Scalable subunit-based strategy to fabricate autologous vaginal tissue grafts

Abstract

Vaginal reconstruction is limited by the lack of biomaterials that replicate the structure, biomechanics, and biochemistry of the native tissues. Synthetic meshes, xenografts, and autologous skin or bowel grafts are hindered by their immunogenicity, poor integration, and non-physiological properties. We report a scalable platform for the fabrication of patient-specific living vaginal grafts from autologous fibroblasts. Using scaffold-free micromolding and automated assembly, fibroblasts from small full-thickness vaginal biopsies self-assembled into a collagen-rich, highly aligned extracellular matrix. To improve mechanical integrity, we create twisted subunit assemblies that displayed highly aligned collagen, dense cellularity, and a predominantly quiescent fibroblast phenotype with minimal myofibroblast activation. This autologous tissue-specific construct addresses the shortcomings of current materials and offers a customizable and biocompatible solution for regenerative gynecology. By combining tissue specificity, immunologic safety, and modular scalability, this approach has the potential to transform surgical options for congenital anomalies, post-oncologic reconstruction, fistula repair, and pelvic organ prolapse.