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Strengthening the pelvic floor with bioactive tissue\u2010engineered meshes is an emerging concept. This study investigates tissue regenerative design parameters, including degradability, porosity, and angulation, to develop alternative degradable melt electrowritten (MEW) constructs for surgical applications of POP. MEW constructs were fabricated in hierarchical geometries by two\u2010way stacking of the fibers with three different inter layer angles of 90\u00b0, 45\u00b0, or 22.5\u00b0. Implants printed at 22.5\u00b0 have higher tensile strength under dry conditions and show better vaginal fibroblast (VF) attachment in vitro. In vivo assessment using preclinical mouse and ovine models demonstrates more effective degradation and improved tissue integration in 22.5\u00b0 angular meshes compared to 90\u00b0 and 45\u00b0 meshes, with evidence of neo\u2010collagen deposition within implants at 6 weeks. The pattern and geometry of the layered MEW implants also influence the foreign body response, wherein the anti\u2010inflammatory phenotype shows a greater ratio of anti\u2010inflammatory CD206+ M2 macrophages\/pro\u2010inflammatory CCR7+ M1 macrophages. This presents an attractive strategy for improving the design and fabrication of next\u2010generation vaginal implants for pelvic reconstructive surgery.<\/jats:p>","DOI":"10.1002\/advs.202405004","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T05:43:23Z","timestamp":1726724603000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["3D Printed Mesh Geometry Modulates Immune Response and Interface Biology in Mouse and Sheep Model: Implications for Pelvic Floor Surgery"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0953-3263","authenticated-orcid":false,"given":"Kallyanashis","family":"Paul","sequence":"first","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton 3168 Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Clayton 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeedeh","family":"Darzi","sequence":"additional","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton 3168 Australia"},{"name":"Department of Obstetrics and Gynaecology Monash University  Clayton 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1690-9505","authenticated-orcid":false,"given":"Cathal D.","family":"O'Connell","sequence":"additional","affiliation":[{"name":"Biofab3D@ACMD St Vincent's Hospital  Melbourne VIC 3065 Australia"},{"name":"Discipline of Electrical and Biomedical Engineering School of Engineering RMIT University  Melbourne VIC 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M. 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