A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this work, a multilevel approach was employed to assess the implant-induced and biocorrosion-related inflammation in the adjacent vascular tissue using a mouse stent implantation model. The implications of biocorrosion on peri-implant tissue were assessed at the macroscopic level via in vivo imaging and histomorphology. Elevated matrix metalloproteinase activity, colocalized with the site of implantation, and histological staining indicated that stent surface condition and implantation time affect the inflammatory response and subsequent formation and extent of neointima. Hematological measurements also demonstrated that accumulated metal particle contamination in blood samples from corroded-stetted mice causes a stronger immune response. At the cellular level, the stent-induced alterations in the nanostructure, cytoskeleton, and mechanical properties of circulating lymphocytes were investigated. It was found that cells from corroded-stented samples exhibited higher stiffness, in terms of Young's modulus values, compared to noncorroded and sham-stented samples. Nanomechanical modifications were also accompanied by cellular remodeling, through alterations in cell morphology and stress (F-actin) fiber characteristics. Our analysis indicates that surface wear and elevated metal particle contamination, prompted by corroded stents, may contribute to the inflammatory response and the multifactorial process of in-stent restenosis. The results also suggest that circulating lymphocytes could be a novel nanomechanical biomarker for peri-implant tissue inflammation and possibly the early stage of in-stent restenosis. Large-scale studies are warranted to further investigate these findings.

B.D. Ratner, Biomaterials Science: An Interdisciplinary Endeavor. Materials Science and Engineering--Properties of Materials: J.E. Lemons, Introduction. F.W. Cooke, Bulk Properties of Materials. B.D. Ratner, Surface Properties of Materials. Classes of Materials Used in Medicine: A.S. Hoffman, Introduction. J.B. Brunski, Metals. S.A. Visser, R.W. Hergenrother, and S.L. Cooper, Polymers. N.A. Peppas, Hydrogels. J. Kohnand R. Langer, Bioresorbable and Bioerodible Materials. L.L. Hench, Ceramics, Glasses, and Glass Ceramics. I.V. Yannas, Natural Materials. H. Alexander, Composites. B.D. Ratner and A.S. Hoffman, Thin Films, Grafts, and Coatings. S.W. Shalaby, Fabrics. A.S. Hoffman, Biologically Functional Materials. Biology, Biochemistry, and Medicine--Some Background Concepts: B.D. Ratner, Introduction. T.A. Horbett, Proteins: Structure, Properties, and Adsorption to Surfaces. J.M. Schakenraad, Cells: Their Surfaces and Interactions with Materials. F.J. Schoen, Tissues. Host Reactions to Biomaterials and Their Evaluations: F.J. Schoen, Introduction. J.M. Anderson, Inflammation, Wound Healing, and the Foreign Body Response. R.J. Johnson, Immunology and the Complement System. K. Merritt, Systemic Toxicity and Hypersensitivity. S.R. Hanson and L.A. Harker, Blood Coagulation and Blood-Materials Interaction. F.J.Schoen, Tumorigenesis and Biomaterials. A.G. Gristina and P.T. Naylor, Implant-Associated Infection. Testing Biomaterials: B.D. Ratner, Introduction. S.J. Northup, In Vitro Assessment of Tissue Compatibility. M. Spector and P.A. Lalor, In Vivo Assessment of Tissue Compatibility. S. Hanson and B.D. Ratner, Testing of Blood-Material Interactions. B.H. Vale, J.E. Willson, and S.M. Niemi, Animal Models. Degradation of Materials in the Biological Environment: B.D. Ratner, Introduction. A.J. Coury, Chemical and Biochemical Degradation of Polymers. D.F. Williams and R.L. Williams, Degradative Effects of the Biological Environment on Metals and Ceramics. C.R. McMillin, Mechanical Breakdown in the Biological Environment. Y. Pathak, F.J. Schoen, and R.J. Levy, Pathologic Calcification of Biomaterials. Application of Materials in Medicine and Dentistry: J.E. Lemons, Introduction. D. Didisheim and J.T. Watson, Cardiovascular Applications. S.W. Kim, Nonthrombogenic Treatments and Strategies. J.E. Lemons, Dental Implants. D.C. Smith, Adhesives and Sealants. M.F. Refojo, Ophthalmologic Applications. J.L. Katz, Orthopedic Applications. J. Heller, Drug Delivery Systems. D. Goupil, Sutures. J.B. Kane, R.G. Tompkins, M.L. Yarmush, and J.F. Burke, Burn Dressings. L.S. Robblee and J.D. Sweeney, Bioelectrodes. P. Yager, Biomedical Sensors and Biosensors. Artificial Organs: F.J. Schoen, Introduction. K.D. Murray and D.B. Olsen, Implantable Pneumatic Artificial Hearts. P. Malchesky, Extracorporeal Artificial Organs. Practical Aspects of Biomaterials--Implants and Devices: F.J. Schoen, Introduction. J.B. Kowalski and R.F. Morrissey, Sterilization of Implants. L.M. Graham, D. Whittlesey, and B. Bevacqua, Cardiovascular Implantation. A.N. Cranin, M. Klein, and A. Sirakian, Dental Implantation. S.A. Obstbaum, Ophthalmic Implantation. A.E. Hoffman, Implant and Device Failure. B.D. Ratner, Correlations of Material Surface Properties with Biological Responses. J.M. Anderson, Implant Retrieval and Evaluation. New Products and Standards: J.E. Lemons, Introduction. S.A. Brown, Voluntary Consensus Standards. N.B. Mateo, Product Development and Regulation. B. Ratner, Perspectives and Possibilities in Biomaterials Science. Appendix: S. Slack, Properties of Biological Fluids. Subject Index.

There has been increased interest in the role of corrosion in early implant failures and adverse local tissue reaction in total hip arthroplasty. We review the relationship between the different types of corrosion in orthopaedic surgery including uniform, pitting, crevice, and fretting or mechanically assisted crevice corrosion (MACC). Passive layer dynamics serves a critical role in each of these processes. The femoral head-neck trunnion creates an optimal environment for corrosion to occur because of the limited fluid diffusion, acidic environment, and increased bending moment.

Description Get 21 peer-reviewed papers that cover retrieval analysis of medical implants as well as host issues that may contribute to clinical outcomes where revision is the endpoint. Featured topics include You will also find related information on inflammatory cytokine and biomarker analyses; the need for histological staging and standard terminology; genetic related issues; imaging modality analysis of surrounding anatomy; and the need for tissue and fluid analysis that may include a repository for retrieval databases.

Beginning in the 1970s, device retrieval analysis was conducted at our institution, the University of Alabama at Birmingham, to better understand surgical implant device biocompatibilities through studies of element (biomaterial) and force (biomechanical) transfers at host-device interfaces. Multidisciplinary investigations were initiated from analyses of clinical outcomes and examination of explants. Analyses included physical, mechanical, chemical, electrical, and combinations thereof for orthopedic and dental implants fabricated from synthetic origin biomaterials, with more than 8,000 specimens received. Hypotheses were tested concerning cause-effect relationships using a tiered classification approach, which resulted in peer-reviewed presentations and publications (STP1560, Metal-on Metal Total Hip Replacement, and STP1591, Modularity and Tapers in Total Joint Replacement Devices). In the 1990s, the focus evolved to include the analysis of function of implants obtained through postmortem retrieval, with more than 1,000 "en bloc" specimens collected. Opportunities included longer-term evaluations of human outcomes for devices that were in place and functional at the time of donation. Direct comparisons of devices and tissues with laboratory and in vivo studies tested theories about cause-effect relationships. Selected studies are presented as examples that include the application of calcium phosphate coatings, particulates and porous blocks for bone grafting with dental implants, and surface stability of a contemporary total knee replacement intended to reduce the generation of wear debris. We conclude with recommendations for expanded analysis of postmortem specimens by qualified investigators as input to new consensus standards.

Statement of problem. The etiology (chemical, friction, abfraction) of noncarious cervical lesion (NCCL) progression is poorly understood.Purpose. The purpose of this 5-year prospective clinical trial was to measure the relationship between NCCLs and various etiologic factors.Material and methods. After review board approval, 29 participants with NCCLs were enrolled. Polyvinyl siloxane impressions were made of each NCCL, and casts were poured at baseline, 1, 2, and 5 years. The casts were scanned with a noncontact profilometer, and 1-, 2-, and 5-year scans were superimposed over baseline scans to measure volumetric change in NCCLs. T-scan and Fujifilm Prescale films were used to record relative and absolute occlusal forces on teeth with NCCLs at the 5-year recall. Participant diet, medical condition, toothbrushing, and adverse oral habit questionriaires were given at the 5-year recall. Occlusal analysis was completed on mounted casts to determine the presence of wear facets and group function. Volumetric lesion progression from 1 to 5 years was correlated to absolute and relative occlusal force using mixed model analysis. The Kruskall-Wallis and Mann-Whitney analyses compared lesion progression with diet, medical condition, toothbrushing, adverse oral habits, wear facets, and group function.Results. The NCCL progression rate over 5 years was 1.50 +/- 0.92 mm(3)/yr. The rate of progression of NCCLs was related to mean occlusal stress (P=.011) and relative occlusal force (P=.032) in maximum intercuspation position. No difference was seen in NCCL progression between participants with any other factors.Conclusion. Heavy occlusal forces play a significant role in the progression of NCCLs.

Journal of Biomedical Materials Research Part AVolume 104, Issue 5 p. 1062-1063 Obituary In Memoriam—Samuel F. Hulbert, Ph.D., 1936–2016: On January 29th of this year, the world of biomaterials and biomedical engineering lost a true visionary and champion with the passing of Samuel “Sam” Hulbert Jack Lemons, Jack Lemons UAB University Professor Emeritus, Schools of Dentistry, Engineering and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 35294Search for more papers by this authorJerome Klawitter, Jerome Klawitter Extremity Reconstruction, Integra Life Sciences, Vice President for Advanced Development, Austin, Texas, 78754Search for more papers by this author Jack Lemons, Jack Lemons UAB University Professor Emeritus, Schools of Dentistry, Engineering and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 35294Search for more papers by this authorJerome Klawitter, Jerome Klawitter Extremity Reconstruction, Integra Life Sciences, Vice President for Advanced Development, Austin, Texas, 78754Search for more papers by this author First published: 24 February 2016 https://doi.org/10.1002/jbm.a.35694Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume104, Issue5May 2016Pages 1062-1063 RelatedInformation

Despite a considerable clinical and investigative emphasis on the problem of in-stent restenosis (ISR), complications arising from the interaction of stent materials with the surrounding vessel wall as well as from the mechanical forces developing during and after implantation, remain a significant problem. Nanoindentation studies performed on various locations along the stent struts have shown that the hardness of specific stent locations significantly increases after mechanical expansion. The increase in hardness was associated with a reduction of the material‘s ability to dissipate energy in plastic deformations and therefore with an increased vulnerability to fracture and fatigue. It was concluded that the locations of fatigue fractures in stent struts are controlled not only by the geometrically-driven stress concentrations developing during cyclic loading but also by the local material mechanical changes that are imparted on various parts of the stent during the deployment process. Additionally, the project focused on investigating the effect of stent corrosion in an animal model in order to explore a possible link between metal ion release, inflammation and factors thought to initiate ISR. To evaluate the vessel inflammatory response, stents with active corrosion were implanted in mice abdominal aortas and novel in vivo imaging techniques were employed to assess the trafficking and accumulation of fluorescent donor monocytes as well as the proliferation of vascular smooth muscle cells at the implantation site. The in vivo imaging analysis revealed that elevated metal particle contamination, prompted by corroded stents, triggers an inflammatory response and promotes monocyte recruitment with upregulation of MMPs at the site of injury.

In vivo damage to modular connections for medical and dental multipart construct implant devices, such as hip and tooth root replacements, that transfer forces from host function to bone, has been shown to be complex and multifactorial. Many investigators have recommended that if we are to better understand the most critical factors that influence in vivo modular connection damage, studies should include interrelated data from the patient health and function, the details of surgery and rehabilitation, and the biomaterial and biomechanical properties of the device. Once again, focusing on the device construct design, biomaterial bulk and surface properties, and the established mechanisms of general, pitting, crevice, fretting, fatigue, stress, intergranular, and galvanic corrosion, evaluations have shown that a multifactorial series of considerations exist. These various properties and mechanisms may or may not influence modular interface region damage, and these also should be considered. The intent of this summary is to review and provide relative information based on past (1970-1990s) and more recent (2000-2014) experiences with a focus on the mental-on-metal, ceramic-on-ceramic, and metal- or ceramic-on-polymer assemblies, including articulations for orthopaedic and dental implant systems. This paper also focuses on modifications and new consensus standards that may be needed for future (after 2015) device evaluations related to treatments that include device modularity.

Objective. To compare the marginal gap using different types of die stones and titanium dies with and without powders for imaging.Methods. A melamine tooth was prepared and scanned using a laboratory 3-shape scanner to mill a polyurethane die, which was duplicated into different stones (Jade, Lean, CEREC) and titanium. Each die was sprayed with imaging powders (NP, IPS, Optispray, Vita) to form 15 groups. Ten of each combination of stone/titanium and imaging powders were used to mill crowns. A light-bodied impression material was injected into the intaglio surface of each crown and placed on the corresponding die. Each crown was removed, and the monophase material was injected to form a monophase die, which was cut into 8 sections. Digital images were captured using a stereomicroscope to measure marginal gap. Scanning electron microscopy was used to determine the particle size and shape of imaging powders and stones.Results. Marginal gaps ranged from mean (standard deviation) 49.32 to 91.20 micrometers (3.97-42.41 mm). There was no statistical difference (P > .05) in the marginal gap by any combination of stone/titanium and imaging powders. All of the imaging powders had a similar size and rounded shape, whereas the surface of the stones showed different structures.Conclusions. When a laboratory 3-shape scanner is used, all imaging powders performed the same for scanning titanium abutments. However, there was no added value related to the use of imaging powder on die stone. It is recommended that the selection of stone for a master cast be based on the physical properties.Practical Implications. When a laboratory 3-shape scanner is used, the imaging powder is not required for scanning die stone. Whenever scanning titanium implant abutments, select the least expensive imaging powder.

The popularity of vascular stents continues to increase for a variety of applications, including coronary, lower limb, renal, carotid, and neurovascular disorders. However, their clinical effectiveness is hindered by numerous postdeployment complications, which may stimulate inflammatory and fibrotic reactions. The purpose of this study was to evaluate the vessel inflammatory response via in vivo imaging in a mouse stent implantation model. Corroded and noncorroded self-expanding miniature nitinol stents were implanted in mice abdominal aortas, and novel in vivo imaging techniques were used to assess trafficking and accumulation of fluorescent donor monocytes as well as cellular proliferation at the implantation site. Monocytes were quantitatively tracked in vivo and found to rapidly clear from circulation within hours after injection. Differences were found between the test groups with respect to the numbers of recruited monocytes and the intensity of the resulting fluorescent signal. Image analysis also revealed a subtle increase in matrix metalloproteinase activity in corroded compared with the normal stented aortas. In conclusion, this study has been successful in developing a murine stent inflammation model and applying novel in vivo imaging tools and methods to monitor the complex biological processes of the host vascular wall response.

In-stent restenosis (ISR) remains a significant limitation despite the considerable previous clinical and investigative emphasis on the problem. Complications arising from the interaction of stent materials with the surrounding vessel wall as well as from the mechanical forces developing after implantation, play an important role in the development of ISR. To investigate the relation between mechanical factors and stent structural integrity, and to identify any structural weakness points on the geometry of commercially available Stainless Steel and Cobalt–Chromium stents, accelerated pulsatile durability tests were carried out in a simulated physiological environment. Potential spatial variations in the mechanical properties on stent struts and their role in the observed premature failures of the stent devices during operation were also examined. Fretting wear and fatigue-induced fractures were found on stent surfaces after exposure to cyclic loading similar to that arising in vivo. Nanoindentation studies performed on various locations along the stent struts have shown that the hardness of specific stent locations significantly increases after mechanical expansion. The increase in hardness was associated with a reduction of the material's ability to dissipate energy in plastic deformations, therefore an increased vulnerability to fracture and fatigue. We conclude that the locations of fatigue fractures in stent struts are controlled not only by the geometrically-driven stress concentrations developing during cyclic loading but also by the local material mechanical changes that are imparted on various parts of the stent during the deployment process.

Intravascular nitinol stents are used in the treatment of atherosclerosis and intracranial aneurysms. Despite the unique physical properties of shape memory and superelasticity, the chemical composition of NiTi has raised concerns due to the presence of nickel ions within the alloy which can have adverse effects on human health. Currently, stents are manufactured from corrosion resistant alloys which form protective titanium oxide films, insulating the bulk material from the corrosive physiologic fluid. However, nanometer thick regions of oxides are lost at locations of high strain due to significant bending, micromotion between overlapping stents or local calcification1‐2. Recent studies have revealed that some stents undergo corrosion in vivo, with significant release of metallic ions into surrounding tissues3–4. In this project, a range of techniques has been employed to modify the surface of miniature NiTi stents in order to mimic in vivo corrosion and correlate the amount of nickel ions released with the findings in explanted tissue.

PURPOSE To investigate the effects of abutment design to correct for implant angulation and aging on the fracture resistance of zirconia abutments. Greater understanding of the fracture strength of the zirconia abutments under various clinical conditions may lead to improvement of clinical protocols and possibly limit potential failures of implant prosthetics. MATERIALS AND METHODS Test specimens consisted of an implant-zirconia abutment-zirconia crown assembly with implant apex positioned at 0°, 20° to the facial (20F), and 20° to the lingual (20L) with respect to a constant crown contour. To keep the abutment design as the only variable, CAD/CAM technology was used to generate monolithic zirconia crowns identical both in external and internal dimensions and marginal contours to precisely fit all the abutments in an identical fashion. The monolithic zirconia abutments were designed to fit the constant crown contours and the internal connection of the implant at the three angulations. The customized abutments for the three implant angulations varied in emergence profile, screw hole location, and material thickness around the screw hole. Half the specimens from each group were subjected to steam autoclaving and thermocycling to simulate aging of the restorations in vivo. To mimic the off-axis loading of the central incisor, the specimens were loaded at the recommended cephalometric interincisal relationship of 135° between the long axis of the crown supported by the implant and the Instron force applicator simulating the mandibular incisor. The force applicator was positioned 2 mm from the incisal edge and loaded at a 1 mm/min crosshead speed. Data were evaluated by 2-way ANOVA (α = 0.05) and Tukey's HSD. RESULTS The 20F group had the highest fracture values followed by the 0° group, and the 20L group had the lowest fracture values. Aging did not yield any significant difference in fracture force magnitudes. CONCLUSION Within the limitations of this study, tilting the implant apex to the lingual significantly reduced the fracture strength of angle-corrected zirconia abutments. Accordingly, while the angle between the occlusal force application and the long axis of the implant decreases, the resistance (force) to fracture decreases.

Nitrogen additions are known to improve both the pitting potentials and fatigue response of high-nitrogen austenitic stainless steels (HNASS). HNASS alloys are of particular interest to the biomedical industry due to patient allergy concerns. Available HNASS fatigue studies in the literature were all performed on materials in the solution annealed condition, and not the 20–30% cold-worked condition often ordered for implant manufacturing. Previous studies in our laboratories evaluated the corrosion fatigue response of commercially available cold-worked 316L and HNASS implant grade steels, and found evidence of unusual cleavage-like facets in the crack initiation and early propagation regions of the fracture surfaces in the HNASS. The 316L steel showed a typical ductile fatigue striated fracture surface with no evidence of cleavage-like facets. These findings suggested the fatigue crack initiation mechanisms may be different between the two austenitic steels. The purpose of the present study was to compare and contrast fatigue crack initiation mechanisms in the cold-worked 316L and HNASS steels, using an SEM and EBSD based examination technique, under both low-cycle and high-cycle conditions. Under both fatigue conditions, cracks were shown to preferentially initiate along former annealing twin boundaries in the HNASS steel. In contrast, fatigue crack initiation was shown to occur primarily along extrusions or intrusions associated with trans-granular slip markings in the 316L steel.