Novel patterning of nano-bioceramics: template-assisted electrohydrodynamic atomization spraying

The ability to create patterns of bioactive nanomaterials particularly on metallic and other types of implant surfaces is a crucial feature in influencing cell response, adhesion and growth. In this report, we uncover and elucidate a novel method that allows the easy deposition of a wide variety of predetermined topographical geometries of nanoparticles of a bioactive material on both metallic and non-metallic surfaces. Using different mesh sizes and geometries of a gold template, hydroxyapatite nanoparticles suspended in ethanol have been electrohydrodynamically sprayed on titanium and glass substrates under carefully designed electric field conditions. Thus, different topographies, e.g. hexagonal, line and square, from hydroxyapatite nanoparticles were created on these substrates. The thickness of the topography can be controlled by varying the spraying time

Electrosprayed calcium phosphate coatings for biomedical purposes.

Contains fulltext : 29833.pdf (publisher's version ) (Open Access)In this thesis, the suitability of the Electrostatic Spray Deposition (ESD) technique was studied for biomedical purposes, i.e., deposition of calcium phosphate (CaP) coatings onto titanium substrates. Using ESD, which is a simple and cheap deposition method for inorganic and organic coatings, it was possible to obtain thin CaP layers with an extremely wide range of chemical and morphological characteristics. Various CaP phases and phase mixtures were deposited and a broad diversity of coating morphologies was produced by varying deposition parameters related to the ESD-apparatus and/or the precursor solutions. Electrosprayed CaP coatings were shown to be biocompatible to soft tissue in this thesis, while the osteoconductive nature of electrosprayed CaP coatings was also proven in vivo. Particular interest was given to a unique, reticular coating morphology consisting of a porous network of variable pore size. This specific coating morphology offers the possibility of varying the specific surface area of electrosprayed CaP coatings to a large extent. Consequently, the degradation rate of CaP coatings as well as the incorporation and subsequent release of biological agents (such as growth factors) can be influenced by chemical as well as physical coating properties using the ESD technique. In that way, control over the biological activity of drug-releasing CaP-coatings can be improved significantly as compared to conventional coating techniques, which lack this chemical and morphological variability.RU Radboud Universiteit Nijmegen, 08 november 2006Promotores : Jansen, J.A., Schoonman, J. Co-promotor : Wolke, J.G.C.152 p

Sustained delivery of biomolecules from gelatin carriers for applications in bone regeneration

Item does not contain fulltextLocal delivery of therapeutic biomolecules to stimulate bone regeneration has matured considerably during the past decades, but control over the release of these biomolecules still remains a major challenge. To this end, suitable carriers that allow for tunable spatial and temporal delivery of biomolecules need to be developed. Gelatin is one of the most widely used natural polymers for the controlled and sustained delivery of biomolecules because of its biodegradability, biocompatibility, biosafety and cost-effectiveness. The current study reviews the applications of gelatin as carriers in form of bulk hydrogels, microspheres, nanospheres, colloidal gels and composites for the programmed delivery of commonly used biomolecules for applications in bone regeneration with a specific focus on the relationship between carrier properties and delivery characteristics

The Use of Fibers in Bone Tissue Engineering

Bone tissue engineering aims to restore and maintain the function of bone by means of biomaterial-based scaffolds. This review specifically focuses on the use of fibers in biomaterials used for bone tissue engineering as suitable environment for bone tissue repair and regeneration. We present a bioinspired rationale behind the use of fibers in bone tissue engineering and provide an overview of the most common fiber fabrication methods, including solution, melt, and microfluidic spinning. Subsequently, we provide a brief overview of the composition of fibers that are used in bone tissue engineering, including fibers composed of (i) natural polymers (e.g., cellulose, collagen, gelatin, alginate, chitosan, and silk, (ii) synthetic polymers (e.g., polylactic acid [PLA], polycaprolactone, polyglycolic acid [PGA], polyethylene glycol, and polymer blends of PLA and PGA), (iii) ceramic fibers (e.g., aluminium oxide, titanium oxide, and zinc oxide), (iv) metallic fibers (e.g., titanium and its alloys, copper and magnesium), and (v) composite fibers. In addition, we review the most relevant fiber modification strategies that are used to enhance the (bio)functionality of these fibers. Finally, we provide an overview of the applicability of fibers in biomaterials for bone tissue engineering, with a specific focus on mechanical, pharmaceutical, and biological properties of fiber-functionalized biomaterials for bone tissue engineering. Impact statement Natural bone is a complex composite material composed of an extracellular matrix of mineralized fibers containing living cells and bioactive molecules. Consequently, the use of fibers in biomaterial-based scaffolds offers a wide variety of opportunities to replicate the functional performance of bone. This review provides an overview of the use of fibers in biomaterials for bone tissue engineering, thereby contributing to the design of novel fiber-functionalized bone-substituting biomaterials of improved functionality regarding their mechanical, pharmaceutical, and biological properties

Functionalization of oligo(poly(ethylene glycol)fumarate) hydrogels with finely dispersed calcium phosphate nanocrystals for bone-substituting purposes.

Contains fulltext : 53564.pdf (publisher's version ) (Closed access)Biodegradable polymers that can be processed into injectable hydrogel matrices are promising candidates for bone-substituting purposes. Furthermore, by incorporating degradable calcium phosphate (CaP) particles and growth factors into these hydrogel matrices, a bone construct can be designed which stimulates the formation of new bone by the surrounding tissue, thereby compensating for the loss of structural integrity of the degrading synthetic bone-substitute. Generally, a major challenge in synthesis of nanoceramic-reinforced polymers is the achievement of a fine dispersion of nanoparticles throughout the polymer, since the unique properties of nanocomposites are lost when nanoparticles aggregate. In the current study, composite hydrogels consisting of oligo(poly(ethylene glycol)fumarate) (OPF) matrices and CaP dispersions of varying crystallinity were successfully developed using physical or chemical preparation strategies. Physical mixing of dried, micrometer-sized CaP powders resulted into formation of irreproducible composites with a highly heterogeneous dispersion of large and agglomerated CaP microparticles throughout the OPF matrix. On the contrary, reproducible and homogeneous hydrogels were fabricated using a chemical mixing strategy, whereby CaP crystals were formed in the presence of dissolved OPF macromers. This co-precipitation technique resulted into a much higher degree of dispersion of the CaP crystals, which can enable higher CaP contents in organic matrices such as OPF. By using these CaP suspensions instead of dried powders, the nanosized structure of separated CaP crystals was preserved, resulting into a higher reactivity of the CaP phase, as indicated by a reduced swelling behavior of these hydrogels. This effect was most likely caused by a physicochemical interaction between Ca(2+) and unreacted COOH end-groups, thereby leading to increased physical cross-linking of the composite hydrogels

Mineralization of hydrogels for bone regeneration.

Contains fulltext : 88923.pdf (publisher's version ) (Open Access)Hydrogels are an important class of highly hydrated polymers that are widely investigated for potential use in soft tissue engineering. Generally, however, hydrogels lack the ability to mineralize, preventing the formation of chemical bonds with hard tissues such as bone. A recent trend in tissue engineering involves the development of hydrogels that possess the capacity to mineralize. The strategy that has attracted most interest has been the incorporation of inorganic phases such as calcium phosphate ceramics and bioglasses into hydrogel matrices. These inorganic particles act as nucleation sites that enable further mineralization, thus improving the mechanical properties of the composite material. A second route to create nucleation sites for calcification of hydrogels involves the use of features from the physiological mineralization process. Examples of these biomimetic mineralization strategies include (1) soaking of hydrogels in solutions that are saturated with respect to calcium phosphate, (2) incorporation of enzymes that catalyze deposition of bone mineral, and (3) incorporation of synthetic analogues to matrix vesicles that are the initial sites of biomineralization. Functionalization of the polymeric hydrogel backbone with negatively charged groups is a third mechanism to promote mineralization in otherwise inert hydrogels. This review summarizes the main strategies that have been developed in the past decade to calcify hydrogel matrices and render these hydrogels suitable for applications in bone regeneration.01 december 201

Electrostatic spray deposition (ESD) of calcium phosphate coatings.

Item does not contain fulltextUsing electrostatic spray deposition (ESD), thin calcium phosphate layers were deposited onto commercially pure cp-Ti substrates. ESD is a thin-film technique that enables the deposition of inorganic thin films onto metallic substrates using a simple and cheap experimental set-up. The results show that coating structure and morphology can be tailored by choosing the appropriate combination of deposition parameters. Scanning electron microscopy revealed that various surface morphologies, ranging from dense to very porous coatings, can be obtained. Particularly interesting was a unique reticular coating morphology characterized by a three-dimensionally interconnected pore network. X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FTIR) analyses showed that crystalline carbonate apatite coatings were formed after heat treatment of as-deposited ESD coatings

Sodium citrate as an effective dispersant for the synthesis of inorganic-organic composites with a nanodispersed mineral phase.

Contains fulltext : 89226.pdf (publisher's version ) (Closed access)Although extensive efforts have been devoted to the development of polymer-ceramic composites for bone repair, those developed thus far were not able to mimic the nanostructure of bone, partly because of the aggregated, microscale organization of the mineral component. As a consequence, homogenization and intermixing of organic and inorganic components remain a major engineering challenge for the development of functional, biomimetic bone-substituting composites. In the current study, various dispersants were evaluated for their potential to be used as biocompatible dispersants in the synthesis of biomimetic composites with a nanodispersed mineral phase. Based on sedimentation experiments, tribasic sodium citrate was selected as the most effective dispersant for the stabilization of calcium phosphate (CaP) suspensions. Specific adsorption of citrate anions onto CaP nanocrystals was shown to result in a strong increase in the negative surface charge of the CaP particles and consequently increased repulsive interparticle forces that were able to overcome attractive van der Waals forces. Using sodium citrate as dispersant at a CaP/citrate ratio of 4.0, CaP-gelatin nanocomposites were fabricated which displayed a nanostructured mineral phase without occurrence of microscale CaP particles. Consequently, aggregation and sedimentation of CaP mineral phase was reduced considerably.1 maart 201

Synthesis and application of nanostructured calcium phosphate ceramics for bone regeneration

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Facilitating the mineralization of oligo(poly(ethylene glycol) fumarate) hydrogel by incorporation of hydroxyapatite nanoparticles.

Item does not contain fulltextExploring strategies to induce the mineralization of hydrogels is an important step toward the development of hydrogel-based materials for bone regeneration. In the current study, the effect of incorporating hydroxyapatite (HA) nanoparticles on the mineralization capacity of an inert poly(ethylene glycol) (PEG)-based hydrogel was investigated. HA nanoparticles were either directly loaded into oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel or loaded into commonly used gelatin microsphere porogens that were subsequently integrated in the OPF matrix. Mineralization of composites after immersion of the samples in simulated body fluid up to 28 days was assessed. In contrast to the blank OPF hydrogel, the HA-containing constructs strongly mineralized such that the average rate of calcium uptake by the material was enhanced by orders of magnitude. The mineral formed was observed to be apatitic and needle shaped. The presented method allows modification of inert PEG-based hydrogels into bioactive biomaterials for applications in bone regeneration.1 mei 201