Presentation Information
[P01-141]Spatiotemporal Theragenerative Treatment of Urethral Stricture Using the Joule-Assisted Bioresorbable Stent JANUS
○Yuhyeon Na1, Jae-young Lee1 (1. Seoul National University (Korea))
Keywords:
Urethelial stent,Magnetic hyperthermia,Theragenerative
[Purpose]
Urethral stricture is a common and recurrent urological disorder caused by injury, infection, or inflammation. Because pathological fibrosis and epithelial damage occur simultaneously, effective treatment requires both suppression of hyperplastic scar formation and promotion of urothelial regeneration. In this study, we developed a spatiotemporally controllable theragenerative platform, the Joule-assisted nanotherapeutic urethral stent (JANUS), to address both therapeutic needs in a single bioresorbable system.
[Method]
JANUS was fabricated from a biodegradable magnesium alloy stent coated with an inner polycaprolactone (PCL) layer and an outer thermoresponsive PCL/phase-change matrix containing sirolimus nanoparticles (nSRL). Under an alternating magnetic field, the Mg stent generated localized Joule heating, which melted the thermoresponsive coating and triggered controlled nSRL release. The platform was evaluated for coating morphology, mechanical durability, corrosion resistance, thermal responsiveness, and drug-release behavior. Its antibacterial activity and cellular effects were assessed in vitro, and therapeutic efficacy was investigated in a rat urethral stricture model.
[Results]
JANUS showed stable coating integrity, sufficient mechanical strength, and improved corrosion resistance compared with bare Mg stents. Magnetic stimulation induced reversible local heating in the therapeutic range and significantly enhanced sirolimus release from the dual-layer coating. In vitro, JANUS inhibited bacterial growth and suppressed smooth muscle cell proliferation, while Mg ion release supported epithelial cell proliferation. In vivo, JANUS maintained urethral patency for 4 weeks and significantly reduced granulation tissue formation, fibrosis, and inflammatory responses compared with controls. Histological analyses further confirmed decreased submucosal fibrosis and improved tissue recovery in the JANUS-treated group.
[Consideration]
The significance of JANUS lies in its dual-function design, which enables on-demand antifibrotic therapy on the abluminal side while preserving a regenerative luminal environment. This spatiotemporal strategy overcomes the limitations of conventional urethral stents, which often fail because of restenosis, infection, and insufficient tissue repair.
[Conclusion]
JANUS is a bioresorbable theragenerative urethral stent that integrates magnetic Joule heating-triggered drug delivery with Mg-mediated regenerative activity. This platform effectively suppresses fibrosis and inflammation while promoting urothelial repair, suggesting strong potential for urethral stricture treatment and broader application in other hollow-organ diseases.
Urethral stricture is a common and recurrent urological disorder caused by injury, infection, or inflammation. Because pathological fibrosis and epithelial damage occur simultaneously, effective treatment requires both suppression of hyperplastic scar formation and promotion of urothelial regeneration. In this study, we developed a spatiotemporally controllable theragenerative platform, the Joule-assisted nanotherapeutic urethral stent (JANUS), to address both therapeutic needs in a single bioresorbable system.
[Method]
JANUS was fabricated from a biodegradable magnesium alloy stent coated with an inner polycaprolactone (PCL) layer and an outer thermoresponsive PCL/phase-change matrix containing sirolimus nanoparticles (nSRL). Under an alternating magnetic field, the Mg stent generated localized Joule heating, which melted the thermoresponsive coating and triggered controlled nSRL release. The platform was evaluated for coating morphology, mechanical durability, corrosion resistance, thermal responsiveness, and drug-release behavior. Its antibacterial activity and cellular effects were assessed in vitro, and therapeutic efficacy was investigated in a rat urethral stricture model.
[Results]
JANUS showed stable coating integrity, sufficient mechanical strength, and improved corrosion resistance compared with bare Mg stents. Magnetic stimulation induced reversible local heating in the therapeutic range and significantly enhanced sirolimus release from the dual-layer coating. In vitro, JANUS inhibited bacterial growth and suppressed smooth muscle cell proliferation, while Mg ion release supported epithelial cell proliferation. In vivo, JANUS maintained urethral patency for 4 weeks and significantly reduced granulation tissue formation, fibrosis, and inflammatory responses compared with controls. Histological analyses further confirmed decreased submucosal fibrosis and improved tissue recovery in the JANUS-treated group.
[Consideration]
The significance of JANUS lies in its dual-function design, which enables on-demand antifibrotic therapy on the abluminal side while preserving a regenerative luminal environment. This spatiotemporal strategy overcomes the limitations of conventional urethral stents, which often fail because of restenosis, infection, and insufficient tissue repair.
[Conclusion]
JANUS is a bioresorbable theragenerative urethral stent that integrates magnetic Joule heating-triggered drug delivery with Mg-mediated regenerative activity. This platform effectively suppresses fibrosis and inflammation while promoting urothelial repair, suggesting strong potential for urethral stricture treatment and broader application in other hollow-organ diseases.
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