Hypothesis: Platelet-rich plasma accelerate diabetic wound healing via dynamic modulation of multiple signaling pathways

Abstract

Diabetic wounds are a prevalent complication in patients with diabetes. Incremental platelet-rich plasma (PRP) administration has recently been used as an adjunct therapy for the treatment of diabetic ulcers. However, the exact signaling pathways involved in PRP-induced healing remain unclear. We speculated that PRP could mediate diabetic wound healing by dynamic modulation of signaling pathways including TGF-β/Smad, Wnt/β-catenin, Notch, NF-κB, MAPK, and PI3K/Akt, at different levels. PRP may have different effects (activation or inhibition) on different or even the same signal pathways depending on the stage of the healing process and concentration of growth factors within the PRP preparation. In the early stages of wound healing, some signaling pathways are initiated to reduce wound inflammation and oxidative stress, and promote angiogenesis and collagen regeneration. In the late stages of wound healing and scar formation, PRP may inhibit some signal pathways to prevent excessive fibroblast proliferation and deposition of extracellular matrix proteins such as collagen, thereby controlling excessive tissue proliferation at the wound site and minimizing scars. The various signaling pathways exhibit complex and context-dependent interactions; crosstalk between these pathways can lead to synergistic or antagonistic effects and regulate various cellular responses. This knowledge could be used to develop targeted therapies to optimize healing and reduce the risk of subsequent complications.