Analysis of Enhanced Wound Closure Potential of ADSC-Derived Secretome Compared to Aquacel Extra in Diabetic Rats

Background: Diabetes Mellitus (DM) can lead to serious complications, such as Diabetic Foot Ulcers (DFUs). Currently, Aquacel Extra is one of the standard therapies for DFUs, but its efficacy has some limitations that may be overcome by alternative treatments, such as the secretome derived from Adipose-Derived Stem Cells (ADSCs). ADSC secretome has shown promising results in promoting wound healing by enhancing cell proliferation, collagen synthesis, and migration of fibroblasts. Aims: This study aims to compare the effect of the adipose-derived stem cell (ADSC) secretome to Aquacel Extra, a hydrofiber dressing containing gel-forming agents, on wound healing in a diabetic rat model. Aquacel Extra has sodium carboxymethylcellulose fibers, which contribute to its unique properties. Objective: The objective of this study is to compare the wound healing outcome of ADSC secretome and Aquacel Extra in streptozotocin-induced diabetic rats. Methods: Sprague Dawley rats received a single intravenous administration of streptozotocin to induce diabetes mellitus (DM). A full-thickness excisional circular wound was created at the dorsum aspect of the rats two weeks after diabetic induction. Rats were randomly divided into two groups: the Aquacel Extra group, which received the hydrofiber dressing Aquacel Extra containing gel-forming agents, and the secretome group, which received the ADSC secretome on days 0, 3, and 7. The gross examination was performed on days 0, 3, 7, and 14. On day 14, the rats were euthanized, and full-thickness skin biopsies of the wounds were taken for histological and immunohistochemical analysis. Results: The secretome group demonstrated accelerated cutaneous wound healing compared to the Aquacel Extra group, as indicated by faster wound closure (p < 0.05). Hematoxylin and eosin staining revealed a thicker epidermal layer in the secretome group than in the Aquacel Extra group (p < 0.05). The mean histological score of the secretome group was higher at 10 ± 1.73 compared to the score of 8.33 ± 1.52 in the Aquacel Extra group, indicating a more mature tissue architecture. Immunohistochemical analysis showed lower expression of α-smooth muscle actin (α-sma) in the secretome group than in the Aquacel Extra group, which correlated with reduced collagen secretion and deposition in the secretome group, as indicated by Masson’s trichrome staining. Conclusion: The ADSC secretome accelerated the healing of diabetic wounds compared to Aquacel Extra. However, as this study is preliminary, future studies should be conducted similar to this study with a larger sample and wound size. In addition, the optimal dosage of ADSC secretome and the components of the secretome that promoted wound healing should be determined to fully elucidate the clinical potential of ADSC secretome.