Dissertation committee:
Τεντολούρης Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργόπουλος Σωτήριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μακρυλάκης Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κόκκινος Αλέξανδρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Λυμπερόπουλος Ευάγγελος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αγγελούση Άννα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Θανοπούλου Αναστασία, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Introduction:
Diabetic foot ulcers are a serious complication of diabetes mellitus and their management remains a challenge for clinicians. ReGenerating Tissue Agents (RGTA) technology is a minimally invasive approach in the field of regenerative medicine that acts as a heparin sulfate glycosaminoglycan mimetic and promotes wound healing. Clinical data from the use of RGTAs in patients with diabetic foot ulcers are scarce.
Objectives:
The objective of this study was to evaluate the efficacy of RGTA matrix technology, when used on top of standard of care, in the management of diabetic foot ulcers. For this purpose, a randomized controlled study was conducted in a tertiary hospital.
Materials and methods:
Patients with diabetes and chronic, hard-to-heal, neuroischemic ulcers were randomized 1: 1 to the control group, that received the standard of care in the management of diabetic foot ulcers, (surgical debridement, gauze binding and offloading) and to the intervention group, that received the standard of care and the application of RGTA in the form of spray twice per week. The duration of the intervention was 12 weeks, followed by a follow-up period of 4 weeks. The primary end-point of the study was complete healing at the end of the intervention period. Skin biopsies from the borders of the wounds were taken at baseline, at 6 weeks and at 12 weeks from a sample of patients. Immunoreactions with antibodies against markers of M1 macrophages (CD64), M2 macrophages (CD163), the receptor 2 of vascular endothelial growth factor (VEGFR2), structural protein collagen I and III (COL1A1 και COL3Α1), vimentin and Ki67 were performed.
Results:
Thirty one patients completed the study (16 in the intervention and 15 in the control group). No significant differences in terms of demographics, laboratory values and baseline ulcer characteristics were observed between the 2 groups. Five (31.2%) patients in the intervention group achieved complete healing at the end of the intervention period versus 0 in the control group (p= 0.043). Also, the intervention group showed superiority in terms of the number of ulcers with at least 80% healing of their surface [10 (66,7%) vs. 2 (13,3%), p=0,008], the absolute surface reduction [1,5 (0,7, 5,2) vs. 0,6 (0,3, 1,0), p=0,026] and the percentage of surface reduction [94 (67,100) vs. 40 (26,75), p=0,001] at the end of the intervention period. Furthermore, significantly more ulcers in the intervention group achieved at least 50% healing at the 4th week of the study [9 (64,3%) 2 vs. (14,3%) p=0,018.] Eight (50%) patients in the intervention group achieved complete healing at the final visit versus 2 (13,3 %) in the control group (p= 0,054). The adverse effects (infections and amputations) were similar between the 2 groups. As far as the immunohistochemical analyses are concerned, the expression levels of CD163, COL31A and VEGFR2 were greater in the intervention in comparison with the control group.
Conclusions:
The data from the present study suggest that the adjunction of RGTA technology in the management of diabetic foot ulcers is a safe practice that could promote wound healing. More evidence from larger trials is needed to further support these results.
Keywords:
Diabetes mellitus, Diabetic foot ulcers, RGTA technology, Advanced treatments, Wound healing
