Hyaluronic acid-g-poly(lactic acid) and poly(vinyl alcohol) inks for 3D printed berberine loaded foldable dressings

Abstract

Antimicrobial resistance (AMR) has increased the urgency for novel wound care strategies. Semi Solid Extrusion (SSE)-3D printing technology holds significant promise in this area, allowing for the creation of personalized and customizable wound dressings. This study focused on developing a foldable and flexible dressing capable of incorporating and releasing non-antibiotic antimicrobial compounds, such as berberine (Ber). To this end, a hyaluronic acid (HA)-g-poly(lactic acid) (PLA)-based polymer (DAC®) was combined with poly(vinyl alcohol) (PVA) to enhance the mechanical properties and foldability of 3D-printed dressings. On the other hand, propylene glycol (PG) was incorporated to facilitate the integration of non-water soluble natural antimicrobial compounds like berberine (Ber). The rheological profile of DAC/PVA/PG blends was optimized for 3D printing, resulting in printing-compatible inks. After freeze-drying, a sterilization/crosslinking process through autoclave allowed to reduce dressings swelling (∼98 % less in simulated wound fluid and ∼ 99 % less in water), suitable to preserve their foldability without losing structural shape, while improving mechanical properties (from 1.74 MPa to 2.85 MPa tensile strength). The antimicrobial efficacy of Ber-loaded dressings against Staphylococcus aureus was demonstrated by microcalorimetry, although the incorporation of Ber did not significantly enhance antibiofilm activity when compared to blank dressings. In vitro cytotoxicity tests confirmed that over 70 % of human dermal fibroblasts remained viable after 24 h of exposure to the Ber-loaded dressings. This work suggests the chosen polymer combination is promising to produce flexible and foldable dressings that can be adapted to anatomically complex wounds. The loading of natural antimicrobial agents, such as Ber, holds potential for addressing infected wounds as an alternative to traditional treatments in the face of AMR.