This paper describes a study of fatigue-crack propagation behavior in the superelastic alloy Nitinol. This work is motivated by biomedical applications, and the current interest to improve the design and performance of medical stents for implantation in the human body. Specifically, the objective of this work is to study the effect of environment on cyclic crack- growth resistance in a ∼50Ni-5OTi (at. %) alloy, and to provide the necessary data for the safe life predication of Nitinol endovascular stents. The material selected for this study has been heat treated such that it is superelastic at human body temperature. Characterization of fatigue-crack growth rates has been performed at 37°C on disc-shaped compact-tension samples, in environments of air, aerated deionized water, and aerated Hank's solution. Results indicate that, in fact, Nitinol has the lowest fatigue-crack growth resistance of metallic alloys currently used for implant-applications.

In vitro, groups have demonstrated that peptide modified surfaces influence short and long term cell responses like attachment, shape and function via cell receptors known as integrins. These receptors translate information to the nucleus via sets of complex signaling pathways. Little is known about the ability of these surfaces to influence the inherently complex in vivo environment, however. The present study was designed to evaluate the quality and quantity of new bone formed in response to gold coated titanium rods modified with the peptide sequence Arg-Gly-Asp-Cys (RGDC). Quantitative histomorphometric analysis of histologic sections perpendicular to the implant long axis showed a thicker (P < 0.01) shell of new bone formed in response to peptide modified implants (26.2 microns ± 1.9 vs. 20.5 microns ± 2.9) as early as 2 weeks. Mechanical pull-out testing conducted at 4 weeks revealed the average pull-out force of peptide modified rods was 38% greater than gold control rods. The significant difference in the thickness of new bone formed around the implant was maintained at 4 weeks (32.7 microns ± 4.6 vs. 22.6 microns ± 4.0). These results demonstrate the feasibility of developing peptide coated biomaterials designed to elicit a host response at the cell receptor level.

A long-term objective of many involved in blood vessel research is the development of a small diameter vascular substitute which can be used in coronary bypass graft surgery. If these efforts are to be successful, there are critical functional characteristics which must be achieved. In recent years many of those interested have turned their attention to tissue engineering, and over the past decade some progress has been reported. The results of some of these efforts are briefly reviewed here. Included is the strategy of the Georgia Tech team and recent results which demonstrate that in vitro mechanical stimulation of smooth muscle cell-seeded tubular collagen constructs induces a remodeling with the result that the associated material properties are considerably enhanced.

Schwann cells play a dual role serving as a physical framework for regenerating nerves, providing extracellular matrix proteins and specific adhesion molecules facilitating attachment and cell movement, and as a source of stimulatory factors mediated by the release or reception of different ligands important in growth and cell signaling events. To investigate the role of one such ligand, glial growth factor (GGF), in peripheral nerve regeneration, a bioabsorbable nerve guide, prepared from a poly(lactic-co-glycolic) acid (PLGA) foam was seeded with autogenous Schwann cells in the presence and absence of growth factor and evaluated in vivo using a rat sciatic nerve regeneration model. Four weeks post-operatively peripheral nerve regeneration was evident. The resorbable foam implant demonstrated extensive neo-vascularization in and around the guide with no evidence of an inflammatory response or encapsulation. The study showed a statistically significant increase in all measured parameters of nerve regeneration in the presence of GGF. Increased numbers of blood vessels in the regenerated tissue accompanied increased total axon counts after twelve weeks. The addition of exogenous Schwann cells resulted in reduced total axon counts perhaps due to the competition for limited growth factors released by the regenerating tissues. The Schwann cell groups, however, displayed the highest myelination indices recorded likely reflecting the role of Schwann cells in the myelination process. Measurements of conduction velocities (EMGs) revealed the highest conductance velocities recorded in nerves regenerated in the presence of both GGF and Schwann cells. Clearly, the inclusion of GGF in the nerve regenerative process is beneficial with respect to both the generation of new axons and the establishment of a functional endpoint.

Silicone rubber multiple-lumen (ML) nerve cuffs were used for side-by-side comparisons of the effectiveness of two varieties of nerve growth stimulants (collagen gel and a gel mixture of collagen, fibronectin, and laminin) for regenerating cables across a 15 mm gap in 10 adult Sprague-Dawley rats. The filling pattern of the six tubes of the multiple-lumen portion of the cuff alternated with the collagen gel and the gel mixture of collagen, fibronectin, and laminin. After an 8 week implantation period, 53% (32 of 60) of the 0.5 mm diameter lumens displayed successful cable regeneration for both material fillings. The ML cuff experiments demonstrate the ability to bridge a 15 mm gap in the sciatic nerve of the rat by 8 weeks for relatively small diameter conduits in ML cuffs loaded with two varieties of growth stimulants. A more advanced organization including a smaller acellular region fraction and a higher vascularity is seen in the cables from the mixture-filled lumens compared to those in the cables from the collagen-filled lumens.

Synthetic bone grafts resistant to random dissolution at physiological pH, yet capable of being gradually resorbed in vitro by osteoclasts have been created. Bulk ceramics and ceramic coatings formed from an additive stabilized colloidal sol possess two characteristic features: a phase mixture of calcium hydroxyapatite (HA) and a silicon stabilized tricalcium phosphate, and a microporous morphology based on inter-connected particles (0.2-1.0 μm). The characteristic phase composition arises during sintering through substitution reactions where silicon enters the calcium phosphate lattice under conditions of high chemical reactivity. Evidence for in vitro resorption lacunae on bulk ceramics is presented.

Bone loss (osteolysis) following total joint arthroplasty has been a subject of increasing concern in the orthopedic research community. Depending on the distribution and severity, bone loss can lead to aseptic loosening, periprosthetic fracture and formidable reconstructive problems at revision surgery. Bone loss is believed to be primarily a response to particulate wear and corrosion debris derived from the prosthetic materials. Phagocytosed particulates activate macrophages and osteoblasts (and perhaps fibroblasts) to produce factors which stimulate osteoclastic bone resorption and reduce osteoblastic bone formation. To investigate the responses of these cells to particulate corrosion and wear debris, in vitro studies have been performed by measuring factors at both the molecular and cellular levels that may trigger, maintain and/or regulate particulate biomaterial-induced pathologic bone resorption. The biological effect of a particulate species depends upon their size, concentration (number) and composition, in the order listed. Particulate wear debris of phagocytosable size (less that 10 micrometers) activate macrophages, fibroblasts and osteoblasts more effectively that those of larger sizes. As a response to phagocytosed particulates, i) macrophages produce a number of cytokines (interleukins such as II-1, II-6, TNF-alpha) and prostaglandins, which may act either in an autocrine fashion or further stimulate cells present in the periprosthetic tissue; ii) fibroblasts secrete active forms of metalloproteinases; and iii) osteoblasts have diminished collagen type I synthesis. Taken together, particulate corrosion and wear debris provoke a series of biological responses which generate an active microenvironment around prosthetic components. Strategies to modify the host response to particulate degradation products have emerged from these in vitro studies. These strategies may provide pharmacotherapeutic solutions to this important clinical problem.

Ultra-high molecular weight polyethylene (UHMWPE) is the principal material used to replace damaged cartilage in total joint replacement surgeries. This publication presents preliminary results from a new class of surface treatments to modify the surface chemistry and microstructure of UHMWPE under controlled processing conditions. Radio frequency plasmas were used to lightly crosslink the subsurface of UHMWPE and to modify the surface chemical state through the attachment of low-surface-energy fluorocarbon groups. A pin-on-disk apparatus was used to slide CoCrWNi pins with spherical tips on polished disks of plasma- treated and untreated UHMWPE immersed in a bath of preserved bovine serum. The wear resistance and surface chemical composition of tested specimens were characterized by surface profilometry and X-ray photoelectron spectroscopy (XPS), respectively. Changes in the surface hydrophobicity due to plasma treatment were evaluated using contact angle measurements. The prospect of surface plasma treatment in orthopedic applications is elucidated in the context of the obtained friction, wear, distilled water contact angle, and XPS results.

Oxidized Zr-2.5Nb is being developed as an articular bearing surface for the femoral component in total joint arthroplasty. It has so far demonstrated superior wear performance against ultrahigh molecular weight polyethylene (UHMWPE) with respect to traditional articulating materials such as Co-Cr-Mo alloys. In this investigation, we used thermogravimetric analysis, transmission electron microscopy, and in situ x-ray diffraction techniques to study the microstructure and stress state of the oxide scale grown on Zr-2.5Nb.

The oxidation temperature not only determines the kinetics of oxidation but the morphology of the various oxidation products. We have identified the oxidation products of both phases of the two phase alloy and correlated them with the original alloy microstructure. These include not only monoclinic zirconia but also small amounts of tetragonal zirconia and a mixed oxide phase combining both zirconium and niobium. The alloy microstructure both influences the final oxidation products and is reflected in the microstructure of the oxide. The oxide scale itself has a predominantly columnar microstructure which extends from the oxide/metal interface to the outer surface of the oxide. In situ x-ray diffraction measurements revealed that the oxide scale is stressed in compression following cooling and exhibits strong crystallographic texture. The oxide/metal interface is continuous, without pores or voids which might be detrimental to oxide adhesion. In addition, we have identified a phase which develops at the interface between the beta-zirconium grains and the oxide. We have also identified amorphous regions within the oxide scale which serve as sinks for silicon and other impurity elements found in the alloy.

The ability to provide depth-resolved chemical information is an important attribute for analytical methods employed in the biomaterials laboratory, both research and production. Radio frequency glow discharge atomic emission spectroscopy (rf-GD-AES) is shown to provide profiles of nitrogen content in prosthetic alloys to depths of greater than 50 micrometers, with analysis times of less than 30 minutes.

Glasses in the system Si-Ca-Na-Mg-P-K-O with thermal expansions coefficients close to that of Ti6AI4V were used to coat the titanium alloy by a simple enameling technique. Firings were done in air at temperatures between 800 and 840°C and times up to 1 minute. Graded compositions were obtained by firing multilayered glass coatings. Hydroxyapatite (HA) particles were mixed with the glass powder and the mixture was placed on the outer surface of the coatings to render them more bioactive. Coatings with excellent adhesion to the substrate and able to form apatite when immersed in a simulated body fluid (SBF) can be fabricated by this methodology.

A new series of bioactive glasses have been prepared with thermal expansion coefficients that more closely match that of Ti-based implant alloys. It is proposed that these glasses be used as coatings on biological implants that would provide improved fixation between the implant and tissue. As glasses are subject to environmentally assisted crack growth, it is important to develop an understanding of the stress corrosion crack growth (SCCG) behavior of this new family of glasses; furthermore, it is equally important to determine the effect of bioactivity on the SCCG properties of these glasses. This report will present the progress to date in the study of the SCCG properties of these new bioactive glasses

Thin coatings of various calcium phosphates including tricalcium phosphate (TCP), calcium pyrophosphate, and hydroxyapatite were synthesized by plasma-enhanced metalorganic chemical vapor deposition (MOCVD). Structure, composition, and surface morphology of the coatings were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, and atomic force microscopy. All coatings were very dense and free of cracks. X- ray diffraction showed that the as-grown coatings with the Ca/P ratio of 1.5±0.5 and 1.0±0.5 were crystalline μ- TCP and pyrophosphate, respectively. However, hydroxyapatite coatings with the Ca/P ratio of ∼1.67 were amorphous. The crystalline μ-TCP and pyrophosphate coatings exhibited strong growth texture. The textured orientations varied with different growth temperatures. In addition, the microstructure of the μ-TCP coatings strongly depended on the growth temperatures.

This study introduces a new method for evaluating the adhesion strength of a coating on a substrate. The interfacial fracture toughness, Γi is used to assess the work per unit area required to separate an interface. Γi is measured for the as-received specimens of hydroxyapatite plasma sprayed on Ti-6A1-4V substrate. Calculation of the interfacial fracture toughness requires that the elastic modulus of the coating to be known. The Young's modulus of the plasma sprayed hydroxyapatite is assessed using a bend test. The effect of aqueous environment on the interfacial fracture toughness is also investigated.