Browsing by Author "Sinha, Ravi"
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Item 3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration(2021-04) 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; Biomateriales; ECOEFICIENCIA DE PRODUCTOS DE CONSTRUCCIÓNBone 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.Item Additive Manufactured Scaffolds for Bone Tissue Engineering: Physical Characterization of Thermoplastic Composites with Functional Fillers: Physical Characterization of Thermoplastic Composites with Functional Fillers(2021-08-13) Sinha, Ravi; Sanchez, Alberto; Camara-Torres, Maria; Uriszar-Aldaca, Iñigo Calderon; Calore, Andrea Roberto; Harings, Jules; Gambardella, Ambra; Ciccarelli, Lucia; Vanzanella, Veronica; Sisani, Michele; Scatto, Marco; Wendelbo, Rune; Perez, Sergio; Villanueva, Sara; Matanza, Amaia; Patelli, Alessandro; Grizzuti, Nino; Mota, Carlos; Moroni, Lorenzo; ECOEFICIENCIA DE PRODUCTOS DE CONSTRUCCIÓN; Tecnalia Research & InnovationThermoplastic polymer–filler composites are excellent materials for bone tissue engineering (TE) scaffolds, combining the functionality of fillers with suitable load-bearing ability, biodegradability, and additive manufacturing (AM) compatibility of the polymer. Two key determinants of their utility are their rheological behavior in the molten state, determining AM processability and their mechanical load-bearing properties. We report here the characterization of both these physical properties for four bone TE relevant composite formulations with poly(ethylene oxide terephthalate)/poly(butylene terephthalate (PEOT/PBT) as a base polymer, which is often used to fabricate TE scaffolds. The fillers used were reduced graphene oxide (rGO), hydroxyapatite (HA), gentamicin intercalated in zirconium phosphate (ZrP-GTM) and ciprofloxacin intercalated in MgAl layered double hydroxide (MgAl-CFX). The rheological assessment showed that generally the viscous behavior dominated the elastic behavior (G″ > G′) for the studied composites, at empirically determined extrusion temperatures. Coupled rheological–thermal characterization of ZrP-GTM and HA composites showed that the fillers increased the solidification temperatures of the polymer melts during cooling. Both these findings have implications for the required extrusion temperatures and bonding between layers. Mechanical tests showed that the fillers generally not only made the polymer stiffer but more brittle in proportion to the filler fractions. Furthermore, the elastic moduli of scaffolds did not directly correlate with the corresponding bulk material properties, implying composite-specific AM processing effects on the mechanical properties. Finally, we show computational models to predict multimaterial scaffold elastic moduli using measured single material scaffold and bulk moduli. The reported characterizations are essential for assessing the AM processability and ultimately the suitability of the manufactured scaffolds for the envisioned bone regeneration application.Item Effect of high content nanohydroxyapatite composite scaffolds prepared via melt extrusion additive manufacturing on the osteogenic differentiation of human mesenchymal stromal cells(2022-06) Cámara-Torres, Maria; Sinha, Ravi; Sanchez, Alberto; Habibovic, Pamela; Patelli, Alessandro; Mota, Carlos; Moroni, Lorenzo; ECOEFICIENCIA DE PRODUCTOS DE CONSTRUCCIÓNThe field of bone tissue engineering seeks to mimic the bone extracellular matrix composition, balancing the organic and inorganic components. In this regard, additive manufacturing (AM) of high content calcium phosphate (CaP)-polymer composites holds great promise towards the design of bioactive scaffolds. Yet, the biological performance of such scaffolds is still poorly characterized. In this study, melt extrusion AM (ME-AM) was used to fabricate poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT)-nanohydroxyapatite (nHA) scaffolds with up to 45 wt% nHA, which presented significantly enhanced compressive mechanical properties, to evaluate their in vitro osteogenic potential as a function of nHA content. While osteogenic gene upregulation and matrix mineralization were observed on all scaffold types when cultured in osteogenic media, human mesenchymal stromal cells did not present an explicitly clear osteogenic phenotype, within the evaluated timeframe, in basic media cultures (i.e. without osteogenic factors). Yet, due to the adsorption of calcium and inorganic phosphate ions from cell culture media and simulated body fluid, the formation of a CaP layer was observed on PEOT/PBT-nHA 45 wt% scaffolds, which is hypothesized to account for their bone forming ability in the long term in vitro, and osteoconductivity in vivo.