Is Silver Addition to Scaffolds Based on Polycaprolactone Blended with Calcium Phosphates Able to Inhibit Candida albicans and Candida auris Adhesion and Biofilm Formation?

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.

Tuning of Silver Content on the Antibacterial and Biological Properties of Poly(ɛ-caprolactone)/Biphasic Calcium Phosphate 3D-Scaffolds for Bone Tissue Engineering.

There is a growing interest in tissue engineering, in which biomaterials play a pivotal role in promoting bone regeneration. Furthermore, smart functionalization can provide biomaterials with the additional role of preventing orthopedic infections. Due to the growing microbial resistance to antimicrobials used to treat those infections, metal ions, such as silver, thanks to their known wide range of bactericidal properties, are believed to be promising additives in developing antibacterial biomaterials. In this work, novel poly(ε-caprolactone) (PCL)-based 3D scaffolds have been designed and developed, where the polymer matrix was modified with both silver (Ag), to supply antibacterial behavior, and calcium phosphates (biphasic calcium phosphate, BCP) particles to impart bioactive/bioresorbable properties. The microstructural analysis showed that constructs were characterized by square-shaped macropores, in line with the morphology and size of the templating salts used as pore formers. Degradation tests demonstrated the important role of calcium phosphates in improving PCL hydrophilicity, leading to a higher degradation degree for BCP/PCL composites compared to the neat polymer after 18 days of soaking. The appearance of an inhibition halo around the silver-functionalized PCL scaffolds for assayed microorganisms and a significant (p < 0.05) decrease in both adherent and planktonic bacteria demonstrate the Ag+ release from the 3D constructs. Furthermore, the PCL scaffolds enriched with the lowest silver percentages did not hamper the viability and proliferation of Saos-2 cells. A synergic combination of antimicrobial, osteoproliferative and biodegradable features provided to 3D scaffolds the required potential for bone tissue engineering, beside anti-microbial properties for reduction in prosthetic joints infections.

Combination of Poly(ε-Caprolactone) Biomaterials and Essential Oils to Achieve Anti-Bacterial and Osteo-Proliferative Properties for 3D-Scaffolds in Regenerative Medicine.

Biomedical implants, an essential part of the medical treatments, still suffer from bacterial infections that hamper patients' recovery and lives. Antibiotics are widely used to cure those infections but brought antibiotic resistance. Essential oils (EOs) demonstrate excellent antimicrobial activity and low resistance development risk. However, EO application in medicine is still quite scarce and almost no research work considers its use in combination with bioresorbable biomaterials, such as the poly(ε-caprolactone) (PCL) polymer. This work aimed to combine the antibacterial properties of EOs and their components, particularly eugenol and cinnamon oil, against Staphylococcus aureus, S. epidermidis and Escherichia coli, with those of PCL for medical applications in which good tissue regeneration and antimicrobial effects are required. The PCL porous scaffolds, added with increasing (from 30% to 50%) concentrations of eugenol and cinnamon oil, were characterized by square-shaped macropores. Saos-2 cells' cell viability/proliferation was hampered by 40 and 50% EO-enriched PCL, whereas no cytotoxic effect was recorded for both 30% EO-added PCL and pure-PCL. The antibacterial tests revealed the presence of a small inhibition halo around the 30% eugenol and cinnamon oil-functionalized PCL scaffolds only for staphylococci, whereas a significant decrease on both adherent and planktonic bacteria was recorded for all the three microorganisms, thus proving that, even if the EOs are only in part released by the EO-added PCL scaffolds, an anti-adhesive feature is anyway achieved. The scaffold will have the ability to support new tissue formation and simultaneously will be able to prevent post-surgical infection. This research shows the great potential in the use of EOs or their single components, at low concentrations, for biomaterial functionalization with enhanced anti-bacterial and biointegration properties.

DLP Fabrication of Zirconia Scaffolds Coated with HA/ß-TCP Layer: Role of Scaffold Architecture on Mechanical and Biological Properties.

In order to merge high-mechanical properties and suitable bioactivity in a single scaffold, zirconia porous structures are here coated with a hydroxyapatite layer. The digital light processing (DLP) technique is used to fabricate two types of scaffolds: simple lattice structures, with different sizes between struts (750, 900 and 1050 µm), and more complex trabecular ones, these latter designed to better mimic the bone structure. Mechanical tests performed on samples sintered at 1400 °C provided a linear trend with a decrease in the compressive strength by increasing the porosity amount, achieving compressive strengths ranging between 128-177 MPa for lattice scaffolds and 34 MPa for trabecular ones. Scaffolds were successfully coated by dipping the sintered samples in a hydroxyapatite (HA) alcoholic suspension, after optimizing the HA solid loading at 20 wt%. After calcination at 1300 °C, the coating layer, composed of a mixture of HA and ß-TCP (ß-TriCalcium Phospate) adhered well to the zirconia substrate. The coated samples showed a proper bioactivity, well pronounced after 14 days of immersion into simulated body fluid (SBF), with a more homogeneous apatite layer formation into the trabecular samples compared to the lattice ones.

Novel Silver-Functionalized Poly(ε-Caprolactone)/Biphasic Calcium Phosphate Scaffolds Designed to Counteract Post-Surgical Infections in Orthopedic Applications.

In this study, we designed and developed novel poly(ε-caprolactone) (PCL)-based biomaterials, for use as bone scaffolds, through modification with both biphasic calcium phosphate (BCP), to impart bioactive/bioresorbable properties, and with silver nitrate, to provide antibacterial protection against Staphylococcus aureus, a microorganism involved in prosthetic joint infections (PJIs). Field emission scanning electron microscopy (FESEM) showed that the samples were characterized by square-shaped macropores, and energy dispersive X-ray spectroscopy analysis confirmed the presence of PCL and BCP phases, while inductively coupled plasma-mass spectrometry (ICP-MS) established the release of Ag+ in the medium (~0.15-0.8 wt% of initial Ag content). Adhesion assays revealed a significant (p < 0.0001) reduction in both adherent and planktonic staphylococci on the Ag-functionalized biomaterials, and the presence of an inhibition halo confirmed Ag release from enriched samples. To assess the potential outcome in promoting bone integration, preliminary tests on sarcoma osteogenic-2 (Saos-2) cells indicated PCL and BCP/PCL biocompatibility, but a reduction in viability was observed for Ag-added biomaterials. Due to their combined biodegrading and antimicrobial properties, the silver-enriched BCP/PCL-based scaffolds showed good potential for engineering of bone tissue and for reducing PJIs as a microbial anti-adhesive tool used in the delivery of targeted antimicrobial molecules, even if the amount of silver needs to be tuned to improve osteointegration.

Controlling osteoblast morphology and proliferation via surface micro-topographies of implant biomaterials.

Current research on surface modifications has yielded advanced implant biomaterials. Various implant surface modifications have been shown to be promising in improving bone target cell response, but more comprehensive studies whether certain implant surface modifications can directly target cell behavioural features such as morphogenesis and proliferation are needed. Here, we studied the response of primary alveolar bone cells on various implant surface modifications in terms of osteoblast morphology and proliferation in vitro. Analyses of surface modifications led to surface-related test parameters including the topographical parameters micro-roughness, texture aspect and surface enlargement as well as the physicochemical parameter surface wettability. We compared osteoblast morphology and proliferation towards the above-mentioned parameters and found that texture aspect and surface enlargement but not surface roughness or wettability exhibited significant impact on osteoblast morphology and proliferation. Detailed analysis revealed osteoblast proliferation as a function of cell morphology, substantiated by an osteoblast size- and morphology-dependent increase in mitotic activity. These findings show that implant surface topography controls cell behavioural morphology and subsequently cell proliferation, thereby opening the road for cell instructive biomaterials.

Role of Natural Stone Wastes and Minerals in the Alkali Activation Process: A Review.

This review aims to provide a comprehensive assessment concerning alkali activation of natural stone wastes and minerals. In particular, the structure of the review is divided into two main sections in which the works dealing with alumino-silicate and carbonatic stones are discussed, respectively. Alumino-silicate stones are generally composed of quartz and feldspars, while carbonatic stones are mainly made of calcite and dolomite. The role of these minerals in the alkali activation process is discussed, attesting their influence in the development of the final product properties. In most of the works, authors use mineral additions only as fillers or aggregates and, in some cases, as a partial substitution of more traditional raw powders, such as metakaolin, fly ash, and granulated blast furnace slag. However, a few works in which alumino-silicate and carbonatic stone wastes are used as the main active components are discussed as well. Not only the raw materials, but also the entire alkali activation process and the curing conditions adopted in the literature studies here reviewed are systematically analyzed to improve the understanding of their effect on the physical, mechanical, and durability properties of the final products and to eventually foster the reuse of natural stone wastes for the purposes of sustainability in different applications.

Novel calcium phosphate/PCL graded samples: Design and development in view of biomedical applications.

Scaffolds for bone tissue engineering require a combination of bioactivity and bioresorption at the sample surface and high mechanical properties in the bulk. This work presents a novel calcium phosphate (CaP)/polycaprolactone (PCL) scaffold with graded composition and porosity fraction. The scaffold is made of (i) a dense hydroxyapatite (HA)/ß-tricalcium phosphate (ß-TCP) core, (ii) a macroporous HA/ß-TCP transition layer and (iii) a macroporous PCL/(HA/ß-TCP) external layer. The ceramic layers were fabricated by gel-casting whereas the outer composite layer was obtained by a solvent casting/particle leaching process. The microstructure, phase composition and biodegradation of the scaffolds were characterized. The gradient of porosity was clearly obtained whereas the gradation of phase composition was less pronounced. An in vitro dissolution test was performed by immersing the scaffolds in a TRIS solution. The results showed a dissolution phenomenon with possible differentiated mechanisms in the different layers, in relation with the targeted multi-functionality.

Cellular transcriptional response to zirconia-based implant materials.

OBJECTIVE: To adequately address clinically important issues such as osseointegration and soft tissue integration, we screened for the direct biological cell response by culturing human osteoblasts and gingival fibroblasts on novel zirconia-based dental implant biomaterials and subjecting them to transcriptional analysis. METHODS: Biomaterials used for osteoblasts involved micro-roughened surfaces made of a new type of ceria-stabilized zirconia composite with two different topographies, zirconium dioxide, and yttria-stabilized zirconia (control). For fibroblasts smooth ceria- and yttria-stabilized zirconia surface were used. The expression of 90 issue-relevant genes was determined on mRNA transcription level by real-time PCR Array technology after growth periods of 1 and 7 days. RESULTS: Generally, modulation of gene transcription exhibited a dual dependence, first by time and second by the biomaterial, whereas biomaterial-triggered changes were predominantly caused by the biomaterials' chemistry rather than surface topography. Per se, modulated genes assigned to regenerative tissue processes such as fracture healing and wound healing and in detail included colony stimulating factors (CSF2 and CSF3), growth factors, which regulate bone matrix properties (e.g. BMP3 and TGFB1), osteogenic BMPs (BMP2/4/6/7) and transcription factors (RUNX2 and SP7), matrix collagens and osteocalcin, laminins as well as integrin ß1 and MMP-2. SIGNIFICANCE: With respect to the biomaterials under study, the screening showed that a new zirconia-based composite stabilized with ceria may be promising to provide clinically desired periodontal tissue integration. Moreover, by detecting biomarkers modulated in a time- and/or biomaterial-dependent manner, we identified candidate genes for the targeted analysis of cell-implant bioresponse during biomaterial research and development.

Towards long lasting zirconia-based composites for dental implants: Transformation induced plasticity and its consequence on ceramic reliability.

Zirconia-based composites were developed through an innovative processing route able to tune compositional and microstructural features very precisely. Fully-dense ceria-stabilized zirconia ceramics (84vol% Ce-TZP) containing equiaxed alumina (8vol%Al2O3) and elongated strontium hexa-aluminate (8vol% SrAl12O19) second phases were obtained by conventional sintering. This work deals with the effect of the zirconia stabilization degree (CeO2 in the range 10.0-11.5mol%) on the transformability and mechanical properties of Ce-TZP-Al2O3-SrAl12O19 materials. Vickers hardness, biaxial flexural strength and Single-edge V-notched beam tests revealed a strong influence of ceria content on the mechanical properties. Composites with 11.0mol% CeO2 or above exhibited the classical behaviour of brittle ceramics, with no apparent plasticity and very low strain to failure. On the contrary, composites with 10.5mol% CeO2 or less showed large transformation-induced plasticity and almost no dispersion in strength data. Materials with 10.5mol% of ceria showed the highest values in terms of biaxial bending strength (up to 1.1GPa) and fracture toughness (>10MPa√m). In these ceramics, as zirconia transformation precedes failure, the Weibull modulus was exceptionally high and reached a value of 60, which is in the range typically reported for metals. The results achieved demonstrate the high potential of using these new strong, tough and stable zirconia-based composites in structural biomedical applications. STATEMENT OF SIGNIFICANCE: Yttria-stabilized (Y-TZP) zirconia ceramics are increasingly used for developing metal-free restorations and dental implants. Despite their success related to their excellent mechanical resistance, Y-TZP can undergo Low Temperature Degradation which could be responsible for restoration damage or even worst the failure of the implant. Current research is focusing on strategies to improve the LTD resistance of Y-TZP or to develop alternative composites with better stability in vivo. In this work the mechanical characterization of a new type of very-stable zirconia-based composites is presented. These materials are composed of ceria-stabilized zirconia (84vol%Ce-TZP) containing two second phases (α-alumina and strontium hexa-aluminate) and exhibit exceptional strength, toughness and ductility, which may allow the processing of dental implants with a perfect reliability and longer lifetime.

Role of structural barriers for carotenoid bioaccessibility upon high pressure homogenization.

A specific approach to investigate the effect of high pressure homogenization on the carotenoid bioaccessibility in tomato-based products was developed. Six different tomato-based model systems were reconstituted in order to target the specific role of the natural structural barriers (chromoplast substructure/cell wall) and of the phases (soluble/insoluble) in determining the carotenoid bioaccessibility and viscosity changes upon high pressure homogenization. Results indicated that in the absence of natural structural barriers (carotenoid enriched oil), the soluble and insoluble phases determined the carotenoid bioaccessibility upon processing whereas, in their presence, these barriers governed the bioaccessibility. Furthermore, it was shown that the increment of the viscosity upon high pressure homogenization is determined by the presence of insoluble phase, however, this result was related to the initial ratio of the soluble:insoluble phases in the system. In addition, no relationship between the changes in viscosity and carotenoid bioaccessibility upon high pressure homogenization was found.

Environmentally-Friendly Dense and Porous Geopolymers Using Fly Ash and Rice Husk Ash as Raw Materials.

This paper assesses the feasibility of two industrial wastes, fly ash (FA) and rice husk ash (RHA), as raw materials for the production of geopolymeric pastes. Three typologies of samples were thus produced: (i) halloysite activated with potassium hydroxide and nanosilica, used as the reference sample (HL-S); (ii) halloysite activated with rice husk ash dissolved into KOH solution (HL-R); (iii) FA activated with the alkaline solution realized with the rice husk ash (FA-R). Dense and porous samples were produced and characterized in terms of mechanical properties and environmental impact. The flexural and compressive strength of HL-R reached about 9 and 43 MPa, respectively. On the contrary, the compressive strength of FA-R is significantly lower than the HL-R one, in spite of a comparable flexural strength being reached. However, when porous samples are concerned, FA-R shows comparable or even higher strength than HL-R. Thus, the current results show that RHA is a valuable alternative to silica nanopowder to prepare the activator solution, to be used either with calcined clay and fly ash feedstock materials. Finally, a preliminary evaluation of the global warming potential (GWP) was performed for the three investigated formulations. With the mix containing FA and RHA-based silica solution, a reduction of about 90% of GWP was achieved with respect to the values obtained for the reference formulation.

Enzymatic cell wall degradation of high-pressure-homogenized tomato puree and its effect on lycopene bioaccessibility.

BACKGROUND: High-pressure homogenization disrupts cell structures, assisting carotenoid release from the matrix and subsequent micellarization. However, lycopene bioaccessibility of tomato puree upon high-pressure homogenization is limited by the formation of a process-induced barrier. In this context, cell wall-degrading enzymes were applied to hydrolyze the formed barrier and enhance lycopene bioaccessibility. RESULTS: The effectiveness of the enzymes in degrading their corresponding substrates was evaluated (consistency, amount of reducing sugars, molar mass distribution and immunolabeling). An in vitro digestion procedure was applied to evaluate the effect of the enzymatic treatments on lycopene bioaccessibility. Enzymatic treatments with pectinases and cellulase were proved to effectively degrade their corresponding cell wall polymers; however, no further significant increase in lycopene bioaccessibility was obtained. CONCLUSION: A process-induced barrier consisting of cell wall material is not the only factor governing lycopene bioaccessibility upon high-pressure homogenization.

Microbial adhesion on novel yttria-stabilized tetragonal zirconia (Y-TZP) implant surfaces with nitrogen-doped hydrogenated amorphous carbon (a-C:H:N) coatings.

OBJECTIVES: Biomaterial surfaces are at high risk for initial microbial colonization, persistence, and concomitant infection. The rationale of this study was to assess the initial adhesion on novel implant surfaces of Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans upon incubation. MATERIALS AND METHODS: The tested samples were 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) samples with nitrogen-doped hydrogenated amorphous carbon (a-C:H:N) coating (A) and 3Y-TZP samples coated with ceria-stabilized zirconia-based (Ce-TZP) composite and a-C:H:N (B). Uncoated 3Y-TZP samples (C) and bovine enamel slabs (BES) served as controls. Once the surface was characterized, the adherent microorganisms were quantified by estimating the colony-forming units (CFUs). Microbial vitality was assessed by live/dead staining, and microbial-biomaterial surface topography was visualized by scanning electron microscopy (SEM). RESULTS: Overall, A and B presented the lowest CFU values for all microorganisms, while C sheltered significantly less E. faecalis, P. aeruginosa, and C. albicans than BES. Compared to the controls, B demonstrated the lowest vitality values for E. coli (54.12 %) and C. albicans (67.99 %). Interestingly, A (29.24 %) exhibited higher eradication rates for S. aureus than B (13.95 %). CONCLUSIONS: Within the limitations of this study, a-C:H:N-coated 3Y-TZP surfaces tended to harbor less initially adherent microorganisms and selectively interfered with their vitality. CLINICAL RELEVANCE: This could enable further investigation of the new multi-functional zirconia surfaces to confirm their favorable antimicrobial properties in vivo.

Towards long lasting zirconia-based composites for dental implants. Part I: innovative synthesis, microstructural characterization and in vitro stability.

In order to fulfill the clinical requirements for strong, tough and stable ceramics used in dental applications, we designed and developed innovative zirconia-based composites, in which equiaxial α-Al2O3 and elongated SrAl12O19 phases are dispersed in a ceria-stabilized zirconia matrix. The composite powders were prepared by an innovative surface coating route, in which commercial zirconia powders were coated by inorganic precursors of the second phases, which crystallize on the zirconia particles surface under proper thermal treatment. Samples containing four different ceria contents (in the range 10.0-11.5 mol%) were prepared by carefully tailoring the amount of the cerium precursor during the elaboration process. Slip cast green bodies were sintered at 1450 °C for 1 h, leading to fully dense materials. Characterization of composites by SEM and TEM analyses showed highly homogeneous microstructures with an even distribution of both equiaxial and elongated-shape grains inside a very fine zirconia matrix. Ce content plays a major role on aging kinetics, and should be carefully controlled: sample with 10 mol% of ceria were transformable, whereas above 10.5 mol% there is negligible or no transformation during autoclave treatment. Thus, in this paper we show the potential of the innovative surface coating route, which allows a perfect tailoring of the microstructural, morphological and compositional features of the composites; moreover, its processing costs and environmental impacts are limited, which is beneficial for further scale-up and real use in the biomedical field.

Structural Ceramic Nanocomposites: A Review of Properties and Powders' Synthesis Methods.

Ceramic nanocomposites are attracting growing interest, thanks to new processing methods enabling these materials to go from the research laboratory scale to the commercial level. Today, many different types of nanocomposite structures are proposed in the literature; however, to fully exploit their exceptional properties, a deep understanding of the materials' behavior across length scales is necessary. In fact, knowing how the nanoscale structure influences the bulk properties enables the design of increasingly performing composite materials. A further key point is the ability of tailoring the desired nanostructured features in the sintered composites, a challenging issue requiring a careful control of all stages of manufacturing, from powder synthesis to sintering. This review is divided into four parts. In the first, classification and general issues of nanostructured ceramics are reported. The second provides basic structure-property relations, highlighting the grain-size dependence of the materials properties. The third describes the role of nanocrystalline second-phases on the mechanical properties of ordinary grain sized ceramics. Finally, the fourth part revises the mainly used synthesis routes to produce nanocomposite ceramic powders, underlining when possible the critical role of the synthesis method on the control of microstructure and properties of the sintered ceramics.

Al2O3/ZrO2/Y3Al5O12 Composites: A High-Temperature Mechanical Characterization.

An Al2O3/5 vol%·ZrO2/5 vol%·Y3Al5O12 (YAG) tri-phase composite was manufactured by surface modification of an alumina powder with inorganic precursors of the second phases. The bulk materials were produced by die-pressing and pressureless sintering at 1500 °C, obtaining fully dense, homogenous samples, with ultra-fine ZrO2 and YAG grains dispersed in a sub-micronic alumina matrix. The high temperature mechanical properties were investigated by four-point bending tests up to 1500 °C, and the grain size stability was assessed by observing the microstructural evolution of the samples heat treated up to 1700 °C. Dynamic indentation measures were performed on as-sintered and heat-treated Al2O3/ZrO2/YAG samples in order to evaluate the micro-hardness and elastic modulus as a function of re-heating temperature. The high temperature bending tests highlighted a transition from brittle to plastic behavior comprised between 1350 and 1400 °C and a considerable flexural strength reduction at temperatures higher than 1400 °C; moreover, the microstructural investigations carried out on the re-heated samples showed a very limited grain growth up to 1650 °C.

Role of carotenoid type on the effect of thermal processing on bioaccessibility.

Cell walls and chromoplast substructures constitute natural structural barriers governing carotenoid bioaccessibility. In order to enhance carotenoid bioaccessibility, thermal processes were applied to fractions surrounded by different levels of structural barriers. The matrices studied were orange carrots, red carrots, red tomatoes and atomic red carrots. In the case of carrots, no effect of thermal treatments on carotenoid bioaccessibility at the chromoplast level was obtained. However, in the case of tomatoes, lycopene bioaccessibility decreased upon thermal processing of chromoplasts. At the cell cluster level, low intensities of thermal processing resulted in a decrease of ß-carotene and lycopene bioaccessibility. Nonetheless, at high intensities of thermal processing, only ß-carotene bioaccessibility was increased. This observation was confirmed by the results obtained in the matrix rich in both types of carotenoids (atomic red carrots). It was therefore suggested, that the type of carotenoid constitutes an important factor determining the effect of thermal processing on their bioaccessibility.

Issues in nanocomposite ceramic engineering: focus on processing and properties of alumina-based composites.

Ceramic nanocomposites, containing at least one phase in the nanometric dimension, have received special interest in recent years. They have, in fact, demonstrated increased performance, reliability and lifetime with respect to monolithic ceramics. However, a successful approach to the production of tailored composite nanostructures requires the development of innovative concepts at each step of manufacturing, from the synthesis of composite nanopowders, to their processing and sintering.This review aims to deepen understanding of some of the critical issues associated with the manufacturing of nanocomposite ceramics, focusing on alumina-based composite systems. Two case studies are presented and briefly discussed. The former illustrates the benefits, in terms of sintered microstructure and related mechanical properties, resulting from the application of an engineering approach to a laboratory-scale protocol for the elaboration of nanocomposites in the system alumina-ZrO2-YAG (yttrium aluminium garnet). The latter illustrates the manufacturing of alumina-based composites for large-scale applications such as cutting tools, carried out by an injection molding process. The need for an engineering approach to be applied in all processing steps is demonstrated also in this second case study, where a tailored manufacturing process is required to obtain the desired results.