Vaginal delivery of tissue engineered endometrial mesenchymal stem/stromal cells in an aloe vera-alginate hydrogel alleviates maternal simulated birth injury

Vaginal childbirth causes significant maternal tissue injury which can later leads to incurable disorders such as pelvic organ prolapse (POP). This study introduces an immediate vaginal tissue treatment using Aloe Vera (AV)-Alginate (ALG) hydrogel (Hyd) for delivering maternal endometrium derived Mesenchymal stem cells (eMSCs) to promote early healing in a rat simulated birth injury (SBI) model. Vaginal trauma after SBI was evidenced by increased vaginal diameter and inflammatory response. A lack of therapy showed significant reduction of smooth muscle content, increased elastin and increased tissue stiffness, indicative of fibrotic healing. Local injection with hydrogel (Hyd T) or with eMSC in hydrogel (Hyd/eMSC T) had significant impact on birth injury reversal. Hyd/eMSC T significantly improvement smooth muscle and elastin content, comparable to uninjured control vagina. At the nanoscopic level, injury caused disorganisation of structural collagen with increased D period but intervention with Hyd/eMSC T, normalised collagen structure and significantly reduced tissue stiffness. Hyd/eMSC injection showed significant immunomodulation evidenced by lowered M1:M2 ratio while restoring connective tissue composition after 6-weeks. Immediate treatment of severe vaginal birth trauma with therapeutic eMSCs delivered in AV-ALG hydrogel may be a potential new treatment strategy for healing birth injury and preventing future POP in women.