The development of a 3D printed PEG-Chitosan-PCL dressing loaded with peptide-microRNA nanoparticles for wound healing

The heating process is conducted to mimic the conditions of hot melt extrusion (HME) for fabricating polymer-based filaments, followed by Arburg Plastic Freeforming (APF) three-Dimensional Printing (3DP) process to produce 3D porous patches. Moreover, heated NPs effectively regulated target gene expression via RT-PCR and ELISA. PCL/PEG/chitosan-based 3D printed wound patches were fabricated with ideal physiochemical properties for wound healing via HME and 3DP, optimised through a Design of Experiments approach.

Lyophilised peptide-DNA nanoparticles were successfully loaded into optimal PCL/PEG/chitosan filaments and the nanoparticles remained intact. The delivery of RALA/pmiR NPs from biocompatible 3D-printed patches to NCTC-929 and HacaT cells significantly improved cell migration, resulting in 50% wound reduction without hindering cell attachment, potentially preventing secondary injury upon patch removal. In the C57BL/6N murine full-thickness wound-healing model, NP-loaded 3D printed patches outperformed a commercial dressing, showing accelerated wound closure rate (80%), increased epidermal thickness (~80 µm) and blood vessel count (~2 fold) after 7 days.

Taken together, these results demonstrated that peptide-DNA can be loaded in PCL/PEG/chitosan-based 3D printed patches without compromising the integrity of the biological cargo to result in improved wound closure and tissue repair.<br><br><i>Thesis is embargoed until 31 December 2029.</i>