Fabrication of an rhBMP-2 loaded porous β-TCP microsphere-hyaluronic acid-based powder gel composite and evaluation of implant osseointegration

Methods to improve osseointegration that include implantation of rhBMP-2 with various kinds of carriers are currently of considerable interest. The present study was conducted to evaluate if the rhBMP-2 loaded β-TCP microsphere-hyaluronic acid-based powder-like hydrogel composite (powder gel) can act as an effective rhBMP-2 carrier for implantation in host bone with a bone defect or poor bone quality. The release pattern for rhBMP-2 was then evaluated against an rhBMP-2-loaded collagen sponge as a control group. Dental implants were also inserted into the tibias of three groups of rabbits: an rhBMP-2 (200 µg) loaded powder gel composite implanted group, an implant only group, and a powder gel implanted group. Micro-CT and histology of the implanted areas were carried out four weeks later. The rhBMP-2 powder gel released less rhBMP-2 than the collagen sponge, but it continued a slow release for more than 7 days. The rhBMP-2 powder gel composite improved osseointegration of the dental implant by increasing the amount of new bone formation in the implant pitch and it improved the bone quality and bone quantity of new bone. The histology results indicated that the rhBMP-2 powder gel composite improved the osseointegration in the cortical bone as well as the marrow space along the fixture. The bone-to-implant contact ratio of the rhBMP-2 (200 µg) loaded powder gel composite implanted group was significantly higher than those of the implant only group and the powder gel implanted group. The powder gel appeared to be a good carrier and could release rhBMP-2 slowly to promote the formation of new bone following implantation in a bone defect, thereby improving implant osseointegration.     

In Vivo Performance and Structural Relaxation of Biodegradable Bone Implants Made from Mg?Zn?Ca Bulk Metallic Glasses

A study of Mg‐based bulk metallic glasses (BMGs) as biodegradable bone implants is presented. The implantation site can affect performance, so the BMGs were evaluated in vivo in rat femurs using µ‐CT scans at various times for more than 90 days. Estimates of H₂ evolution correlate well with previous in vitro studies and bone–implant contact is similar to that for Ti pins. One potential drawback of Mg‐based BMGs in this application is embrittlement due to structural relaxation. Here, relaxation at 20 and 37 °C is examined, and an increase in the characteristic relaxation time, from 10 to 30 days at 20 °C, is observed as Zn increases from 29 to 32 at.%, correlating with dramatically reduced hydrogen evolution.     

Global exponential stabilization for a class of nonlinear singularly perturbed systems

Abstract

A globally exponentially (asymptotically) stabilizing composite feedback control is proposed in this paper for a general class of nonlinear multiple time‐delay singularly perturbed systems in which the slow subsystem is exponentially stable in the absence of the fast states. The chosen design manifold under this composite feedback control becomes an exact integral manifold and the trajectories of the closed‐loop systems are steered globally along the integral manifold to the origin exponentially, with some guaranteed convergence rate, for all sufficiently small singular perturbation parameter ?.     

Bioactive TiOB‐Coating on Titanium Alloy Implants Enhances Osseointegration in a Rat Model

The surface properties of titanium alloy implants for improved osseointegration in orthopaedic and dental surgery have been modified by many technologies. Hydroxyapatite coatings with a facultative integration of growth factors deposited by plasma spraying showed improved osseointegration. Our approach in order to enhance osseointegration was carried out by a surface modification method of titanium alloy implants called plasma chemical oxidation (PCO). PCO is an electrochemical procedure that converts the nm‐thin natural occurring titanium‐oxide layer on an implant to a 5 µm thick ceramic coating (TiOB‐surface). Bioactive TiOB‐surfaces have a porous microstructure and were loaded with calcium and phosphorous, while bioinert TiOB‐surfaces with less calcium and phosphorous loadings are smooth. A rat tibial model with bilateral placement of titanium alloy implants was employed to analyze the bone response to TiOB‐surfaces in vivo. 64 rats were randomly assigned to four groups of implants: (i) pure titanium alloy (control), ii) titanium alloy, type III anodization, (iii) bioinert TiOB‐surface, and (iv) bioactive TiOB‐surface. Mechanical fixation was evaluated by pull out tests at 3 and 8 weeks. The bioactive TiOB‐surface showed significantly increased shear strength at 8 weeks compared to all other groups.     

Research on the Biocompatibility of the New Magnesium Alloy LANd442—An In Vivo Study in the Rabbit Tibia over 26 Weeks

Research on magnesium based degradable implant materials has finally obtained success in orthopaedics. Based on the previous good results with LAE442 magnesium alloy, the new LANd442 alloy was developed. In doing this, the single element neodymium replaces the rare earth compound. The primary objective of this study is to assess the biocompatibility of the new alloy in the rabbit model. During a 26 week period, the animals were investigated using clinical, radiological and in vivo µ‐CT techniques. Following euthanasia, histological, fluorescent microscopy and ex vivo µ‐CT investigations were done. Clinically, additional bone formed at the implant's location and accumulation of small amounts of subcutaneous gas can be observed. Radiological investigations show brightening of the medullary cavity and thickening in the region of the diaphysis. The µ‐computed tomographies reveal a reduction in the bone density from 1226.31 to 1192.95 mg HA/ccm together with increases in bone porosity from 4.55 to 6.6% and bone volume from 1.51 to 2.06 mm³ · slice^?1. By means of fluorochrome sequential marking, the determined MARs lie between day 93 and 120 at 3.58 µm · d^?1 and between day 120 and 179 at 2.25 µm · d^?1. Elevated remodelling processes in the bone are histologically confirmed due to the periosteal and endosteal growths and an increased appearance of osteoclasts. Owing to the established considerable bone remodelling processes following intramedullary implantation, LANd442 appears to be a less suitable degradable implant material for cortical bone applications.     

Titanium levels in rats implanted with Ti6Al4V treated samples in the absence of wear

The effect of implantation time and implant nitriding on titanium ion concentration in several tissues of rats carrying Ti6Al4V implants was studied by means of inductively coupled plasma-mass spectroscopy (ICP-MS). Histological studies were also performed in order to check for tissue degeneration due to the Ti6Al4V implantation. The animals were divided into four groups: one received Ti6Al4V implants, the second received nitrided Ti6Al4V implants, the third group received nitrided and descaled Ti6Al4V implants and the last one was the control group. Half the animals of the implanted groups received the Ti6Al4V implant for 30 days, while the other half received the implant for 120 days. Spleen, muscle, kidney, lung, brain and bone samples were retrieved from these rats as well as the control group. Ion concentration measures did not show significant differences between control and implanted rats for the studied period of time, although histological studies showed minor differences, especially on liver tissue samples.     

A new numerical algorithm for sub‐optimal control of earthquake excited linear structures

Exact optimal classical closed–open‐loop control is not achievable for the buildings under seismic excitations since it requires the whole knowledge of earthquake in the control interval. In this study, a new numerical algorithm for the sub‐optimal solution of the optimal closed–open‐loop control is proposed based on the prediction of near‐future earthquake excitation using the Taylor series method and the Kalman filtering technique. It is shown numerically that how the solution is related to the predicted earthquake acceleration values. Simulation results show that the proposed numerical algorithm are better than the closed‐loop control and the instantaneous optimal control and proposed numerical solution will approach the exact optimal solution if the more distant future values of the earthquake excitation can be predicted more precisely. Effectiveness of the Kalman filtering technique is also confirmed by comparing the predicted and the observed time history of NS component of the 1940 El Centro earthquake. Copyright © 2001 John Wiley & Sons, Ltd.     

Matrix generation within a macroporous non-degradable implant for osteochondral defects is not enhanced with partial enzymatic digestion of the surrounding tissue: evaluation in an in vivo rabbit model

Articular cartilage defects are a significant source of pain, have limited ability to heal, and can lead to the development of osteoarthritis. However, a surgical solution is not available. To tackle this clinical problem, non-degradable implants capable of carrying mechanical load immediately after implantation and for the duration of implantation, while integrating with the host tissue, may be viable option. But integration between articular cartilage and non-degradable implants is not well studied. Our objective was to assess the in vivo performance of a novel macroporous, nondegradable, polyvinyl alcohol construct. We hypothesized that matrix generation within the implant would be enhanced with partial digestion of the edges of articular cartilage. Our hypothesis was tested by randomizing an osteochondral defect created in the trochlea of 14 New Zealand white rabbits to treatment with: (i) collagenase or (ii) saline, prior to insertion of the implant. At 1 and 3-month post-operatively, the gross morphology and histologic appearance of the implants and the surrounding tissue were assessed. At 3 months, the mechanical properties of the implant were also quantified. Overall, the hydrogel implants performed favorably; at all time-points and in all groups the implants remained well fixed, did not cause inflammation or synovitis, and did not cause extensive damage to the opposing articular cartilage. Regardless of treatment with saline or collagenase, at 1 month post-operatively implants from both groups had a contiguous interface with adjacent cartilage and were populated with chondrocyte-like cells. At 3 months fibrous encapsulation of all implants was evident, there was no difference between area of aggrecan staining in the collagenase versus saline groups, and implant modulus was similar in both groups; leading us to reject our hypothesis. In summary, a porous PVA osteochondral implant remained well fixed in a short term in vivo osteochondral defect model; however, matrix generation within the implant was not enhanced with partial digestion of adjacent articular cartilage.     

Porous nitinol vs. titanium intervertebral fusion implants: Computer tomography,radiological and histological study of osseointegration capacity

The functionality of a new metallic interbody fusion implant manufactured out of porous nitinol (PNT) was evaluated in sheep and compared to a conventional titanium intervertebral cage packed with autologous iliac crest bone. Both device types were implanted at two non‐contiguous intervertebral lumbar sites. The objective was to evaluate the osseointegration capacity after 3, 6 and 12 months of implantation in the presence of these two implant types subjected to the same mechanical loads. Two‐dimensional radiolology, computer tomography, and histology were used as techniques of parameters evaluation. The results indicated that PNT obtained a better intervertebral osseointegration capacity compared to the TiAlV cage. The functional difficulties of the titanium implant were related to its instability at the implantation site possibly due to a biofunctionality problem. The biocompatibility of both implants seemed however comparable.     

Effect of Postmolding Heat Treatment on In Vitro Properties of a Polyanhydride Implant Containing Gentamicin Sulfate

A polyanhydride implant containing gentamicin sulfate was fabricated using a laboratory‐scale injection‐molding machine. After injection molding, the implants were subject to heat treatment at 60°C for various time periods with or without nitrogen protection. The impact of this heat treatment on the in vitro properties of the implants including copolymer molecular weights, mechanical properties, and in vitro drug‐release profiles was investigated. This heat treatment caused a drastic drop in the molecular weight of the copolymer. Heating without nitrogen protection resulted in the hardening of the implant, but heating in the presence of nitrogen rendered the implant less rigid. It was also found that a faster in vitro drug release profile was shown by implants heated without nitrogen protection and a pronounced slowing down in drug release was exhibited by implants heated with nitrogen protection.     

Exploring the Use of Design of Experiments in Industrial Processes Operating Under Closed‐Loop Control

Industrial manufacturing processes often operate under closed‐loop control, where automation aims to keep important process variables at their set‐points. In process industries such as pulp, paper, chemical and steel plants, it is often hard to find production processes operating in open loop. Instead, closed‐loop control systems will actively attempt to minimize the impact of process disturbances. However, we argue that an implicit assumption in most experimental investigations is that the studied system is open loop, allowing the experimental factors to freely affect the important system responses. This scenario is typically not found in process industries. The purpose of this article is therefore to explore issues of experimental design and analysis in processes operating under closed‐loop control and to illustrate how Design of Experiments can help in improving and optimizing such processes. The Tennessee Eastman challenge process simulator is used as a test‐bed to highlight two experimental scenarios. The first scenario explores the impact of experimental factors that may be considered as disturbances in the closed‐loop system. The second scenario exemplifies a screening design using the set‐points of controllers as experimental factors. We provide examples of how to analyze the two scenarios. © 2017 The Authors Quality and Reliability Engineering International Published by John Wiley & Sons Ltd     

充液成形设备双闭环控制分析

目的 研究先进充液成形设备的精度控制技术,以满足充液成形过程中对成形介质压力及侧推油缸位置的高精度控制要求,并确保模具型腔的密封性和零件成形的稳定性。方法 基于PLC控制器下的PID闭环控制功能,将速度闭环和位置或压力闭环进行集成,开发应用于液压系统的双闭环控制方法。结果 使用双闭环控制方法,可以调整侧推油缸的位置控制精度及响应速度,并将精度控制在0.1 mm以内,也可调整增压装置的输出端压力控制精度,使精度达到0.3 MPa。结论 在利用充液成形设备进行液压成形的过程中,双闭环技术可以实现设备侧向密封的精确位置控制以及型腔内压力的精确控制。     

Free‐Standing Patterned Ceramic Structures Obtained by Soft Micromolding

Patterned ceramic films with constant thickness can be processed by a soft lithographic method. By using micromolding in capillaries, the slurry is forced to flow through channels created in an elastomer stamp. After drying, layers deposited on an amorphous carbon substrate were sintered under inert atmosphere. Free‐standing ceramic structures with high aspect ratio were obtained with lateral resolution better than 1 µm. Dimensional changes were monitored in comparison to films deposited on stiff sapphire substrate. This technique enables to process a large variety of structures, from optical or electronic components to sieve and MEMS applications.     

Antimicrobial Potential of Copper‐Containing Titanium Surfaces Generated by Ion Implantation and Dual High Power Impulse Magnetron Sputtering

The application of antimicrobial surfaces to titanium alloy (Ti) implants would be beneficial to prevent implant‐associated infections of joint endoprostheses and osteosyntheses. Copper (Cu) could be advantageously applied for this purpose, since it exhibits a well‐known antimicrobial activity and is a trace element in the human body, i.e., it is non‐toxic in small concentrations. This approach was evaluated with two plasma‐based surface modification procedures:

• 1) Implantation of Cu ions into Ti by means of plasma immersion ion implantation (PIII) and
• 2) Coating of Ti surfaces with Cu? Ti films by means of dual high power impulse magnetron sputtering (dual HiPIMS).

In this manner, the surfaces could be equipped with various amounts of Cu, as it was analyzed by X‐ray photoelectron spectroscopy (XPS). The surfaces released up to 8 mmol · L^?1 of Cu within 24 h, measured with atomic absorption spectroscopy (AAS). Hence, the surfaces possessed an antimicrobial potential against typical infect‐associated bacteria (Staphylococcus aureus). Surfaces with a higher Cu release prepared by HiPIMS technique revealed a higher antimicrobial effect, while surfaces implanted by PIII were less cytotoxic to osteoblasts (MG‐63 cells). These results show that Cu doped and coated implants could be useful for prevention and therapy of implant‐associated infections.     

Three-Dimensional Finite Element Analysis of Prosthetic Finger Joint Implants

The purpose of this study was to develop high resolution three-dimensional (3D) finite element (FE) models of the Swanson^® (No. 2) and NeuFlex^® (No. 10) joint implants to: simulate implant function; evaluate stress distributions and bending stiffness of these implants; and assess their comparative potential for fracture and range of motion (ROM) in flexion and extension. Geometric representations of the implants accurate to within 20 μm were achieved using digital laser imaging technology. Images were transferred to ANSYS 5.7 using appropriate interfacing software and 3D FE models of the implants were constructed. Hyperelastic material properties of the silicone elastomers were derived experimentally from uniaxial tensile tests on implant sections. Both implants experienced maximum von Mises stresses at 90° of flexion and minimum stresses at the neutral position of flexion (Swanson: 0°, NeuFlex: 30°). Within the reported functional ROM (33°–73°), the NeuFlex implant exhibited lower maximum von Mises stress and bending stiffness than the Swanson. The Swanson implant, which has a straight hinge, exhibited lower peak stresses and bending stiffness than the NeuFlex for flexion less than 20°. Areas of high von Mises stress for the Swanson implant included the stem–hinge junction and the peripheral zone of the body of the hinge, corresponding to clinical reports of fractures. In the NeuFlex implant, the maximum stress occurred on the dorsal surface of the hinge. Bending stiffness of the NeuFlex implant was modelled to be substantially less than that of the Swanson throughout the functional ROM (33°–73° of flexion). The resting position of the Swanson implant is at 0° of flexion. A moment was required to extend the NeuFlex implant from 30° to 0° of flexion. These results suggest that the NeuFlex may potentially facilitate flexion of the metacarpophalangeal (MP) joint, whereas the Swanson may promote a more extended position of the joint.     

Effect of FGF-2 and melatonin on implant bone healing: a histomorphometric study

Melatonin influences the release of growth hormone and cortisol in humans, and it was recently reported that it promoted bone formation. On the other hand, fibroblast growth factor-2 (FGF-2) was reported to facilitate the proliferation of osteoblasts. In the present study, we examined the effect of recombinant human FGF-2 and melatonin on the promotion of osteogenesis around titanium implants. Twenty-four 10-week-old female rats of the Wistar strain received titanium implants in both tibiae. In the experimental groups, 100 mg/kg body weight of melatonin was administered by intraperitoneal injection for 4 weeks after implantation and 10 microg of FGF-2 was locally injected around the implant sites 5 days after implantation. The control groups were administered saline only. In the control group, few newly formed bone could be seen around the implants. It was observed to be in direct contact with the implant surface, but otherwise unmineralized connective tissue was occasionally interposed. In the experimental group, newly formed bone was observed around the titanium implant. In addition, in contrast to the control group, abundant bone trabeculae were seen in the medullary canal region. Bone trabeculae were directly connected to existing cortical bone. These results strongly suggested that melatonin and FGF-2 have the potential to promote osseointegration.     

3D-printed surface promoting osteogenic differentiation and angiogenetic factor expression of BMSCs on Ti6Al4V implants and early osseointegration in vivo

Three-dimensional-printed (3D-P) titanium implants display many advantages, such as design flexibility, higher efficiency, the capability to easily construct complex or customized structures, etc., and is believed to potentially replace traditional implants. However, the biological performance of the 3D-P titanium surface has not been investigated systematically. Herein, we analyzed the surface characteristics of 3D-P Ti6Al4V implants and evaluated the biological responses of bone marrow derived mesenchymal stromal cells (BMSCs) to the 3D-P surface in vitro. Moreover, after implantation into the rat femoral condyle for 3 and 6 weeks, the osseointegration performance was evaluated. The results showed the 3D-P Ti6Al4V implant presented distinct fluctuant macroscale rough surface and relatively better hydrophilicity which enhanced the adhesion, proliferation, osteogenic differentiation and angiogenetic factor expression of BMSCs. Moreover, the in vivo osseointegration performance was also better than that of the control group at the early stage. The present study suggested the 3D-P titanium alloy is a promising candidate to be used as implant material.     

Applying a calcium phosphate layer on PEO/PBT copolymers affects bone formation in vivo

Recently a copolymer (Polyactive^R) has been introduced that combines elastomeric and bone-bonding properties. Since calcification of the copolymer is a prerequisite for bone bonding. Polyactive was precalcified in vitro in order to increase the bone-bonding rate. Precalcification was performed by subsequent incubation in Ca and P solutions and resulted in formation of a hydroxyapatite layer on the surface of the implant. Within one week after implantation this layer had disappeared from the surface and a new calcification zone was formed under the surface of the copolymer. Longer implantation periods showed that in precalcified implants bone was apposited along the walls of the pores, while in control implants new bone was first formed in the centre of the pores. Consequently, the percentage of bone contact was increased in precalcified implants, however, the amount of bone ingrowth was equal in both control and precalcified implants. Transmission electron microscopy showed the presence of an electron-dense layer at the bone implant interface, which was indicative for bone-bonding. It is concluded from these experiments that precalcification of PEO/PBT copolymers affected the direction of bone apposition and increased the bone-bonding rate.     

Flexible Micropillar Electrode Arrays for In Vivo Neural Activity Recordings

Flexible electronics that can form tight interfaces with neural tissues hold great promise for improving the diagnosis and treatment of neurological disorders and advancing brain/machine interfaces. Here, the facile fabrication of a novel flexible micropillar electrode array (µPEA) is described based on a biotemplate method. The flexible and compliant µPEA can readily integrate with the soft surface of a rat cerebral cortex. Moreover, the recording sites of the µPEA consist of protruding micropillars with nanoscale surface roughness that ensure tight interfacing and efficient electrical coupling with the nervous system. As a result, the flexible µPEA allows for in vivo multichannel recordings of epileptiform activity with a high signal‐to‐noise ratio of 252 ± 35. The ease of preparation, high flexibility, and biocompatibility make the µPEA an attractive tool for in vivo spatiotemporal mapping of neural activity.     

In vivo osseointegration of dental implants with an antimicrobial peptide coating

This study aimed to evaluate the in vivo osseointegration of implants with hydrophobic antimicrobial GL13K-peptide coating in rabbit femoral condyles by micro-CT and histological analysis. Six male Japanese Rabbits (4 months old and weighing 2.5?kg each) were included in this study. Twelve implants (3.75?mm wide, 7?mm long) were randomly distributed in two groups, with six implants in the experimental group coated with GL13K peptide and six implants in the control group without surface coating. Each implant in the test and the control group was randomly implanted in the left or right side of femoral condyles. On one side randomly-selected of the femur, each rabbit received a drill that was left without implant as control for the natural healing of bone. After 3?weeks of healing radiographic evaluation of the implant sites was taken. After 6?weeks of healing, rabbits were sacrificed for evaluation of the short-term osseointegration of the dental implants using digital radiography, micro-CT and histology analysis. To perform evaluation of osseointegration, implant location and group was double blinded for surgeon and histology/radiology researcher. Two rabbits died of wound infection in sites with non-coated implants 2?weeks after surgery. Thus, at least four rabbits per group survived after 6?weeks of healing. The wounds healed without suppuration and inflammation. No implant was loose after 6?weeks of healing. Radiography observations showed good osseointegration after 3 and 6?weeks postoperatively, which proved that the tissues followed a natural healing process. Micro-CT reconstruction and analysis showed that there was no statistically significant difference (P?>?0.05) in volume of bone around the implant between implants coated with GL13K peptide and implants without coating. Histomorphometric analysis also showed that the mineralized bone area was no statistically different (P?>?0.05) between implants coated with GL13K peptide and implants without coating. This study demonstrates that titanium dental implants with an antimicrobial GL13K coating enables in vivo implant osseointegration at similar bone growth rates than gold-standard non-coated dental implants up to 6?weeks of implantation in rabbit femurs.