The treatment of diabetic wounds (DWs) is always challenging for the medical community because of its multifaceted pathophysiology. Due to practical and ethical considerations, direct studies of therapeutic interventions on human subjects are limited. Thus, it is ideal for performing studies on animals having less genetic and biological variability. An ideal DW model should progress toward reproducibility, quantifiable interpretation, therapeutic significance, and effective translation into clinical use. In the last couple of decades, various animal models were developed to examine the complex cellular and biochemical process of skin restoration in DW healing. Also, these models were used to assess the potency of developed active pharmaceutical ingredients and formulations. However, many animal models lack studying mechanisms that can appropriately restate human DW, stay a huge translational challenge. This review discusses the available animal models with their significance in DW experiments and their limitations, focusing on levels of proof of effectiveness in selecting appropriate models to restate the human DW to improve clinical outcomes. Although numerous newer entities and combinatory formulations are very well appreciated preclinically for DW management, they fail in clinical trials, which may be due to improper selection of the appropriate model. The major future challenge could be developing a model that resembles the human DW environment, can potentiate translational research in DW care.

The healing of oral lesions that are associated with diabetes mellitus is a matter of great concern. Bioactive glass is a highly recommended bioceramic scaffold for bone and soft tissue regeneration. In this study, we aimed to assess the efficacy of a novel formula of bioactive glass nanofibers in enhancing oral mucosal wound regeneration in diabetes mellitus. Bioactive glass nanofibres (BGnf) of composition (1-2) mol% of B2O3, (68-69) mol% of SiO2, and (29-30) mol% of CaO were synthesized via the low-temperature sol-gel technique followed by mixing with polymer solution, then electrospinning of the glass sol to produce nanofibers, which were then subjected to heat treatment. X-Ray Diffraction analysis of the prepared nanofibers confirmed its amorphous nature. Microstructure of BGnf simulated that of the fibrin clot with cross-linked nanofibers having a varying range of diameter (500-900 nm). The in-vitro degradation profile of BGnf confirmed its high dissolution rate, which proved the glass bioactivity. Following fibers preparation and characterization, 12 healthy New Zealand male rabbits were successfully subjected to type I diabetic induction using a single dose of intravenous injection of alloxan monohydrate. Two weeks after diabetes confirmation, the rabbits were randomly divided into two groups (control and experimental groups). Bilateral elliptical oral mucosal defects of 10 × 3.5 mm were created in the maxillary mucobuccal fold of both groups. The defects of the experimental group were grafted with BGnf, while the other group of defects considered as a control group. Clinical, histological, and immune-histochemical assessment of both groups of wounds were performed after one, two and three weeks\' time interval. The results of the clinical evaluation of BGnf treated defects showed complete wound closure with the absence of inflammation signs starting from one week postoperative. Control defects, on the other hand, showed an open wound with suppurative exudate. On histological and immunohistochemical level, the BGnf treated defects revealed increasing in cell activity and vascularization with the absence of inflammation signs starting from one week time interval, while the control defects showed signs of suppurative inflammation at one week time interval with diminished vascularization. The results advocated the suitability of BGnf as bioscaffold to be used in a wet environment as the oral cavity that is full of microorganisms and also for an immune-compromised condition as diabetes mellitus.