Sustained release of stromal cell–derived factor‐1 alpha from silk fibroin microfiber promotes urethral reconstruction in rabbits

Abstract

We developed a stromal cell–derived factor‐1 alpha (SDF‐1α)‐aligned silk fibroin (SF)/three‐dimensional porous bladder acellular matrix graft (3D‐BAMG) composite scaffold for long‐section ventral urethral regeneration and repair in vivo. SDF‐1α‐aligned SF microfiber/3D‐BAMG, aligned SF microfiber/3D‐BAMG, and nonaligned SF microfiber/3D‐BAMG scaffolds were prepared using electrostatic spinning and wet processing. Adipose‐derived stem cell (ADSC) and bone marrow stromal cell (BMSC) migration was assessed in the SDF‐1α‐loaded scaffolds. Sustained SDF‐1α release in vitro and vivo was analyzed using enzyme‐linked immunosorbent assay (ELISA) and western blotting, respectively. The scaffolds were used to repair a 1.5 × 1 cm2 ventral urethral defect in male rabbits in vivo. General observation and retrograde urinary tract contrast assessment were used to examine urethral lumen patency and continuity at 1 and 3 months post‐surgery. Postoperative rehabilitation was evaluated using histological detection. The composite scaffolds sustained SDF‐1α release for over 16 days in vitro. SDF‐1α‐aligned SF nanofiber promoted regeneration of urethral mucosa, submucosal smooth muscles, and microvasculature, increased cellular proliferation, and reduced collagen deposition. SDF‐1α expression was increased in reconstructed urethra at 3 months post‐surgery in SDF‐1α‐aligned SF group. SDF‐1α‐aligned SF microfiber/3D‐BAMG scaffolds may be used to repair and reconstruct long urethral defects because they accelerate urethral regeneration.

A biomimetic hyaluronic acid‐silk fibroin nanofiber scaffold promoting regeneration of transected urothelium

“…These scaffolds are loaded with biochemical and biophysical clues to recruit endogenous cells for tissue healing. As alternatives to autografts, artificial urethra made of natural degradable biomaterials (such as collagen and SF) are promising candidates in terms of tissue integration, 5,15–17 but lack the capability to induce tissue regeneration due to the bio‐inert characteristics. Hence, the manufacture process of bioactive or bio‐functional urethral grafts has been widely explored through the application of surface modifications and the addition of bioactive molecules.…”

“…In situ tissue‐engineering using degradable biomaterials can utilize the regeneration potential of human body through reasonable scaffold design (including structural optimization and functionalization) and reproduce natural tissue regeneration 14 . In this field, some studies have shown that in situ tissue‐engineered scaffolds produced new urethras nearly free of foreign materials in vivo 15–17 . However, few of them can reproduce the biological function of damaged urethra in the early stage of transplantation, and there are difficulties in subsequent lumen epithelial tissue remodeling.…”

“…The results showed that scaffolds mimicking ECM by using protein and HA‐based biomaterials may play a much more important role in guiding the development of cell behavior and the formation of functional tissue than previously thought. However, limited mechanical properties and rapid degradation restrict the use of collagen‐based scaffolds in tubular geometry 15–17,34 …”

“…14 In this field, some studies have shown that in situ tissue-engineered scaffolds produced new urethras nearly free of foreign materials in vivo. [15][16][17] However, few of them can reproduce the biological function of damaged urethra in the early stage of transplantation, and there are difficulties in subsequent lumen epithelial tissue remodeling.…”

“…However, limited mechanical properties and rapid degradation restrict the use of collagen-based scaffolds in tubular geometry. [15][16][17]34 Silk fibroin (SF) is a natural protein with excellent mechanical properties, good cell compatibility, controllable degradation, and versatile process-ability in different material formats. [35][36][37] The potential of SF nanofibers in regenerative medicine has been investigated in some tissue-engineering applications, such as urethras, 5,16 skin, 38 tendon, 39 and bone regeneration.…”