Production of 3D Bioprinted Autologous Vaginal Tissue Constructs for Reconstructive Applications

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PROJECT SUMMARY Many congenital and acquired conditions resulting in the abnormality of the vagina often require reconstructive surgery to achieve anatomical and physiological function. Unfortunately, reparative procedures are challenged by the availability of vaginal tissues. Unfortunately, the use of non-native vaginal tissues and biomaterial substitutes has contributed to various complications, including mechanical, structural, functional, or biocompatibility problems. It is evident that native vaginal tissue, with its inherent functional properties, is most suitable for surgical reconstruction. Recent advances in tissue engineering and regenerative medicine have provided a solution to create autologous tissues for various clinical applications, including skin, bone, cartilage, urethra, and bladder. Applying the principles of tissue engineering, we have previously applied bioengineered autologous neovaginal tissues to create a functionally normal vaginal vault in pediatric patients born with vaginal aplasia. Due to the varying levels of pathologic conditions in each patient, manufacturing the target bioengineered vaginal tissue construct for reconstruction is challenging, requiring a better solution to meet the clinical needs. 3D bioprinting technology has emerged as a solution to develop patient-specific personalized tissue constructs with precision and reproducibility, addressing the current translational limitation of biomanufacturing for wide reconstructive applications. To address this unmet clinical need, our central hypothesis is that developing a bioprinting workflow will permit the fabrication of personalized autologous vaginal tissue constructs for clinical use. Thus, the objective of this study is to establish a clinically applicable 3D bioprinting workflow to manufacture personalized autologous vaginal tissue constructs that consist of patient-derived vaginal epithelial cells (EPCs) and smooth muscle cells (SMCs) for vaginal tissue reconstruction. The central hypothesis will be tested by pursuing three Specific Aims: 1) Develop and optimize a bioprinting workflow to bioengineer a readily implantable vaginal tissue construct; 2) Validate the individualized bioprinted vaginal tissue constructs using a preclinical animal model; 3) Establish a process development and batch record for regulatory approval. Successful completion of the proposed work will provide a standardized 3D bioprinting workflow that generates personalized vaginal tissue constructs with the required precision for vaginal tissue reconstruction. Using personalized autologous bioengineered tissue constructs will significantly impact patient care and change how we approach vaginal reconstruction in growing children and adults.