The state-of-the-art sustained drug delivery systems are related to features to improve pharmacological transport through a controlled ratio between drug release and the desired therapeutic effect. Microspheres of biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), play an important role in these approaches, directing the release in a specific region of interest. In this way, the encapsulation of doxycycline (DOX) as a microbial agent turns the PLGA microspheres into a potential device for the treatment of topic oral diseases. Thus, this work aimed to produce DOX-loaded PLGA microspheres and see how they interfered with mesenchymal stem cell viability and in the sustained release in antimicrobial assays. Scanning electron microscopy showed the spherical microstructured pattern, revealing assorted sized distribution, with major diameters ranging 1–3 µm. The encapsulation efficiency presented a mean of 80% in both methods to obtain the microspheres (sonication and magnetic rotation). The DOX release test revealed a gradual and continuous profile of 30–40% between 120 and 168 h. Mesenchymal stem cells cultured in PLGA with or without DOX at several concentrations revealed no effect on the cell metabolic activity. Striking morphology changes were observed by confocal microscopy after 1 to 3 days under culture. The live/dead assay indicated that when microsphere densities were increased (from 10 to 100 µg/mL) cultured cells presented an internalized pattern of microspheres in both groups of PLGA containing DOX or not, while slight cell death signals were identified nearby microsphere clusters. Microbiological assays performed by the agar diffusion test pointed out that an inhibition zone was identified in Staphylococcus aureus (S. aureus) cultures at earlier times of DOX release. Despite the well-known use of PLGA as a drug delivery vehicle, when synthesized with DOX, it presents both characteristics of the desired treatment to prevent healthy tissue damage while avoiding bacterial growth in a microenvironment with anatomical features, such as grooves, projections, and other tough conditions that favor the development of oral diseases.

Background: 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. Methods: 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% w/w in hydroxypropyl methylcellulose, HPMC) were applied and evaluated for drug release, cytotoxicity, and activity against Staphylococcus aureus. Biocompatibility was tested in an endothelial cell and myoblast co-culture. Results: 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. Conclusions: 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.