Enhancing burn wound care with pre-crosslinked 3D-printed patches: Bromelain delivery and aloe vera bioactives integration for improved healing outcomes

Burn wounds remain a major clinical challenge due to the limitations of traditional dressings, which often fail to address the diverse needs of patients and varying wound types. This study aimed to advance burn care by developing a 3D-printed patch incorporating natural bioactive compounds from bromelain and aloe vera. The patch was formulated using pre-crosslinked chitosan and alginate hydrogels to ensure suitability for 3D printing and subsequent use. Rheological analysis revealed weak gel behaviour and shear-thinning properties, ensuring excellent printability. The patches exhibited outstanding swelling behaviour and controlled degradation (30 %), alongside notable antioxidant and anti-inflammatory potential, with a polyphenolic content of 1.43 ± 0.07 mg CAE/g and effective scavenging of DPPH, ABTS, and NO radicals, with IC50 values of 29.51 ± 0.30, 10.31 ± 0.28, and 5.94 ± 0.42 mg/mL, respectively. Bioactive compounds from bromelain were consistently released across various pH levels, supporting their therapeutic efficacy. Cell viability studies confirmed strong support for cell growth, while in vitro scratch tests demonstrated biocompatibility and promotion of wound closure. Histological analysis of ex vivo burn models revealed cellular necrosis and protein denaturation characteristic of burn wounds. Application of the patches significantly improved epidermal morphology and enhanced proliferation markers such as Ki67 and α-SMA, indicative of accelerated wound healing. While further clinical validation is needed, these findings underscore the potential of the 3D-printed patches as an innovative solution for burn wound care, offering improved bioactive delivery and enhanced healing outcomes compared to conventional dressings.