Immunogenicity and Integration of a Decellularized Extracellular-Matrix Scaffold for the Reconstruction of Human Foreskin: Experimental Study in Animal Model.

Circumcision is one of the most surgical techniques performed around the world just considered that globally about 38% of people and 2.6% in Italy are circumcised. Million of people suffer from physical and psychological damage caused by circumcision. To date, there is not yet therapeutic and effective surgery for foreskin restoration. Recently, a group of Italian researchers have developed a novel decellularized method for epithelial tissue to obtain an extracellular matrix scaffold derived from human donor foreskin. The aim of this study was to evaluate the immune response and integration of this scaffold when implanted in the host. The study, approved by Ministry of Health (n. 424/2021-PR), involved twenty-six Wistar male rats. Under complete asepsis, an infrascapular skin incision of about 1 cm was made and a decellularized membrane (about 2 cm of diameter) was implanted in hypodermal layer. To evaluate different stages of inflammatory response, rats were subdivided in two groups: A group (13 rats) that had a follow up of 30 days; B group (13 rats) that had a follow up only of 5 days. The infrascapular region was monitored in aZempt to score key signs of inflammation: calor, rubor and tumor, scoring from 0 (no alterations) to 3 (severe alterations). After 5 days for B group and 30 days for A group, the subjects underwent general anesthesia and euthanasia. A tissue explant centered on the surgical scar was performed and sent to the pathology lab for histological and immunohistochemical analyses, in aZempt to assess the presence and degree of the inflammatory infiltrate, related to the host's immune response to the implant. The clinical evaluation showed slight signs of inflammation in the first five days post implantation. After this period, all clinical scores were 0 for the remaining 25 days. Histological and immunohistochemical finds highlighted a mild acute inflammatory response in both groups at the two different times of the study. Differently, a moderate degree of chronic inflammation was observed. The analysis of data related to scaffold integration showed interesting results. Specifically, neovascularization and cell colonization were significantly higher in A compared to B group. In contrast, the presence of the capsule was mild in all subjects, and it was no different between two groups of the study. In conclusion, the decellularized extracellular matrix derived from human foreskin did not evoke a significative immune response and supported the neovascularization and cell colonization when implanted in the host.