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Purpose: Polymer-xerogel composite materials have been introduced to better optimize local anesthetics release kinetics for the pain management. In a previous study, it was shown that by adjusting various compositional and nano-structural properties of both inorganic xerogels and polymers, zero-order release kinetics over 7 days can be achieved in vitro. In this study, in vitro release properties are confirmed in vivo using a model that tests for actual functionality of the released local anesthetics., Methods: Composite materials made with tyrosine-polyethylene glycol(PEG)-derived poly(ether carbonate) copolymers and silica-based sol-gel (xerogel) were synthesized. The in vivo release from the composite controlled release materials was demonstrated by local anesthetics delivery in a rat incisional pain model., Results: The tactile allodynia resulting from incision was significantly attenuated in rats receiving drug-containing composites compared with the control and sham groups for the duration during which natural healing had not yet taken place. The concentration of drug (bupivacaine) in blood is dose dependent and maintained stable up to 120 h post-surgery, the longest time point measured., Conclusions: These in vivo studies show that polymer-xerogel composite materials with controlled release properties represent a promising class of controlled release materials for pain management.

Ideally, bioactive ceramics for use in alveolar ridge augmentation should possess the ability to activate bone formation and, thus, cause the differentiation of osteoprogenitor cells into osteoblasts at their surfaces. Therefore, in order to evaluate the osteogenic potential of novel bone substitute materials, it is important to examine their effect on osteoblastic differentiation. This study examines the effect of rapidly resorbable calcium-alkali-orthophosphates on osteoblastic phenotype expression and compares this behavior to that of beta-tricalcium phosphate (TCP) and bioactive glass 45S5. Test materials were three materials (denominated GB14, GB9, GB9/25) with a crystalline phase Ca(2)KNa(PO(4))(2) and with a small amorphous portion containing either magnesium potassium phosphate (GB14) or silica phosphate (GB9 and GB9/25, which also contains Ca(2)P(2)O(7)); and a material with a novel crystalline phase Ca(10)[K/Na](PO(4))(7) (material denominated 352i). SaOS-2 human bone cells were grown on the substrata for 3, 7, 14, and 21 days, counted, and probed for an array of osteogenic markers. GB9 had the greatest stimulatory effect on osteoblastic proliferation and differentiation, suggesting that this material possesses the highest potency to enhance osteogenesis. GB14 and 352i supported osteoblast differentiation to the same or a higher degree than TCP, whereas, similar to bioactive glass 45S5, GB9/25 displayed a greater stimulatory effect on osteoblastic phenotype expression, indicating that GB9/25 is also an excellent material for promoting osteogenesis., ((c) 2007 Wiley Periodicals, Inc.)

Bioactive glass is used as both a bone filler and as a coating on implants, and has been advocated as a potential osteogenic scaffold for tissue engineering. Rat-derived mesenchymal stem cells (MSCs) show elevated levels of alkaline phosphatase activity when grown on 45S5 bioactive glass as compared to standard tissue culture plastic. Similarly, exposure to the dissolution products of 45S5 elevates alkaline phosphatase activity and other osteogenic markers in these cells. We investigated whether human MSCs grown under the same laboratory conditions as rat MSCs would exhibit similar responses. In general, human MSCs produce markedly less alkaline phosphatase activity than rat MSCs, regardless of cell culture conditions, and do not respond to the growth factor BMP-2 in the same way as rat MSCs. In our experiments there was no difference in alkaline phosphatase activity between human MSCs grown on 45S5 bioactive glass or tissue culture plastic, in samples from five different orthopaedic patients, regardless of culture media composition. Neither was there any consistent effect of 45S5 dissolution products on human MSCs from three different donors. These results suggest that the positive effects of bioactive glass on bone growth in human patients are not mediated by accelerated differentiation of mesenchymal stem cells.

Materials in particulate form have been the subjects of intensive research in view of their use as drug delivery systems. While within this application there are still issues to be addressed, these systems are now being regarded as having a great potential for tissue engineering applications. Bone repair is a very demanding task, due to the specific characteristics of skeletal tissues, and the design of scaffolds for bone tissue engineering presents several difficulties. Materials in particulate form are now seen as a means of achieving higher control over parameters such as porosity, pore size, surface area and the mechanical properties of the scaffold. These materials also have the potential to incorporate biologically active molecules for release and to serve as carriers for cells. It is believed that the combination of these features would create a more efficient approach towards regeneration. This review focuses on the application of materials in particulate form for bone tissue engineering. A brief overview of bone biology and the healing process is also provided in order to place the application in its broader context. An original compilation of molecules with a documented role in bone tissue biology is listed, as they have the potential to be used in bone tissue engineering strategies. To sum up this review, examples of works addressing the above aspects are presented., (2007 John Wiley & Sons, Ltd)

There is a clear need for the development of microparticles that can be used simultaneously as carriers of stem/progenitor cells and as release systems for bioactive agents, such as growth factors or differentiation agents. In addition, when thinking on bone-tissue-engineering applications, it would be very useful if these microparticles are biodegradable and could be made to be bioactive. Microparticles with all those characteristics could be cultured together with adherent cells in appropriate bioreactors to form in vitro constructs that can then be used in tissue-engineering therapies. In this work, we have characterized the response of MC3T3-E1 pre-osteoblast cells to starch-based microparticles. We evaluated the adhesion, proliferation, expression of osteoblastic markers and mineralization of cells cultured at their surface. The results clearly show that MC3T3-E1 pre-osteoblast cells adhere to the surface of both polymeric and composite starch-based microparticles and express the typical osteoblastic marker genes. Furthermore, the cells were found to mineralize the extracellular matrix (ECM) during the culture period. The obtained results indicate that starch-based microparticles, known already to be biodegradable, bioactive and able to be used as carriers for controlled release applications, can simultaneously be used as carriers for cells. Consequently, they can be used as templates for forming hybrid constructs aiming to be applied in bone-tissue-engineering applications.

The ability of fibronectin (Fn) to mediate cell adhesion through binding to alpha(5)beta(1) integrins is dependent on the conditions of its adsorption to the surface. Using a model system of alkylsilane SAMs with different functional groups (X=OH, COOH, NH(2) and CH(3)) and an erythroleukemia cell line expressing a single integrin (alpha(5)beta(1)), the effect of surface properties on the cellular adhesion with adsorbed Fn layers was investigated. (125)I-labeled Fn, a modified biochemical cross-linking/extraction technique and a spinning disc apparatus were combined to quantify the Fn adsorption, integrin binding and adhesion strength, respectively. This methodology allows for a binding equilibrium analysis that more closely reflects cellular adhesion found in stable tissue constructs in vivo. Differences in detachment strength and integrin binding were explained in terms of changes in the adhesion constant (psi, related to affinity) and binding efficiency of the adsorbed Fn for the alpha(5)beta(1) integrins (CH(3) approximately NH(2)

Bioactive glass granules were implanted in the paraspinal muscle of rabbits to determine the pathway of the silicon released from bioactive glass in vivo. We traced and quantified the silicon released by obtaining 24-h urine and blood samples for up to 6 months after implantation. Furthermore, local muscle tissue as well as the following organs were resected for chemical and histopathological analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. The urinary silicon of the group with implanted granules was significantly higher than in the sham-operated, control group. The average excretion rate was 2.4 mg/day, and as such, 100% of the implanted silicon was excreted in 19 weeks. No elevated concentrations of silicon were found at the implant sites or in the other organs at sacrifice, that is, 24 weeks. The histological appearance of all organs was normal throughout. The concentrations of silicon measured in the urine were well below saturation and because no significant increase in silicon was found in any organ, including kidney, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine.

The contribution of non-specific interactions between cells and model functional surfaces was measured using a spinning disc apparatus. These model functional surfaces were created using self-assembled monolayers (SAM) of alkylsilanes terminated with epoxide, carboxyl (COOH), amine (NH(2)), and methyl (CH(3)) groups. These SAMs were characterized using ellipsometry, atomic force microscopy, contact angle goniometry, and X-ray photoelectron spectroscopy to confirm the presence of well-formed monolayers of expected physicochemical characteristics. All substrates also demonstrated excellent stability under prolonged exposure (up to 18 h) to aqueous conditions. The adhesion strength of K100 erythroleukemia cells to the functional substrates followed the trend: CH(3) < COOH approximately epoxide << NH(2). The NH(2) SAM surface exhibited nearly an order of magnitude greater adhesion strength than the other SAMs and this non-specific effect exceeded the adhesion measured when RGD tri-peptides were also immobilized on the surface. These findings illustrate the importance of substrate selection in quantitative studies of peptide-mediated cellular adhesion.

The aim of the development of composite materials is to combine the most desired properties of two or more materials. In this work, the biodegradable character, good controlled-release properties, and natural origin of starch-based biomaterials are combined with the bioactive and bone-bonding properties of bioactive glass (BG). Novel, bioactive composite starch-BG microparticles were synthesized starting from a blend of starch and polylactic acid (50%/50% wt) with BG 45S5 powder using a simple emulsion method. Morphological and chemical characterization showed that these particles exhibited a spherical morphology with sizes up to 350 microm and that BG 45S5 was incorporated successfully into the composite particles. Upon immersion in a solution simulating body fluids, for periods up to 3 weeks, their bioactive nature was confirmed, as a calcium-phosphate layer resembling biological apatite was formed onto their surface. The short-term cytotoxicity of these materials was also tested by placing 24-h leachables of the materials extracted in culture medium in contact with a fibroblastic cell line (L929) up to 72 h. At this time period, two biochemical tests--MTT and total protein quantification--were performed. The results showed that these materials are not cytotoxic. These results constitute the basis of future encapsulation studies using bone-acting therapeutic agents such as bone morphogenetic proteins or other bone-relevant factors. The particles developed here may be very useful for applications in which controlled release, degradability, and bone-bonding ability are the main requirements., (Copyright 2004 Wiley Periodicals, Inc.)

Cell adhesion to biomaterials is a prerequisite for tissue integration with the implant surface. Herein, we show that we can generate a model silica surface that contains a minimal-length arginine-glycine-aspartic acid (RGD) peptide that maintains its biological activity. In the first part of this study, attachment of MC3T3-E1 osteoblast-like cells was investigated on silicon oxide, amine terminated substrates [i.e., 3-aminopropyl triethoxysilane (APTS)], grafted RGD, and physisorbed RGD control. The APTS layer exhibited nanoscale roughness and presented amine functional groups for grafting a minimal RGD tripeptide devoid of any flanking groups or spacers. Contact angle measurements indicated that the hydrophobicity of the APTS surface was significantly lower than that of the surface with grafted RGD (RGD-APTS). Atomic force microscopy showed that surfaces covered with RGD-APTS were smoother (Ra = 0.71 nm) than those covered with APTS alone (Ra = 1.59 nm). Focusing mainly on cell morphology, experiments showed that the RGD-APTS hybrid provided an optimum surface for cell adhesion, spreading, and cytoskeletal organization. Discrete focal adhesion plaques were also observed consistent with successful cell signaling events. In a second set of experiments, smooth, monolayers of APTS (Ra = 0.1 nm) were used to prepare arginine-glycine-aspartic acid-serine (RGDS)-APTS and arginine-glycine-glutamic acid-serine (RGES)-APTS (control) substrates. Focusing mainly on cell function, integrin and gene expression were all enhanced for rate osteosarcoma cells on surfaces containing grafted RGDS. Both sets of studies demonstrated that grafted molecules of RGD(S) enhance both osteoblast-like cell adhesion and function., (Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 615-627, 2004)

Composite microspheres with two different fillers were developed using a solid-in-oil-in-water (s/o/w) emulsion solvent removal method. Two types of bioactive ceramic powders, specifically calcium hydroxyapatite (HA) and modified bioactive glass (MBG), were incorporated into degradable poly(lactic acid) (PLA) polymer matrix to form composite microspheres. For each filler material, microspheres with three different weight ratios of filler material to polymer, namely, 1: 1, 1: 3, and 1: 9, were synthesized. In vitro immersion using simulated physiological fluid (SPF) was employed to evaluate the surface reactivity of the microspheres. SEM analysis revealed that after a 14-day immersion the surface of the microspheres containing 50% MBG was fully transformed into a bone-like apatite. In contrast, a limited number of mineral nodules were present on the surface of microspheres containing HA. The solution chemical analyses performed to determine changes of Ca, P, and Si concentrations as a function of the immersion time showed that the ion concentration profiles were similar for all microspheres, except the [Si] profile. A higher Si concentration was detected in the SPF immersed with MBG-containing microspheres. These data show that the MBG filler significantly enhances the surface reactivity of the composite microspheres. This observation enables us to conclude that the composite MBG-containing microspheres are the preferable microspheres for three-dimensional bone tissue engineering.

Revision cases of total hip implants are complicated by the significant amount of bone loss. New materials and/or approaches are needed to provide stability to the site, stimulate bone formation, and ultimately lead to fully functional bone tissue. Porous bioactive glasses (prepared from 45S5 granules, 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5) have been developed as scaffolds for bone tissue engineering and have been studied in vitro. In this study, we investigated the incorporation of tissue-engineered constructs utilizing these scaffolds in large, cortical bone defects in the rat simulating revision conditions. With implantation times of 2, 4, and 12 weeks the results were compared to those using the bioactive ceramic scaffold alone. Two tissue-engineered constructs were studied: osteoprogenitor cells that were either seeded onto the scaffold prior to implantation ("primary") or those that were culture expanded to form bonelike tissue on the scaffold prior to implantation ("hybrid"). Defects treated with the hybrid had the greatest amount of bone in the available pore space of the defect over all other groups at 2 weeks (p < 0.05). For both the primary and hybrid groups, woven and lamellar bone was present along the interface of the scaffold and the host cortex and within the porous space of the scaffold at 2 weeks. By 4 weeks, very uniform, lamellar bone was present throughout the scaffold for both tissue-engineered groups. The amount of bone significantly increased over time for all groups while the bioactive ceramic gradually resorbed by 40% at 12 weeks (p < 0.05). Structural properties of the treated long bones improved over time. Long bones treated with the hybrid had an early return in torsional stiffness by 2 weeks. Both tissue-engineered constructs achieved normal torsional strength and stiffness by 4 weeks as compared to the scaffold alone, which achieved this by 12 weeks. Porous, surface modified bioactive ceramic is a promising scaffold material for tissue-engineered bone repair., (Copyright 2002 Wiley Periodicals, Inc.)

Room temperature-processed silica-based sol-gel, termed silica xerogel, is a novel type of controlled release material. As shown previously, these materials are porous, degradable and can release biologically functional molecules in a controlled manner. It was also demonstrated that these materials are biocompatible in vivo. Herein we report on the ability of silica-based xerogels to form a bioactive, apatite-like (AP) surface and the effect of AP surface on the xerogel stability in vitro. Formation of a crystalline, carbonated AP (c-AP) was found on all silica xerogels studied, with or without Ca- and P-oxides. Calcium and phosphate (Ca-P) free xerogels showed long times to Ca-P precipitation and to formation of a detectable AP-layer (up to 2 weeks). In contrast, the times to precipitation were reduced by 2-3 orders of magnitude, and the c-AP layer was formed within 24 h on all Ca-P containing xerogels. Mechanisms of the c-AP formation on these xerogels were similar to those typical for Ca-P based ceramics: dissolution of calcium and phosphate ions, solution oversaturation with respect to AP and subsequent precipitation of bone-like minerals. The presence of the c-AP surface film produced a remarkable surface stabilizing effect: the rates and the amounts of Si release were significantly reduced in comparison to those for xerogels without the film. This evidence of in vitro bioactivity and controlled degradation, combined with previous in vitro and in vivo reports, suggests that silica xerogel is a promising controlled release material.

Bioactive glass granules were implanted in the tibiae of rabbits in order to determine the pathway of the silicon released from bioactive glass in vivo. We traced and quantified the silicon released by obtaining 24-h urine samples and blood samples for up to 7 months after implantation. Bone tissue as well as the following organs were resected for chemical and histopathological analyses: kidney, liver, lung, lymph nodes, and spleen. The urinary silicon of the implanted group was significantly higher than in the control group. From the data, the calculated average excretion rate was approximately 1.8 mg/day, and as such, the amount of implanted silicon was excreted within statistical bounds in 24 weeks. At this point, only elevated concentrations of silicon were found at the implant site and not in the other organs. The concentrations of silicon measured in the urine were well below saturation. Since no significant increase in silicon was found in any of the organs including the kidney, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine.

The objective of this study was to determine the effect of porous bioactive glass (45S5) substrate characteristics on the expression and maintenance of the osteoblastic phenotype. We cultured ROS 17/2. 8 cells on substrates with different pore size and porosity for periods up to 14 days and analyzed the characteristics of the cells and extracellular matrix. Results of the study show that the glass substrates supported the proliferation and growth of osteoblast-like cells. Although the morphologies of the cells differed on the various substrates, their shape and the extent of membrane ruffling suggested that they maintained high levels of metabolic activity. Cells on all substrates expressed high levels of alkaline phosphatase activity and produced extracellular matrices that mineralized to form nonstoichiometric, carbonated, calcium-deficient apatites. An important finding was that at a given porosity of 44%, the pore size neither directed nor modulated the in vitro expression of the osteoblastic phenotype. In contrast, porosity did affect cellular function. We noted that at an average pore size of 92 microm, as the porosity increased from 35 to 59%, osteoblast activity was reduced. As designed in this experiment, an increase in the porosity led to a corresponding increase in total surface area of the specimens. With increasing porosity and surface area, glass reactions in the media may persist for longer durations at higher intensities, thereby affecting local media composition. As such, we suggest that extensive conditioning treatments before cell seeding can reduce this effect. Our results also revealed that the expression of the osteoblastic phenotype is enhanced by the ongoing glass dissolution. The reaction pathway at the origin of this effect still needs to be elucidated. Taken together, the findings support the overall hypothesis that in vitro cell activity can be controlled by a careful selection of substrate properties., (Copyright 2000 John Wiley & Sons, Inc.)

Upon implantation, bioactive glass undergoes a series of reactions that leads to the formation of a calcium phosphate-rich layer. Most in vitro studies of the changes that occur on the surface of bioactive glass have employed the use of buffer solutions with compositions reflecting the ionic composition of interstitial fluid. Although these studies have documented the physical and chemical changes associated with bioactive glass immersed in aqueous media, they do not reveal the effect of serum proteins and cells that are present at the implantation site. In the present study, we document, using atomic force microscopy (AFM) and Rutherford backscattering spectrometry (RBS), significant differences in the reaction layer composition, thickness, morphology, and kinetics of formation arising from the presence of serum proteins. The data reveal that the uniform and rapid adsorption of serum proteins on the surface may serve to protect the surface from further direct interaction with the aqueous media, slowing down the transformation reactions. This finding is in agreement with previous studies that have shown that the presence of serum proteins significantly delays the formation of hydroxyapatite at the surface of bioactive glass. These data also support the hypothesis that initial reaction layers in vivo interact with cells in order to produce the tissue-bioactive glass interface typically observed on ex vivo specimens., (Copyright 2000 John Wiley & Sons, Inc.)

Novel bioactive, degradable polymer/glass/ceramic composite microspheres were developed using a solid-in-oil-in-water (s/o/w) emulsion solvent removal method. Modified bioactive glass (MBG) powders were encapsulated into the polylactic acid (PLA) matrix. Scanning electron microscopy and energy-dispersive X-ray analyses revealed that the MBG powders were mostly embedded in the polymer matrix, and submicron-size pores were present at the surface. Immersion in simulated physiological fluid (SPF) was used to evaluate the surface reactivity of the microspheres. The polymeric surface was fully transformed into carbonated calcium hydroxyapatite (c-HA) after 3 weeks of immersion. In contrast, PLA microspheres showed no evidence of any calcium phosphate deposition. Ion concentration analyses revealed a decrease in Ca and P concentrations and an increase in Si concentration in the SPF immersed with composite microspheres during the 3-week period. The Ca and P uptake rates decreased after 2 days of incubation. This coincided with the decrease of the Si release rate. These data lend support to the suggestion that the Si released from the MBG powders present in the polymer matrix is involved in the formation of the Ca-P layer. Our results support the concept that these new bioactive, degradable composite microspheres may serve as microcarriers for synthesis of bone and other tissues in vitro and in vivo., (Copyright 2000 John Wiley & Sons, Inc.)

The objective of the study was to investigate the capability of bioactive glass 45S5 to serve as a substrate for nucleus pulposus cells in vitro. Nucleus pulposus cells were isolated from adult rabbit discs and seeded onto bioactive glass. At selected time intervals, the cells and glass were evaluated. We found that the cells rapidly attached to the substrate, colonizing it within 12 h. By 21 days, they had formed a lawn of cells over the glass substrate. DNA measurements showed a progressive increase in cell number with time. The phenotype was maintained; the cells expressed aggrecan, and collagen type II and I, but were negative for collagen type X. CD44, a cell-surface glycoprotein that binds hyaluronate, was also expressed by these cells. Electron dispersive X-ray analysis and Fourier transform infrared spectroscopy revealed calcium phosphate-rich layer formation on the substrate surface. The results of this study suggest that nucleus pulposus cell proliferation may be an anchorage dependent event, and that the cells use the calcium phosphate-rich layer to facilitate cell adhesion, and subsequent proliferation. These findings point to the importance of the conditioned bioactive glass as a substrate for nucleus pulposus cells.

45S5 bioactive glass (BG) is a bioactive material known to bond to bone in vivo through a surface calcium phosphate (Ca-P) layer. The goal of this study was to address the importance of BG surface charge in the bioactive response by examining the relationship between charge variations and the formation of the surface Ca-P layer. The zeta potential of BG in an electrolyte solution (TE) was measured by particle electrophoresis, and the formation of a Ca-P layer was characterized using SEM, EDXA, and FTIR. Si, Ca, and P solution concentrations also were determined. The initial BG surface was negatively charged, and two sign reversals were detected during 3 days of immersion. The first, from negative to positive after 1 day, is attributed to the adsorption of cations at the BG surface, and the second reversal was due to the precipitation of phosphate ions from solution. A strong correlation was found between the formation of a Ca-P layer and BG surface zeta potential variations. The dynamic shift in zeta potential from an initially negative surface to a positively charged surface directly corresponded with the formation of an amorphous Ca-P layer. In addition, when the glass surface matured into a crystalline Ca-P layer, it was associated with a reversal from a positive to a negative surface. Future work will focus on the effects of protein adsorption on BG surface charge and Ca-P layer formation kinetics as well as on cellular response to a changing BG surface., (Copyright 2000 John Wiley & Sons, Inc.)

Previous studies have shown that neonatal rat calvaria osteoblasts elaborate substantial amounts of extracellular material with bone-like characteristics when cultured on porous bioactive glass substrates in vitro. However, the osteoblastic response to this material has not been fully characterized. The objective of this study was to characterize osteoblast response to porous bioactive glass substrates following the expression of the classical markers for osteoblast differentiation. In this study we synthesized porous bioactive glass substrates, seeded them with osteoblast-like cells (ROS 17/2.8) and followed the temporal expression of alkaline phosphatase (AP) activity, as well as the expression of mRNA for collagen type I (Coll-1), osteonectin (OSN), osteopontin (OPN), osteocalcin (OCN), and bone sialoprotein (BSP). The data confirm that porous bioactive glass substrates are capable of supporting the in vitro growth and maturation of osteoblast-like cells. At a porosity of 42% and an average pore size of 80 microm, the substrates promote the expression and maintenance of the osteoblastic phenotype. The results additionally suggest that there is both a solution-mediated and a surface-controlled effect on cell activity.

Bioactive glass (BG) granules of narrow size are excavated when implanted in mandibular bone of beagles. Bone tissue forms within these internally hollowed particles without a connection to the bone at the margins of the defect. In this study the internal excavation of BG granules was simulated by in vitro immersion experiments. Postimmersion solutions were analyzed for changes in Si, Ca, and P concentrations. Using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and Fourier Transform Infrared (FTIR) spectroscopy, granules were analyzed for compositional, morphologic, and structural changes resulting from immersion. Only when the solution was continuously replenished and only if this solution was composed of electrolyte- and protein-containing serum was excavation achieved. Without solution replenishment, that is, under so-called integral immersion conditions, the solution quickly became saturated in silicon, and the silicon no longer dissolved. When the glass was immersed in a solution with serum, a porous surface structure with fine precipitates was formed, in contrast to a dense surface reaction layer with closely packed globular precipitates that was formed in a solution without serum. The combined effect of continuous solution replenishment and the use of a solution containing serum proteins led to the formation of a surface reaction layer that did not impede continued corrosion. As such, all Si was released, and eventually a hollow Ca-P shell was formed. Thus this study supports the hypothesis that there is a physico-chemical mechanism of Si transport through the Ca-P-rich layer followed by Si dissolution. This mechanism may be operative in vivo and thereby may contribute to the observed in vivo excavation., (Copyright 2000 John Wiley & Sons, Inc.)

Surface reactivity is one of the common characteristics of bone bioactive ceramics. It contributes to their bone bonding ability and their enhancing effect on bone tissue formation. During implantation, reactions occur at the material-tissue interface that lead to time-dependent changes in the surface characteristics of the implant material and the tissues at the interface. This review describes some of the current concepts regarding the surface reactivity of bone bioactive materials and its effect on attachment, proliferation, differentiation and mineralization of bone cells.

Novel bioactive ceramic hollow microspheres with an apparent density in the range 0.8-1.0 g cm(-3) have been developed as microcarriers for 3-D bone tissue formation in rotating-wall vessels (RWV). Hollow ceramic microspheres with a composition of 58-72% SiO2, 28-42% Al2O3 (wt%) and an apparent density 0.8-1.0 g cm(-3) were pretreated in 1.0 N NaOH for 2 h before being coated with synthesized calcium hydroxyapatite (HA) particulate sol. The HA-coated hollow microspheres were sintered for 1 h at 600, 800 and 1000 degrees C. SEM analysis revealed that the grain size and pore size of the calcium phosphate coating increased with the sintering temperature. FTIR analysis showed that crystalline calcium hydroxyapatite was present in the coatings sintered at 600 and 800 degrees C. When sintered at 1000 degrees C, the coating consisted of alpha-tricalcium phosphate. All the coatings adhered well, independent of sintering temperature. The trajectory analysis revealed that the hollow microsphere remained suspended in a rotating-wall vessel (RWV), and experienced a low shear stress (approximately 0.6 dyn cm(-2)). Cell culture studies using rat bone marrow stromal cells and osteosarcoma cells (ROS 17/2.8) showed that the cells attached to and formed 3-D aggregates with the hollow microspheres in a RWV. Extracellular matrix was observed in the aggregates. These data suggest that these hollow bioactive ceramic microspheres can be used as microcarriers for 3-D bone tissue formation in vitro, as well as for the study of the effects of microgravity on bone cell functions.

Commercially pure titanium (c.p.Ti) is capable of inducing the formation of a carbonated apatite onto its surface in a simulated body fluid (SBF) comprised of calcium ions, phosphate ions, and other inorganic species present in the body fluid. In addition to the incorporation of carbonate ions, such formed apatite has other important characteristics of the bone mineral phase, such as a small crystal size and ionic substitution by Mg2+ and Cl-. Thus, we call this apatite a quasi-biological apatite. The formation of the quasi-biological apatite is proposed to be related to TiOH groups that develop on the titanium surface through interaction with the SBF. The results suggest that titanium implants may be activated such that they can form a strong bond with bone tissue through the in vivo formation of apatite. Since the solution can reach any open space, the process discussed in this study is very suitable for coating porous titanium implants with a quasi-biological apatite film.

Bioactive glasses and ceramics enhance bone formation and bond directly to bone, and have emerged as promising substrates for bone tissue engineering applications. Bone bioactivity involves physicochemical surface reactions and cellular events, including cell attachment to adsorbed extracellular matrix proteins. The effects of fibronectin (Fn) adsorption and glass surface reaction stage on the attachment of osteoblast-like cells (ROS 17/2.8) to bioactive glass were analyzed. Bioactive glass disks were pretreated in a simulated physiologic solution to produce three reaction layers: unreacted glass (BG0), amorphous calcium phosphate (BG1d), and carbonated hydroxyapatite (BG7d). Synthetic hydroxyapatite (sHA) and nonreactive borosilicate glass (CG) were used as controls. A spinning disk device which applied a linear range of forces to attached cells while maintaining uniform chemical conditions at the interface was used to quantify cell adhesion. The number of adherent cells decreased in a sigmoidal fashion with applied force, and the resulting detachment profile provided measurements of adhesion strength. For the same amount of adsorbed Fn, cell adhesion was higher on surface-reacted bioactive glasses (BG1d and BG7d) than on BG0, CG, and sHA. For all substrates, cell attachment was primarily mediated by the RGD binding site of Fn, as demonstrated by blocking experiments with antibodies and RGD peptides. Cell adhesion strength increased linearly with adsorbed Fn surface density. Analysis of this fundamental relationship revealed that improved adhesion to reacted bioactive glasses resulted from enhanced cell receptor-Fn interactions, suggesting substrate-dependent conformational changes in the adsorbed Fn.

Bioactive glass fibers were investigated for use as a fixation vehicle between a low modulus, polymeric composite and bone tissue. In an initial pilot study, bioactive glass fiber/polysulfone composites and all-polysulfone control rods were implanted into the rabbit tibia; the study was subsequently expanded with implantation into the rabbit femur. Bone tissue exhibited direct contact with the glass fibers and adjacent polymer matrix and displayed a mechanical bond between the composite and bone tissue after six weeks implantation. Interfacial bond strengths after six weeks implantation averaged 12.4 MPa, significantly higher than those of the all-polymer controls. Failure sites for the composite at six weeks generally occurred in the bone tissue or composite, whereas the failure site for the polymer implants occurred exclusively at the implant/tissue interface. The bioactive glass fiber/polysulfone composite achieved fixation to bone tissue through a triple mechanism: a bond to the bioactive glass fiber, mechanical interlocking between the tissue and glass fibers, and close apposition and possible chemical bond between the portions of the polymer and bone tissue. This last mechanism resulted from an overspill of bioactivity reactions from the fibers onto the surface of the surrounding polymer which we call the "halo" effect.

Using one parametric variation in solution composition, this paper documents that the surface reactions on bioactive glass (BG) 45S5 are exquisitely dependent upon the modeling conditions. The solutions used were 0.05 M tris hydroxymethyl aminomethane/HCl (tris buffer), tris buffer complemented with plasma electrolyte and/or serum, and serum. The reacted surfaces were analyzed using Fourier transform infrared (FTIR), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDXA), and Rutherford backscattering spectroscopy (RBS). Post-immersion solutions were analyzed for changes in Ca and PO4 concentrations. After a short immersion (3 h), a crystalline, carbonated hydroxyapatite (c-HA) layer formed only in tris. Reaction surfaces of different structure, morphology, and composition were observed after various short and longer term immersions in all other solutions. They comprised two layers with the layer in contact with the bulk consisting mainly of Si; the outer layer, composed of Si, Ca, and P, was amorphous, and had a Ca/P ratio of about 1. Serum proteins adsorbed on the BG surfaces at the early stages of the solution-mediated BG reactions. Formation of a crystalline c-HA layer was delayed up to three or more days in solution with plasma ions. In the presence of serum, only amorphous surfaces composed of Si, Ca, and P were observed for any time up to seven days of immersion. The present data suggest that serum proteins adsorb in tandem with the occurrence of solution-mediated reactions leading to formation of a silica-gel. Amorphous Ca-P phases accumulate in the Si-rich matrix. Furthermore, the present data, in conjunction with the data published before, suggest that physicochemical and cell-mediated reactions occur in parallel to form the glass-tissue interfacial layer.

We describe the effects on cell function of treating porous bioactive glass (BG) such that its surface is a composite of carbonated hydroxyapatite and serum protein. The effects on bone cell function of porous hydroxyapatite (HA) ceramic and porous glass treated to become amorphous calcium phosphate only also were studied subsequent to their having adsorbed a serum protein layer. Substrates treated for different durations were seeded with MC3T3-E1 cells and cultured for 3-17 days. Whereas cells seeded on any substrates, BG and HA produced collagen types I and III, bone sialoprotein, and osteopontin, there were significant differences between HA and BG, and among the various surface conditions created on BG. Covering the glass surface with hydroxyapatite and serum protein enhanced expression of high alkaline phosphatase activity, high rates of cell proliferation, and production of mineralized extracellular matrix. The enhancement may be due to the adsorption of a high quantity of fibronectin from the serum onto the reacted bioactive glass surface.

As an alternative to commercially available porous beads and fiber metal mesh, a new porous coating, orderly oriented wire mesh (OOWM), was developed. Rectangular plugs, 10 x 5 x 5 mm with porous-coated beads, and four different OOWM configurations were inserted into bilateral femoral condyles of adult beagles. Dogs were sacrificed immediately after implantation, and at 4 weeks, 8 weeks, and 12 weeks postimplantation. Mechanical pullout strength of plugs revealed that porous beads are equivalent to the simplest OOWM at 12 weeks postimplantation. Of the four OOWMs tested, the 25 x 25 single layer was significantly more stable than others at 4 weeks postimplantation. These results indicate that in an in vivo unloaded model, OOWM is just as effective as the porous beads in achieving early bone ingrowth and stability.

The aim of this study was to evaluate bone growth around bioactive glass particles in bone defects in comparison to hydroxylapatite particles. The bioactive glass particles were implanted in the partial edentulous jaws of Beagle dogs in two different compositions and several sizes and size ranges. After 1, 2, 3, 6, 12 and 24 months the samples were harvested and processed for undecalcified sectioning. Histological analysis showed a superior response of the bioactive glass particles of composition A and narrow size range (300-355 microns). Besides extensive osteoconductive properties, the bone repair was also stimulated by bone growth in the internally eroded particles. The data demonstrate conclusively that the well known corrosion reactions of the bioactive glass lead to the formation of protective pouches. In these protective pouches formation of new bone is detected without this bone being connected to the bone tissue outside the particles. These islands of newly formed bone tissue function as nuclei for further bone growth and enhance the repair of the defect.

In order to develop total joint prostheses with moduli of elasticity close to bone while retaining excellent strength characteristics, composite materials are being developed. Composites consist of graphite fibers embedded in a polymer matrix. We studied the inflammatory potential of particulates derived from two composites with different matrix components, polysulfone (PFS) and polyetherketoneketone (PEKK), in the rat subcutaneous air pouch model. Neat components of the composites were studied separately in the air pouch. Particulates also were studied in culture using the macrophage cell line RAW 264.7, adherent synovial cells (ASC), and human polymorphonuclear neutrophils (PMNs). Particles derived from the PEKK-containing composite material consistently were less inflammatory than the PFS composite-derived particles, as measured by PMN infiltration, neutral metalloprotease activity, tumor necrosis factor (TNF) activity, and prostaglandin E2 (PGE2) accumulation. Results from the neat materials confirmed the findings in the composite-derived material. PEKK composite-derived material produced less TNF from macrophage cultures, but there were no significant differences noted in PGE2 production from ASC or in superoxide anion generation from PMNs. Particles from both PSF and PEKK produced minimal inflammatory responses in the rat subcutaneous air pouch. PEKK elicited a response virtually the same as the saline control and significantly less than that produced by particles of PSF.

Titanium and its alloys, like the majority of metallic implant materials, release passive metal dissolution products. This raises the issues of amount and fate, i.e. transport, storage, and/or excretion of these metal dissolution products. In this paper we document titanium levels in tissues local to a commercially pure titanium implant in the absence of wear; compare these values to control tissues; and determine the relative contribution of the local accumulation to total release. Titanium fiber felts were implanted into the tibia of rabbits for periods up to 1 year. Bone and muscle tissue samples near the implant were collected. Using electrothermal atomic absorption spectrophotometry the samples were analyzed for titanium content. Compared to controls, titanium levels in the bone near the implant were elevated at 1-, 4-, and 12-month postoperative time points. The 12-month time point had higher periprosthetic bone titanium levels than both the 1- and the 4-month implant groups. Titanium levels in muscle tissue near the felt also indicated release was occurring. The data support the hypothesis that metal species released from titanium implants in the absence of wear have a limited solubility. As a result, they tend to remain in an area local to the implant.

The kinetics of immersion-induced surface transformation reactions of synthetic bone bioactive ceramics were studied in vitro in either protein-free or protein-containing simulated physiological solutions. Both solutions had an ion content similar to that of plasma. Synthetic ceramics used for the study included Ca-deficient hydroxyapatite (CDHA), stoichiometric HA either not well crystallized or well crystallized (s-HA nwc or s-HA wc), oxyhydroxyapatite (OHA), beta-tricalcium phosphate (beta-TCP), and porous coralline HA (I-HA) and calcium carbonate (CC). Only CDHA and nwc s-HA led to immediate precipitation in both protein-free and protein-containing solutions. In contrast, reactions of wc HA and I-HA showed lag times to onset of precipitation in the protein-free solution and a further delay in the presence of proteins. The reactions of nonapatitic ceramics whose lag times in the protein-free solution were longer than those of apatitic, were completely blocked in the presence of proteins within the duration of the experiment (up to 3 days). CDHA and nwc s-HA were the only ceramics that, in the presence of serum proteins, led to the formation of B-type carbonated apatite, typical for calcified tissue apatite.

The contributions to fatigue resistance in poly(methyl methacrylate) bone cement (PMMA) by centrifugation and titanium fiber addition were studied. Three modified bone cements were tested: porosity reduced cement (C-PMMA); titanium (Ti) fiber-reinforced cement (R-PMMA), using a novel method to incorporate fibers; and porosity reduced and Ti fiber-reinforced cement (C-R-PMMA). Specimens of untreated bone cement (PMMA) were included as controls. Non-notched and notched specimens were cyclically loaded in fully reversed bending. For the non-notched specimens, at all stress levels, C-R-PMMA had significantly greater fatigue life than either C-PMMA or R-PMMA (except C-PMMA at 30 MPa). R-PMMA had lower fatigue life than the control at 30 MPa (nominal maximum stress), but higher fatigue life at 20 and 15 MPa. At both 20 and 15 MPa, there was no statistical difference between the fatigue lives of C-PMMA and R-PMMA. Fractography revealed that, at 30 MPa, characteristics of rapid fracture predominated. At 20 and 15 MPa, in contrast, almost the entire fracture surface showed the characteristic fatigue morphology, indicating that subcritical crack growth was predominant. For the notched specimens, C-PMMA showed greater life than PMMA at the highest stress intensity, but the lifetimes converged with decreasing stress intensity. In contrast, the life-times for PMMA and R-PMMA diverged with decreasing stress intensity. The effect of centrifugation appeared to be strongest at higher stress intensities, and diminished with decreasing stress intensity. The reinforcing effect of Ti fiber addition increased the notched fatigue life at high initial stress intensities, and the reinforcing effect increased with decreased stress intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Using in vitro synthesized bone tissue with cells aspirated from the patient's marrow is an appealing idea to avoid the profound limitations of biological and synthetic grafts. Procedures to synthesize bone tissue in vitro primarily relied on seeding various substrates with cells that have osteogenic capacity in culture. It should be noted that in an in vitro system, osteoprogenitor cells, as well as bone cells themselves can rapidly change their phenotype, hence the substrate needs to promote the expression of the bone cell phenotype. Furthermore, it needs to provide a template for bone deposition while gradually resorbing once bone tissue has been laid down. This paper presents initial evidence that bioactive glass, a synthetic material with documented extensive bone bioactivity properties, represents a material that optimally combines the requirements of the ideal template for in vitro synthesis of bone tissue. When made in porous form, and conditioned to develop a bone-like surface prior to being seeded with pluripotential cells capable of expressing the osteoblastic phenotype, these templates lead to expeditious and abundant in vitro synthesis of extracellular matrix with most important characteristics of bone tissue.

A clinical trial to treat dental osseous lesions with bioactive glass granules of narrow size range (300 to 360 microns) has been conducted since early spring 1990. This study followed an animal study in which the osseous tissue repair properties of bioactive glass granules of narrow size range and hydroxyapatite granules were compared for up to 2 years of implantation. The therapeutic response to the bioactive glass material exceeded the response to the hydroxyapatite as evidenced by very extensive osteoconduction, as well as the capacity to cause differentiation of osteoprogenitor cells to osteoblasts. The clinical study was started by virtue of the bioactive glass granules of narrow size range eliciting expeditious bone tissue formation throughout a defect. In this clinical study 87 patients and 106 defects were treated. The indications selected were apical resection areas, cystic defects, extraction sites, and defects of the alveolar ridge due to surgery or resorption. After insertion, the particles remained well in place and only small changes in the contours of the restored defects were seen, at the most up to 2 months postinsertion. At 3 months the application sites had fully solidified. Radiographic analysis indicated that the material integrated into the bone tissue, and at 6 months any difference between glass particles and bone tissue had nearly disappeared. The few initial cases with limited clinical results were caused by factors unrelated to the glass granules, mostly the surgical technique. By adapting the surgical technique, no unfavorable clinical results were subsequently experienced.(ABSTRACT TRUNCATED AT 250 WORDS)

The concept of bioactive ceramic coatings on macroscopically smooth prostheses tries to reconcile opposing principles: the ceramic with beneficial bone tissue growth effects is used as a coating since it does not have sufficient strength and toughness to be used by itself as a prosthesis material. But strength is still an issue since the coating is the primary means of transferring stresses from prosthesis to surrounding tissues. The interface between the metal core and ceramic surface is then critical, since it essentially depends on the strength characteristics of the ceramic. Conversely, when the ceramic coating is used as a means to enhance bone-tissue formation around and into the prosthesis surface, thereby helping to establish a mechanical form of retention, the adhesion of ceramic coating to metallic substrate is not critical. The optimum characteristics of the ceramic are then those that produce the highest effect on bone-tissue growth rates immediately after surgery. The rate of bioactivity is related to the chemical reactivity of the material causing interfacial dissolution, precipitation, and ion exchange reactions. Furthermore, it also appears to depend on a substratum function affecting mineral precipitation, collagen deposition, and cellular differentiation and proliferation.

The osteoconductive nature of calcium phosphate ceramics (CPC) follows from several proven effects, such as a direct bone attachment and enhanced bone tissue formation. Mechanisms leading to these phenomena are still largely undiscovered. Specifically, little is known about the CPC surface and cell-driven reactions. These atomic and molecular level events are involved in tissue attachment and enhanced tissue formation. It is hypothesized that the zeta potential of these ceramics is directly related to the surface reactivity governing osteoconductivity. As a first step in our analysis, the zeta potential of stoichiometric and Ca-deficient hydroxyapatite was determined as a function of immersion time. It is concluded that, under the conditions of the experiment, the observations support the hypothesis in a dual way. First, the absolute values of the zeta potential which were measured are related to electrokinetic potentials known to cause substantial effect on the cellular activities and bone tissue formation when applied exogenously. Second, the magnitude and duration of the changes in zeta potential are related to an ion exchange between the hydrated layer around the ceramic and the ceramic surface, and a net precipitation of new material. If these findings could be confirmed in other solutions, i.e., solutions with a substantially equivalent composition as the fluids in developing bone tissue, a basis would be provided to explain the bridging of the ceramic surface with the surrounding developing tissue.

Surface sensitive spectroscopies, Auger electron and X-ray photoelectron (XPS), were used to determine changes in titanium oxide composition, oxide stoichiometry, and adsorbed surface species as a function of exposure to human serum in a balanced electrolyte (serum/SIE) and 8.0 mM ethylenediaminetetraacetic acid in a balanced electrolyte (EDTA/SIE) at 37 degrees C. Before immersion, the oxide was near ideal TiO2, covered by two types of hydroxyl groups: acidic OH(s) with oxygens doubly coordinated to titanium, and basic Ti-OH groups singly coordinated. After extended exposure to both solutions, up to 5000 h (ca. 208 d), the surface concentration of OH groups increased and non-elemental P appeared. The P LVV Auger transition and P 2p spectra indicated the peak positions were similar to reference phosphate compounds. The adsorbed phosphate species were presumed to be either Ti-H2PO4 or Ti-HPO4-. The XPS data suggested that a lipoprotein and/or glycolipid film was adsorbed to the specimens exposed to serum/SIE. Analysis of the preferential lipoprotein/glycolipid adsorption using electrostatic bonding concepts contributed to the refinement of the hierarchical model for the Ti-tissue interface. The salient features are that Ti metal is not in direct contact with the biological milieu, rather there is a gradual transition from the bulk metal, near-stoichiometric oxide, Ca and P substituted hydrated oxide, adsorbed lipoproteins and glycolipids, proteoglycans, collagen filaments and bundles to cells.

The possible mechanism of minimization of prosthesis-derived bone growth inhibitors by shielding of the metal and the reduction, if not elimination, of the associated metal dissolution was investigated. Titanium, aluminium and vanadium release rates were determined in vitro for Ti alloy specimens both with and without a calcium phosphate coating. Ti orderly oriented wire mesh (OOWM) porous coatings on Ti-6Al-4V substrates were used as the metal specimens. Half of the specimens were coated with a 75 microns calcium phosphate ceramic (CPC coating). Seven reference (OOWM) and seven coated (OOWM-CPC) specimens were immersed and placed along with seven control solutions for various periods in an incubator maintained at 37 degrees C and 5% CO2 - air atmosphere. Whereas the reference solutions showed a Ti release increasing as a function of time, the solutions that had the CPC-coated specimens contained no measurable amounts of titanium. The Al in solution around the CPC-coated specimens was significantly greater than the concentration around non-coated specimens. The Al, however, did not increase significantly with time, at least up to 4 wk immersion. The ceramic coating had a small beneficial effect on V concentration. In the absence of a significant adverse effect of Ti on local bone tissue formation, we focus on the Al data of our study. The possible adverse effect of this element is well documented. The calcium phosphate coating produced a significant increase of biological fixation, yet at the same time a greater Al release into solution, calling into question the significance of CPC coating in shielding adverse metal passive dissolution to explain enhanced bone growth [corrected].

Calcium-phosphate ceramic particulates are often used as filler material for enhanced repair of dental bone defects. Although evidence of bone ingrowth in the scaffold of these particles has been described, it is not observed consistently. Fibrous tissue often encapsulates these particles, which can subsequently become dispersed into the surrounding tissues or even exfoliated. The aim of the present study was to evaluate bioactive glass granules (Biogran) as a filler for osseous lesions, and to compare them with two commercially available Hydroxylapatite (HA) granules. The particulates were implanted in the jaws of five beagle dogs, resected and evaluated after 1, 2, 3, 6 and 12 months of implantation. Histological analysis revealed an improvement in repair of all the lesions. A massive osteoconductive bone growth was seen near the walls of the bony cavities, but in greater amounts around the bioactive glass granules than around the HA materials. On top of this massive growth a trabecular bone growth was observed in the centre of the bony cavities. These trabeculae were associated with the glass particles, which exhibited osteophilic properties, while fibrous tissue separated the bone tissue from the HA particles. The centres of many of the particles are excavated, and are subsequently filled by newly formed bone tissue. This internally formed bone tissue is not necessarily connected to the surrounding bone tissue, and functions as a nucleation site for further bone repair. For the mesenchymal cells within the eroded glass particles this inner environment acts as a stimulus to differentiate into osteoblasts and to start their osteogenetic potential. This phenomenon was not observed around the HA materials. If the latter were surrounded by fibrous tissue, disintegration of the surface by giant cells was observed.

The compositions of the surface and the interface of calcium phosphate ceramic (CPC) coatings electrophoretically deposited and sintered on titanium or its alloy, were determined by scanning Auger electron spectroscopy before and after 4 wk of immersion in a simulated physiological solution. In the CPC coating-metal interfaces, the phosphorus diffused beyond the titanium oxide layer. The phosphorus concentration in the interface followed a Gaussian distribution for both unalloyed and alloyed titanium. The diffusion depleted P in the ceramic adjacent to the metal. The surface of the ceramic, however, was substantially unchanged. A major change in the compositional depth profiles was induced by immersion: thick and uniform titanium phosphide layers of constant composition were observed on the Ti-based metal substrates.

X-ray photoelectron spectroscopy (XPS) was used to determine changes in titanium oxide composition, oxide stoichiometry, and adsorbed surface species as a function of exposure to model physiologic environments. The oxide on titanium became heterogeneous and polarized as a function of exposure. Changes included an increase in surface hydroxyl groups, and adsorption of H2PO4- and HPO4(2-). The heterogeneous nature of the surface led to preferential adsorption of lipoproteins, glycolipids, or both from serum.

The high cycle fatigue strength of porous coated Ti-6A1-4V is approximately 75% less than the fatigue strength of uncoated Ti-6A1-4V. This study separates the effects of three parameters thought to be responsible for this reduction: interfacial geometry, microstructure, and surface alterations brought about by sintering. To achieve the goal of one parameter variations, hydrogen-alloying treatments, which refined the lamellar microstructure of beta-annealed and porous coated Ti-6A1-4V, were formulated. The fatigue strength of smooth-surfaced Ti-6A1-4V subjected to hydrogen-alloying treatments is 643-669 MPa, significantly greater than the fatigue strength of beta-annealed Ti-6A1-4V (497 MPa) and also greater than the fatigue strength of pre-annealed, equiaxed Ti-6A1-4V (590 MPa). The fatigue strength of porous coated Ti-6A1-4V, however, is independent of microstructure. This leads to the conclusion that the notch effect of the surface porosity does not allow the material to take advantage of the superior fatigue crack initiation resistance of a refined alpha-grain size. Thus, sinternecks acts as initiated microcracks and fatigue of porous coated Ti-6A1-4V is propagation controlled.

The synthesis of model porous metal-CPC materials, and their use in one-parametric studies of bone tissue ingrowth enhancement were considered. By using the same starting calcium-deficient hydroxyapatite powder, three different coatings, CAP1, CAP2 and CAP3, were obtained of thicknesses 50 +/- 5, 75 +/- 5 and 75 +/- 5 microns, respectively. CAP1 and 2 were either the starting powder mixed in a 3:1 ratio CPC: poly(lactic acid) or the powder by itself. The CAP3 coating was the result of a thermal treatment producing a mixture of oxyhydroxyapatite, alpha- and beta-tricalcium phosphate. Orderly oriented wire mesh porous coated specimens were implanted, along with the same specimens lined with CAP 1, 2 or 3. Subsequently, the total of 156 specimens was retrieved at 2, 4 or 6 wk, and tested mechanically and processed for histomorphometry. The data produced considerable evidence for the CPC-dependent enhancement of bone tissue ingrowth in porous metals immediately after implantation. They prove that the materials processing of CPC coatings influences the resulting biological behaviour substantially. Furthermore, they support the hypothesis that ceramic dissolution is a causative factor on the bone tissue growth enhancement mechanisms.

Bioactive calcium phosphate ceramics (CPC) guide bone formation along their surface. This property is conceptually attractive from the viewpoint of enhancing early bone tissue formation in porous metal coatings. The various studies conducted to exploit this idea, however, reveal a considerable variability of the effect. This suggests material- and processing-induced parametric influences. Thus this study focuses on the formulation of model porous metal-CPC materials for use in one-parametric analyses of material factors. Easily reproducible, porous metals with a uniform porous structure and CPC coating are made with orderly oriented wire mesh (OOWM) porous metal coatings and electrophoretically deposited CPC films. The deposition of the ceramic can be hampered by adsorbed water. Subsequent vacuum sintering leads to several phase transformations: hydroxyapatite is transformed to a mixture of oxyhydroxyapatite and tetracalcium phosphate; the underlying titanium promotes the beta- to alpha-tricalcium phosphate transformation; and Ca-deficient hydroxyapatite is transformed to a mixture containing oxyhydroxyapatite and alpha- and beta-tricalcium phosphate. These phase transformations provoke a considerable increase of in vitro dissolution in 0.05 M tris buffered physiological solution.

Cementing with poly(methyl methacrylate) (PMMA) is a common means of fixing total hip prostheses. Bone cement fails mechanically, and subsequent loosening frequently requires correction via revision surgery. An initial step in optimizing bone cement properties is to establish which properties are critical to the material's in vivo performance. The objectives were to discern the critical in vivo failure mechanisms of bone cement. Fracture surfaces of bone cement specimens that failed in vivo were compared with fatigue and rapid fracture surfaces created in vitro. In vivo fracture processes of bone cement were positively identified and explained by the elucidation of PMMA fracture micromechanisms. The ex vivo fracture surfaces are remarkably similar to in vitro fatigue fracture surfaces. The fractographic data document that the primary in vivo failure mechanism of bone cement is fatigue, and the fatigue cracks grow by developing a microcraze shower damage zone. Agglomerates of BaSO4 particles can be implicated in some bone cement failures, large flaws or voids in vivo can lead to a rapid, unstable fracture, pores in the PMMA mass have a clear influence on a propagating crack, and wear of the fracture surfaces occurs, and may produce PMMA debris, exacerbating bone destruction.