3D printing of a microfluidic chip-generated liposome-loaded hydrogel scaffold for accelerated wound closure and reduced fibrotic remodeling in burn wounds: an in vivo study.

Growth factor-based therapies for burn wound healing are limited by rapid clearance, poor bioavailability, and inadequate efficacy of single agents. Here, we report a 3D printed chitosan hydrogel scaffold loaded with PEGylated liposomes encapsulating TGF-β3 and cationic lipoplexes carrying miR-132 mimic for localized co-delivery. The optimized formulation exhibited favorable printability and rheological properties, and liposome incorporation modulated swelling, accelerated degradation, and altered the tensile profile while maintaining scaffold structural integrity, as confirmed by SEM, DSC, and FTIR. Release studies, based on total analytically quantified cargo without verification of molecular integrity, showed that encapsulation extended TGF-β3 release to 96.64 % over 312 h compared with free TGF-β3, whereas cumulative miR-132 release from the lipoplexes remained limited to 9.84 % over 312 h, indicating strong retention within the delivery system. In a murine burn wound model, the dual-loaded scaffold accelerated wound closure between days 7 and 15, reduced the COL1/COL3 ratio, IL-1α and RASA1 expression compared with the burn control. Consistent with our previous in vitro findings, the combined treatment produced favorable modulation of fibrosis-related molecular responses; however, its superiority at the tissue level was not confirmed by the day-21 histological and immunohistochemical assessments. These findings demonstrate that combining a 3D-printable hydrogel with miR-132/TGF-β3 localized co-delivery system provides an early macroscopic benefit and downstream molecular/biological responses, supporting its further investigation as a localized strategy for pro-regenerative burn wound healing and modulation of fibrotic remodeling.