References of "Acta Biomaterialia"
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See detailSmart nanocarriers for pH-triggered targeting and release of hydrophobic drugs
Cajot, Sébastien; Van Butsele, Kathy; Paillard, A. et al

in Acta Biomaterialia (2012), 8(12), 4215-4223

The use of hybrid pH-sensitive micelles mainly based on the PEO129-P2VP43-PCL17 ABC miktoarm star copolymer as potential triggered drug delivery systems has been investigated. Co-micellization of this ... [more ▼]

The use of hybrid pH-sensitive micelles mainly based on the PEO129-P2VP43-PCL17 ABC miktoarm star copolymer as potential triggered drug delivery systems has been investigated. Co-micellization of this star copolymer with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH sensitive block (poly-2-vinylpyridine, P2VP) has been considered here in order to impart possible active targeting of the tumor cells. Two architectures have been studied for these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer and the respective hybrid micelles have been compared in terms of cytotoxicity (cells viability) and cellular uptake (by using fluorescent dye loaded micelles). Finally, the triggered drug release in the cytosol of tumor cells was investigated by studying on one hand the lysosomal integrity after internalization and on the other hand the release profile in function of the pH. [less ▲]

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See detailMechanical testing of electrospun PCL fibers
Croisier, Florence ULg; Duwez, Anne-Sophie ULg; Jérôme, Christine ULg et al

in Acta Biomaterialia (2012), 8(1), 218-224

Poly(ε-caprolactone) (PCL) fibers ranging from 250 to 700 nm in diameter were produced by electrospinning a polymer tetrahydrofuran/N,N-dimethylformamide solution. The mechanical properties of the fibrous ... [more ▼]

Poly(ε-caprolactone) (PCL) fibers ranging from 250 to 700 nm in diameter were produced by electrospinning a polymer tetrahydrofuran/N,N-dimethylformamide solution. The mechanical properties of the fibrous scaffolds and individual fibers were measured by different methods. The Young’s moduli of the scaffolds were determined using macro-tensile testing equipment, whereas single fibers were mechanically tested using a nanoscale three-point bending method, based on atomic force microscopy and force spectroscopy analyses. The modulus obtained by tensile-testing eight different fiber scaffolds was 3.8 ± 0.8 MPa. Assuming that PCL fibers can be described by the bending model of isotropic materials, a Young’s modulus of 3.7 ± 0.7 GPa was determined for single fibers. The difference of three orders of magnitude observed in the moduli of fiber scaffolds vs. single fibers can be explained by the lacunar and random structure of the scaffolds. [less ▲]

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See detailThe effect of pore geometry on the in vitro biological behavior of human periosteum-derived cells seeded on selective laser-melted Ti6Al4V bone scaffolds.
Van Bael, S.; Chai, Y. C.; Truscello, S. et al

in Acta biomaterialia (2012), 8(7), 2824-34

The specific aim of this study was to gain insight into the influence of scaffold pore size, pore shape and permeability on the in vitro proliferation and differentiation of three-dimensional (3-D) human ... [more ▼]

The specific aim of this study was to gain insight into the influence of scaffold pore size, pore shape and permeability on the in vitro proliferation and differentiation of three-dimensional (3-D) human periosteum-derived cell (hPDC) cultures. Selective laser melting (SLM) was used to produce six distinct designed geometries of Ti6Al4V scaffolds in three different pore shapes (triangular, hexagonal and rectangular) and two different pore sizes (500 mum and 1000 mum). All scaffolds were characterized by means of two-dimensional optical microscopy, 3-D microfocus X-ray computed tomography (micro-CT) image analysis, mechanical compression testing and computational fluid dynamical analysis. The results showed that SLM was capable of producing Ti6Al4V scaffolds with a broad range of morphological and mechanical properties. The in vitro study showed that scaffolds with a lower permeability gave rise to a significantly higher number of cells attached to the scaffolds after seeding. Qualitative analysis by means of live/dead staining and scanning electron micrography showed a circular cell growth pattern which was independent of the pore size and shape. This resulted in pore occlusion which was found to be the highest on scaffolds with 500 mum hexagonal pores. Interestingly, pore size but not pore shape was found to significantly influence the growth of hPDC on the scaffolds, whereas the differentiation of hPDC was dependent on both pore shape and pore size. The results showed that, for SLM-produced Ti6Al4V scaffolds with specific morphological and mechanical properties, a functional graded scaffold will contribute to enhanced cell seeding and at the same time can maintain nutrient transport throughout the whole scaffold during in vitro culturing by avoiding pore occlusion. [less ▲]

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See detailPrediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study.
Truscello, S.; Kerckhofs, Greet ULg; Van Bael, S. et al

in Acta biomaterialia (2012), 8(4), 1648-58

Scaffold permeability is a key parameter combining geometrical features such as pore shape, size and interconnectivity, porosity and specific surface area. It can influence the success of bone tissue ... [more ▼]

Scaffold permeability is a key parameter combining geometrical features such as pore shape, size and interconnectivity, porosity and specific surface area. It can influence the success of bone tissue engineering scaffolds, by affecting oxygen and nutrient transport, cell seeding efficiency, in vitro three-dimensional (3D) cell culture and, ultimately, the amount of bone formation. An accurate and efficient prediction of scaffold permeability would be highly useful as part of a scaffold design process. The aim of this study was (i) to determine the accuracy of computational fluid dynamics (CFD) models for prediction of the permeability coefficient of three different regular Ti6Al4V scaffolds (each having a different porosity) by comparison with experimentally measured values and (ii) to verify the validity of the semi-empirical Kozeny equation to calculate the permeability analytically. To do so, five CFD geometrical models per scaffold porosity were built, based on different geometrical inputs: either based on the scaffold's computer-aided design (CAD) or derived from 3D microfocus X-ray computed tomography (micro-CT) data of the additive manufactured (AM) scaffolds. For the latter the influence of the spatial image resolution and the image analysis algorithm used to determine the scaffold's architectural features on the predicted permeability was analysed. CFD models based on high-resolution micro-CT images could predict the permeability coefficients of the studied scaffolds: depending on scaffold porosity and image analysis algorithm, relative differences between measured and predicted permeability values were between 2% and 27%. Finally, the analytical Kozeny equation was found to be valid. A linear correlation between the ratio Phi(3)/S(s)(2) and the permeability coefficient k was found for the predicted (by means of CFD) as well as measured values (relative difference of 16.4% between respective Kozeny coefficients), thus resulting in accurate and efficient calculation of the permeability of regular AM scaffolds. [less ▲]

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See detailCurrent views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies.
Chai, Y. C.; Carlier, Aurélie ULg; Bolander, J. et al

in Acta Biomaterialia (2012), 8(11), 3876-87

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP ... [more ▼]

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP-based biomaterials are produced and have been extensively used for dental and orthopaedic applications. This is justified by their biocompatibility, osteoconductivity and osteoinductivity (i.e. the intrinsic material property that initiates de novo bone formation), which are attributed to the chemical composition, surface topography, macro/microporosity and the dissolution kinetics. However, the exact molecular mechanism of action is unknown. This review paper first summarizes the most important aspects of bone biology in relation to CaP and the mechanisms of bone matrix mineralization. This is followed by the research findings on the effects of calcium (Ca(2)(+)) and phosphate (PO(4)(3)(-)) ions on the migration, proliferation and differentiation of osteoblasts during in vivo bone formation and in vitro culture conditions. Further, the rationale of using CaP for bone regeneration is explained, focusing thereby specifically on the material's osteoinductive properties. Examples of different material forms and production techniques are given, with the emphasis on the state-of-the art in fine-tuning the physicochemical properties of CaP-based biomaterials for improved bone induction and the use of CaP as a delivery system for bone morphogenetic proteins. The use of computational models to simulate the CaP-driven osteogenesis is introduced as part of a bone tissue engineering strategy in order to facilitate the understanding of cell-material interactions and to gain further insight into the design and optimization of CaP-based bone reparative units. Finally, limitations and possible solutions related to current experimental and computational techniques are discussed. [less ▲]

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See detailStealth properties of poly(ethylene oxide)-based triblock copolymer micelles: A prerequisite for a pH-triggered targeting system
Van Butsele, Kathy; Morille, M.; Passirani, Catherine et al

in Acta Biomaterialia (2011), 7(10), 3700-3707

Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon ... [more ▼]

Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(E-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment. [less ▲]

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See detailComputational modelling of biomaterial surface interactions with blood platelets and osteoblastic cells for the prediction of contact osteogenesis.
Amor, N.; Geris, Liesbet ULg; Vander Sloten, J. et al

in Acta Biomaterialia (2011), 7(2), 779-90

Surface microroughness can induce contact osteogenesis (bone formation initiated at the implant surface) around oral implants, which may result from different mechanisms, such as blood platelet ... [more ▼]

Surface microroughness can induce contact osteogenesis (bone formation initiated at the implant surface) around oral implants, which may result from different mechanisms, such as blood platelet-biomaterial interactions and/or interaction with (pre-)osteoblast cells. We have developed a computational model of implant endosseous healing that takes into account these interactions. We hypothesized that the initial attachment and growth factor release from activated platelets is crucial in achieving contact osteogenesis. In order to investigate this, a computational model was applied to an animal experiment [7] that looked at the effect of surface microroughness on endosseous healing. Surface-specific model parameters were implemented based on in vitro data (Lincks et al. Biomaterials 1998;19:2219-32). The predicted spatio-temporal patterns of bone formation correlated with the histological data. It was found that contact osteogenesis could not be predicted if only the osteogenic response of cells was up-regulated by surface microroughness. This could only be achieved if platelet-biomaterial interactions were sufficiently up-regulated as well. These results confirmed our hypothesis and demonstrate the added value of the computational model to study the importance of surface-mediated events for peri-implant endosseous healing. [less ▲]

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See detailDesigning optimal calcium phosphate scaffold-cell combinations using an integrative model-based approach.
Carlier, Aurélie ULg; Chai, Y.C.; Moesen, M. et al

in Acta Biomaterialia (2011), 7(10), 3573-85

Bone formation is a very complex physiological process, involving the participation of many different cell types and regulated by countless biochemical, physical and mechanical factors, including ... [more ▼]

Bone formation is a very complex physiological process, involving the participation of many different cell types and regulated by countless biochemical, physical and mechanical factors, including naturally occurring or synthetic biomaterials. For the latter, calcium phosphate (CaP)-based scaffolds have proven to stimulate bone formation, but at present still result in a wide range of in vivo outcomes, which is partly related to the suboptimal use and combination with osteogenic cells. To optimize CaP scaffold selection and make their use in combination with cells more clinically relevant, this study uses an integrative approach in which mathematical modeling is combined with experimental research. This paper describes the development and implementation of an experimentally informed bioregulatory model of the effect of calcium ions released from CaP-based biomaterials on the activity of osteogenic cells and mesenchymal stem cell driven ectopic bone formation. The amount of bone formation predicted by the mathematical model corresponds to the amount measured experimentally under similar conditions. Moreover, the model is also able to qualitatively predict the experimentally observed impaired bone formation under conditions such as insufficient cell seeding and scaffold decalcification. A strategy was designed in silico to overcome the negative influence of a low initial cell density on the bone formation process. Finally, the model was applied to design optimal combinations of calcium-based biomaterials and cell culture conditions with the aim of maximizing the amount of bone formation. This work illustrates the potential of mathematical models as research tools to design more efficient and cell-customized CaP scaffolds for bone tissue engineering applications. [less ▲]

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See detailControlled release of drugs from multi-component biomaterials
Zalfen, Alina ULg; Nizet, D.; Jérôme, Christine ULg et al

in Acta Biomaterialia (2008), 4(6), 1788-1796

In order to control their release, drugs are encapsulated into systems which are expected to provide a certain site with a predetermined amount of drug over a well-defined period of time. Here we report ... [more ▼]

In order to control their release, drugs are encapsulated into systems which are expected to provide a certain site with a predetermined amount of drug over a well-defined period of time. Here we report on a multi-component drug delivery biomaterial that consists of a hydrogel matrix in which drug-loaded biodegradable microcarriers are dispersed, and whose potential applications could be found in the design of implantable devices with long-term activity, as required by contraceptive and hormone replacement treatments. The release profile of the drug can actually be tuned by the complex interplay of several release mechanisms, including the permeability and eventually the degradation rate of the microcarriers and the diffusion through the hydrogel. The hydrogel consisted of 2-hydroxyethyl methacrylate cross-linked by ethylene glycol dimethacrylate. The microcarriers were biodegradable poly-ε-caprolactone (PCL) microspheres in which active molecules, such as levonorgestrel (LNG), were encapsulated. The hydrogels were characterized by water swelling, thermal properties, LNG diffusion through drug-free and drug-depleted hydrogel membranes and LNG release from devices with drug dispersed in the hydrogel. The PCL microspheres were observed by scanning electron microscopy; their size distribution, LNG loading and release were also investigated. The hydrogel-microsphere assemblies were characterized in terms of the distribution of the microspheres within the hydrogel, water swelling and the release of the encapsulated molecules. The developed device, due to its composite structure, has the ability to combine several release mechanisms, leading to drug release obeying zero-order kinetics for most of the time. [less ▲]

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See detailMechanical properties of highly porous PDLLA/Bioglass (R) composite foams as scaffolds for bone tissue engineering
Blaker, Jonny J.; Maquet, Véronique; Jérôme, Robert ULg et al

in Acta Biomaterialia (2005), 1(6), 643-652

This study developed highly porous degradable composites as potential scaffolds for bone tissue engineering. These scaffolds consisted of poly-d,l-lactic acid filled with 2 and 15 vol.% of 45S5 Bioglass® ... [more ▼]

This study developed highly porous degradable composites as potential scaffolds for bone tissue engineering. These scaffolds consisted of poly-d,l-lactic acid filled with 2 and 15 vol.% of 45S5 Bioglass® particles and were produced via thermally induced solid–liquid phase separation and subsequent solvent sublimation. The scaffolds had a bimodal and anisotropic pore structure, with tubular macro-pores of 100 μm in diameter, and with interconnected micro-pores of 10–50 μm in diameter. Quasi-static and thermal dynamic mechanical analysis carried out in compression along with thermogravimetric analysis was used to investigate the effect of Bioglass® on the properties of the foams. Quasi-static compression testing demonstrated mechanical anisotropy concomitant with the direction of the macro-pores. An analytical modelling approach was applied, which demonstrated that the presence of Bioglass® did not significantly alter the porous architecture of these foams and reflected the mechanical anisotropy which was congruent with the scanning electron microscopy investigation. This study found that the Ishai–Cohen and Gibson–Ashby models can be combined to predict the compressive modulus of the composite foams. The modulus and density of these complex foams are related by a power-law function with an exponent between 2 and 3. [less ▲]

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See detailStudy of the connectivity properties of Bioglass®-filled polylactide foam scaffolds by image analysis and impedance spectroscopy
Blacher, Silvia ULg; Maquet, Véronique; Jérôme, Robert ULg et al

in Acta Biomaterialia (2005), 1(5), 565-574

The porous structure of two series of poly(d,l-lactide)/Bioglass® composite foams prepared by thermal-induced phase separation was investigated by image analysis and impedance spectroscopy. Polymer ... [more ▼]

The porous structure of two series of poly(d,l-lactide)/Bioglass® composite foams prepared by thermal-induced phase separation was investigated by image analysis and impedance spectroscopy. Polymer solutions of either low or high molecular weight containing different concentrations (up to 50 wt.%) of Bioglass® particles of mean particle size d < 5 µm were studied. The morphology of both macro- and micropores was studied by scanning electron microscopy and image analysis of both neat and composite foams (containing 10-50 wt.% Bioglass®). The pore connectivity of both neat polymer and composite foams was characterized by impedance spectroscopy in relation with their transport properties. The influence of the foam composition (i.e., polymer molecular weight and concentration of Bioglass®) on pore microstructure was studied using these non-destructive methods. It was found that addition of Bioglass® particles has a pronounced effect on pore orientation, leading to increasing loss of order of pore structure, especially for low-molecular weight PDLLA foams. [less ▲]

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