Systematic review on the rational use of amniotic membrane allografts in diabetic foot ulcer treatment

Abstract

Background Diabetic foot ulcer is a complication with multiple aetiological factors which has a significant impact to patients’ lives and costs to the healthcare system. The potential of human amniotic membrane to act as an allograft has been studied in relation to this condition. Aim of this study is to evaluate the current scientific evidence on its effectiveness in healing diabetic foot ulcers. Methods Pubmed, Cochrane library, and Google scholar were searched using the search terms, “Amnion” OR “Placenta” AND “Diabetic foot”. (MeSH terms) in the title or the abstract field from 1st of January 2000 to 30th March 2020. The quality of published reports was assessed using standard methods. We searched for experimental and observational studies in terms of randomized control trials, prospective cohort, retrospective cohort studies and case series. Results When searched with Mesh terms, 12 citations in PubMed, 22 citations in Cochrane library and 30 in other data bases were found. After screening the studies and their reference lists, 12 studies met the inclusion criteria and the others were excluded. There were 8 randomized control trials (RCTs), 2 prospective studies and 2 retrospective studies employing different preparation methods of the amniotic membranes. A wide variation in study end points were noted. Majority of the RCTs (n = 7) were concluded with significantly higher wound closure rate compared to the conventional treatment groups. In prospective and retrospective studies, it was shown that large chronic ulcers which were resistant to closure with standard therapy achieved wound closure with amniotic membrane allografts. A meta-analysis could not be performed due to study heterogeneity, and publication bias was not assessed due to the small number of available studies which was not sufficient for accurate comparison. Conclusion Even though, the studies had some inherent heterogeneity due to different preparation methods, different study end points and outcome measurements. According to our review the current studies using amniotic membrane allografts give reliable evidence of reduction in healing time over conventional methods.

The clinical effectiveness of cryopreserved human amniotic membrane in diabetic foot syndrome

“…Our results can be explained by the fact that thawed living amnio-chorionic membrane provides delivery to the wound of numerous regulatory proteins, which include chemokines and cytokines, as well as angiogenic proteins [26,74]. The influence of growth factors, in particular EGF, KGF, HGF, bFGF, TGF β and extracellular matrix, produced by placental tissue cells has been shown to be crucial in wound healing and to achieve complete closure [9,80,81,82].…”

“…Chronic wounds that did not heal for a long time with standard treatment regimens were successfully regenerated under the influence of AM allografts. In addition, the frequency of recurrences after their healing decreased [81].…”

Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria

“…Other available treatments that utilize growth factors and chemokines are Platelet-rich plasma (PRP) and amniotic membrane allografts (reviewed in [6]). PRP contains the plasma fraction with high concentrations of platelets and thereby increases the amount of growth factors such as TGF-β, PDGF, and epidermal growth factor (EGF) in the wound following release from platelets [43,44]. Amniotic membranes allografts have in multiple studies been shown to have a clinical effect on non-healing wounds, and there are some commercially available options (EpiFix, MiMedx Group, and the Grafix, Osiris Therapeutics) [45].…”

How can we optimize the development of drugs for wound healing?

“…However, further investigations documenting the efficacy of allogeneic PRP in treatment of non-healing wounds especially are needed [11]. Furthermore, amniotic membrane allografts and other human-derived membranes have in multiple studies shown clinical effect in non-healing wounds, and there are some commercially available options, but only in a limited number of countries [12]. Neither membranes nor derivatives thereof of human origin, or autologous/allogeneic PRP represents completely defined products due to sourcing and handling during their preparation.…”