Care for the patient with diabetic foot ulcers (DFUs) entails understanding the epidemiology, pathophysiology, and a systematic approach to diagnosis and treatment. The authors will review elements of DFU in geriatric patients including the pathophysiology of diabetes, epidemiology and management of DFU in the context of developing a Plan for Healing. The authors will discuss comprehensive principles of a Plan for Healing, which applies to all aspects of chronic wounds.

The increasing global prevalence of chronic wounds underscores the growing importance of developing effective animal models for their study. This review offers a critical evaluation of the strengths and limitations of rat models frequently employed in chronic wound research and proposes potential improvements. It explores these models in the context of key comorbidities, including diabetes, venous and arterial insufficiency, pressure-induced blood flow obstruction, and infections. Additionally, the review examines important wound factors including age, sex, smoking, and the impact of anesthetic and analgesic drugs, acknowledging their substantial effects on research outcomes. A thorough understanding of these variables is crucial for refining animal models and can provide valuable insights for future research endeavors.

The challenges in achieving optimal outcomes for wound healing have persisted for decades, prompting ongoing exploration of interventions and management strategies. This study focuses on assessing the potential benefits of implementing a nano-gelatin scaffold for wound healing. Using a rat skin defect model, full-thickness incisional wounds were created on each side of the thoracic-lumbar regions after anesthesia. The wounds were left un-sutured, with one side covered by a gelatin nano-fibrous membrane and the other left uncovered. Wound size changes were measured on days 1, 4, 7, and 14, and on day 14, rats were sacrificed for tissue sample excision, examined with hematoxylin and eosin, and Masson\'s trichrome stain. Statistical comparisons were performed. The gelatin nanofibers exhibited a smooth surface with a fiber diameter of 260 ± 40 nm and porous structures with proper interconnectivity. Throughout the 14-day experimental period, significant differences in the percentage of wound closure were observed between the groups. Histological scores were higher in the experiment group, indicating less inflammation but dense and well-aligned collagen fiber formation. A preliminary clinical trial on diabetic ulcers also demonstrated promising results. This study highlights the potential of the nano-collagen fibrous membrane to reduce inflammatory infiltration and enhance fibroblast differentiation into myofibroblasts during the early stages of cutaneous wound healing. The nano-fibrous collagen membrane emerges as a promising candidate for promoting wound healing, with considerable potential for future therapeutic applications.

Increasing evidence has revealed the emerging role of ferroptosis in the pathophysiology of type 2 diabetes mellitus (T2DM) and its complications. Platelet-rich plasma (PRP) has been demonstrated to facilitate the healing of T2DM ulcers. However, the mechanism by which PRP repairs T2DM ulcers remains unclear. Here, we sought to investigate the interaction between PRP and ferroptosis in repairing T2DM ulcers. The results showed that the cellular activity, proliferation, and migration of fibroblasts were down-regulated, and the cellular activity and normal function of vascular endothelial cells were impaired in the high glucose environment or under RSL3 conditions (a GSH peroxidase 4 inhibitor and ferroptosis inducer). Additionally, both cells experienced over-activation of multiple forms of reactive oxygen species (ROS) and lipid peroxidation. In the T2DM rat model, we observed a decreased rate of ulcer wound healing, impaired proliferative capacity, diminished vascular regeneration, and marked inflammation and hyperfibrosis. More importantly, there was typical damage to mitochondria, increased levels of iron ions, and consistent alterations in protein expression of ferroptosis-related factors. These factors include cyclooxygenase-2 (COX2), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and Solute Carrier Family 7 Member 11 (SLC7A11), among others. Due to the strong association between ferroptosis and T2DM ulcers, the use of allogeneic platelet-rich plasma (Al-PRP) exhibited physiological effects similar to those of the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In vivo experiments, both drugs inhibited a range of impediments to wound healing caused by T2DM and ameliorated the adverse effects associated with ferroptosis. Moreover, Al-PRP attenuated the impairment of normal cellular function, activation of ROS and lipid peroxidation induced by high glucose or RSL3. These results suggested that ferroptosis was involved in the development of T2DM ulcers, which could be treated with Al-PRP by inhibiting ferroptosis, and inhibition of ferroptosis may be a suitable treatment strategy for T2DM ulcers.

Background: Chronic wounds present a significant clinical, social, and economic challenge. This study aimed to objectify the risk factors of healing outcomes and the duration of chronic wounds from various etiologies. Methods: Patients treated for non-healing wounds at the surgical outpatient clinic of the Olomouc Military Hospital were involved. Data from patients treated between 8/2021 and 9/2023 were selected. Patients were mostly treated as outpatients, with microbiological follow-up indicated in cases of advanced signs of inflammation. Results: There were 149 patients who met our selection criteria (the mean age was 64.4 years). Predominant causes of wounds involved diabetes (30.9%), post-trauma (25.5%), pressure ulcers (14.8%), surgical site infections (14.8%), and vascular ulcers (14.1%). Patient outcomes included wound resolution in 77.2% of patients (with a mean healing time of 110.9 days), amputation in 14.1%, and wound-related death in 8.7% of patients. Non-healing cases (amputation/death) were predicted by several local factors including an initial depth greater than 1 cm, wound secretion, inflammatory base, and a maximum wound size. Systemic factors included most strongly clinically manifested atherosclerosis and its risk factors. Of the 110 swabs performed, 103 identified at least 1 bacterial genus. The dominant risk factor for a prolonged healing duration was bacterial infection. Wounds contaminated by Proteus or Pseudomonas had prolonged healing times of 87 days (p = 0.02) and 72 days (p = 0.045), respectively. Conclusions: The early identification of local and systemic risk factors contributes to the successful resolution of chronic wounds and a reduced duration of healing.

Bidirectional photobiomodulation (PBM) therapy is an active research area. However, most studies have focused on its dependence on optical parameters rather than on its tissue-dependent effects. We constructed mouse models of wounds in three inflammatory states (normal, low, and high levels of inflammations) to assess the bidirectional regulatory effect of PBM on inflammation. Mice were divided into three groups to prepare common wounds, diabetic wounds, and bacteria-infected wounds. The same PBM protocol was used to regularly irradiate the wounds over a 14 d period. PBM promoted healing of all three kinds of wounds, but the inflammatory manifestations in each were significantly different. In common wounds, PBM slightly increased the aggregation of inflammatory cells and expression of IL-6 but had no effect on the inflammatory score. For wounds in a high level of inflammation caused by infection, PBM significantly increased TNF-α expression in the first 3 d of treatment but quickly eliminated inflammation after the acute phase. For the diabetic wounds in a low level of inflammation, PBM intervention significantly increased inflammation scores and prevented neutrophils from falling below baseline levels at the end of the 14 d observation period. Under fixed optical conditions, PBM has a bidirectional (pro- or anti-inflammatory) effect on inflammation, depending on the immune state of the target organism and the presence of inflammatory stimulants. Our results provide a basis for the formulation of clinical guidelines for PBM application.

Pseudomonas aeruginosa is one of the most common causes of diabetic foot infection globally. This study aimed to determine the global distribution of P. aeruginosa isolated from diabetic foot ulcer infection. PRISMA procedure was used to perform the current systematic review and meta-analysis. The Web of Science, MEDLINE/PubMed, Scopus, and other databases were searched for studies published in English from 2000 to 2022. Data was analyzed using the Comprehensive Meta-Analysis software (CMA). Keywords and MESH phrases included Pseudomonas aeruginosa, diabetic foot ulcer, P. aeruginosa, and diabetic foot infection. As a result of this review, 16.6% of diabetic foot wound infections were caused by P. aeruginosa. About 37.9% of strains were multidrug resistant (MDR). P. aeruginosa infection rates in diabetic foot ulcers ranged from 0.5 to 100% globally. In total, the prevalence rates of P. aeruginosa in diabetic foot ulcer infection from Asia, Africa, and Western countries were reported at 18.5%, 16.3%, and 11.1%, respectively. Data have shown that the prevalence of P. aeruginosa, particularly MDR strains, isolated from diabetic foot ulcer infection was relatively high; inherent resistance to antibiotics is also high; the wound either does not heal or if it does, it will be delayed. Therefore, timely treatment is essential.

Chronic wounds, especially diabetic, foot and pressure ulcers are a major health problem affecting >10 % of the world\'s populace. Calcium phosphate materials, particularly, bioactive glasses (BG), used as a potential material for hard and soft tissue repair. This study combines nanostructured 45S5 BG with titania (TiO2) and alumina (Al2O3) into a composite via simple sol-gel method. Prepared composites with alginate (Alg) formed a bioactive nanocomposite hydrogel membrane via freezing method. X-ray diffraction revealed formation of two phases such as Na1.8Ca1.1Si6O14 and β-Na2Ca4(PO4)2SiO4 in the silica network. Fourier transformed InfraRed spectroscopy confirmed the network formation and cross-linking between composite and alginate. <2 % hemolysis, optimal in vitro degradation and porosity was systematically evaluated up to 7 days, resulting in increasing membrane bioactivity. Significant cytocompatibility, cell migration and proliferation and a 3-4-fold increase in Collagen (Col) and Vascular Endothelial Growth Factor (VEGF) expression were obtained. Sustained delivery of 80 % Dox in 24 h and effective growth reduction of S. aureus and destruction of biofilm development against E. coli and S. aureus within 24 h. Anatomical fin regeneration, rapid re-epithelialization and wound closure were achieved within 14 days in both zebrafish and in streptozotocin (STZ) induced rat in vivo animal models with optimal blood glucose levels. Hence, the fabricated bioactive membrane can act as effective wound dressing material, for diabetic chronic infectious wounds.

BACKGROUND: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain.
UNASSIGNED: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers.
RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1β, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway.
CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

Diabetes is a widespread epidemic that includes a number of comorbid conditions that greatly increase the chance of acquiring other chronic illnesses. Every year, there are significantly more people with diabetes because of the rise in type-2 diabetes prevalence. The primary causes of illness and mortality worldwide are, among these, hyperglycemia and its comorbidities. There has been a lot of interest in the creation of peptide-based hydrogels as a potentially effective platform for the treatment of diabetes and its consequences. Here, we emphasize the use of self-assembled hydrogel formulations and their unique potential for the treatment/management of type-2 diabetes and its consequences. (i.e., wounds). Key aspects covered include the characteristics of self-assembled peptide hydrogels, methods for their preparation, and their pre-clinical and clinical applications in addressing metabolic disorders such as type-2 diabetes.