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Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:15-26. doi: 10.1016/j.msec.2019.03.056. Epub 2019 Mar 19.

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

Author information

1
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
2
CQE Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.
3
EST Setúbal, CDP2T, Instituto Politécnico de Setúbal, Campus IPS, 2910 Setúbal, Portugal; IDMEC, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
4
Laboratory for Bone Metabolism and Regeneration - Faculty of Dental Medicine, U. Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; LAQV/REQUIMTE, U. Porto, Porto 4160-007, Portugal.
5
CQE Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal; EST Setúbal, CDP2T, Instituto Politécnico de Setúbal, Campus IPS, 2910 Setúbal, Portugal. Electronic address: catarina.santos@estsetubal.ips.pt.
6
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: asimao@ff.ulisboa.pt.

Abstract

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.

KEYWORDS:

Additive manufacturing; Antibiofilm; Bone regeneration; Local-drug-delivery; Staphylococcus aureus; Tetracyclines

PMID:
31029308
DOI:
10.1016/j.msec.2019.03.056

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