Porous Photocrosslinkable Hydrogel Functionalized with USC Derived Small Extracellular Vesicles for Corpus Spongiosum...

Area of Science:

• Regenerative Medicine
• Urology
• Biomaterials

Background:

• Corpus spongiosum (CS) defects pose significant challenges for urethral reconstruction.
• Current methods like self-healing or substitution urethroplasty are often insufficient for CS repair.
• Small extracellular vesicles (sEVs) derived from urine-derived stem cells (USC-sEVs) show potential in promoting vascular regeneration.

Purpose of the Study:

• To investigate the efficacy of USC-sEVs in promoting the repair of corpus spongiosum (CS) defects.
• To develop a sustained-release delivery system for USC-sEVs to enhance their in vivo therapeutic effects.
• To evaluate a novel hydrogel-based patch for CS defect regeneration.

Main Methods:

• Preparation of a void-forming photoinduced imine crosslinking hydrogel (vHG).
• Encapsulation of USC-sEVs within the vHG to create vHG-sEVs.
• Application of vHG-sEVs to repair a 1.5 cm x 0.8 cm CS defect in a preclinical model.
• Histological analysis and photoacoustic microscopy to assess vascular regeneration and blood flow.

Main Results:

• The vHG-sEVs significantly promoted the regeneration and repair of CS defects.
• Histological examination revealed abundant sinusoid-like vascular structures in the vHG-sEV treated group.
• Photoacoustic microscopy demonstrated that blood flow and microvascular structure in the defect area were comparable to normal CS tissue.

Conclusions:

• In situ-formed vHG-sEV patches represent a viable and promising strategy for repairing CS defects.
• USC-sEVs, delivered via a hydrogel, effectively support vascular regeneration in CS tissue.
• This approach offers a potential breakthrough for complex urethral reconstruction challenges.