Abstract Introduction Erectile dysfunction and Peyronie’s disease are prevalent and frequently coexisting disorders in which guideline-based therapies improve symptoms more reliably than they reverse underlying corporal remodeling or tunical fibrosis. Regenerative biologics and nano-enabled delivery systems aim to intervene upstream in inflammatory and fibrotic pathways by improving local exposure, tissue persistence, and target engagement within the emerging field of regenerative sexual medicine. Objectives To synthesize current evidence on regenerative biologics and nano-enabled delivery platforms for erectile dysfunction and Peyronie’s disease, with emphasis on disease-specific delivery barriers, payload characterization, and translational readiness. Methods This article was designed as a narrative translational review informed by a scoping search of PubMed/MEDLINE, Embase, and Web of Science (January 2000 to March 2025), supplemented by hand-searching of reference lists. Evidence was synthesized qualitatively by disease context (erectile dysfunction vs Peyronie’s disease), payload class, delivery constraints, and translational maturity. Results For erectile dysfunction, platelet-rich plasma has widespread clinical uptake but remains limited by heterogeneous preparation methods, placebo susceptibility, and rapid corporal washout. Early stem cell studies support feasibility, yet converging mechanistic evidence suggests that paracrine signaling predominates, favoring acellular approaches such as extracellular vesicles (EVs) delivered with hydrogels or engineered nanocarriers. For Peyronie’s disease, intralesional collagenase clostridium histolyticum (CCH) remains the current clinical benchmark for plaque-targeted minimally invasive therapy in selected stable disease, whereas platelet-rich plasma and cell/vesicle-based approaches remain investigational. Across Peyronie’s disease platforms, dense plaque architecture, restricted diffusion, and calcification constrain intralesional exposure, supporting plaque-confined depots, matrix-interactive materials, and targeted antifibrotic nanomedicines. Conclusion Regenerative sexual medicine is evolving from empiric biologic injections toward better-characterized, anatomy-aligned, exposure-controlled therapeutic platforms, where durable clinical benefit will depend on sustained target engagement within penile tissues. Near-term progress is most likely through phenotype-enriched early-phase trials with rigorous sham-aware design and objective hemodynamic or imaging endpoints, whereas longer-term translation will depend on standardized potency assays, reproducible manufacturing, and durable penile tissue targeting.
Kaltsas et al. (Tue,) studied this question.