Tissue Engineering Neovagina for Vaginoplasty in MRKHS and GD patients - a systematic review

BACKGROUND: Vaginoplasty is a surgical solution to multiple disorders, including Mayer-Rokitansky-Küster-Hauser syndrome and Male-to-Female gender dysphoria. Using non-vaginal tissues for these reconstructions is associated with many complications and autologous vaginal tissue may not be sufficient. The potential of tissue engineering for vaginoplasty was studied through a systematic bibliography search. Cell type, biomaterial and signalling factors were analyzed by investigating advantages, disadvantages, complications and research quantity.

SEARCH METHODS: A systematic search was performed in Medline, EMBASE, Web of Science and Scopus until March 8, 2022. Term combinations for tissue engineering, guided tissue regeneration, regenerative medicine and tissue scaffold were applied, together with vaginoplasty and neovagina. The snowball method on references and a Google Scholar search on the first 200 hits were performed. Original studies on human and/or animal subjects, that met the inclusion (reconstruction of vaginal tissue; tissue engineering method) and no exclusion criteria (not available as full text; written in foreign language; non-original study article; genital surgery other than neovagina reconstruction; vaginal reconstruction with autologous or allogenic tissue without tissue engineering or scaffold) were assessed. The STROBE checklist, Newcastle Ottawa Scale and Gold Standard Publication Checklist were used to evaluate article quality and bias.

OUTCOMES: A total of 31 out of 1569 articles were included. Data extraction was based on cell origin and type, biomaterial nature and composition, host specy, number of hosts and controls, neovagina size, replacement fraction and signalling factors. An overview of used tissue engineering methods for neovagina formation was created, showing high variance of cell type, biomaterial and signalling factors and topics were rarely covered multiple times. Autologous vaginal cells and Extracellular Matrix-based biomaterials showed preferential properties and stem cells carry potential. However, quality confirmation of orthotopic cell-seeded Acellular Vaginal Matrix by clinical trials is needed as well as exploration of signalling factors for vaginoplasty.

IMPACT STATEMENT: Autologous cells prevent complications and compatibility issues like healthy cell destruction, whereas stem cells prevent cross-talk and rejection (but need confirmation testing beyond animal trials). Natural (orthotopic) ECM biomaterials have great preferential properties that encourage future research and signalling factors for vascularization are important for tissue engineering full-size neovagina.