Near-infrared-responsive aFGF-loaded polydopamine nanoplatform for ischemic skin flap salvage through microenvironment remodeling

This is the authors' abstract. We don't add key points for this paper.

Ischemic necrosis remains a major challenge in skin flap transplantation, largely due to insufficient perfusion, oxidative stress, persistent inflammation, endothelial apoptosis, and delayed vascular reconstruction. Conventional free acidic fibroblast growth factor (aFGF) suffers from poor stability, rapid degradation, and short local retention, while conventional PDA lacks angiogenic effects. Here, we developed a multifunctional, integrated nanoplatform responsive to near-infrared light (NIR) for sustained aFGF delivery and ischemic microenvironment regulation. aFGF was immobilized onto PDA nanoparticles through multivalent noncovalent interactions, preserving the photothermal responsiveness of PDA while enabling sustained growth factor release. Bioinformatics analysis identified MAPK signaling as a key pathway associated with aFGF-mediated flap salvage. In TBHP-injured HUVECs, aFGF@PDA reduced ROS accumulation, suppressed inflammatory cytokine expression, restored the Bax/Bcl-2 balance, and attenuated excessive phosphorylation of JNK, p38, and ERK, thereby protecting endothelial cells from oxidative injury. The nanoplatform also enhanced endothelial migration and angiogenesis-associated protein expression. In a random-pattern ischemic flap model, aFGF@PDA combined with mild NIR irradiation reduced distal necrosis, improved perfusion, promoted CD31/α-SMA-positive vascular reconstruction, and supported organized collagen remodeling. These findings demonstrate that PDA-enabled aFGF delivery integrates antioxidative, anti-inflammatory, anti-apoptotic, and pro-angiogenic functions, offering an externally regulated biomaterial strategy for ischemic flap repair.