3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration

• Published in: Bioactive materials 2021-04, Vol.6 (4), p.1073-1082
• Main Authors: Cámara-Torres, María, Duarte, Stacy, Sinha, Ravi, Egizabal, Ainhoa, Álvarez, Noelia, Bastianini, Maria, Sisani, Michele, Scopece, Paolo, Scatto, Marco, Bonetto, Alessandro, Marcomini, Antonio, Sanchez, Alberto, Patelli, Alessandro, Mota, Carlos, Moroni, Lorenzo
• Format: Article
• Language: English
• Subjects: Antibiotic delivery; Bone infection; Bone regeneration; Human mesenchymal stromal cells; Lamellar inorganic fillers; Melt extrusion additive manufacturing
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2020.09.031

Bone infections following open bone fracture or implant surgery remain a challenge in the orthopedics field. In order to avoid high doses of systemic drug administration, optimized local antibiotic release from scaffolds is required. 3D additive manufactured (AM) scaffolds made with biodegradable polymers are ideal to support bone healing in non-union scenarios and can be given antimicrobial properties by the incorporation of antibiotics. In this study, ciprofloxacin and gentamicin intercalated in the interlamellar spaces of magnesium aluminum layered double hydroxides (MgAl) and α-zirconium phosphates (ZrP), respectively, are dispersed within a thermoplastic polymer by melt compounding and subsequently processed via high temperature melt extrusion AM (~190 °C) into 3D scaffolds. The inorganic fillers enable a sustained antibiotics release through the polymer matrix, controlled by antibiotics counterions exchange or pH conditions. Importantly, both antibiotics retain their functionality after the manufacturing process at high temperatures, as verified by their activity against both Gram + and Gram - bacterial strains. Moreover, scaffolds loaded with filler-antibiotic do not impair human mesenchymal stromal cells osteogenic differentiation, allowing matrix mineralization and the expression of relevant osteogenic markers. Overall, these results suggest the possibility of fabricating dual functionality 3D scaffolds via high temperature melt extrusion for bone regeneration and infection prevention. [Display omitted] •Antibiotic-eluting scaffolds are processed via melt extrusion at high temperature.•Inorganic lamellar fillers dispersed in the scaffold carry the antibiotics.•Antibiotics are released via ion-exchange in a controlled and tunable manner.•Antibiotics preserve their activity after the high temperature printing process.•Human mesenchymal stromal cells undergo osteogenic differentiation on the scaffolds.