Failure Modes of Biomedical Implants

The metallic biomaterials are very well known among various biomaterials. Stainless steel was used successfully as an implant material in the surgical field, then Vitallium, cobalt based alloys were used as implant materials. Titanium is the newest metallic biomaterial among three main metallic biomaterials, stainless steels, Co-based alloys and titanium alloys. These materials are used for the instrumentation replacing failed hard tissue, for example, artificial hip joints, artificial knee joints, bone plates, dental implants and in similar applications. Biocompatibility characteristics of titanium alloys make it the preferred choice for such applications, additional factors being light weight, excellent mechanical properties, corrosion and wear resistance. The fatigue behavior of biomedical materials is as important as other properties, yet fatigue characteristics are not considered while selecting a particular material for bio applications. This report summarizes the fatigue behavior of biomaterials and also presents a summary from published sources where inferior fatigue resistance lead to the total joint replacement recalls. This paper reviews the fatigue, wear and corrosion resistance of biomaterials that will be useful in the design of bio prostheses

Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice

The high mobility group AT-hook 2 (HMGA2) protein works as an architectural regulator by binding AT-rich DNA sequences to induce conformational changes affecting transcription. Genomic deletions disrupting HMGA2 coding sequences and flanking noncoding sequences cause dwarfism in mice and rabbits. Here, CRISPR/Cas9 was used in mice to generate an Hmga2 null allele that specifically disrupts only the coding sequence. The loss of one or both alleles of Hmga2 resulted in reduced body size of 20% and 60%, respectively, compared to wild-type littermates as well as an allometric reduction in skull length in Hmga2(-/-) mice. Both male and female Hmga2(-/-) mice are infertile, whereas Hmga2(+/-) mice are fertile. Examination of reproductive tissues of Hmga2(-/-) males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed. Sperm analyses revealed severe oligospermia in mutant males and slightly decreased sperm viability, increased DNA damage but normal sperm chromatin compaction. Testis histology surprisingly revealed a normal seminiferous epithelium, despite the significant reduction in testis size. In addition, Hmga2(-/-) mice showed a significantly reduced exploratory behavior. In summary, the phenotypic effects in mouse using targeted mutagenesis confirmed that Hmga2 is affecting prenatal and postnatal growth regulation, male reproductive tissue development, and presents the first indication that Hmga2 function is required for normal mouse behavior. No specific effect, despite an allometric reduction, on craniofacial development was noted in contrast to previous reports of an altered craniofacial development in mice and rabbits carrying deletions of both coding and noncoding sequences at the 5 ' part of Hmga2

Can Acute Galactic Cosmic Radiation-Induced Bone Loss Be Mitigated By Dietary Modulation Of Inflammatory Cytokines?

The space environment includes weightlessness and galactic cosmic radiation (GCR), both of which can have a negative impact on bone parameters. In particular, acute exposures to space-relevant doses (2 Gy or less) of simulated GCR lead to a rapid acceleration of bone resorption activity and suppression of bone forming osteoblasts, resulting in diminished bone mineral density (BMD), strength and altered microarchitecture. A key mechanism driving these changes may be a radiation-induced increase in pro-inflammatory cytokines, such as TNF-α. Consuming a diet rich in omega-3 fatty acids has been associated with attenuated reductions in bone parameters in astronauts, mice and elderly humans with corresponding reductions in circulating inflammatory cytokines. PURPOSE: To test the hypothesis thata diet high in omega-3 fatty acids will mitigate radiation-induced bone loss and reduce inflammatory cytokines in bone osteocytes and serum. METHODS: Adult (30- to 50-week-old) female Lgr5-EGFP C57BL/6 mice (n=4-6 per group) were acclimated to a corn oil/cellulose (COC) or fish oil/pectin (FOP) diet for 3 weeks. Animals were subsequently randomized to total body low dose high-energy radiation (0.1, 0.25, 0.5 Gy of 1000 MeV/n 56Fe at 25 cGy/min at Brookhaven National Lab) or non-irradiated control (sham) and euthanized 8 weeks later. MicroCT (ScanCo, Switzerland) analyses were performed to assess bone geometry and microarchitecture at the mid-shaft and distal end of the femur. Significance was assessed using an αof 0.10. RESULTS:There was a significant main effect of diet on mid-shaft femur periosteal diameter (Peri.Dm) (p=0.001) and endocortical diameter (Endo. Dm.) (p\u3c0.001). The FOP diet led to larger Peri.Dm. (p\u3c0.051 for all) and Endo.Dm. (p\u3c0.41 for all) than did the COC diet at all doses. We could not detect an impact of 56Fe on cortical area or cancellous bone volume at the distal femur. Irradiation with 0.25 and 0.5 Gy in the FOP mice showed significant increases in distal femur volumetric BMD (p=0.014, p=0.063) and trabecular thickness (p=0.058, p=0.028), as compared with sham FOP mice. CONCLUSION: Though we did not detect a significant impact of radiation on bone parameters, these early data analyses suggest some modest benefits from a diet high in omega-3 fatty acids on cortical and cancellous bone parameters

Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice

ABSTRACT Chronic ethyl alcohol (EtOH) consumption results in reactive oxygen species (ROS) generation in bone and osteopenia due to increased bone resorption and reduced bone formation. In this study, transgenic C57Bl/6J mice overexpressing human catalase (TgCAT) were used to test whether limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. Micro-computed tomography analysis of the skeletons of 6-week-old female chow-fed TgCAT mice revealed a high bone mass phenotype with increased cortical bone area and thickness as well as significantly increased trabecular bone volume (P , 0.05). Six-week-old wild-type (WT) and TgCAT female mice were chow fed or pair fed (PF) liquid diets with or without EtOH, approximately 30% of calories, for 8 weeks. Pair feeding of WT had no demonstrable effect on the skeleton; however, EtOH feeding of WT mice significantly reduced cortical and trabecular bone parameters along with bone strength compared with PF controls (P , 0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared with PF controls. At 14 weeks of age, there was significantly less trabecular bone and cortical cross-sectional area in TgCAT mice than WT mice (P , 0.05), suggesting impaired normal bone accrual with age. TgCAT mice expressed less collagen1a and higher sclerostin mRNA (P , 0.05), suggesting decreased bone formation in TgCAT mice. In conclusion, catalase overexpression resulted in greater bone mass than in WT mice at 6 weeks and lower bone mass at 14 weeks. EtOH feeding induced significant reductions in bone architecture and strength in WT mice, but TgCAT mice were partially protected. These data implicate ROS signaling in the regulation of bone turnover in an age-dependent manner, and indicate that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia

Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone

During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility

Resolving the Two “Bony” Faces of PPAR-γ

Bone loss with aging results from attenuated and unbalanced bone turnover that has been associated with a decreased number of bone forming osteoblasts, an increased number of bone resorbing osteoclasts, and an increased number of adipocytes (fat cells) in the bone marrow. Osteoblasts and adipocytes are derived from marrow mesenchymal stroma/stem cells (MSC). The milieu of intracellular and extracellular signals that controls MSC lineage allocation is diverse. The adipocyte-specific transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) acts as a critical positive regulator of marrow adipocyte formation and as a negative regulator of osteoblast development. In vivo, increased PPAR-γ activity leads to bone loss, similar to the bone loss observed with aging, whereas decreased PPAR-γ activity results in increased bone mass. Emerging evidence suggests that the pro-adipocytic and the anti-osteoblastic properties of PPAR-γ are ligand-selective, suggesting the existence of multiple mechanisms by which PPAR-γ controls bone mass and fat mass in bone