Bioactive hyperbranched polymer dot combined laser-induced optical breakdown for accelerating wound repair and regeneration in a nude mice model

Abstract

Chronic wounds pose a significant challenge in clinical practice, with current treatments often failing to address the complex underlying pathophysiology. This study introduces a novel therapeutic strategy combining bioactive hyperbranched polymer dots (PDs) with picosecond laser-induced optical breakdown (LIOB) to synergistically enhance wound healing. The bioactive PDs exhibited unique antioxidant activity, decreasing the degree of oxidative stress, and featured wholly-aliphatic hyperbranched poly(amic acid) structures with low cytotoxicity and nanoscale dimensions of approximately 10 nm in aqueous environments. In a nude mouse model, the PDs + LIOB combination therapy significantly accelerated wound closure, with a 75.13% reduction in wound size by day 6 compared to untreated controls. Histological and molecular analyses revealed enhanced angiogenesis, stem cell recruitment, and collagen deposition in the PDs + LIOB group, as evidenced by increased expression of CD31 and CD34, and a higher type I/III collagen ratio. Optical coherence tomography confirmed the formation of persistent cavitation bubbles at the dermal–epidermal junction following LIOB, potentially providing dermal and epidermal repair. Immunohistochemical analysis demonstrated reduced inflammation and MMP-9 expression in the PDs + LIOB group, while ELISA results showed increased levels of TGF-β and Smad2/3, key regulators of wound repair. Masson's trichrome staining revealed more organized and densely packed collagen fibers in the PDs + LIOB group, indicating superior tissue remodeling and reduced fibrosis. This innovative approach harnessed the synergistic effects of LIOB and PDs, with PDs modulating key signaling pathways to accelerate healing and LIOB enhancing the repair functions of dermal and epidermal regeneration. The combination therapy not only accelerated wound closure but also improved scar appearance and tissue regeneration, highlighting its potential as a targeted treatment for chronic wounds. These findings advance the field of wound care, offering a promising solution to address the limitations of current therapies and improve patient outcomes.