Engineering a multifunctional 3D-printed PLA-collagen-minocycline-nanoHydroxyapatite scaffold with combined antimicrobial and osteogenic effects for bone regeneration

Apr 29, 2019Materials science & engineering. C, Materials for biological applications

3D-printed bone scaffold combining infection control and bone growth using PLA, collagen, minocycline, and nano-hydroxyapatite

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Abstract

3D-printed PLA-Col-MH-cHA scaffolds significantly enhance osteogenic activity and reduce bacterial biofilm formation.

The scaffolds are designed to mimic native bone structure, featuring uniform macroporosity and excellent compressive strength.
Incorporation of minocycline provides an effective antibiotic release profile, demonstrating antibacterial activity against Staphylococcus aureus.
Human bone marrow-derived mesenchymal stem cells show increased adhesion, proliferation, and expression of osteogenesis-related genes when exposed to the scaffolds.
The combination of bioinspired citrate-hydroxyapatite nanoparticles with minocycline may enhance both osteogenic activity and antibacterial properties.
The multifunctionalized scaffolds present a promising approach to improve outcomes in bone repair while reducing infection risks.

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3D-printing and additive manufacturing can be powerful techniques to design customized structures and produce synthetic bone grafts with multifunctional effects suitable for bone repair. In our work we aimed the development of novel multifunctionalized 3D printed poly(lactic acid) (PLA) scaffolds with bioinspired surface coatings able to reduce bacterial biofilm formation while favoring human bone marrow-derived mesenchymal stem cells (hMSCs) activity. For that purpose, 3D printing was used to prepare PLA scaffolds that were further multifunctionalized with collagen (Col), minocycline (MH) and bioinspired citrate- hydroxyapatite nanoparticles (cHA). PLA-Col-MH-cHA scaffolds provide a closer structural support approximation to native bone architecture with uniform macroporous, adequate wettability and an excellent compressive strength. The addition of MH resulted in an adequate antibiotic release profile that by being compatible with local drug delivery therapy was translated into antibacterial activities against Staphylococcus aureus, a main pathogen associated to bone-related infections. Subsequently, the hMSCs response to these scaffolds revealed that the incorporation of cHA significantly stimulated the adhesion, proliferation and osteogenesis-related gene expression (RUNX2, OCN and OPN) of hMSCs. Furthermore, the association of a bioinspired material (cHA) with the antibiotic MH resulted in a combined effect of an enhanced osteogenic activity. These findings, together with the antibiofilm activity depicted strengthen the appropriateness of this 3D-printed PLA-Col-MH-cHA scaffold for future use in bone repair. By targeting bone repair while mitigating the typical infections associated to bone implants, our 3D scaffolds deliver an integrated strategy with the combined effects further envisaging an increase in the success rate of bone-implanted devices.

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Engineering a multifunctional 3D-printed PLA-collagen-minocycline-nanoHydroxyapatite scaffold with combined antimicrobial and osteogenic effects for bone regeneration

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