Autologous Fat Promotes Second Degree Burn Wound Healing in Diabetic Rats: A Mechanistic Approach

Abstract

Introduction: Adipocytes have several roles in different tissues that go beyond simple energy storage to include metabolism regulation and growth. There is evidence that adipocytes have immunological and stem cells like properties when it comes to tissue regeneration and vascularization. In addition, transplanted fat improve facial and body proportions and the surrounding tissue as well as the quality of aging skin and scaring especially in damaged skin conditions. In a study in drosophila, skin wound healing with fat cells transfer, it was observed that adipocytes have motility and migration properties which aid in wound repair and prevention of infection. Hence, this study was conducted, in order to gain a better understanding of the role of autologous fat tissue transferred in second degree burn wounds in diabetes.

Methods: A total of 80 adult male rats, 200-250g weight, were used according to IACUC guidelines. The interscapular region was selected as a site of burn and fat transplantation. Diabetes was induced by a 60mg/kg intravenous injection of Sterptozotocin (STZ). Glucose serum levels and body weights were monitored regularly. The burn was performed at 80°c for 40 sec and 4 animals were sacrificed on days 3-7-14-21-28 post-burn from each group. The clinical status of the burn was checked on daily basis. Routine histology was performed as well as the levels of interleukins IL-6, IL-12, and IL-1α were determined by qRT-PCR.

Results: Redness around the rim of the burn was reduced in the presence of transferred fat in both diabetic and non-diabetic rats on days 3 and 7. Crust formation started at day 7 post-op in all subgroups. however, on day 14 the edges of the crusts started to peel off in the diabetics treated with fat as well as non-diabetic with fat alone to a more advanced degree. On day 21, the crust has fallen first in the groups having fat both diabetic and non-diabetic and the wound surface area got smaller than the controls. At the last time point, day 28, groups with fat healed better with a smaller surface area and hairs in most of the burned surface, almost 90% in non-diabetics,70% in diabetics, and 50% in the absence of fat in non-diabetics. The histological studies showed a movement of the fat deep to the dermis with accumulation of myofibroblasts, inflammatory cells and collagen fibers, as well as earlier reepithelialization and early foundation of skin adnexa. The molecular analysis of IL-1α, IL-6, and IL-12 showed a distinct modulation of the interleukin levels in the presence of fatty tissue by increase till day 14 then a decrease to day 28 corresponding to the progress in healing.

Conclusion: Our preliminary results have shown that fat transfer improved healing of the burned wounds, leading to a faster and improved wound recovery with reduced scaring, especially in the diabetic rat model. The mechanism was explored further with the completion of the molecular part of the study, which indicated control of inflammation in early stages with induction of more myofibroblastic activities leading to early contraction of the wound and improved scar.