Placental Cells and Tissues: The Transformative Rise in Advanced Wound Care

The fetal environment has a remarkable capacity for facilitating and guiding tissue development. Placental tissues including the placental disc, umbilical cord, amniotic fluid and amniotic sac are highly specialized tissues responsible for transporting nutrients and coordinating developmental cues during pregnancy and fetal develop‐ ment. Placental tissues are nutrient‐rich, structurally complex and immunologically privileged, making them promising allograft therapies for advanced wound care. Amniotic membrane allografts in particular have been shown to be effective therapies for treatment of chronic wounds, including diabetic and venous ulcers, by modulating inflammation, reducing scar tissue formation and enhancing healing. Amniotic membrane has also demonstrated the ability to promote cell proliferation, cell migration and modulate cytokine secretion by a variety of cell types involved in wound healing, including human dermal fibroblasts, microvascular endothelial cells and stem cells. In addition, amniotic membrane allografts have been shown to stimulate stem cell activity, promote angiogenesis and modulate inflammation in vitro and in vivo . Placental tissues are complex tissues composed of extracellular matrix (ECM), cells and a broad array of cytokines that may collectively enhance wound healing by modulating wound environments and stimulating endogenous cells to progress through the normal healing stages of inflammation, proliferation and remodeling. same location [53]. These results reinforce that a significant healing response was observed in chronic DFUs in response to dHACM treatment. In a separate study to determine the optimal dosing frequency for application of PURION® Processed dHACM allografts, a weekly application ( n = 20) was compared with biweekly applications ( n = 20) of dHACM (EpiFix®, MiMedx Group, Inc.) in a prospective, randomized clinical study. The weekly application of dHACM healed diabetic foot ulcers in a mean time to complete healing of 2.4 ± 1.8 weeks, compared to 4.1 ± 2.9 weeks with biweekly applications [54]. Complete healing occurred in 90% of wounds by 4 weeks in the weekly group, while 50% of wounds completely healed by 4 weeks with biweekly treatment. Therefore, these results indicate that with weekly applications wounds healed in approximately half of the time and using a similar number of grafts applied as the biweekly application, even though overall 92.5% of ulcers completely healed during the 12‐week study period with dHACM treatment. These results further demonstrated that dHACM allografts are an effective treatment to promote healing in diabetic foot ulcers and suggest that wounds treated with a weekly application of dHACM heal more rapidly than with biweekly application. In a prospective, randomized multicenter comparative effectiveness study, weekly applica‐ tions of PURION® Processed dHACM (EpiFix®, MiMedx Group, Inc.; n = 20) was compared with bioengineered skin substitute (Apligraf®, Organogenesis, Inc., Canton, MA; n = 20) and standard of care (collagen‐alginate dressing; n = 20) for treatment of chronic lower extremity diabetic ulcers. After 4 and 6 weeks, 85 and 95% of ulcers treated with dHACM, respectively, achieved complete wound closure, which was significantly higher than for patients receiving the bioengineered skin substitute which healed 35 and 45% of wounds, respectively, or standard of care treatment with 30 and 35%, respectively [57]. Median time to healing with dHACM was 13 days, compared to 49 days with bioengineered skin substitute and the mean number of dHACM grafts used was 2.5 applications at an average cost of $1669 per patient, compared to 6.2 bioengineered skin substitute grafts used at a cost of $9216, indicating that costs were significantly less for dHACM than the bioengineered skin substitute by a factor of five. These results reaffirm both the efficacy and cost effectiveness of dHACM amniotic membrane allografts to promote healing in chronic diabetic ulcers in comparison with a leading skin substitute.