Nano- to Macroscale Remodeling of Functional Tissue-Engineered Bone

Authors

Maria Ann Woodruff, Claudia Lange, Fulin Chen, Peter Fratzl, Dietmar Werner Hutmacher

Abstract

A higher degree of mineralization is found within scaffold groups implanted with cells compared to scaffold alone, demonstrating greater bone regenerative potential of cell-scaffold constructs Tissue engineered bone analysed using ESEM and SAXS demonstrates bone formation within the scaffold to be preferentially aligned around the scaffold struts. The mineral particles are not shown to orientate around the osteons within the native bone.

Link to Article

http://dx.doi.org/10.1002/adhm.201200289

Antagonism of Inhibitor of Apoptosis Proteins Increases Bone Metastasis via Unexpected Osteoclast Activation

Authors

Chang Yang, Jennifer L. Davis, Rong Zeng, Paras Vora, Xinming Su, Lynne I. Collins, Suwanna Vangveravong, Robert H. Mach, David Piwnica-Worms, Katherine N. Weilbaecher, Roberta Faccio, and Deborah Veis Novack

Abstract

Inhibitor of apoptosis (IAP) proteins play a central role in many types of cancer, and IAP antagonists are in development as anticancer agents. IAP antagonists cause apoptosis in many cells, but they also activate alternative NF-κB signaling through NF-κB–inducing kinase (NIK), which regulates osteoclasts. In bone metastasis, a positive feedback loop between tumors and osteoclasts promotes tumor growth and osteolysis. We therefore tested the effect of IAP antagonists on the bone microenvironment for metastasis. In both drug-sensitive and drug-resistant tumors, growth in bone was favored, as compared with other sites during IAP antagonist treatment. These drugs also caused osteoporosis and increased osteoclastogenesis, mediated by NIK, and enhanced tumor-associated osteolysis. Cotreatment with zoledronic acid, a potent osteoclast inhibitor, reduced IAP antagonist–enhanced tumor growth in bone and osteolysis. Thus, IAP antagonist–based cancer treatment may be compromised by osteoporosis and enhanced skeletal metastasis, which may be prevented by antiresorptive agents. Significance: Although IAP antagonists are a class of anticancer agents with proven efficacy in multiple cancers, we show that these agents can paradoxically increase tumor growth and metastasis in the bone by stabilizing NIK and activating the alternative NF-κB pathway in osteoclasts. Future clinical trials of IAP antagonist–based therapy may require detailed examination of this potential for enhanced bone metastasis and osteoporosis, as well as possible combination with antiresorptive agents.

Link to Article

http://dx.doi.org/10.1158/2159-8290.CD-12-0271

Effects of Non-Weight-Bearing on the Immature Femoral Head Following Ischemic Osteonecrosis: An Experimental Investigation in Immature Pigs

Authors

Harry K.W. Kim, Olumide Aruwajoye, Jeffrey Stetler, Alec Stall

Abstract

Local non-weight-bearing as a treatment for Legg-Calvé-Perthes disease remains controversial since a clear scientific basis for this treatment is lacking. The purpose of this study was to determine the effects of non-weight-bearing on decreasing the femoral head deformity following ischemic osteonecrosis and to investigate its biological effects. Unilateral femoral head ischemia was induced in sixteen piglets by placing a ligature around the femoral neck and transecting the ligamentum teres. Eight animals received a hind-limb amputation to prevent weight-bearing on the ischemic side (NWB group). The remaining eight piglets were allowed to bear weight as tolerated (WB group). The contralateral femoral heads of the WB group were used as normal controls. All animals were killed at eight weeks after induction of ischemia, when a deformity is expected in this model. Radiographic, microcomputed tomographic (micro-CT), and histomorphometric assessments were performed. Radiographic and micro-CT assessments showed significantly greater flattening of the infarcted epiphysis in the WB group compared with the NWB group. The mean epiphyseal quotient (ratio of femoral head height to diameter) was significantly lower in the WB group (0.29 ± 0.06) compared with the NWB group (0.41 ± 0.06, p < 0.001). Histomorphometric analyses showed that the mean percentage revascularization of the infarcted epiphysis was significantly greater in the NWB group (95% ± 14%) compared with the WB group (34% ± 33%, p < 0.0004), suggesting that revascularization was more rapid in the NWB group. Both histomorphometric and micro-CT analyses of trabecular bone parameters showed significantly decreased bone volume and decreased trabecular number in the infarcted epiphysis of the NWB group compared with the WB group (p < 0.05). Local non-weight-bearing decreased the deformity following ischemic femoral head osteonecrosis and increased the rates of revascularization and resorption of the infarcted epiphysis. Local non-weight-bearing was mechanically protective but biologically suboptimal following ischemic osteonecrosis since it increased the imbalance of bone resorption and formation.

Link to Article

http://dx.doi.org/10.2106/JBJS.L.00300

Nano-crystalline diamond-coated titanium dental implants – A histomorphometric study in adult domestic pigs

Authors

Philipp Metzler, Cornelius von Wilmowsky, Bernd Stadlinger, Wolfgang Zemann, Karl Andreas Schlegel, Stephan Rosiwal, Stephan Rupprecht

Abstract

Promising biomaterial characteristics of diamond-coatings in biomedicine have been described in the literature. However, there is a lack of knowledge about implant osseointegration of this surface modification compared to the currently used sandblasted acid-etched Ti-Al6-V4 implants. The aim of this study was to investigate the osseointegration of microwave plasma-chemical-vapour deposition (MWP-CVD) diamond-coated Ti-Al6-V4 dental implants after healing periods of 2 and 5 months. Twenty-four MWP-CVD diamond-coated and 24 un-coated dental titanium-alloy implants (Ankylos®) were placed in the frontal skull of eight adult domestic pigs. To evaluate the effects of the nano-structured surfaces on bone formation, a histomorphometric analysis was performed after 2 and 5 months of implant healing. Histomorphometry analysed the bone-to-implant contact (BIC). No significant difference in BIC for the diamond-coated implants in comparison to reference implants could be observed for both healing periods. Scanning electron microscopy revealed an adequate interface between the bone and the diamond surface. No delamination or particle-dissociation due to shearing forces could be detected. In this study, diamond-coated dental titanium-alloy implants and sandblasted acid-etched implants showed a comparable degree of osseointegration.

Link to Article

http://dx.doi.org/10.1016/j.jcms.2012.11.020

Validation of histologic bone analysis following Microfil vessel perfusion

Authors

Sarhaddi, D; Poushanchi, B; Merati, M; Tchanque-Fossuo, C; Donneys, A; Baker, J; Buchman, S R

Abstract

The ability to examine bone vascularity using micro-computed tomography following vessel perfusion with Microfil® and to subsequently perform histologic bone analysis in the same specimen would provide an efficient method by which the vascular and cellular environment of bone can be examined simultaneously. The purpose of this report is to determine if the administration of Microfil precludes accurate histologic assessment of bone quality via osteocyte count and empty lacunae count. Sprague‐Dawley rats (n = 6) underwent perfusion with Microfil. Left hemi-mandibles were harvested, decalcified, and underwent vascular analysis via micro-computed tomography prior to sectioning and staining with Gomori’s trichrome. Quantitative histomorphometric evaluation was performed. Ninety-five percent confidence intervals (CIs) were used to determine statistical differences from an established set of controls (n = 12). Histologic analyses were successfully performed on specimens that had been perfused. Quantitative measures of bone cellularity of perfused versus control specimens revealed no statistical difference in osteocyte count per high-power field (95·33 versus 94·66; 95% CI: −7·64 to 6·30) or empty lacunae per high-power field (2·73 versus 1·89; 95% CI: −1·81 to 0·13). A statistical validation is reported that allows histologic analysis of cell counts in specimens which had been perfused with Microfil.

Link to Article

http://dx.doi.org/10.1179/2046023612Y.0000000012

The Effects of Delayed Puberty on the Growth Plate

Authors

Butler, Tiffiny A.; Yingling, Vanessa R

Abstract

Many athletes are beginning intense training before puberty, a time of increased bone accrual when up to 25% of total bone mineral accrual occurs. Female athletes experiencing late or delayed pubertal onset may have open epiphyseal plates that are vulnerable to injury. This investigation's purpose was to determine whether a delay in puberty (primary amenorrhea) affects the growth plate immediately postpuberty and at maturity. Forty-eight female Sprague-Dawley rats (23 d old) were randomly assigned to 4 groups (n=12); short-term control (C-ST), long-term control (C-LT), short-term GnRH antagonist (G-ST), and long-term GnRH antagonist (G-LT). At 25 days of age, daily gonadotropin-releasing hormone antagonist (GnRH-a) injections were administered delaying pubertal onset. Left tibias were analyzed. Stained frontal slices of proximal tibia (5 µm thick) were analyzed in hypertrophic, proliferative, and reserve zones for total height, zone height, and cell/column counts. All procedures were approved by Institutional Animal Care and Use Committee at Brooklyn College. Growth plate height was 19.7% wider in delayed puberty (G-ST) group and at maturity was 27.9% greater in G-LT group compared with control (C-LT) (P<0.05). No significant differences were found in short-term or long-term growth plate zone heights or cell/column counts between groups (P>0.05). Growth plate zone height normalized to total height resulted in 28.7% larger reserve zone in the short-term GnRH-a group but the proliferative zone was 8.5% larger in the long-term group compared with the control group (P<0.05). Normalized to growth plate height a significant decrease was found in column counts in proliferative zones of the short-term and long-term GnRH-a groups. Current data illustrate that delayed puberty using GnRH-a injections results in significant growth plate height and decreases proliferative column counts and zone height, thus potentially contributing to decreases in bone mass at maturity. Growth plate height increases indicate increased potential for growth and bone accrual. However, previous models report decreased bone volume following delayed puberty via GnRH-a injections that may have detrimental effects in the long term.

Link to Article

http://dx.doi.org/10.1097/BPO.0b013e31826a53f2