Dual-Nozzle 3D Printed Nano-Hydroxyapatite Scaffold Loaded with Vancomycin Sustained-Release Microspheres for Enhancing Bone Regeneration

Abstract

Background Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects. Methods Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation. Results The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 μg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration. Conclusion Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.

Promotion of In Vitro Osteogenic Activity by Melt Extrusion-Based PLLA/PCL/PHBV Scaffolds Enriched with Nano-Hydroxyapatite and Strontium Substituted Nano-Hydroxyapatite

“…Their implantation into cranial defects in ovariectomized mice to show in vivo new bone formation in an osteoporotic model is subject of a future work. Reports on the implantation of 3D printed PLA-HA composite scaffolds in rabbits indicated their effectiveness on repairing bone defects [ 73 , 74 ]. Moreover, the implantation of composite scaffolds comprising PLLA with mineralized strontium-doped hydroxyapatite in rabbits has been reported to promote bone regeneration [ 51 ].…”

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

“…Due to their unique properties, nanoparticles can improve the mechanical properties of hydrogels, enhance surface interactions, and increase drug release rate and bioavailability. The addition of nanoparticles to hydrogels allows better access to tissues through capillaries and more effective delivery of therapeutic drugs to the site of injury ( Li et al, 2023 ).…”

Vancomycin-Loaded 3D-Printed Polylactic Acid–Hydroxyapatite Scaffolds for Bone Tissue Engineering

“…This fact can be justified by the hydrophilic nature of these scaffolds (contact angle measurements provided in Supplementary Material Figure S1), which can influence the bacterial adherence to the surface of the biomaterial [19]. Maikranz et al showed that S. aureus adheres more strongly to hydrophobic than hydrophilic surfaces [44]. It may then be relevant to consider the hydrophilicity of the biomaterials used to manufacture the scaffolds, as they may play a key role in the initial adhesion of bacteria that help to prevent infections related to their implantation.…”

“…Moreover, despite the fact that the absence of cytotoxicity was confirmed, together with the antibacterial activity of the scaffolds loaded by the three methodologies, the physicochemical properties of the unloaded 3D-printed PLA-HA scaffolds were proven to present a certain degree of antibacterial activity (with an unexpectedly high number of dead bacteria) against S. aureus. In relation to this, several authors have investigated the influence of the surface of a biomaterial on the bacterial adherence [19], which in the case of S. aureus seems to be significantly higher on hydrophobic surfaces [44]. The hydrophilicity of the 3D-printed PLA-HA scaffolds proposed may play a key role in the initial adhesion of bacteria and should be considered as an added advantage for their local prevention of infections.…”