Bioactive Implants Research Articles

Glass Bone Implants: The Effect of Surface Topology on Attachment and Proliferation of Osteoblast Cells on 45S Bioactive Glass

AbstractBioglass 45S is a promising bone implant material with superior biocompatibility. Past research showed that adhesion of bone cells to titanium is strongly affected by its surface architecture. However, little is known about the role of surface topology of glass on its use as an implant. Thus, we systematically investigated the effect of surface roughness (Ra ∼ 0.01 – 1.2 μm) on cell adhesion and proliferation on 45S Bioglass in vitro. MG63 osteosarcoma and MC3T3 osteoblast precursor cells were seeded on the glass samples, and incubated for up to 6 days. The attachment, morphology and proliferation of cells were investigated using fluorescence microscopy. Our results show that cell attachment (as indicated by cell spreading and number of focal adhesion sites), and proliferation rate decrease with increasing roughness of bioactive glass surface. These findings provide important insight for improving surface characteristics of bioactive glass bone implants.

The Kinetics of Ampicillin Release from Hydroxyapatite for Bones Regeneration

Semisynthetic beta-lactam antibiotics are among the most used pharmaceuticals. Their use in veterinary and human medicine is in continuous expansion. There is a growing need for developing bioactive implants. Advantages of implantable drug delivery tools can include high release efficiency, precise dose control, low toxicity, and allow to overcome disadvantages connected with conventional methods. In this respect, hydroxyapatite (HA) is an elective material. It enables to produce architectures similar to those of real bones. Here we studied a kinetic model to describe ampicillin release from HA. In the course of adsorption experiment, ampicillin was dissolved, maintained at and shaken at 60 strokes/minute. Samples were withdrawn periodically for analysis and then returned to the mixture. Adsorbed amounts were measured by the difference of the concentration of the antibiotics before and after adsorption using UV adsorption at 225 nm. The aim of this work was to evaluate its application as ampicillin delivery carrier.

Micro/nanostructural porous surface on titanium and bioactivity

Porous surfaces can improve both early fixation and long-term stabilization of implants by contrast with smooth surfaces. In this study, a microporous surface on titanium was prepared by acid etching and the size of micropores ranged from 1 to 60 microm. The micro/nanostructural porous layer on this microporous surface was obtained by acid etching and anodization. In this micro/nanostructural porous layer, the diameter of nanotubes was about 100 nm. After heat treatment at 450 degrees C for 6 h, the oxides on micro/nanostructural surface transformed into anatase crystals and the grain size of anatase was about 20 nm. The bioactivity of samples was investigated respectively in simulated body fluid and a bovine serum albumin (BSA) solution. The information of specimen surfaces was detected using scanning electron microscope, X-ray diffractometer, and attenuated total reflection Fourier transform infrared spectroscope. The results showed that the sample with micro/nanostructural porous surface and anatase had excellent bioactivity under nonpretreatment. It had more hydroxyapatite (HA) formation and faster BSA adsorption than other samples under the same conditions. Besides, the HA coating on the micro/nanostructure surface had larger range thickness, no microcrack, and no separated interface from substrate. Therefore, this micro/nanostructural porous surface may be an ideal modification layer for preparing bioactive implants.

Concept of a Bioactive Implant with Functional Gradient Structure

A material able to be used as bone implant for specific applications was developed. The proposed solution establishes that all implant surfaces should be bioactive since porous surfaces in contact with bone are extremely necessary for bone adhesion. The bioactive material composite with high mechanical strength designed with a PMMA functional structure gradient produced in this work has a dense core enveloped by a porous bioactive surface. Pore sizes and shapes as well their interconnectivity was analyzed by SEM tests; the cytotoxicity was investigated in vitro using Vero cell and bone conductivity and biocompatibility was investigated in vivo in rabbits. The implant porous bioactive part analyzed in vitro showed no toxicity and tests in vivo showed a remarkable biocompatibility and bone cell growth. Some samples with hydroxyapatite (HAp) were analyzed by EDX and SEM tests, the results showed a fair hydroxyapatite distribution in the implant pore surfaces as much as a part which was retained inside the PMMA inner porous. The average scaffold pore sizes obtained was around 250.0µm and the diameter shrinkage of 4.0% was observed in all samples. This study demonstrated that the functional gradient structure composite studied can be a good candidate for cranial bone implants due to its good bone conductivity and biocompatibility.

Mechanical Properties of Anti-Infectious, Bio-Active and Wear Resistant Ceramic Implant Surface Coatings

Implant failure due to aseptic loosening is a major complication in total hip arthroplasty. Different implant coatings aim to reduce the risk of implant loosening by anti-infectious, bio-active or wear resistant approaches. The mechanical properties, especially bonding strength and wear resistance, of a Cu-TiO2, CaP and TiN coating were investigated in this study. A scratch test and a standard adhesive test were used to determine the bonding strength of the coatings. To analyse the wear resistance a modified special testing machine was used to evaluate wear with PU-foam and PMMA as counterparts. The investigations showed that all coatings have greater bonding strengths than the minimum required 22 N/mm2 for medical implant coatings. Significant differences in total wear were determined during the wear tests. With the exception of the CaP no removal of the coatings was detected.

Clinical Use of Bioactive Glasses for Maxillo-Facial Repair

Autogenous bone grafts are considered to be the gold standard in maxillo-facial surgery. However, drawbacks of donor site morbidity and unpredictable rates of resorbtion often limit their use. In vivo tests have shown that 45S5 bioactive glass particles placed in critical size bone defects lead to regeneration of new bone that has the structural characteristics and architecture of mature trabecular bone. In vitro tests using primary osteoblast cultures have shown that the bioactive glass particles release ionic dissolution products that provide genetic stimuli that control osteoblast cell cycles and lead to rapid growth of mineralized bone nodules. These in vitro and in vivo results led to approval of use of bioactive glass particles and monolithic bioactive glass implants for use in maxillo-facial reconstructions after removal of bone cysts and trauma, as described by several case histories.

Physicochemical Characterization of Bioactive Polyacrylic Acid Organogels as Potential Antimicrobial Implants for the Buccal Cavity

This study describes the formulation and physicochemical characterization of poly(acrylic acid) (PAA) organogels, designed as bioactive implants for improved treatment of infectious diseases of the oral cavity. Organogels were formulated containing a range of concentrations of PAA (3-10% w/w) and metronidazole (2 or 5% w/w, representing a model antimicrobial agent) in different nonaqueous solvents, namely, glycerol (Gly), polyethylene glycol (PEG 400), or propylene glycol (PG). Characterization of the organogels was performed using flow rheometry, compressional analysis, oscillatory rheometry, in vitro mucoadhesion, moisture uptake, and drug release, methods that provide information pertaining to the nonclinical and clinical use of these systems. Increasing the concentration of PAA significantly increased the consistency, compressibility, storage modulus, loss modulus, dynamic viscosity, mucoadhesion, and the rate of drug release. These observations may be accredited to enhanced molecular polymer entanglement. In addition, the choice of solvent directly affected the physicochemical parameters of the organogels, with noticeable differences observed between the three solvents examined. These differences were accredited to the nature of the interaction of PAA with each solvent and, importantly, the density of the resultant physical cross-links. Good correlation was observed between the viscoelastic properties and drug release, with the exception of glycerol-based formulations containing 5 and 10% w/w PAA. This disparity was due to excessive swelling during the dissolution analysis. Ideally, formulations should exhibit controlled drug release, high viscoelasticity, and mucoadhesion, but should flow under minimal stresses. Based on these criteria, PEG 400-based organogels composed of 5% or 10% w/w PAA exhibited suitable physicochemical properties and are suggested to be a potentially interesting strategy for use as bioactive implants designed for use in the oral cavity.

Covalent functionalization of NiTi surfaces with bioactive peptide amphiphile nanofibers

Surface modification enables the creation of bioactive implants using traditional material substrates without altering the mechanical properties of the bulk material. For applications such as bone plates and stents, it is desirable to modify the surface of metal alloy substrates to facilitate cellular attachment, proliferation, and possibly differentiation. In this work we present a general strategy for altering the surface chemistry of nickel–titanium (NiTi) shape memory alloy in order to covalently attach self-assembled peptide amphiphile (PA) nanofibers with bioactive functions. Bioactivity in the systems studied here includes biological adhesion and proliferation of osteoblast and endothelial cell types. The optimized surface treatment creates a uniform TiO 2 layer with low levels of Ni on the NiTi surface, which is subsequently covered with an aminopropylsilane coating using a novel, lower temperature vapor deposition method. This method produces an aminated surface suitable for covalent attachment of PA molecules containing terminal carboxylic acid groups. The functionalized NiTi surfaces have been characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and atomic force microscopy (AFM). These techniques offer evidence that the treated metal surfaces consist primarily of TiO 2 with very little Ni, and also confirm the presence of the aminopropylsilane overlayer. Self-assembled PA nanofibers presenting the biological peptide adhesion sequence Arg-Gly-Asp-Ser are capable of covalently anchoring to the treated substrate, as demonstrated by spectrofluorimetry and AFM techniques. Cell culture and scanning electron microscopy (SEM) demonstrate cellular adhesion, spreading, and proliferation on these functionalized metal surfaces. Furthermore, these experiments demonstrate that covalent attachment is crucial for creating robust PA nanofiber coatings, leading to confluent cell monolayers.

Fabrication of porous bioactive structures using the selective laser sintering technique

Hydroxyapatite, a ceramic with which natural bone inherently bonds, has been incorporated into a polymer matrix to enhance the bioactivity of implant materials. In order to manufacture custom-made bioactive implants rapidly, selective laser sintering has been investigated to fabricate hydroxyapatite and polyamide composites and their properties investigated. One objective of this research was to identify the maximum hydroxyapatite content that could be incorporated into the matrix, which was sintered at various parameters. The study focused on investigating the control of porosity and pore size of the matrix by manipulating the selective laser sintering parameters of the laser power and laser scan speed. The interception method was used to analyse the internal porous morphology of the matrices which were cross-sectioned through the vertical plane. Most notably, all structures built demonstrated interconnection and penetration throughout the matrix. Liquid displacement was also used to analyse the porosity of the matrices. The laser power showed a negative relationship between porosity and variation in parameter values until a critical power value was reached. However, the same relationship for laser scan speed matrices was inconsistent. The effects of the laser power and laser scanning speed on the features of porous structures that could influence cell spreading, proliferation, and bone regeneration are presented.

Formation of nano hydroxyapatite – a straightforward way to bioactivate bone implant surfaces

Abstract Bioactivity has been a field of biomaterials research for more than 25 years. However, clinical application of bioactive implants is progressing rather slowly and is still limited to a few types of bone implants. The increased understanding of the molecular mechanisms underlying bioactivity has opened up new attractive opportunities to render conventional implant materials such as metals, ceramics and even polymers bioactive. In particular, biomimetic nano hydroxyapatite coatings and in-situ mineralising surfaces induced by incorporation of mineralisation seeds are applicable to a wide variety of implant types and materials. They have the potential to set new standards for the improved performance of orthopaedic implants whilst complying with the economic constraints on healthcare.

Literature Reviews

Literature Reviews

Novel Micro-CT Based 3-Dimentional Structural Analyses of Porous Biomaterials

A porous structure comprises pores and pore throats with a complex three-dimensional network structure, and many investigators have described the relationship between average pore size and the amount of bone ingrowth. However, the influence of network structure or pore throats for tissue ingrowth has rarely been discussed. Bioactive porous titanium implants with 48% porosity were analyzed using specific algorithms for three-dimensional analysis of interconnectivity based on a micro focus X-ray computed tomography system. In vivo histological analysis was performed using the very same implants implanted into the femoral condyles of male rabbits for 6 weeks. This matching study revealed that more poorly differentiated pores tended to have narrow pore throats, especially in their shorter routes to the outside. Data obtained suggest that this sort of novel analysis is useful for evaluating bone and tissue ingrowth into porous biomaterials.

Metallographic Characterization of Some New Bioactive Implant Titanium Alloys

Extended abstract of a paper presented at Microscopy and Microanalysis 2006 in Chicago, Illinois, USA, July 30 – August 3, 2006

Oxidized, bioactive implants are rapidly and strongly integrated in bone. Part 1 – experimental implants

The study presented was designed to investigate the speed and the strength of osseointegration of oxidized implants at early healing times in comparison which machined, turned implants. Screw-shaped titanium implants were prepared and divided into two groups: magnesium ion incorporated, oxidized implants (Mg implants, n=10) and machined, turned implants (controls, n=10). Mg implants were prepared using micro-arc oxidation methods. Surface oxide properties of implants such as surface chemistry, oxide thickness, morphology/pore characteristics, crystal structures and roughness were characterized with various surface analytic techniques. Implants were inserted into the tibiae of ten New Zealand white rabbits. After a follow-up period of 3 and 6 weeks, removal torque (RTQ), osseointegration speed (DeltaRTQ/Deltahealing time) and integration strength of implants were measured. Bonding failure analysis of the bone-to-implant interface was performed. The speed the and strength of osseointegration of Mg implants were significantly more rapid and stronger than for turned implants at follow-up periods of 3 and 6 weeks. Bonding failure for Mg implants dominantly occurred within the bone tissue, whereas bonding failure for turned implants mainly occurred at the interface between implant and bone. Oxidized, bioactive implants are rapidly and strongly integrated in bone. The present results indicate that the rapid and strong integration of oxidized, bioactive Mg implants to bone may encompass immediate/early loading of clinical implants.

Effects of material morphology and processing conditions on the characteristics of hydroxyapatite and high-density polyethylene biocomposites by selective laser sintering

Hydroxyapatite (HA), a ceramic to which bone inherently bonds, incorporated into a polymer matrix enhances the bioactivity of implants. In order to rapid-manufacture bioactive implants, selective laser sintering (SLS) has been used to fabricate HA and high-density polyethylene (HDPE) composite (HA-HDPE). The properties of SLS-fabricated specimens have been investigated. The main aspects to be considered in the SLS technology are the properties of the materials used in the process and processing parameters (PPs). HA-HDPE composite specimens have been fabricated using five different powders with variations in particle size (PS), PS distribution, and five different laser PPs. The sintering height, the width, and the shrinkage of the specimens were determined and the effects of the particles and PPs on the physical properties were investigated. The HA-HDPE specimens were found to be highly porous and the sintered density and porosity of the specimens were influenced by the PS and PPs. The interparticle connectivity and the pore size range of the specimens were found to be predominantly determined by the PS and to a lesser extent also influenced by the PPs. The strength of these specimens and the relationship with porosity are discussed.

Selective Laser Sintering of Hydroxyapatite Reinforced Polyethylene Composites for Bioactive Implants and Tissue Scaffold Development

Selective laser sintering (SLS) has been investigated for the production of bioactive implants and tissue scaffolds using composites of high-density polyethylene (HDPE) reinforced with hydroxyapatite (HA) with the aim of achieving the rapid manufacturing of customized implants. Single-layer and multilayer block specimens made of HA-HDPE composites with 30 and 40 vol % HA were sintered successfully using a CO2 laser sintering system. Laser power and scanning speed had a significant effect on the sintering behaviour. The degree of particle fusion and porosity were influenced by the laser processing parameters, hence control can be attained by varying these parameters. Moreover, the SLS processing allowed exposure of HA particles on the surface of the composites and thereby should provide bioactive products. Pores existed in the SLS-fabricated composite parts and at certain processing parameters a significant fraction of the pores were within the optimal sizes for tissue regeneration. The results indicate that the SLS technique has the potential not only to fabricate HA-HDPE composite products but also to produce appropriate features for their application as bioactive implants and tissue scaffolds.

Electrochemical Characterization of The Passive Films on The Bioactive Implant Titanium Alloys

not Available.

Collective Review: Bioactive Implants Coated with Poly(D,L-lactide) and Growth Factors IGF-I, TGF-β1, or BMP-2 for Stimulation of Fracture Healing

Demographic data reveal that due to the increasing aging of the population, complications with the musculoskeletal system will increase in the next years. One major problem in orthopedic and trauma surgery are the delayed healing or non-unions of long bone fractures. The exogenous application of growth factors can stimulate the bone healing to reduce these complications. Beside the choice of the optimal growth factor the application system is important. Therefore, we developed a new bioactive coating method for implants, which is based on a biodegradable poly(D,L-lactide) (coating thickness: 10 mum). This coating allows the incorporation of growth factors and the controlled release of these factors during the healing process without the need for further devices. The effect of different growth factors (IGF-I, TGF-beta1, and BMP-2) locally released from coated intramedullary implants on fracture healing was investigated with biomechanical and histological analysis in rats. All investigated growth factors stimulated the fracture healing as assessed with biomechanical tests and histological analysis. The local application of combined IGF-I and TGF-beta1 had the most stimulating effect on fracture healing, followed by the effect of BMP-2, IGF-I, and TGF-beta1 alone. Bioactive coating of biomechanical well-established implants can on the one hand stabilize the fracture and on the other hand stimulate healing processes to increase healing and to reduce the rate of complications.

The bone response of oxidized bioactive and non-bioactive titanium implants

A number of experimental and clinical data on so-called oxidized implants have reported promising outcomes. However, little is investigated on the role of the surface oxide properties and osseointegration mechanism of the oxidized implant. Sul [On the Bone Response to Oxidized Titanium Implants: The role of microporous structure and chemical composition of the surface oxide in enhanced osseointegration (thesis). Göteborg: Department of Biomaterials/Handicap Research, University of Göteborg, Sweden; 2002; Biomaterials 2003; 24: 3893–3907] recently proposed two action mechanisms of osseointegration of oxidized implants, i.e. mechanical interlocking through bone growth in pores/other surface irregularities (1) and biochemical bonding (2). The aim of the present study is two-fold: (i) investigating the role of the implant surface chemistry on bone responses; (ii) investigating the validity of the biochemical bonding theory of the oxidized, bioactive bone implants with specific implant surface chemistry. Two groups of oxidized implants were prepared using micro arc oxidation process and were then inserted in rabbit bone. One group consisted of magnesium ion incorporated implants (MgTiO implant), the other consisted of TiO 2 stoichiometry implants (TiO implant). Surface oxide properties of the implants were characterized with various surface analytic techniques. After 6 weeks of follow up, the mean peak values of removal torque of Mg implants dominated significantly over TiO implants ( p ⩽ 0.0001 ). Bonding failure generally occurred in the bone away from the bone to implant interface for the MgTiO implant and mainly occurred at the bone to implant interface for the TiO implant that consisted mainly of TiO 2 chemistry and significantly rougher surface as compared to the MgTiO implant. Between bone and the Mg- incorporated implant surface, ionic movements and ion concentrations gradient were detected. The current in vivo experimental data may provide positive evidence for the surface chemistry-mediated biochemical bonding theory of oxidized bioactive implants. However, the present study does not rule out potential synergy effects of the oxide thickness, micro-porous structure, crystal structure and surface roughness on improvements of bone responses to oxidized bioactive implants.

Bioactive NiTi Implants Used for Bone Repairing Applications

In this study, chemical methods were used to treat NiTi for the purpose of preparing bioactive NiTi implants. The surface of the bioactive NiTi alloy was investigated by XRD and ESEM. The biocompatibility and bioactivity of the bioactive NiTi samples were evaluated by in vivo implantation experiments. The results show that a Ca-P layer composed mainly of hydroxyapatite (HA) with a trace amount of other apatites and a Ca/P ratio of 1.59 covers the surface of the bioactive NiTi alloy. In vivo tests show that osteoblasts actively proliferated on the bioactive NiTi implants after 6 weeks implantation. A large amount of new bone directly in contact with the host bone was observed after 13 weeks implantation. These revealed the excellent biocompatibility and bioactivity of the prepared bioactive NiTi alloy.