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Customized pH-responsive poly(urethane)-based formulations treating chronic skin wound inflammation and promoting tissue regeneration
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Severe inflammation and infections are major contributors to wound chronicity. Although various wound dressings have been engineered to deliver therapeutics locally, the lack of patient personalization is still a limiting factor. In this endeavor, this work aims to establish an adaptable therapeutic strategy by combining stimuli-responsive materials and 3D bioprinting for the prospective fabrication of shape-personalized patches capable of tuning payload release in response to the alkalinity of infected wound exudates. First, a –COOH-bearing amphiphilic poly(ether urethane) was synthesized and used to formulate thermo-/alkaline-pH-responsive hydrogels, while human recombinant lactoferrin (hrLF) was selected for its naturally derived therapeutic properties. Then, the hrLF-loaded hydrogel thermo-responsiveness was rheologically assessed, while the hrLF suitability for the biologically aggressive environment of chronic wounds was evaluated through UV/Vis spectroscopy and a colorimetric assay. Moreover, a finely tuned drug release was observed in response to pH via a non-Fickian diffusion mechanism. Furthermore, in in vitro studies on simplified inflamed wounds, hrLF promoted human dermal fibroblast proliferation (increased DNA content), exerted anti-inflammatory effects (reduced expression of TNF-α, IL-1β and IL-6), and exhibited bacteriostatic activity against Staphylococcus aureus. Finally, the hrLF-loaded hydrogel showed promising processability as a biomaterial ink. Overall, the engineered system showed strong adaptation to the dynamic wound environment.
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Royal Society of Chemistry