Abstract
3 min readVaginal birth is the primary cause of pelvic floor disorders due to the mechanical stress of fetal passage through the birth canal. This leads to significant trauma to pelvic support structures, including overstretching of the pubococcygeus muscle, pudendal nerve damage, suspensory ligament strain, and urinary/anal sphincter injury. At present there is no therapy for the improvement in tissue damaged during birth and associated injury. To address this, we are developing injectable hydrogel therapies designed for administration immediately after birth-related injuries. The growing demand for preventative treatments for POP has driven exploration into novel biologically active scaffolds, such as Aloe Vera-Alginate hydrogel (AV-ALG-Hyd) enriched with xenogeneic SUSD2+ human endometrial mesenchymal stem cells (eMSC). This study investigates the therapeutic potential of AV-ALG-Hyd, both with and without eMSC, in promoting postpartum tissue repair. We hypothesize that this engineered hydrogel, combined with SUSD2+ eMSC, enhances healing at the molecular level. Specifically, we aim to analyze the differential expression of genes involved in inflammation, angiogenesis, and extracellular matrix remodeling, offering insights into its regenerative potential. In this study, we used primiparous ewes and induced birth injury with Bakri balloon catheter, a clinical tool commonly used to manage postpartum uterine bleeding. Following simulated vaginal birth injury, AV-ALG-Hyd containing SUSD2+ eMSC was administered immediately. Control groups included ewes that experienced injury without receiving hydrogel and/or eMSC treatment. Additional controls consisted of ewes treated with AV-ALG-Hyd without eMSCs and those undergoing sham injury. Tissue analysis of vagina was conducted at 30 and 90 days post-treatment, incorporating pre- and post-operative POP-Q assessments alongside gene expression profiling. Gene expression analysis was performed using the Fluidigm Biomark Assay to evaluate fold changes across 96 genes. Our findings indicate that birth injury in ewes leads to disruptions in collagen structure, smooth muscle cells, and elastin content within vaginal tissue. However, treatment with AV-ALG-Hyd combined with SUSD2+ eMSC following simulated injury appeared to reverse these changes. Tissue analysis showed a trend of increased α-Smooth Muscle Actin (αSMA) expression in the hydrogel + eMSC group at 90 days, suggesting potential benefits in preserving smooth muscle integrity. Additionally, elastin levels were maintained at both 30 and 90 days across all groups, highlighting the positive effects of AV-ALG-Hyd and eMSC in supporting tissue elasticity. Our ongoing assessments are looking at measurement of differential gene expression in Vegfa, Pdgfrb, Fgf1, Fgf2, Pecam, Ki67, Fibulin5, Timp1, Timp2, Mmp9, Cdh1, Icam1, Col1a1, Col3a1 as well as gene associated with innate and adaptive immune response Cd80, Arg1, Cd68, Nlrp3, Mrc1, Il4r, Il3r, Cd19, Cd4Il2, Il23ccl5, Cd40. Innovative cell-based tissue-engineered hydrogels, such as AV-ALG-Hyd with xenogeneic SUSD2+ eMSC have the potential to impact the healing at the molecular level, thus offering a promising approach to enhancing tissue repair following birth injury. Administering this therapy in a timely manner could support the regeneration of tissues adversely impacted by vaginal birth trauma. This study provides new perspectives on the clinical use of xenogeneic tissue-engineered biosystems for repairing and reversing childbirth-related injuries, offering a potential solution to a significant women's pelvic health challenge. Funding National Health and Medical Research Council, Australia and Medical Research Future Fund, Australia Clinical Trial No Subjects Animal Species Sheep Ethics Committee Monash Medical Committee A
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