Diabetes mellitus (DM) poses a substantial worldwide public health and economic challenge, being one of the most prevalent chronic diseases globally. It is noteworthy that DM is manifesting at increasingly younger ages and experiencing a yearly escalation in incidence rates [1].T2DM, which accounts for approximately 90% of DM cases, is a metabolic disorder characterized by hyperglycemia, insulin resistance, and insufficient insulin production [2]. According to the 10th edition International Diabetes Federation Atlas, the number of individuals aged 20-79 years affected by DM was estimated to be around 536 million in 2021. The projected increase in the number of individuals affected by DM to over 783 million by 2045 [3] has highlighted the urgent need to address this condition and its associated complications.

Diabetic ulcers (DU) have particularly garnered significant attention from clinical practitioners and researchers due to their refractory nature, high disability rate, and tendency to recur in patients with T2DM. Consequently, extensive scientific investigations have been undertaken to elucidate the molecular mechanisms underlying DU, with the ultimate goal of developing safe and accessible therapeutic agents that exhibit high efficacy. An increasing body of scholarly literature indicates a significant correlation between ferroptosis and the pathological mechanisms implicated in T2DM and its associated complications. These encompass impaired insulin secretion in pancreatic β-cells, perturbation of oxidative stress microenvironmental equilibrium, and mitochondrial dysfunction in adipocytes [[4], [5], [6]].

PRP is a plasma derivative characterized by a significantly elevated platelet concentration achieved through the centrifugation process of whole blood, typically resulting in a platelet concentration 3-7 times higher than that of whole blood [7]. This therapeutic modality has been harnessed as an autologous cell therapy, exhibiting potential efficacy in facilitating regenerative tissue repair owing to the abundance of platelet concentrates and a diverse array of growth factors. Multiple studies have demonstrated the diverse applications of PRP in various medical fields such as orthopedics, plastic surgery, neurosurgery, dentistry, and dermatology [[8], [9], [10], [11], [12]]. Additionally, there have been reports on the potential use of PRP for the repair of diabetic ulcerative wounds (DUs) [13,14]. However, the current body of research lacks in-depth exploration of the specific molecular mechanisms involved in this area. Considering the limitations associated with the availability of autologous platelet-rich plasma (Au-PRP), Al-PRP holds greater promise for application, particularly in the treatment of DUs. This is particularly relevant as patients with DUs often experience poor health and require alternative therapeutic approaches to Au-PRP.

In recent years, ferroptosis, a distinctive mode of cellular demise, has been found to be linked with the progression of various diseases, such as cancers, ischemia reperfusion-induced diseases (IRI), brain and neurological injuries, liver and kidney transplantation injuries, as well as possibly having positive physiological functions in tumor suppression and immune surveillance [15]. This form of cell death is primarily driven by iron-dependent lipid peroxidation and is precisely regulated by a network of cellular metabolisms, encompassing redox homeostasis, iron metabolism, amino acid metabolism, lipid metabolism, and glucose metabolism [16]. Numerous tumor suppressors have demonstrated the ability to enhance cellular sensitivity to ferroptosis. Notably, the correlation between apoptosis-inducing P53 and ferroptosis has been extensively examined. Findings have revealed that P53 can facilitate ferroptosis by suppressing the transcription of system xc-subunit SLC7A11 [17,18]. Furthermore, investigations have indicated that the inhibition of ferroptosis through the down-regulation of P53 targets mitigates acute lung injury (ALL) [19,20]. Therefore, the aim of this study is to dissect the intrinsic link between Al-PRP repair of T2DM ulcer wounds and ferroptosis patterns.