A Photothermal-Responsive PRP-Loaded Hydrogel Engineered with Composite Nanobottle for Controllable Delivery of Growth Factors and Multifunctional Therapy of Diabetic Wounds.

ABSTRACT In this paper, we develop a photothermal‐responsive hydrogel (CNB‐ePRP) based on engineered platelet‐rich plasma (PRP)/sodium alginate (SA) hydrogel integrating thrombin‐functionalized composite nanobottle (CNB) to treat diabetic wounds. Within CNB‐ePRP, the CNB consists of polydopamine nanobottle loaded with thrombin, personalized drugs and a phase‐change material. As a photothermal agent and dual‐stage controller, CNB not only enables in situ PRP activation at physiological temperature to slowly release various growth factors (GFs) via thermal‐triggered thrombin release, avoiding premature burst release of GFs, but also accelerates the release of GFs from the CNB‐ePRP hydrogel through mild photothermal heating under 808 nm laser irradiation. Meanwhile, SA enhances hydrogel stability and prolongs GF release kinetics. Consequently, CNB‐ePRP achieves on‐demand delivery of GFs, significantly promoting angiogenesis, cell proliferation and M2 macrophage polarization. Moreover, CNB‐ePRP can mitigate oxidative stress via the antioxidant activity of CNB. Furthermore, vancomycin is loaded into CNB to construct a multimodal antimicrobial hydrogel (VCNB‐ePRP) that combines antibiotic and photothermal therapy to efficiently eradicate MRSA and promote healing in MRSA‐infected diabetic mouse wounds. Collectively, this study offers a smart PRP‐derived platform, characterized by in situ PRP activation, on‐demand GFs release, personalized antimicrobial loading and multifunctional therapy, for managing diabetic wounds with great translational potential.