Effects of Anti‐Inflammatory Nanofibers on Urethral Healing

Abstract

Protracted postsurgical inflammation leading to postoperative complications remains a persistent problem in urethral reconstruction. Nanofibers in the form of peptide amphiphiles expressing anti‐inflammatory peptides (AIF‐PA) have positively modulated local inflammatory responses. Urethroplasty is performed to repair 5 mm ventral urethral defects with: uncoated small intestinal submucosa (SIS); SIS dip‐coated with AIF‐PA1 (anti‐inflammatory treatment), or SIS dip‐coated with AIF‐PA6 (control) on 12‐week‐old male Sprague Dawley rats (n = 6/group/timepoint). Animals are euthanized at 14 and 28 d postsurgery. Hematoxylin‐eosin, Masson's Trichrome, and immunohistochemistry with primary antibodies against myeloperoxidase (MPO; neutrophils), CD68, CD86, CD206 (macrophages), and proinflammatory cytokines TNFα and IL‐1β are performed. Complete urethral healing occurs in 3/6 uncoated SIS (50%), 2/6 SIS+AIF‐PA6 (33.3%), and 5/6 SIS+AIF‐PA1 (83.3%) animals at 14 d and all at 28 d. Application of AIF‐PA1 to SIS substitution urethroplasty decreases MPO+ neutrophils, CD86+ M1 proinflammatory macrophages, TNFα, and IL‐1β levels while concurrently increasing levels of CD206+ M2 proregenerative/anti‐inflammatory macrophages at the anastomoses and the regenerated tissue at the wound bed (REGEN). AIF‐PA1 treatment enhances the healing process, contributing to earlier, complete urethral healing, and increased angiogenesis. Further studies are needed to elucidate the specific mechanism of inflammatory response modulation on angiogenesis and overall urethral healing.

Age-Related Changes in Urethral Structure and Responds to Injury: Single-Cell Atlas of a Rat Model of Vaginal Birth Injury induced Stress Urinary Incontinence

“…Our study showed that macrophages increased and were predominantly of M1 type in middle-age rat urethra. M1 macrophages are involved in pro-inflammatory responses, and associated with poor urethral injury repair and fibrosis 30 . In addition, mast cells are an unexpected subcluster that appears in the middle-age rat urethra, mast cell-derived histamine and transforming growth factor beta play an important role in inflammation, fibrosis, and smooth muscle cell dysfunction of many tissues 31 , 32 .…”

CD73-positive pediatric urethral mesenchymal stem-like cell-derived small extracellular vesicles stimulate angiogenesis

“…Urethral repair is a complex process involving the proliferation and regeneration of epithelial cells, smooth muscle cells, and endothelial cells, all of which rely on blood vessels to deliver nutrients and oxygen [ 17 , 18 ]. Angiogenesis is an important mechanism for urethral repair, and VECs are the main cells maintaining the physiological functions of blood vessels [ 19 ].…”

Evolving Experimental Platforms to Evaluate Ulcerative Colitis

“…Self-assembling PAs have demonstrated utility in a wide range of settings and applications. [144][145][146][147][148][149][150] PAs are comprised of a hydrophobic alkyl segment attached to a peptide domain that includes a β-sheet forming segment (Figure 4). In aqueous environments, these molecules self-assemble through hydro-phobic collapse of the alkyl domain in combination with hydrogen bonding in the β-sheet domain to produce high aspect-ratio nanofibers.…”