Application of Sub-Micrometer Vibrations to Mitigate Bacterial Adhesion

Authors

Will R. Paces, Hal R. Holmes, Eli Vlaisavljevich, Katherine L. Snyder, Ee Lim Tan, Rupak M. Rajachar and Keat Ghee Ong

Abstract

As a prominent concern regarding implantable devices, eliminating the threat of opportunistic bacterial infection represents a significant benefit to both patient health and device function. Current treatment options focus on chemical approaches to negate bacterial adhesion, however, these methods are in some ways limited. The scope of this study was to assess the efficacy of a novel means of modulating bacterial adhesion through the application of vibrations using magnetoelastic materials. Magnetoelastic materials possess unique magnetostrictive property that can convert a magnetic field stimulus into a mechanical deformation. In vitro experiments demonstrated that vibrational loads generated by the magnetoelastic materials significantly reduced the number of adherent bacteria on samples exposed to Escherichia coli, Staphylococcus epidermidis and Staphylococcus aureus suspensions. These experiments demonstrate that vibrational loads from magnetoelastic materials can be used as a post-deployment activated means to deter bacterial adhesion and device infection.

Link To Article

http://dx.doi.org/10.3390/jfb5010015

Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

Authors

Tracy A. Brennan, Kevin P. Egan, Carter M. Lindborg, Qijun Chen, Mariya T. Sweetwyne, Kurt D. Hankenson, Sharon X. Xie, Frederick B. Johnson and Robert J. Pignolo

Abstract

A major challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. Using mice with disrupted telomere maintenance mechanisms, including mutants in Werner helicase (Wrn-/-), telomerase (Terc-/-) and Wrn-/- Terc-/- double mutants, we evaluated their skeletal phenotypes as models for human bone aging. Compared to young wild-type (WT) mice, micro-computerized tomography analysis revealed that young Terc-/- and Wrn-/-Terc-/- mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc-/- and Wrn-/-Terc-/- mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc-/- and Wrn-/-Terc-/- mice compared to older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc-/- and Wrn-/-Terc-/- bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn-/- single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy, and moment of inertia) of the Terc-/- and Wrn-/-Terc-/- femurs compared to WT mice were also observed. Young Wrn-/-Terc-/- mice had a statistically significant increase in bone marrow fat content compared to young WT mice, which remained elevated in aged double mutants. Taken together, our results suggest that Terc-/- and Wrn-/-Terc-/- mutants recapitulate the human bone aging phenotype and are useful models for studying age-related osteoporosis.

Link To Article

http://dx.doi.org/10.1242/dmm.014928

The Swaying mouse as a model of Osteogenesis Imperfecta caused by WNT1 mutations

Authors

Kyu Sang Joeng, Yi-Chien Lee, Ming-Ming Jiang, Terry K. Bertin, Yuqing Chen, Annie Mary Abraham, Hao Ding, Xiaohong Bi, Catherine Ambrose and Brendan H. Lee

Abstract

Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue characterized by bone fragility and low bone mass. Recently, our group and others reported that WNT1 recessive mutations cause OI while WNT1 heterozygous mutations cause early onset osteoporosis. These findings support the hypothesis that WNT1 is an important WNT ligand regulating bone formation and bone homeostasis. While these studies provided strong human genetic and in vitro functional data, an in vivo animal model to study the mechanism of WNT1 function in bone is lacking. Here, we show that Swaying (Wnt1sw/sw) mice previously reported to carry a spontaneous mutation in Wnt1 share major features of OI including propensity to fractures and severe osteopenia. In addition, biomechanical and biochemical analyses showed that Wnt1sw/sw mice exhibit reduced bone strength with altered levels of mineral and collagen in the bone matrix that is also distinct from type I collagen-related form of OI. Further histomorphometric analyses and gene expression studies demonstrate that the bone phenotype is associated with defects in osteoblast activity and function. Our study thus provides the in vivo evidence that WNT1 mutations contribute to bone fragility in OI patients and demonstrates that the Wnt1sw/sw mouse is a murine model of OI caused by WNT1 mutations.

Link To Article

http://dx.doi.org/10.1093/hmg/ddu117

Development of new criteria for cortical bone histomorphometry in femoral neck: intra- and inter-observer reproducibility

Authors

Xiao-Yu Tong, Markus Malo, Inari S. Tamminen, Hanna Isaksson, Jukka S. Jurvelin, Heikki Kröger

Abstract

Histomorphometry is commonly applied to study bone remodeling. Histological definitions of cortical bone boundaries have not been consistent. In this study, new criteria for specific definition of the transitional zone between the cortical and cancellous bone in the femoral neck were developed. The intra- and inter-observer reproducibility of this method was determined by quantitative histomorphometry and areal overlapping analysis. The undecalcified histological sections of femoral neck specimens (n = 6; from men aged 17–59 years) were processed and scanned to acquire histological images of complete bone sections. Specific criteria were applied to define histological boundaries. “Absolute cortex area” consisted of pure cortical bone tissue only, and was defined mainly based on the size of composite canals and their distance to an additional “guide” boundary (so-called “preliminary cortex boundary,” the clear demarcation line of density between compact cortex and sparse trabeculae). Endocortical bone area was defined by recognizing characteristic endocortical structures adjacent to the preliminary cortical boundary. The present results suggested moderate to high reproducibility for low-magnification parameters (e.g., cortical bone area). The coefficient of variation (CV %) ranged from 0.02 to 5.61 in the intra-observer study and from 0.09 to 16.41 in the inter-observer study. However, the intra-observer reproducibility of some high-magnification parameters (e.g., osteoid perimeter/endocortical perimeter) was lower (CV %, 0.33–87.9). The overlapping of three histological areas in repeated analyses revealed highest intra- and inter-observer reproducibility for the absolute cortex area. This study provides specific criteria for the definition of histological boundaries for femoral neck bone specimens, which may aid more precise cortical bone histomorphometry.

Link To Article

http://dx.doi.org/10.1007/s00774-014-0562-1

Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings

Authors

Inari S. Tamminen, Helena Valta, Hannu Jalanko, Sari Salminen, Mervi K. Mäyränpää, Hanna Isaksson, Heikki Kröger, Outi Mäkitie

Abstract

Background

Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis.

Methods

Iliac crest biopsies were obtained from 19 children (7.6–18.8 years, 11 male) who had undergone kidney (n = 6), liver (n = 9), or heart (n = 4) transplantation a median 4.6 years (range 0.6–16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy.

Results

Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below −2.0. Histomorphometric analyses showed low trabecular bone volume (< −1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease.

Conclusions

There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.

Link To Article

http://dx.doi.org/10.1007/s00467-014-2771-1

Deferoxamine Enhances Bone Regeneration in Mandibular Distraction Osteogenesis

Authors

Farberg, Aaron S. M.D.; Sarhaddi, Deniz B.A.; Donneys, Alexis M.D.; Deshpande, Sagar S. B.S.; Buchman, Steven R. M.D.

Abstract

Background: Distraction osteogenesis is a powerful reconstructive technique for bone growth and repair. An angiogenic means of enhancing the efficacy of this metabolically demanding procedure would be beneficial in expanding its therapeutic potential. The authors posit that the angiogenic effect of deferoxamine, an iron chelator that has been shown to increase angiogenesis, will improve bone regeneration by means of augmentations in quality and quantity of bone and bone-producing cells.

Methods: Two groups of rats (n = 12) underwent surgical external fixation and subsequent distraction. During the distraction stage, the experimental deferoxamine group (n = 5) was treated with injections into the distraction gap. After 28 days of consolidation, mandibles were harvested and prepared for histologic analysis.

Results: The authors found a proliferation of osteocytes in the deferoxamine-treated group when compared with the regenerate of the control group. Deferoxamine effected a significant increase in osteocytes and an increase in bone volume fraction, with subsequent decreased osteoid volume fraction. The data also demonstrated no significant difference in empty lacunae.

Conclusions: The authors’ study demonstrates the effectiveness of deferoxamine treatment to enhance the number of osteocytes within the regenerate in a murine mandibular distraction osteogenesis model. Maintenance of full lacunae supports the authors’ finding of a robust cellular response to deferoxamine therapy. These results suggest that the angiogenic capabilities of deferoxamine translate into an increase in the number of bone-forming cells in the regenerate. Deferoxamine may have utility in optimizing bone formation in distraction osteogenesis and lead to superior reconstructive capabilities for craniofacial surgeons in the future.

Link To Article

http://dx.doi.org/10.1097/01.prs.0000438050.36881.a9