Professor of Obstetrics, Gynecology and Reproductive Sciences; Professor of Urology University of California, San Diego; Sanford Consortium for Regenerative Medicine, California, United States
Disclosure(s):
Marianna Alperin, MD MS: No financial relationships to disclose
Pelvic floor soft tissue dysfunction has been identified as one of the leading risk factors for the development of morbid pelvic floor disorders. Vaginal delivery is the most important potentially modifiable risk factor for maternal pelvic soft tissue injury, including pelvic floor muscles (PFMs). However, the precise mechanisms of PFM dysfunction after parturition, in the absence of radiologically-evident avulsions, remain elusive. The above hinders development of effective preventive or therapeutic strategies. We demonstrate that tissue-level alterations of PFMs in parous women with symptomatic pelvic organ prolapse include atrophy and fibrotic degeneration. These pathological features were recapitulated in a preclinical rat model of simulated birth injury (SBI). The transcriptional signature of PFMs after injury demonstrated an impairment in muscle anabolism, persistent expression of genes that promote extracellular matrix (ECM) deposition, and a sustained inflammatory response. Given the above, the role of acellular injectable skeletal muscle ECM hydrogel for the prevention of these pathological alterations was explored. Treatment of PFMs with the ECM hydrogel either at the time of birth injury or 4 weeks after injury mitigated PFM atrophy and fibrosis. Based on gene expression, these changes are mainly driven by the hydrogel-induced enhancement of endogenous myogenesis, ECM remodeling, and modulation of the immune response. The above furthers our understanding of PFM birth injury and demonstrates proof of concept for future investigations of pro-regenerative biomaterial approaches for the treatment of injured pelvic soft tissues.
