SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.     

How bone marrow-derived human mesenchymal stem cells respond to poorly crystalline apatite coated orthopedic and dental titanium implants

Due to the delayed and weak bone-implant integration in dental and orthopedic devices, there have been several attempts to enhance implant–bone interactions for rapid osseointegration. In this paper, the interactions of human bone marrow-derived stromal (mesenchymal) stem cells (hMSCs) with uncoated and coated titanium alloy implants with poorly crystalline apatite are studied. First the configuration and chemical composition of the apatite coatings and their deposition progress in different experimental conditions are investigated and discussed. Then, hMSCs are cultured on different substrates and cell attachment and proliferation are monitored and evaluated for different time intervals. Although the uncoated and coated substrates indicate good cell attachment, the differences in proliferation and morphology of the cells spread over the coated samples are significant. It is concluded that the coated samples improve the capability for accepting the cells in three-dimensional and slender shapes. The migration of hMSCs on both substrates are discussed. As such cell migration is directly associated to the osteoconduction, the findings confirm the hypothesis of enhancement in bone formation on the surface of biomimetically poorly crystalline apatite coated titanium implants. This in vitro study demonstrates that the coated samples are nontoxic and biocompatible enough for ongoing osteogenic studies in bone or dental defects in animal models in vivo.     

Revisiting shrinking particle and product layer models for fluid-solid reactions - From ideal surfaces to real surfaces

A general model based on an arbitrary geometry was developed for reactive solid particles which have surface defects and porosity. The model equations comprising intrinsic kinetics as well as mass transfer effects through the product layer and the fluid film surrounding the solid particle were derived for shrinking particle and product layer models. From the model equations, the fluid (gas or liquid) concentrations at the reaction surface can be calculated and the change of the solid phase can be predicted. The approach was illustrated with monodisperse particle distributions in batch reactors. Complex kinetics as well as simpler special cases were treated. In general, the model predicts a higher reaction order with respect to the solid component than the previous ideal models, which assume slab, cylindrical or spherical geometries for solid particles.     

Design of tailored biodegradable implants: The effect of voltage on electrodeposited calcium phosphate coatings on pure magnesium

Magnesium, as a biodegradable metal, offers great potential for use as a temporary implant material, which dissolves in the course of bone tissue healing. It can sufficiently support the bone and promote the bone healing process. However, the corrosion resistance of magnesium implants must be enhanced before its application in clinical practice. A promising approach of enhancing the corrosion resistance is deposition of bioactive coating, which can reduce the corrosion rate of the implants and promote bone healing. Therefore, a well-designed substrate-coating system allowing a good control of the degradation behavior is highly desirable for tailored implants for specific groups of patients with particular needs. In this contribution, the influence of coating formation conditions on the characteristics of potentiostatically electrodeposited CaP coatings on magnesium substrate was evaluated. Results showed that potential variation led to formation of coatings with the same chemical composition, but very different morphologies. Parameters that mostly influence the coating performance, such as the thickness, uniformity, deposits size, and orientation, varied from produced coating to coating. These characteristics of CaP coatings on magnesium were controlled by coating formation potential, and it was demonstrated that the electrodeposition could be a promising coating technique for production of tailored magnesium-CaP implants.     

Osseointegration of Sandblasted and Acid-Etched Implant Surfaces. A Histological and Histomorphometric Study in the Rabbit

Titanium surface is an important factor in achieving osseointegration during the early wound healing of dental implants in alveolar bone. The purpose of this study was to evaluate sandblasted-etched surface implants to investigate the osseointegration. In the present study, we used two different types of sandblasted-etched surface implants, an SLA™ surface and a Nanoblast Plus™ surface. Roughness and chemical composition were evaluated by a white light interferometer microscope and X-ray photoelectron spectroscopy, respectively. The SLA™ surface exhibited the higher values (Ra 3.05 μm) of rugosity compared to the Nanoblast Plus™ surface (Ra 1.78 μm). Both types of implants were inserted in the femoral condyles of ten New Zealand white rabbits. After 12 weeks, histological and histomorphometric analysis was performed. All the implants were osseointegrated and no signs of infection were observed. Histomorphometric analysis revealed that the bone–implant contact % (BIC) ratio was similar around the SLA™ implants (63.74 ± 13.61) than around the Nanoblast Plus™ implants (62.83 ± 9.91). Both implant surfaces demonstrated a favorable bone response, confirming the relevance of the sandblasted-etched surface on implant osseointegration.     

Early Bone Healing on Hydroxyapatite-Coated and Chemically-Modified Hydrophilic Implant Surfaces in an Ovine Model

Implant topography affects early peri-implant bone healing by changing the osteoconduction rate in the surrounding biological environment. Implant surfaces have been designed to promote faster and stronger bone formation for rapid and stable prosthesis loading. Early peri-implant bone healing has been observed with a sandblasted, acid-etched implant that was chemically modified to be hydrophilic (cmSLA). The present study investigates whether early peri-implant bone healing extends to a rough surface implant with a high crystalline hydroxyapatite surface (TSV MP-1 HA). Three implants were randomly placed in porous trabecular bone within both medial femoral condyles of 10 sheep. Early peri-implant bone stability was measured at 3- and 6-weeks healing time following implant insertion. Results indicated a similar implant stability quotient between the implants at insertion and over time. The significant increase over time of reverse torque values with respect to insertion torque (p < 0.001) did not differ between the implants. However, the bone-to-implant contact of TSV MP-1 HA was significantly higher than that of cmSLA implants at 6 weeks (p < 0.01). These data validate previous findings of a hydrophilic implant surface and extend the observation of early osseointegration to a rough surface implant in porous trabecular bone.     

CSBD Healing in Rats after Application of Bovine Xenogeneic Biomaterial Enriched with Magnesium Alloy

Xenogeneic biomaterials Cerbone^® and OsteoBiol^® are widely used in oral implantology. In dental practice, xenogeneic biomaterial is usually combined with autologous bone to provide bone volume stability needed for long-term dental implants. Magnesium alloy implants dissolve and form mineral corrosion layer that is directly in contact with bone tissue, allowing deposition of the newly formed bone. CSBD heals by intramembranous ossification and therefore is a convenient model for analyses of ostoconductive and osteoinductive properties of different type of biomaterials. Magnesium alloy-enriched biomaterials have not yet been applied in oral implantology. Therefore, the aim of the current study was to investigate biological properties of potentially new bovine xenogeneic biomaterial enriched with magnesium alloy in a 5 mm CSBD model. Osteoconductive properties of Cerabone^®, Cerabone^® + Al. bone, and OsteoBiol^® were also analyzed. Dynamics of bone healing was followed up on the days 3, 7, 15, 21, and 30. Calvary bone samples were analyzed by micro-CT, and values of the bone morphometric parameters were assessed. Bone samples were further processed for histological and immunohistochemical analyses. Histological observation revealed CSBD closure at day 30 of the given xenogeneic biomaterial groups, with the exception of the control group. TNF-α showed high intensity of expression at the sites of MSC clusters that underwent ossification. Osx was expressed in pre-osteoblasts, which were differentiated into mature osteoblasts and osteocytes. Results of the micro-CT analyses showed linear increase in bone volume of all xenogeneic biomaterial groups and also in the control. The highest average values of bone volume were found for the Cerabone^® + Mg group. In addition, less residual biomaterial was estimated in the Cerabone^® + Mg group than in the Cerabone^® group, indicating its better biodegradation during CSBD healing. Overall, the magnesium alloy xenogeneic biomaterial demonstrated key properties of osteoinduction and biodegradidibility during CSBD healing, which is the reason why it should be recommended for application in clinical practice of oral implantology.     

In Vitro and In Vivo Characterization of PLLA-316L Stainless Steel Electromechanical Devices for Bone Tissue Engineering—A Preliminary Study

Bone injuries represent a major social and financial impairment, commonly requiring surgical intervention due to a limited healing capacity of the tissue, particularly regarding critical-sized defects and non-union fractures. Regenerative medicine with the application of bone implants has been developing in the past decades towards the manufacturing of appropriate devices. This work intended to evaluate medical 316L stainless steel (SS)-based devices covered by a polymer poly (L-lactic acid) (PLLA) coating for bone lesion mechanical and functional support. SS316L devices were subjected to a previously described silanization process, following a three-layer PLLA film coating. Devices were further characterized and evaluated towards their cytocompatibility and osteogenic potential using human dental pulp stem cells, and biocompatibility via subcutaneous implantation in a rat animal model. Results demonstrated PLLA-SS316L devices to present superior in vitro and in vivo outcomes and suggested the PLLA coating to provide osteo-inductive properties to the device. Overall, this work represents a preliminary study on PLLA-SS316L devices’ potential towards bone tissue regenerative techniques, showing promising outcomes for bone lesion support.     

Direct observation of bone coherence with dental implants

A newly developed gentle ion beam polishing technique was established for preparing of cross sections of dental implants feasible for high resolution scanning electron microscope investigation. This approach was applied to investigate the interfacial microstructure between newly formed bone and dental implants with modified surfaces extracted after in vivo test in adult miniature pigs. The results obtained so far reveal that it has become possible to analyze the bone coherence to implants besides measuring the bone coverage. The amount and density of the mineralized extra cellular matrix has found to be different in different sub-microscopic regions around the implant. From our observations, it can be seen that new bone grows from the existing bone and advances towards the implant surface by in growth mechanism. The images also reveal that new bone is formed directly at the implant surface; we propose a deposition mechanism to explain this. Eventually the in grown and the deposited bone connect to give a good anchorage of the implant. This achievement bears implication for understanding osseointegration at microscopic level.     

Preclinical study probing primary stability of dental implants in synthetic and natural bones

The natural bone is a biological example of a polymer–ceramic composite with a higher volume fraction of nanosized ceramic (around 65% hydroxyapatite) dispersed in polymer (collagenous) matrix. The loading of a dental implant involves the biomechanical interactions of the implant with such natural composites in the jaw bones of human subjects. In particular, the insertion torque responses of the dental implant are related to the implant design, in particular the external thread morphology, which influences the primary stability of the implant. In this study, the effect of the bone properties (polyurethane-based synthetic bone, porcine and human cadaver lumbar bone) and clinically relevant implant driving protocols on the insertion and removal torques of newly designed implant variants (hybrid threads with macro- and micro-threads) were assessed, quantitatively and qualitatively. It was observed that torque response increased with an increase in bone density, irrespective of the implant designs. The torque response of the implants in both synthetic and natural bones was benchmarked with the commercially available implant. The implants with bone cutting partial macro-threads at the apical end without inter thread gap exhibited comparable clinically relevant results with respect to control implants and were found to be most suitable for implantation into natural bone.     

Insights into Surface Treatment Methods of Titanium Dental Implants

Titanium is the most widely used material for dental implants, due to its desirable properties, e.g., high biocompatibility, low density, high stiffness and strength, etc. More importantly, titanium implants may osseointegrate with living bone, meaning that new bone grows directly onto the surface of the implant, without any intermediate soft tissue layer. A successfully osseointegrated implant generally has a strong bonding to the adjacent bone; consequently, it usually functions well and remains stable for long service period. It also has been clinically proven that surface treatment methods can improve the rate and quality of titanium implants' osseointegration. This article focuses on two such methods, i.e., surface roughening and hydroxyapatite (HA) coating. In addition, we discuss a promising new methodology, which attempts to modify the surface charge of titanium materials. This paper focuses on the current best surface treatment methods for titanium dental implants developed and improved in the past two decades, i.e., 1990–2010.     

First Experimental Study of the Influence of Extracellular Vesicles Derived from Multipotent Stromal Cells on Osseointegration of Dental Implants

Herein, the aim was to study the state of the bone tissue adjacent to dental implants after the use of extracellular vesicles derived from multipotent stromal cells (MSC EVs) of bone marrow origin in the experiment. In compliance with the rules of asepsis and antiseptics under general intravenous anesthesia with propofol, the screw dental implants were installed in the proximal condyles of the tibia of outbred rabbits without and with preliminary introduction of 19.2 μg MSC EVs into each bone tissue defect. In 3, 7, and 10 days after the operation, the density of bone tissue adjacent to different parts of the implant using an X-ray unit with densitometer was measured. In addition, the histological examinations of the bone site with the hole from the removed device and the soft tissues from the surface of the proximal tibial condyle in the area of intra-bone implants were made. It was found out that 3 days after implantation with the use of MSC EVs, the bone density was statistically significantly higher by 47.2% than after the same implantation, but without the injection of MSC EVs. It is possible that as a result of the immunomodulatory action of MSC EVs, the activity of inflammation decreases, and, respectively, the degree of vasodilation in bones and leukocyte infiltration of the soft tissues are lower, in comparison with the surgery performed in the control group. The bone fragments formed during implantation are mainly consolidated with each other and with the regenerating bone. Day 10 demonstrated that all animals with the use of MSC EVs had almost complete fusion of the screw device with the bone tissue, whereas after the operation without the application of MSC EVs, the heterogeneous histologic pattern was observed: From almost complete osseointegration of the implant to the absolute absence of contact between the foreign body and the new formed bone. Therefore, the use of MSC EVs during the introduction of dental implants into the proximal condyle of the tibia of rabbits contributes to an increase of the bone tissue density near the device after 3 days and to the achievement of consistently successful osseointegration of implants 10 days after the surgery.     

Spherical calcium phosphate nanoparticle fillers allow polymer processing of bone fixation devices with high bioactivity

Treatment of bone defects generally requires a fixation device. Biodegradable implants can often prevent second operations in contrast to metallic implants that are surgically removed after healing. In this study, we investigate the preparation of a bone fixation device with additional bioactivity by adding nanoparticulate amorphous tricalcium phosphate (ATCP) to improve bonding to bone. Medically approved poly(lactide‐co‐glycolide) (PLGA) and spherical (ATCP) nanoparticles were blended directly or through a two‐step approach, where ATCP was first dispersed in PLGA by solvent casting, extruded and hot pressed producing blocks and bone screws. The latter route yielded good particle dispersion while blending alone led to inhomogeneous mixtures. Samples were immersed in simulated body fluid and showed rapid formation of surface hydroxyapatite layers (examined by X‐ray diffraction and scanning electron microscopy) already after 3 days, thus confirming very high bioactivity. Polymer degradation during processing and upon simulated implantation conditions was followed by gel permeation chromatography. The elevated temperature during extrusion was the strongest single factor contributing to PLGA degradation. Screws could be machined out of extruded cylinders and demonstrated the ability to process PLGA/ATCP 90/10 composites with regular workshop tools. These properties suggest the use of such composites as improved, bioactive, and degradable bone fixation systems particularly in oral and maxillofacial surgery. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers     

Computational Fluid Dynamics Modeling for Urea Hydrolysis in a Batch Reactor for Flue Gas Conditioning

A computational fluid dynamics (CFD) model is proposed to simulate urea hydrolysis for ammonia synthesis as a safe feed stock to flue gas conditioning in thermal power plants. A series of parametric studies to investigate flow rates, thermal boundary conditions, and reactor geometry was performed and operating conditions and reactor geometry were optimized. Detailed 3D flow, heat, and chemistry simulations of ammonia were carried out with predicted conversions comparable to measurements and the dependence of the experiments on the reaction parameters was evaluated. Through simulation under the same conditions the output was generated and compared to the experimental plot. Profiles of temperature and flow patterns were successfully achieved through simulation.     

Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy?

Angiogenesis is a broad spread term of high interest in regenerative medicine and tissue engineering including the dental field. In the last two decades, researchers worldwide struggled to find the best ways to accelerate healing, stimulate soft, and hard tissue remodeling. Stem cells, growth factors, pathways, signals, receptors, genetics are just a few words that describe this area in medicine. Dental implants, bone and soft tissue regeneration using autologous grafts, or xenografts, allografts, their integration and acceptance rely on their material properties. However, the host response, through its vascularization, plays a significant role. The present paper aims to analyze and organize the latest information about the available dental stem cells, the types of growth factors with pro-angiogenic effect and the possible therapeutic effect of enhanced angiogenesis in regenerative dentistry.     

Simulation of the Hydrodynamics and Drying in a Spouted Bed Dryer

Gas-particle flow behavior in a spouted bed of spherical particles was simulated using the Eulerian-Eulerian two-fluid modeling approach, incorporating a kinetic-frictional constitutive model for dense assemblies of the particulate solid. The interaction between gas and particles was modeled using the Gidaspow drag model and the predicted hydrodynamics is compared with published experimental data. To investigate drying characteristics of particulate solids in axisymmetric spouted beds, a heat and mass transfer model was developed and incorporated into the commercial computational fluid dynamics (CFD) code FLUENT 6.2. The kinetics of drying was described using the classical and diffusional models for surface drying and internal moisture drying, respectively. The overall flow patterns within the spouted bed were predicted well by the model; i.e., a stable spout region, a fountain region, and an annular downcomer region were obtained. Calculated particle velocities and concentrations in the axisymmetric spouted bed were in reasonable agreement with the experimental data of He et al. (Can. J. Chem. Eng. 1994a, 72:229; 1994b, 72:561). Such predictions can provide important information on the flow field, temperature, and species distributions inside the spouted bed for process design and scale-up.     

Ex Vivo and In Vivo Analysis of a Novel Porcine Aortic Patch for Vascular Reconstruction

(1) Background: The aim of the present study was the biocompatibility analysis of a novel xenogeneic vascular graft material (PAP) based on native collagen won from porcine aorta using the subcutaneous implantation model up to 120 days post implantationem. As a control, an already commercially available collagen-based vessel graft (XenoSure^®) based on bovine pericardium was used. Another focus was to analyze the (ultra-) structure and the purification effort. (2) Methods: Established methodologies such as the histological material analysis and the conduct of the subcutaneous implantation model in Wistar rats were applied. Moreover, established methods combining histological, immunohistochemical, and histomorphometrical procedures were applied to analyze the tissue reactions to the vessel graft materials, including the induction of pro- and anti-inflammatory macrophages to test the immune response. (3) Results: The results showed that the PAP implants induced a special cellular infiltration and host tissue integration based on its three different parts based on the different layers of the donor tissue. Thereby, these material parts induced a vascularization pattern that branches to all parts of the graft and altogether a balanced immune tissue reaction in contrast to the control material. (4) Conclusions: PAP implants seemed to be advantageous in many aspects: (i) cellular infiltration and host tissue integration, (ii) vascularization pattern that branches to all parts of the graft, and (iii) balanced immune tissue reaction that can result in less scar tissue and enhanced integrative healing patterns. Moreover, the unique trans-implant vascularization can provide unprecedented anti-infection properties that can avoid material-related bacterial infections.     

Multifunctional hybrid coating on titanium towards hydroxyapatite growth: Electrodeposition of tantalum and its molecular functionalization with organophosphonic acids films

Titanium and its alloys are base materials used in the dental and orthopaedic fields owing to suitable intrinsic properties: good biocompatibility, high corrosion resistance and excellent mechanical properties. However, the bonding between titanium and bone tissue is not always strong enough and can become a critical problem. In this context, the two main objectives of this paper are the increase of the corrosion resistance and the improvement of the hydroxyapatite (HAp) growth. The surface modification considered here is achieved in three main steps and consists in the elaboration of different inorganic and organic coatings. The first step is the elaboration of electrodeposition of tantalum on the titanium oxide film of a titanium substrate. The second step is the modification of the tantalum oxide coating with organophosphonic acids. The last step is the nucleation and growth of HAP on the outermost layer of the system by immersion in a simulated body fluid. The hybrid coating tantalum oxide/organophosphonic acids/molecular layer is shown to be promising for orthopaedic implants.     

Retracted: Effects of the Operating Conditions and Geometry Parameter on the Filtration Performance of the Fibrous Filter

The gas‐solid two‐phase flows in fibrous filters were simulated by computational fluid dynamics (CFD) technology. The pressure drops and filter efficiencies with different operating conditions and geometry parameter, including face velocity, particle size, and solid volume fraction (SVF) were calculated. The effects of the operating conditions and geometry parameter on the filter performance of the fibrous filter were obtained. The results indicate that the pressure drop increases linearly with the face velocity and the predicted values of the pressure drops are in excellent agreement with the experimental correlation. Filtration efficiency decreases with the face velocity for submicrometer particles (0.1 μm) and, for larger particles (1 μm) the tendency is just the opposite. The filtration mechanism is different for different particle sizes. For the filter in this paper, when the particle size is smaller than 0.2 μm, Brownian diffusion plays a significant role in the filtration process. When the particle size is greater than 0.5 μm, inertial impaction becomes an important capture mechanism. For particle sizes in the range of 0.2–0.5 μm, the Brownian diffusion and inertial impaction are both relatively weak and, therefore, the filtration efficiency has the least value in this range. Additionally, the SVF distribution is an important geometry parameter in the filter. The filtration efficiency of the filter with a decreased SVF (geometry B) along the thickness of the filter is higher than that of the filter with the even SVF (geometry A), while maintaining a low pressure drop.     

Evaluation of hydroxyapatite and β-tri calcium phosphate microplasma spray coated pin intra-medullary for bone repair in a rabbit model

Here we report a comparative study of the healing kinetics of surgically created artificial defects in the tibia of New Zealand white rabbits. Comparison of the healing kinetics was made for uncoated conventional SS316L intramedullary pins, and the same pins with microplasma sprayed (MIPS) pure hydroxyapatite (HAp) and beta-tri calcium phosphate (β-TCP) coatings. After thorough material characterizations including XRD, FTIR, SEM, etc., MIPS coated pins were implanted to such animals. Serum biochemistry, radiology and fluorochrome labelling were used to evaluate the comparative healing kinetics of these implants in vivo. In comparison to those of the uncoated pins, the pins coated with both MIPS HAp and β-TCP showed significant increment of alkaline phosphatase up to 15th postoperative day, insignificant changes in serum phosphorus and calcium with uneventful healing of bone defect. There was development of Havarsian canals and well-defined peripherally placed osteoblasts along with evidence of angiogenesis and comparatively more new bone formation in the defect site. On a comparative scale, the performance of the β-TCP coated intramedullary pins was much better than that of the pure HAp coated pins than the uncoated intramedullary pins.