Regenerative Effects of Hypoxia Primed Flowable Placental Formulation in Muscle and Dermal Injury

Abstract

The placental tissue, due to its angiogenic, anti-inflammatory, antioxidative, antimicrobial, and anti-fibrotic properties, has become a compelling source towards a solution for several indications in regenerative medicine. However, methods to enhance and capture the therapeutic properties with formulations that can further the applications of viable placental tissue have not been explored. In this study, we investigated the regenerative effects of a hypoxia primed flowable placental formulation (FPF), composed of amnion/chorion and umbilical tissue, in two in vivo injury models. Laser Doppler data from rodent ischemia hindlimbs treated with FPF revealed significant tissue perfusion improvements compared to control ischemic hindlimbs. To further corroborate FPF’s effects, we used a rodent ischemic bipedicle skin flap wound model. FPF treatment significantly increased the rate of wound closure and the quality of wound healing. FPF-treated wounds displayed reduced inflammation and an increase in angiogenesis. Furthermore, quantitative PCR and next-generation sequencing analysis confirmed these changes in the FPF-treated group at both the gene and transcriptional level. The observed modulation in miRNAs was associated with angiogenesis, regulation of inflammatory microenvironment, cell migration and apoptosis, reactive oxygen species generation, and restoring epithelial barrier function, all processes involved in impaired tissue healing. Taken together, these data validate the tissue regenerative properties of the flowable placental formulation configuration tested.