Combined therapeutic use of umbilical cord blood serum and amniotic membrane in diabetic wounds

Abstract

Diabetic wounds are hard-to-heal due to complex multifactorial dysregulation within the micro-environment, necessitating the development of novel regenerative approaches to stimulate healing. This study investigated whether the combined therapeutic application of two novel cellular tissue products, namely a decellularized collagen-rich amniotic membrane (AmR) and growth factor-rich umbilical cord blood serum (UCBS) could have a positive synergistic effect on long-term healing outcomes by stimulating both superficial wound closure and wound bed regeneration. Full thickness excisional wounds were induced on obese diabetic mice (B6.Cg-lepob/J, ob/ob, n = 23) and treated with either: 1) Standard wound care (control); 2) UCBS; 3) AmR or 4) UCBS + AmR. Macroscopic wound closure was assessed on days 0, 3, 7, 10 and 14 post wounding. To determine the potential impact on wound recurrence, endpoint analysis was performed to determine both the overall quality of healing histologically as well as the molecular state of the wounds on day 14 via proteomic analysis. The data demonstrated the presence of both healers and non-healers. Re-epithelization took place in the healers of all treatment groups, but underlying tissue regeneration was far more pronounced following application of the combined treatment (UCBS + AmR), suggesting improved quality of healing and potentially a reduced change of recurrence long term. In non-healers, wounds failed to heal due to excessive slough formation and a reduction in LTB4 expression, suggesting impaired antimicrobial activity. Care should thus be taken since the cellular tissue product therapy could pose an increased risk for infection in some patients.