Development and mechanistic investigation of 3D-printed biomimetic corpus cavernosum seeded with MSCs for restoring erectile function in pigs.
basic_science · Level V
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- Record sourced from PubMed, PMID 42546581.
- Also identified by DOI 10.1016/j.biomaterials.2026.124491.
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Abstract
Penile injury induces rapid structural disruption of the corpus cavernosum, ultimately culminating in erectile dysfunction (ED). Owing to the inherently limited regenerative capacity of injured tissue, current therapies fail to restore both structure and function. To address this unmet clinical need, we employed 3D printing technology to fabricate a hydrogel-based biomimetic penile corpus cavernosum with a sinusoidal architecture. It can simulate the penile erection process under fluid pressure in vitro. This construct was functionally modified by seeding with porcine umbilical cord-derived mesenchymal stem cells (MSCs), and its therapeutic potential was systematically evaluated in a preclinical porcine model of corpus cavernosum defects. The treatment brought about the relative improvement in reproductive performance compared with defect control groups. Mechanistically, MSCs accelerate hydrogel degradation to support tissue integration and facilitate nearly complete structural regeneration of damaged cavernous sinuses. Single-cell RNA sequencing (scRNA-seq) revealed a multifaceted regulatory network in which MSCs enhance the terminal differentiation of endothelial cells (ECs) to rebuild functional vascular networks, mitigate cluster of differentiation 4-positive (CD4<sup>+</sup>) T-cell-induced endothelial-to-mesenchymal transition (EndMT) by reducing transforming growth factor-beta (TGF-β) secretion, and reprogram the immune microenvironment, specifically by activating anti-inflammatory interleukin-10 (IL-10) signaling in M1 macrophages and downregulating prorejection pathways in M2 macrophages. Collectively, these effects inhibit excessive inflammation and attenuate graft rejection. These findings not only deepen our mechanistic understanding of MSC-based interventions for ED secondary to penile injury but also establish a novel, more efficient therapeutic strategy for penile reconstruction to restore the reproductive capability of males.