Letter to the Editor: Optimizing platelet-rich plasma therapy for diabetic foot ulcers: From bench to bedside

Abstract

Huang et al recently published a study in the World Journal of Diabetes, which reported that platelet-rich plasma (PRP) combined with endovascular angioplasty enhances angiogenesis and promotes healing in diabetic foot ulcers (DFUs). While this study provides valuable translational evidence, several mechanistic and clinical considerations warrant further discussion. Cell type-specific, concentration-dependent responses suggest that a uniform PRP formulation may not optimally address the heterogeneous wound microenvironment. In addition, PRP’s effects on diabetes-related endothelial dysfunction, treatment scalability, and variability in PRP composition were not fully explored. Addressing these issues may help refine PRP-based therapeutic strategies and improve their clinical applicability in DFU management.

Key Words: Diabetic foot ulcer; Platelet-rich plasma; Wound healing; Angiogenesis; Endovascular procedures

Core Tip: This commentary builds upon a recent study to propose key refinements for platelet-rich plasma (PRP) therapy in diabetic foot ulcers. We argue against a uniform PRP concentration, advocating instead for cell-type-specific formulations. Furthermore, we highlight the need to address diabetic endothelial dysfunction beyond angiogenesis, and to establish standardized, clinically-relevant protocols based on PRP bioactivity and precise patient stratification. These steps are crucial to transition PRP from a promising treatment to a reliably optimized and personalized therapeutic strategy.

TO THE EDITOR

We read with great interest the study by Huang et al[1] published a study in the World Journal of Diabetes, which investigated the combined use of platelet-rich plasma (PRP) and endovascular angioplasty for diabetic foot ulcers (DFUs). The authors demonstrated that 6% PRP promotes angiogenesis and tissue repair by activating Akt/ERK pathways and upregulating VEGFR2, with clinical outcomes supporting its efficacy. While this translational work is commendable, we wish to highlight key mechanistic and clinical nuances that could refine PRP’s therapeutic application.

First, the study identified 6% PRP as optimal for human umbilical vein endothelial cell (HUVEC) proliferation, but fibroblasts and keratinocytes exhibited distinct concentration-dependent responses. This suggests that a “one-size-fits-all” PRP concentration may not maximize healing in heterogeneous DFU microenvironments. Tailored PRP formulations based on wound cell composition warrant exploration.

Second, while PRP enhanced tubulogenesis in HUVECs, the study did not address PRP’s impact on diabetic endothelial dysfunction, such as oxidative stress or glycocalyx degradation. Combining PRP with antioxidants (e.g., N-acetylcysteine) could synergistically rescue impaired angiogenesis in hyperglycemia[2].

Clinically, the twice-weekly PRP application for 8 weeks improved ulcer healing, but the protocol’s cost-effectiveness and scalability remain unaddressed. Could fewer applications yield similar results? Additionally, PRP’s efficacy in ischemic wounds relies on restored perfusion via angioplasty; however, the study did not stratify outcomes by angioplasty success (e.g., residual stenosis). Subgroup analyses may identify patients most likely to benefit from adjunct PRP.

Finally, PRP’s composition variability (growth factor levels, platelet concentration) was not detailed. Standardization is critical for reproducibility, as PRP efficacy depends on preparation methods[3,4]. We encourage future studies to correlate PRP bioactivity (e.g., VEGF/PDGF levels) with clinical responses.

In summary, Huang et al[1] provide valuable insights into PRP’s mechanistic role in DFU healing. Optimizing PRP formulations and delivery protocols could further enhance its translational potential.

ACKNOWLEDGEMENTS

We thank the reviewers for their comments that helped to improve the manuscript.