The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers

Abstract

Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings.

Time-dependent bladder tissue regeneration using bilayer bladder acellular matrix graft-silk fibroin scaffolds in a rat bladder augmentation model

“…In addition, bladder stone formation was first found at the 547 second week after implantation. Previous literatures had reported548 that the rough surface of simple scaffold and incompletely549 absorbed matrix fragments within the bladder lumen could serve550 as niduses for stone formation, which also was induced by the 551 inflammatory response caused by the nude biologic scaffold 552[30,31]. So we suppose the urothelium seeding on the BAMG scaf-553 fold before in vivo implantation can make the luminal surface of 554 the scaffold smoother and hamper the urine crystals precipitate 555 and the direct inflammatory response on the scaffold, conse-556 quently reducing the incidence of stone formation.557 During the 12-week implantation period, the volume and area 558 of residual SF remnants significantly decreased.…”

“…Bladder augmentation 27 Tissue engineering 28 2 9 a b s t r a c t 30 With advances in tissue engineering, various synthetic and natural biomaterials have been widely used in 31 tissue regeneration of the urinary bladder in rat models. However, reconstructive procedures remain 32 insufficient due to the lack of appropriate scaffolding, which should provide a waterproof barrier function 33 and support the needs of various cell types.…”

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

“…Bury et al recently incorporated short sequences from the uteroglobin protein into self-assembling peptide amphiphiles [81]. The peptide amphiphiles were then used to coat decellularized small intestinal submucosa (SIS), a material that has shown promise in many tissue engineering applications but is pro-inflammatory.…”

Bone marrow derived cells facilitate urinary bladder regeneration by attenuating tissue inflammatory responses

“…Strategies for tissue regeneration must consider an assortment of factors that influence the proper reformation of functional tissue including inflammation [1][2][3][4][5]. Components of the inflammatory pathway can shape the means in which proper wound healing is attained or negatively effect overall tissue remodeling [2,6,7].…”

“…Components of the inflammatory pathway can shape the means in which proper wound healing is attained or negatively effect overall tissue remodeling [2,6,7]. Specifically, cellular constituents of the innate immune system are typically the first to arrive at areas of tissue injury in an effort to provide the foundation for subsequent tissue regeneration [8][9][10][11].…”