An in-depth analysis on vaginal wound healing post surgery: Transcriptomic effects of autologous micrografting versus acellular grafts

Understanding wound healing in vaginal tissue is crucial for improving female health outcomes, particularly in the context of surgeries like pelvic organ prolapse, post-radiation stricture formation and complications resulting from vaginal childbirth. Tissue-engineered grafts have proven successful for vaginal tissue repair, however, the mechanisms that stimulate tissue repair are unknown. This study aims to explore the transcriptomic signatures during tissue repair after using autologous micrografting versus acellular grafts in a rabbit model for surgical vaginal reconstruction. During a single surgical procedure, we created a graft for vaginal reconstruction consisting of autologous micrografts and supporting biomaterials. This graft was named "perioperative, layered, autologous, tissue expansion (PLATE)." We also produced acellular grafts that lacked autologous micrografts,. Our findings revealed distinct differences in gene expression patterns associated with wound healing, extracellular matrix organization, and smooth muscle regeneration between the two graft types. Notably, our findings revealed that micrografting showed an accelerated progression towards the final stages of wound healing, as evidenced by elevated matrix metalloproteinase (MMP) expression, particularly MMP-13. Additionally, Transforming Growth Factor Beta-1 (TGF-ß1) emerged as an expected vaginal wound healing regulator. This study provides valuable insights into the molecular mechanisms of PLATE grafts and opens new avenues for the development of targeted therapies to improve wound healing in vaginal tissues. Overall design: 16 Female New Zealand White rabbits aged 17-19 weeks (juvenile) and weighing 3,1 kg (+- 0,3 kg) were used for this study. We sequenced mRNA from native rabbit vaginas (control, n=6), sham-operated rabbit vaginas (sham, n=3), acellular graft-inserted vaginas 10 mm from the graft zones (acellular n=3), and PLATE graft inserted vaginas 10 mm from the graft zones (PLATE, n=4).