhibited MSC osteogenesis, with effects noted at 0.1 ng/mL.
    • Increased TNF-α was detected in the fusion mass of the treatment group by postoperative day 2.
    • No fusion occurred in the TNF-α group (0/5) compared to controls (4/5) by manual palpation (P=0.048).
    • Micro-CT and histology showed fusion in 1/5 TNF-α treated rats versus 4/5 controls.

    Conclusions:

    • A short, localized elevation of TNF-α post-surgery significantly impairs posterolateral spinal fusion in rats.
    • Targeting early TNF-α activity at the fusion site could enhance arthrodesis outcomes.
    • This is particularly relevant for patients with heightened inflammatory profiles.