3D-Printed PLDLA–TMC/PEG 400 Vascular Scaffolds with a Poly(hexamethylene Biguanide) Antibacterial Coating

<b>Background:</b> Synthetic vascular scaffolds often exhibit limited mechanical performance and low hydrophilicity, which compromise early vascular integration and increase susceptibility to bacterial colonization. This study developed 3D-printed scaffolds based on poly(L-co-D,L-lactide)-poly(trimethylene carbonate) (PLDLA-TMC) with polyethylene glycol 400 (PEG) to modulate mechanical and interfacial properties and coated with poly(hexamethylene biguanide) (PHMB) to confer antibacterial activity. <b>Methods:</b> PLDLA-TMC scaffolds modified with PEG 400 and coated with PHMB were prepared and systematically characterized to assess their structural, thermal, mechanical, and antimicrobial properties. PHMB coatings (3%, 6%, and 12% <i>w</i>/<i>w</i> in hydroxypropyl methylcellulose, HPMC) were applied and evaluated for drug release, cytotoxicity, and activity against <i>Staphylococcus aureus</i>. Biocompatibility was tested in an endothelial cell and myoblast co-culture. <b>Results:</b> Incorporation of 2% PEG increased the tensile strength from 0.14 ± 0.10 MPa for scaffolds containing 0.5% PEG to 0.79 ± 0.12 MPa and promotes a more elastic scaffold behavior. PHMB at 12% caused cytotoxicity (7.70 ± 0.37% cell viability). The 3% PHMB coating produced a 12.5 ± 0.1 mm inhibition zone but exhibited burst release within 1 h, whereas the 6% coating maintained cell viability (72.95 ± 1.10%), produced a 13.1 ± 0.2 mm inhibition zone, and provided sustained antimicrobial release over 7 days. Scaffolds supported organized adhesion and proliferation of endothelial cells and myoblasts. <b>Conclusions:</b> 3D-printed PLDLA-TMC scaffolds containing 2% PEG and coated with 6% PHMB combined improved mechanical performance, sustained antimicrobial release, antibacterial activity, and biocompatibility in an in vitro vascular model.