Platelet Lysate-Incorporated Sodium Alginate Polymannuronate Nanogel with Mussel-Inspired Chemistry for Scar-Minimized Diabetic Wound Healing

Diabetes affects 537 million people globally, with diabetic wounds being a major complication. Around 34% of diabetics develop foot ulcers, and 15-20% of these result in amputation. Healing is often delayed due to prolonged inflammation, impaired neovascularization, and persistent oxidative stress. Platelet lysate, derived from human blood, is rich in growth factors like EGF, VEGF, PDGF, and TGF-β1, which promote wound healing. However, its short half-life causes rapid degradation and instability, often requiring repeated administration. This increases cost, potential toxicity, and patient discomfort, especially with invasive delivery methods. To overcome these limitations, a controlled platelet lysate delivery system was developed using sodium alginate polymannuronate nanogel with a nonfouling surface, achieved through PEGylation via mussel inspired surface chemistry. This system offers high encapsulation efficiency (∼99%), controlled and sustained release (99.5% over 11 days), and long-term stability, making it suitable for clinical use. Four formulations were developed in a stepwise manner, conducting studies on each to evaluate their efficacy. Among these, the final and the best performing formulation, PEGylated alginate nanogel demonstrated excellent biocompatibility (hemolysis ratio: ∼0.6 ± 0.3%, blood clotting index: ∼14 ± 0.2%) and significantly enhanced wound healing in a diabetic mouse model compared to platelet lysate treatment alone, showing superior regenerative properties such as rapid re-epithelialization, significantly reduced immunogenic response, and minimal scarring. Furthermore, the nanogel's favorable pH (<7) and excellent spreadability support patient compliance, offering a noninvasive platform for localized platelet lysate delivery with promising potential for diabetic wound care and future therapeutic strategies.