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The normal rabbit is a well known model of penis erection; its cavernous tissue and corpus spongiosum layer are in close contact, with the cavernous sinusoid, which contains abundant sinusoidal endothelial cells and smooth muscle cells, providing abundant blood supply and oxygen to maintain normal erection. The cavernous tissue is thin and it has a low self-repair ability; thus, it is a sensitive area in the physiological morphology of the penis. Epididymal fatty tissue can be used as a mechanical barrier to repair the damaged cavernous tissue when necessary. Our results showed that the injected MDSCs into the scrotum of the nude mouse can survive and differentiate into adipose tissue (Fig. 6c and Supplementary Fig. 23) after 4 months, and the implanted scaffold tissue obtained from nude mice showed remarkable angiogenesis activity, which is also suitable for transplantation into injured cavernosum of the penis (Fig. 6d).
To further validate the applicability of the implanted scaffold for vascular regeneration, we transplanted the heparin-coated 3D hydrogel scaffold into a rabbit with a surgically-induced cavernous defect model. Histological analysis showed that the implanted scaffold tissue was integrated with the surrounding tissue of the cavernous sinusoid and showed histomorphological characteristics similar to the normal cavernous sinusoid. The cavernous tissue was thin and small, which is not as durable as healthy cavernous tissue. In particular, cell infiltration and inflammatory cell infiltration in the implanted heparin-coated scaffold group were low compared with the cell-free and negative control groups, as shown in Fig. 5b and Supplementary Fig. 16. The implanted scaffold containing the MDSCs and hypoxia-induced factors repaired the damaged cavernous tissues and promoted wound healing. It may contribute to the promotion of angiogenesis via upregulation of the angiogenic factor VEGF and PDGF through the mHIF-1 mechanism, further facilitating tissue regeneration and repair (Figs. 5b and 5c). 3d9ccd7d82
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