Login to Access Video or Poster Abstract: MP36-05
Sources of Funding: None

Introduction

Tempering the postoperative inflammatory response following graft urethroplasty may accelerate urethral wound healing and minimize fibrosis and stricture recurrence. We investigate the use of anti-inflammatory peptides displayed on self-assembling nanofibers to modulate inflammation and accelerate scar maturation in a rat model of substitution urethroplasty.

Methods

Poly(diol-citrate) [POC] scaffolds were either coated with anti-inflammatory peptide amphiphile (AIF-PA1), control amphiphile (AIF-PA6) or left uncoated, and used in substitution urethroplasty (n=36 Sprague Dawley male rats). Urethral tissue analysis was performed at 2, 12 and 25 days post-operatively using H&E, Trichrome, picrosirius, myeloperoxidase (MPO), TNFα, CD68, IL-10 and IL-1β. Urethral patency was assessed at euthanization.

Results

35/36 rats demonstrated urethral patency at euthanization by functional and anatomic assessment. AIF-PA1 coated POC scaffolds resulted in a 50% reduction of neutrophil (MPO) and inflammatory cytokine IL-1β levels, with simultaneous upregulation in anti-inflammatory cytokine IL-10 relative to controls at 2D and 12D postoperatively. Macrophage (CD68) levels were elevated 1.5-fold in the AIF-PA1 group during the immediate post-surgical period (2D), but demonstrated a rapid decrease to levels half that of control subjects by 12D. Treatment of graft with AIF-PA1 triggered an initial 2.5-fold spike in collagen III periurethral content (2D), consistent with initial, robust collagen deposition, followed by a dramatic shift in collagen type III to I (III:I ratio 15.7:1 [AIF-PA1] vs. 43.4:1 [control] vs. 38.0:1 [AIF-PA6]), consistent with an early transition to tissue remodeling and maturation. By 25D, inflammatory marker and collagen levels tended towards normalization in all groups.

Conclusions

AIF-PA1 nanofiber application onto POC promotes an accelerated wound healing program, characterized by an initial spike in macrophage wound infiltration, followed by a faster reduction of inflammatory markers. The end result is an accelerated wound healing course, with an expedited transition to wound remodeling and maturation with application of AIF-PAs at the time of surgery.

Funding

None