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

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.