Sample records for bone matrix dbm

  1. Demineralized Bone Matrix (DBM) as a Bone Void Filler in Lumbar Interbody Fusion: A Prospective Pilot Study of Simultaneous DBM and Autologous Bone Grafts (United States)

    Kim, Bum-Joon; Kim, Se-Hoon; Lee, Haebin; Lee, Seung-Hwan; Kim, Won-Hyung; Jin, Sung-Won


    Objective Solid bone fusion is an essential process in spinal stabilization surgery. Recently, as several minimally invasive spinal surgeries have developed, a need of artificial bone substitutes such as demineralized bone matrix (DBM), has arisen. We investigated the in vivo bone growth rate of DBM as a bone void filler compared to a local autologous bone grafts. Methods From April 2014 to August 2015, 20 patients with a one or two-level spinal stenosis were included. A posterior lumbar interbody fusion using two cages and pedicle screw fixation was performed for every patient, and each cage was packed with autologous local bone and DBM. Clinical outcomes were assessed using the Numeric Rating Scale (NRS) of leg pain and back pain and the Korean Oswestry Disability Index (K-ODI). Clinical outcome parameters and range of motion (ROM) of the operated level were collected preoperatively and at 3 months, 6 months, and 1 year postoperatively. Computed tomography was performed 1 year after fusion surgery and bone growth of the autologous bone grafts and DBM were analyzed by ImageJ software. Results Eighteen patients completed 1 year of follow-up, including 10 men and 8 women, and the mean age was 56.4 (32–71). The operated level ranged from L3/4 to L5/S1. Eleven patients had single level and 7 patients had two-level repairs. The mean back pain NRS improved from 4.61 to 2.78 (p=0.003) and the leg pain NRS improved from 6.89 to 2.39 (posteoporosis. PMID:28264244

  2. Evaluation of the effect of a gamma irradiated DBM-pluronic F127 composite on bone regeneration in Wistar rat.

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    Tamer Al Kayal

    Full Text Available Demineralized bone matrix (DBM is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127 composite implanted in the femur of rats. Gamma irradiation effects (25 kGy on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability.

  3. Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect. (United States)

    Zhang, Yumin; Wang, Jianru; Wang, Jue; Niu, Xiaojun; Liu, Jianchun; Gao, Lan; Zhai, Xiaoyan; Chu, Kaibo


    Bone substitutes are used in wide range of orthopaedic application. An ideal bone substitute should exhibit superior osteoinductive and osteoconductive properties. Neither bio-derived materials nor synthetic materials can meet the needs of an ideal bone substitute. Preparation of composite materials is a promising way to improve properties of biomaterial. In this study, the porous poly lactic acid (PLA)/demineralized bone matrix (DBM) composite biomaterials prepared by supercritical CO2 technique were implanted to repair rabbit radius segmental bone defect. By comparing with PLA and bone autograft, the X-ray result and histological analysis showed the repair effect of PLA/DBM porous composite materials is significantly better than that of the PLA group and the blank control group, and is similar to autologous bone. The PLA/DBM can promote the healing of bone defects and can be used as a kind of ideal alternative materials to repair bone defects.

  4. Biomimetically Enhanced Demineralized Bone Matrix for Bone Regenerative Applications

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    Sriram eRavindran


    Full Text Available Demineralized bone matrix (DBM is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically-enhanced version of DBM (BE-DBM using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro-osteogenic extracellular matrix (ECM within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice.

  5. Bone induction by composite of bioerodible polyorthoester and deminiralized bone matrix in rats

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    Pinholt, E.M.; Solheim, E. (Institute for Surgical Research, Rikshospitalet, University of Oslo (Norway)); Bang, G. (Department of Oral Pathology and Forensic Odontology, University of Bergen (Norway)); Sudmann, E. (Hagavik Orthopedic Hospital, University of Bergen (Norway))


    A composite of a local, sustained, drug-release system, Alzamer bioerodible polyorthoester, and demineralized bone-matrix (DBM) particles implanted in the abdominal muscle of 89 Wistar rats induced cartilage and bone formation at the same rate as DBM when evaluated histologically and by {sup 85}Sr uptake. The composite implant was technically easier to use than DBM alone. (author).

  6. Bone induction by composite of bioerodible polyorthoester and demineralized bone matrix in rats

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    Pinholt, E M; Solheim, E; Bang, G


    A composite of a local, sustained, drug-release system, Alzamer bioerodible polyorthoester, and demineralized bone-matrix (DBM) particles implanted in the abdominal muscle of 89 Wistar rats induced cartilage and bone formation at the same rate as DBM when evaluated histologically and by 85Sr uptake...

  7. The clinical study on the application of calcium sulfate/Demineralized bone matrix (DBM) granule in the cervical interbody fusion%硫酸钙/脱钙骨基质颗粒在颈椎椎体间融合中的应用

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    谢幼专; 张蒲; 富灵杰; 李华; 赵杰


    Objective To investigate the clinical outcome of interbody fusion with calcium sulfate/demineralized bone matrix ( DBM ) granule in the cervical spine. Methods 35 patients had undergone anterior cervical discectomy and interbody fusion ( 59 segments )with the polyetheretherketone (PEEK )cages filled with calcium sulfate/DBM granule. There were 19 male and 16 female. The mean age was 53.2 years old (range, 32-65 1 The fusion was agumented with anterior cervical plate. There were 12 cases of cervical spondylotic radiculopathy, 15 cases of cervical spondylotic myelopathy and 8 cases of combined cervical spondylosis. The JOA score, cervical curvature and the fusion status were evaluated after the operation. Results All the patients were followed up consecutively for 24 months. The preoperative JOA score was 7.7± 2.1. At final follow-up, the score was 14.2±2.9 (P < 0.01 I The recovery rate was 69.9%. There was no breakage, looseness or migration of the implants. The fusion rate was 100%. Conclusion It is feasible to achieve the cervical interbody fusion with the PEEK cage filled with calcium sulfate/DBM granule.%目的 观察应用硫酸钙/脱钙骨基质颗粒作为植骨替代材料促进颈椎椎体间融合的效果.方法 对35例患者(59个节段)行颈椎前路间隙减压植骨融合钛板固定术,椎体间植骨采用填充硫酸钙/脱钙骨基质颗粒的聚醚醚酮(PEEK)融合器.其中男19例,女16例,年龄32~65岁,平均53.2±12.5岁.其中神经根型颈椎病12例,脊髓型颈椎病15例,混合型颈椎病8例.术后观察JOA评分、颈椎曲度、椎体间融合情况.结果 35例均获随访,随访时间24个月.JOA评分术前为7.7±2.1,随访终止时为14.2±2.9(P<0.01),恢复率为69.9%.术后无钛板、螺钉断裂或松动,无融合器移位现象发生.所有融合节段均融合.结论 颈椎前路减压融合术中使用填充硫酸钙/脱钙骨基质颗粒的PEEK椎体间融合器能够获得满意的椎体间融合.

  8. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow. (United States)

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong


    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic.

  9. When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential. (United States)

    Dozza, B; Lesci, I G; Duchi, S; Della Bella, E; Martini, L; Salamanna, F; Falconi, M; Cinotti, S; Fini, M; Lucarelli, E; Donati, D


    Demineralized bone matrix (DBM) is a natural, collagen-based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1-2 mm), medium (M, 0.5-1 mm), and small (S, structure, with DBM-M being altered but not as much as DBM-S. DBM-M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM-M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. In conclusion, the collagen alteration in DBM-M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5-1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue-engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019-1033, 2017.

  10. Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones

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    Rubenbauer Bianka


    Full Text Available Abstract Background Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the market, this comparative study aims to evaluate healing characteristics of ununited bones treated with ORIF combined with either iliac-crest-autologous-bone-grafting (ICABG or demineralized-bone-matrix (DBM. Methods and results From 2000 to 2006 out of sixty-two consecutive patients with non-unions presenting at our Level I Trauma Center, twenty patients had ununited diaphyseal fractures of long bones and were treated by ORIF combined either by ICABG- (n = 10 or DBM-augmentation (n = 10. At the time of index-operation, patients of the DBM-group had a higher level of comorbidity (ASA-value: p = 0.014. Mean duration of follow-up was 56.6 months (ICABG-group and 41.2 months (DBM-group. All patients were clinically and radiographically assessed and adverse effects related to bone grafting were documented. The results showed that two non-unions augmented with ICABG failed osseous healing (20% whereas all non-unions grafted by DBM showed successful consolidation during the first year after the index operation (p = 0.146. No early complications were documented in both groups but two patients of the ICABG-group suffered long-term problems at the donor site (20% (p = 0.146. Pain intensity were comparable in both groups (p = 0.326. However, patients treated with DBM were more satisfied with the surgical procedure (p = 0.031. Conclusion With the use of DBM, the costs for augmentation of the non-union-site are more expensive compared to ICABG (calculated difference: 160

  11. Effect of allogenic freeze-dried demineralized bone matrix on guided tissue regeneration in dogs. (United States)

    Caplanis, N; Lee, M B; Zimmerman, G J; Selvig, K A; Wikesjö, U M


    This randomized, split-mouth study was designed to evaluate the adjunctive effect of allogenic, freeze-dried, demineralized bone matrix (DBM) to guided tissue regeneration (GTR). Contralateral fenestration defects (6 x 4 mm) were created 6 mm apical to the buccal alveolar crest on maxillary canine teeth in 6 beagle dogs. DBM was implanted into one randomly selected fenestration defect. Expanded polytetrafluoroethylene (ePTFE) membranes were used to provide bilateral GTR. Tissue blocks including defects with overlying membranes and soft tissues were harvested following a four-week healing interval and prepared for histometric analysis. Differences between GTR+DBM and GTR defects were evaluated using a paired t-test (N = 6). DBM was discernible in all GTR+DBM defects with limited, if any, evidence of bone metabolic activity. Rather, the DBM particles appeared solidified within a dense connective tissue matrix, often in close contact to the instrumented root. There were no statistically significant differences between the GTR+DBM versus the GTR condition for any histometric parameter examined. Fenestration defect height averaged 3.7+/-0.3 and 3.9+/-0.3 mm, total bone regeneration 0.8+/-0.6 and 1.5+/-0.8 mm, and total cementum regeneration 2.0+/-1.3 and 1.6+/-1.7 mm for GTR+DBM and GTR defects, respectively. The histologic and histometric observations, in concert, suggest that allogenic freeze-dried DBM has no adjunctive effect to GTR in periodontal fenestration defects over a four-week healing interval. The critical findings were 1) the DBM particles remained, embedded in dense connective tissue without evidence of bone metabolic activity; and 2) limited and similar amounts of bone and cementum regeneration were observed for both the GTR+DBM and GTR defects.

  12. Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1α Promote Bone Regeneration via Recruiting Endogenous Stem Cells. (United States)

    Shi, Jiajia; Sun, Jie; Zhang, Wen; Liang, Hui; Shi, Qin; Li, Xiaoran; Chen, Yanyan; Zhuang, Yan; Dai, Jianwu


    The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1α (CBD-SDF-1α). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1α could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1α-modified DBM scaffolds could efficiently mobilize CD34(+) and c-kit(+) endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1α-modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1α group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson's trichrome staining showed that the CBD-SDF-1α-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1α group had superior strength. In conclusion, CBD-SDF-1α-modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells.

  13. Nanometeric hydroxyapatite in situ formed in demineralized bone matrix by electrochemical technique

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    CHEN Ji-da; WANG Yuan-ling; CAI Hao-xi; CAO Yin


    @@ To prepare biomimic bone materials, some thick meshes of demineralized bone matrix (DBM), which are the interest work of collagen fibrils, have been prepared in normal way, and calcium phosphate of nanometeric was introduced into these mesh works with aqueous calcium and phosphate salt solution by means of the electrochemical technique at room temperature.

  14. Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study

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    Noratep Kulachote


    Full Text Available Background. Delayed union and nonunion are common complications in atypical femoral fractures (AFFs despite having good fracture fixation. Demineralized bone matrix (DBM is a successfully proven method for enhancing fracture healing of the long bone fracture and nonunion and should be used in AFFs. This study aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs fixation with and without DBM. Materials and Methods. A prospective study was conducted on 9 ST-AFFs patients using DBM (DBM group during 2013-2014 and compared with a retrospective consecutive case series of ST-AFFs patients treated without DBM (2010–2012 (NDBM group, 9 patients. All patients were treated with the same standard guideline and followed up until fractures completely united. Postoperative outcomes were then compared. Results. DBM group showed a significant shorter healing time than NDBM group (28.1 ± 14.4 versus 57.9 ± 36.8 weeks, p=0.04. Delayed union was found in 4 patients (44% in DBM group compared with 7 patients (78% in NDBM group (p>0.05. No statistical difference of nonunion was demonstrated between both groups (DBM = 1 and NDBM = 2, p>0.05. Neither postoperative infection nor severe local tissue reaction was found. Conclusions. DBM is safe and effective for accelerating the fracture healing in ST-AFFx and possibly reduces nonunion after fracture fixation. Trial registration number is TCTR20151021001.

  15. Combined effects of porous hydroxyapatite and demineralized bone matrix on bone induction: in vitro and in vivo study using a nude rat model

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    Lee, Jae Hyup; Lee, Kyung-Mee; Baek, Hae-Ri; Jang, Soo-Jeong; Lee, Ji-Ho [Department of Orthopedic Surgery, Seoul National University School of Medicine, SMG-SNU Boramae Medical Center, Seoul 156-707 (Korea, Republic of); Ryu, Hyun-Seung, E-mail: [Research and Development Center, CGBio Inc., Seong-Nam 462-120 (Korea, Republic of)


    Hydroxyapatite (HA) is an osteoconductive material used as a bone graft extender and demineralized bone matrix (DBM) has been used as a source of osteoinductive factors. A combination of DBM and HA is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of DBM and HA on osteogenesis both in vitro and in vivo using an athymic nude rat abdominal muscle pouch model, and evaluated the possibility of HA as a carrier of DBM. Alkaline phosphatase (ALP) staining, ALP assay and measurements of the mRNA expression of ALP and Runx2 by RT-PCR were performed by transplanting human mesenchymal stem cells onto a plate. Five athymic nude rats each were assigned to one of two experimental groups (DBM/HA putty and only HA, i.e. 15 pouches per group). The muscle pouches were filled with DBM/HA putty or only HA. Radiographs were obtained at weeks 4 and 8, postoperatively. The animals were sacrificed at week 8 postoperatively and high resolution microCT was used to confirm the newly formed mineralized tissue. Each pouch was fixed, embedded, sectioned and processed for hematoxylin and eosin staining. The ALP value of the DBM/HA putty was higher than those of HA and control (p < 0.05, each). The expression of ALP mRNA appeared higher on the DBM/HA putty than on HA and control. MicroCT and histology examinations of the DBM/HA putty demonstrated the presence of newly generated mineralized tissues but there was no mineralized tissue in the HA cases. In conclusion, the DBM/HA putty indicated osteoblastic differentiation in vitro and showed ectopic mineralized tissue formation in the rat abdominal pouch model. These findings indicate that the DBM/HA putty can retain its oteoinductivity and HA can be used as a carrier of DBM.

  16. Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix. (United States)

    Liese, Juliane; Marzahn, Ulrike; El Sayed, Karym; Pruss, Axel; Haisch, Andreas; Stoelzel, Katharina


    Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.

  17. Study on biocompatibility of PDLLA/HA/DBM with co-cultured human osteoblasts in vitro

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    郭乔楠; 赵建华; 卢佳友


    Objective: To evaluate the osteocompatibility of D, L-polylactic/hydroxyapatite/decalcifying bone matrix (PDLLA/HA/DBM), and compare with PDLLA and DBM. Methods: Human primary osteoblasts isolated from the femoral head of patients were inoculated onto PDLLA/HA/DBM, PLA and DBM respectively. The proliferation rate and collagen Ⅰ expression were detected. The interface between biomaterial and osteoblasts was investigated with phase contrast microscopy and electron scanning microscopy. Results: Best proliferation rate was observed with the PDLLA/HA/DBM and followed by DBM and PLA, suggesting that PDLLA/HA/DBM satisfying most requirements for the cultivation of human osteoblasts. Scanning electron microscopy showed the morphology of osteoblasts was correlated with the proliferation data. The cells, well spread and flattened, were attached closely on the surface of biomaterial with an arched structure and had normal morphology. The extracellular collagenous matrixs covered the surface of biomaterial and packed the granules of biomaterial. Conclusion: PDLLA/HA/DBM can form osteointerface early and have a good biocompability.

  18. The density of collagen fiber in alveolus mandibular bone of rabbit after augmentation with powder demineralized bone matrix post incisivus extraction

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    Regina TC. Tandelilin


    Full Text Available The bone defect due to tooth extraction contributes the most cases reported in the aspects of oral surgery. The defect can be preventively managed by adding powder bone matrix intended for augmentation which eventually induces the formation of new bones. This hard tissue wound healing is preceded by the presence of collagen fibers. The aim of this study was to determine the density of collagen fiber in the alveolus mandibular bone of rabbit which was augmented using powder demineralized bone matrix (DBM post incisivus extraction. Twenty four male rabbits aged 2.5–3 months weighed 900–1,100 grams were randomly divided into two groups. The treated rabbits were augmented with DBM after the incisivus extraction on mandible. The mucosa was then sutured. On the other hand, the controlled rabbits received similar treatments with those of the treated rabbits except there was no augmentation of DBM. Decapitation of treated and controlled rabbits was made on day 5, 7, 10, and 14 days post surgery, each with three rabbits. Mandibles were cut, decalcified, and imbedded in paraffin block. The staining was done using Mallory. Significant differences in the density of collagen were noted on day 10 and 14 post surgery, indicating that powder demineralized bone matrix successfully induced the stimulation of collagen.

  19. Decellularized bone matrix grafts for calvaria regeneration (United States)

    Lee, Dong Joon; Diachina, Shannon; Lee, Yan Ting; Zhao, Lixing; Zou, Rui; Tang, Na; Han, Han; Chen, Xin; Ko, Ching-Chang


    Decellularization is a promising new method to prepare natural matrices for tissue regeneration. Successful decellularization has been reported using various tissues including skin, tendon, and cartilage, though studies using hard tissue such as bone are lacking. In this study, we aimed to define the optimal experimental parameters to decellularize natural bone matrix using 0.5% sodium dodecyl sulfate and 0.1% NH4OH. Then, the effects of decellularized bone matrix on rat mesenchymal stem cell proliferation, osteogenic gene expression, and osteogenic differentiations in a two-dimensional culture system were investigated. Decellularized bone was also evaluated with regard to cytotoxicity, biochemical, and mechanical characteristics in vitro. Evidence of complete decellularization was shown through hematoxylin and eosin staining and DNA measurements. Decellularized bone matrix displayed a cytocompatible property, conserved structure, mechanical strength, and mineral content comparable to natural bone. To study new bone formation, implantation of decellularized bone matrix particles seeded with rat mesenchymal stem cells was conducted using an orthotopic in vivo model. After 3 months post-implantation into a critical-sized defect in rat calvaria, new bone was formed around decellularized bone matrix particles and also merged with new bone between decellularized bone matrix particles. New bone formation was analyzed with micro computed tomography, mineral apposition rate, and histomorphometry. Decellularized bone matrix stimulated mesenchymal stem cell proliferation and osteogenic differentiation in vitro and in vivo, achieving effective bone regeneration and thereby serving as a promising biological bone graft. PMID:28228929

  20. Demineralized bone matrix and human cancellous bone enhance fixation of porous-coated titanium implants in sheep

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    Babiker, Hassan; Ding, Ming; Overgaard, Søren


    Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic potential and the risk of disease transmission are clinical challenges. The use of osteoinductive materials, such as demineralized bone...... of DBM alone, DBM with CB, or allograft on the fixation of porous-coated titanium implants. DBM100 and CB produced from human tissue were included. Both materials are commercially available. DBM granules are placed in pure DBM and do not contain any other carrier. Titanium alloy implants, 10 mm long × 10...... (gold standard), respectively. A standardized surgical procedure was used. At sacrifice 6 weeks after implantation, both distal femurs were harvested. The implant fixation was evaluated by mechanical push-out testing to test shear mechanical properties between implant and the host bone...

  1. The comparative effectiveness of demineralized bone matrix, beta-tricalcium phosphate, and bovine-derived anorganic bone matrix on inflammation and bone formation using a paired calvarial defect model in rats

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    Khoshzaban A


    Full Text Available Ahad Khoshzaban1,2,3, Shahram Mehrzad1, Vida Tavakoli2, Saeed Heidari Keshel2, Gholam Reza Behrouzi2, Maryam Bashtar2 1Iranian Tissue Bank Research and Preparation Center, Imam Khomeini Hospital Complex, 2Stem Cells Preparation Unit, Eye Research Center, Farabi Hospital, Tehran University of Medical Science, 3Dental Bio Material Department, Tehran University of Medical Science, Faculty of Dentistry, Tehran, Iran Background: In this study, the effectiveness of Iranian Tissue Bank–produced demineralized bone matrix (ITB-DBM, beta-tricalcium phosphate (ßTCP, and Bio-Oss® (Geistlich Pharma AG, Wolhusen, Switzerland were evaluated and compared with double controls. The main goal was to measure the amount of new bone formation in the center of defects created in rat calvaria. Another goal was to compare the controls and evaluate the effects of each treatment material on their adjacent untreated (control defects. Methods: In this study, 40 male Wistar rats were selected and divided into four groups, In each group, there were ten rats with two defects in their calvarias; one of them is considered as control and the other one was treated with ITB-DBM (group 1, BIO-OSS (group2, and ßTCP (group 3, respectively. But in group 4, both defects were considered as control. The amount of inflammation and new bone formation were evaluated at 4 and 10 weeks. In the first group, one defect was filled with ITB-DBM; in the second group, one defect was filled with Bio-Oss; in the third group, one defect was filled with ßTCP; and in the fourth group, both defects were left unfilled. Zeiss microscope (Carl Zeiss AG, Oberkochen, Germany and Image Tool® (version 3.0; University of Texas Health Science Center at San Antonio, San Antonio, TX software were used for evaluation. SPSS Statistics (IBM Corp, Somers, NY was used for statistical analysis. Results: Maximum bone formation at 4 and 10 weeks were observed in the ITB-DBM group (46.960% ± 4.366%, 94.970% ± 0

  2. Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    Denmark, DenmarkAbstractReplacement of extensive local bone loss especially in revision joint arthroplasty and spine fusion is a significant clinical challenge. Allograft and autograft have been considered as gold standard for bone replacement. However, there are several disadvantages such as donor site...... from human tissue were included (IsoTis OrthoBiologics, Inc. USA). Both materials are commercially available. Titanium alloy implants (Biomet Inc.) of 10 mm in length and 10 mm in diameter were inserted bilaterally into the femoral condyles of 8 skeletally mature sheep. Thus four implants...... with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: DBM; DBM/CB with ratio of 1/3; DBM/allograft with ratio of 1/3; or allograft (Gold standard), respectively. Standardised surgical procedure was used1. At sacrifice, 6 weeks after surgery, both distal femurs were harvested...

  3. Biomechanical and radiographic comparison of demineralized bone matrix, and a coralline hydroxyapatite in a rabbit spinal fusion model. (United States)

    Dodds, Robert A; York-Ely, Amanda M; Zhukauskas, Rasa; Arola, Travis; Howell, John; Hartill, Caroline; Cobb, Ronald R; Fox, Casey


    The use of bone grafts is an essential component in spinal fusion. Autologous bone has been shown to result in long-term stable arthrodesis between spinal motion segments. However, autograft can be associated with significant morbidity and a limited supply. Alternatives, such as allogeneic demineralized bone matrix (DBM), are a potential source and supplement to autograft bone. The current study compares the ability of a DBM product (BioSet RT) and a coralline hydroxyapatite (Pro Osteon 500R), for inducing spinal fusion in a rabbit model. BioSet RT, alone or in combination with autograft, and Pro Osteon 500R were implanted in the posterior lateral inter-transverse process region of the rabbit spine. The spines were evaluated at 18 weeks for fusion of the L4-L5 transverse processes using a total of 33 skeletally mature male rabbits; 4 naïve animals were also included in the study. Samples were evaluated radiographically, histologically, by palpation, and through mechanical strength testing. Radiographical, histological, and palpation measurements demonstrated the ability of BioSet RT to induce new bone formation and bridging fusion comparable to autograft. This material performed well alone or in combination with autograft material. Despite significantly higher biomechanical testing results, minimal bone formation and fusion was recorded for the Pro Osteon 500R-treated group. This in vivo study demonstrates the ability of BioSet RT to induce new bone formation, and there was a clear relationship between bridging bone and mechanical strength.

  4. Localized ridge defect augmentation using human pericardium membrane and demineralized bone matrix

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    Arun Kumar Vidyadharan


    Conclusion and Clinical Implications: The results suggested that HP Allograft membrane may be a suitable component for augmentation of localized alveolar ridge defects in conjunction with DBM with bone chips.

  5. Skeletal growth after oral administration of demineralized bone matrix. (United States)

    Martínez, J A; Elorriaga, M; Marquínez, M; Larralde, J


    Oral administration of bone extracts obtained from bovine demineralized bone matrix to rats has a direct effect on bone metabolism, affecting bone proportions and some markers of bone formation such as bone malate dehydrogenase, serum alkaline phosphatase and serum osteocalcin. Furthermore collagen deposition, bone protein synthesis and nucleic acids content were significantly increased by the treatment.

  6. Demineralized bone matrix combined bone marrow mesenchymal stem cells, bone morphogenetic protein-2 and transforming growth factor-β3 gene promoted pig cartilage defect repair.

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    Xin Wang

    Full Text Available OBJECTIVES: To investigate whether a combination of demineralized bone matrix (DBM and bone marrow mesenchymal stem cells (BMSCs infected with adenovirus-mediated- bone morphogenetic protein (Ad-BMP-2 and transforming growth factor-β3 (Ad-TGF-β3 promotes the repair of the full-thickness cartilage lesions in pig model. METHODS: BMSCs isolated from pig were cultured and infected with Ad-BMP-2(B group, Ad-TGF-β3 (T group, Ad-BMP-2 + Ad-TGF-β3(BT group, cells infected with empty Ad served as a negative group(N group, the expression of the BMP-2 and TGF-β3 were confirmed by immunofluorescence, PCR, and ELISA, the expression of SOX-9, type II collagen(COL-2A, aggrecan (ACAN in each group were evaluated by real-time PCR at 1w, 2w, 3w, respectively. The chondrogenic differentiation of BMSCs was evaluated by type II collagen at 21d with immunohistochemical staining. The third-passage BMSCs infected with Ad-BMP-2 and Ad-TGF-β3 were suspended and cultured with DBM for 6 days to construct a new type of tissue engineering scaffold to repair full-thickness cartilage lesions in the femur condyles of pig knee, the regenerated tissue was evaluated at 1,2 and 3 months after surgery by gross appearance, H&E, safranin O staining and O'driscoll score. RESULTS: Ad-BMP-2 and Ad-TGF-β3 (BT group infected cells acquired strong type II collagen staining compared with Ad-BMP-2 (B group and Ad-TGF-β3 (T group along. The Ad-BMP-2 and Ad-TGF-β3 infected BMSCs adhered and propagated well in DBM and the new type of tissue engineering scaffold produced hyaline cartilage morphology containing a stronger type II collagen and safranin O staining, the O'driscoll score was higher than other groups. CONCLUSIONS: The DBM compound with Ad-BMP-2 and Ad-TGF-β3 infected BMSCs scaffold has a good biocompatibility and could well induce cartilage regeneration to repair the defects of joint cartilage. This technology may be efficiently employed for cartilage lesions repair in vivo.

  7. A comparative study of the proliferation and osteogenic differentiation of human periodontal ligament cells cultured on β-TCP ceramics and demineralized bone matrix with or without osteogenic inducers in vitro. (United States)

    An, Shaofeng; Gao, Yan; Huang, Xiangya; Ling, Junqi; Liu, Zhaohui; Xiao, Yin


    The repair of bone defects that result from periodontal diseases remains a clinical challenge for periodontal therapy. β-tricalcium phosphate (β-TCP) ceramics are biodegradable inorganic bone substitutes with inorganic components that are similar to those of bone. Demineralized bone matrix (DBM) is an acid-extracted organic matrix derived from bone sources that consists of the collagen and matrix proteins of bone. A few studies have documented the effects of DBM on the proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The aim of the present study was to investigate the effects of inorganic and organic elements of bone on the proliferation and osteogenic differentiation of hPDLCs using three-dimensional porous β-TCP ceramics and DBM with or without osteogenic inducers. Primary hPDLCs were isolated from human periodontal ligaments. The proliferation of the hPDLCs on the scaffolds in the growth culture medium was examined using a Cell-Counting kit-8 (CCK-8) and scanning electron microscopy (SEM). Alkaline phosphatase (ALP) activity and the osteogenic differentiation of the hPDLCs cultured on the β-TCP ceramics and DBM were examined in both the growth culture medium and osteogenic culture medium. Specific osteogenic differentiation markers were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SEM images revealed that the cells on the β-TCP were spindle-shaped and much more spread out compared with the cells on the DBM surfaces. There were no significant differences observed in cell proliferation between the β-TCP ceramics and the DBM scaffolds. Compared with the cells that were cultured on β-TCP ceramics, the ALP activity, as well as the Runx2 and osteocalcin (OCN) mRNA levels in the hPDLCs cultured on DBM were significantly enhanced both in the growth culture medium and the osteogenic culture medium. The organic elements of bone may exhibit greater osteogenic differentiation effects

  8. Use of a graft of demineralized bone matrix along with TGF-β1 leads to an early bone repair in dogs. (United States)

    Servin-Trujillo, Miguel Angel; Reyes-Esparza, Jorge Alberto; Garrido-Fariña, German; Flores-Gazca, Enrique; Osuna-Martinez, Ulises; Rodriguez-Fragoso, Lourdes


    Tibia fractures are common in small animal practice. Over the past decade, improvements to animal internal fracture fixation have been developed. TGF-β1 has been shown to be crucial in the development, induction and repair of bone. In present study, we investigate the effect of local application of a graft demineralized bone matrix (DBM) along with TGF-β1 in a model of open osteotomy induced experimentally in dogs. Tibia fracture was brought about by using an open osteotomy model in young male dogs. Fracture repair was evaluated by a histological and biochemical analysis. Collagen content, proteolytic activity and urokinase-type plasminogen activator (uPA) expression were analyzed at the end of the study. Radiographic analysis, alkaline phosphatase and hematological evaluation were performed weekly. At the fifth week, there was an improvement and restoration of bone architecture in animals treated with a graft containing TGF-β1 (5 ng/ml) compared with the control and graft groups, as was evidenced by the presence of an early formation of wide callus and bone regeneration. In addition, local application of TGF-β1 led to an increase in collagen and proteolytic activity. More immunopositive osteoclast and mesenchymal cells were found in bone tissue from animals treated with TGF-β1 as compared with the control group. No changes in alkaline phosphatase, hematological and clinical parameters were observed. This study shows that the combined use of DBM along with TGF-β1 is able to improve and accelerate the bone repair.

  9. Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone

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    Yoshinobu Uchihara


    Full Text Available Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.

  10. A strategy to quantitate global phosphorylation of bone matrix proteins. (United States)

    Sroga, Grażyna E; Vashishth, Deepak


    Current studies of protein phosphorylation focus primarily on the importance of specific phosphoproteins and their landscapes of phosphorylation in the regulation of different cellular functions. However, global changes in phosphorylation of extracellular matrix phosphoproteins measured "in bulk" are equally important. For example, correct global phosphorylation of different bone matrix proteins is critical to healthy tissue biomineralization. To study changes of bone matrix global phosphorylation, we developed a strategy that combines a procedure for in vitro phosphorylation/dephosphorylation of fully mineralized bone in addition to quantitation of the global phosphorylation levels of bone matrix proteins. For the first time, we show that it is possible to enzymatically phosphorylate/dephosphorylate fully mineralized bone originating from either cadaveric human donors or laboratory animals (mice). Using our strategy, we detected the difference in the global phosphorylation levels of matrix proteins isolated from wild-type and osteopontin knockout mice. We also observed that the global phosphorylation levels of matrix proteins isolated from human cortical bone were lower than those isolated from trabecular bone. The developed strategy has the potential to open new avenues for studies on the global phosphorylation of bone matrix proteins and their role in biomineralization as well for other tissues/cells and protein-based materials.

  11. The "love-hate" relationship between osteoclasts and bone matrix. (United States)

    Rucci, Nadia; Teti, Anna


    Osteoclasts are unique cells that destroy the mineralized matrix of the skeleton. There is a "love-hate" relationship between the osteoclasts and the bone matrix, whereby the osteoclast is stimulated by the contact with the matrix but, at the same time, it disrupts the matrix, which, in turn, counteracts this disruption by some of its components. The balance between these concerted events brings about bone resorption to be controlled and to contribute to bone tissue integrity and skeletal health. The matrix components released by osteoclasts are also involved in the local regulation of other bone cells and in the systemic control of organismal homeostasis. Disruption of this regulatory loop causes bone diseases, which may end up with either reduced or increased bone mass, often associated with poor bone quality. Expanding the knowledge on osteoclast-to-matrix interaction could help to counteract these diseases and improve the human bone health. In this article, we will present evidence of the physical, molecular and regulatory relationships between the osteoclasts and the mineralized matrix, discussing the underlying mechanisms as well as their pathologic alterations and potential targeting.

  12. Mimicking the nanostructure of bone matrix to regenerate bone

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    Robert Kane


    Full Text Available Key features of bone tissue structure and composition are capable of directing cellular behavior toward the generation of new bone tissue. Bone tissue, as well as materials derived from bone, have a long and successful history of use as bone grafting materials. Recent developments in design and processing of synthetic scaffolding systems has allowed the replication of the bone's desirable biological activity in easy to fabricate polymeric materials with nano-scale features exposed on the surface. The biological response to these new tissue-engineering scaffold materials oftentimes exceeds that seen on scaffolds produced using biological materials.

  13. Spine fusion using cell matrix composites enriched in bone marrow-derived cells. (United States)

    Muschler, George F; Nitto, Hironori; Matsukura, Yoichi; Boehm, Cynthia; Valdevit, Antonio; Kambic, Helen; Davros, William; Powell, Kimerly; Easley, Kirk


    Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting.

  14. Alveolar Ridge Preservation Using Xenogeneic Collagen Matrix and Bone Allograft

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    Andreas O. Parashis


    Full Text Available Alveolar ridge preservation (ARP has been shown to prevent postextraction bone loss. The aim of this report is to highlight the clinical, radiographic, and histological outcomes following use of a bilayer xenogeneic collagen matrix (XCM in combination with freeze-dried bone allograft (FDBA for ARP. Nine patients were treated after extraction of 18 teeth. Following minimal flap elevation and atraumatic extraction, sockets were filled with FDBA. The XCM was adapted to cover the defect and 2-3 mm of adjacent bone and flaps were repositioned. Healing was uneventful in all cases, the XCM remained in place, and any matrix exposure was devoid of further complications. Exposed matrix portions were slowly vascularized and replaced by mature keratinized tissue within 2-3 months. Radiographic and clinical assessment indicated adequate volume of bone for implant placement, with all planned implants placed in acceptable positions. When fixed partial dentures were placed, restorations fulfilled aesthetic demands without requiring further augmentation procedures. Histological and immunohistochemical analysis from 9 sites (4 patients indicated normal mucosa with complete incorporation of the matrix and absence of inflammatory response. The XCM + FDBA combination resulted in minimal complications and desirable soft and hard tissue therapeutic outcomes, suggesting the feasibility of this approach for ARP.

  15. Is DBM Beneficial for the Enhancement of Bony Consolidation in Distraction Osteogenesis? A Randomized Controlled Trial

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    Sang-Heon Song


    Full Text Available The aim of the present study was to compare the radiographic and clinical outcomes of DBM injection and conventional treatment during tibial lengthening over an intramedullary nail in adult patients with short stature. Twenty-nine patients were randomized to receive DBM injection (n=14 or conventional treatment without any injection (n=15 and evaluated. The outcome was measured on the basis of the pixel value ratio (PVR in the digital radiographs during the consolidation period; healing index; clinical assessment; and the rate of complications. In the DBM group, the mean PVR of 1 (mineral density of the callus is comparable to the adjacent bone was reached by 40 weeks in anterior and medial cortices which was significantly different than that in the control group (P=0.03 for anterior cortex; P=0.04 for medial cortex. The average healing index in the DBM group was 39.8 ± 5.3 days/cm compared to 44.3 ± 5.8 days/cm in the control group (P=0.05. There were no significant differences in clinical outcomes (P=0.23 and functional status (P=0.47 including complications (P=0.72 between two groups. In this randomized clinical trial, injection of DBM at the time of initial operation enhanced consolidation of regenerate callus without interfering with clinical outcomes compared to that with conventional treatment.

  16. Induction of Bone Matrix Protein Expression by Native Bone Matrix Proteins in C2C12 Culture

    Institute of Scientific and Technical Information of China (English)



    Objective To study the expression of bone matrix protein (BMP) induced by bovine bone morphogenetic proteins (BMPs) in vitro. Methods Type I collagen, osteopontin (OPN), osteonectin (ON), osteocalcin (OC), and bone sialoprotein (BSP) were detected by immunohistochemistry in C2C12 cultured from day 1 to day 28. Results The signaling of bone matrix protein expression became weaker except for type I collagen, OC and BSP after 5 days. Fourteen days after culture, the positive signaling of type I collagen, OPN, ON, OC, and BSP was gradually declined, and could be detected significantly as compared with that of the negative control on day 28. BMP assay showed that the Ikaline phosphatase (ALP) activity was higher in C2C12 culture than in the control during the 14-day culture. Also, total protein and DNA significantly increased during the 14-day culture. High levels of ALP were seen in preosteoblasts and osteoblsts in vivo and in differentiating ostcoblasts in vitro. ALP was well recognized as a marker reflecting osteoblastic activity. Conclusion Native bovine BMP induces conversion of myoblasts into osteoblasts, produces type 1 collagen, and plays significantly role in osteoinduction and bone matrix mineralization of C2C12 in vitro.

  17. In vitro osteoinduction of demineralized bone. (United States)

    Torricelli, P; Fini, M; Giavaresi, G; Giardino, R


    Among numerous available materials for osseous repair and reconstruction, those presenting osteoinductive characteristics and promoting bone regeneration are preferable. Fresh autologous bone is one of the most effective, but it has some disadvantages and risks. Demineralized bone matrix (DBM) is considered to be a valid alternative, because it seems to show osteogenic potential, ascribed to the presence of bone morphogenetic proteins. In addition it can be prepared without difficulty and preserved without losing osteoinductive properties. The aim of the study was to evaluate the osteoinductive ability of xenogenic DBM, by testing DBM powder obtained from rabbit long bones, in cell culture of murine fibroblasts, alone or associated with electromagnetic field (EMF), that are known to exhibit biologic effects on cells: in particular they are used in orthopedics to improve bone formation. At the end of experiment, alkaline phosphatase (ALP) activity, calcium levels and cell proliferation and morphology were evaluated. A statistically significant stimulation of ALP activity and cell proliferation and a morphological change of fibroblasts were found. The results obtained show how DBM and EMF have different effects on cells, and that together they have synergic action toward bone induction.


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    Yuri M. Iryanov, Nikolay A. Kiryanov, Olga V. Dyuriagina , Tatiana Yu. Karaseva, Evgenii A. Karasev


    Full Text Available Background: The damage or loss of articular cartilage is costly medical problem. The purpose of this work – morphological analysis of reparative chondrogenesis when implanted in the area of the knee joint cartilage of granulated mineralized bone matrix. Material and Methods: The characteristic features of the knee cartilage regeneration studied experimentally in pubertal Wistar rats after modeling a marginal perforated defect and implantation of granulated mineralized bone matrix obtained according to original technology without heat and demineralizing processing into the injury zone. Results: This biomaterial established to have pronounced chondro- and osteoinductive properties, and to provide prolonged activation of reparative process, accelerated organotypical remodeling and restoration of the articular cartilage injured. Conclusion: The data obtained demonstrate the efficacy of МВМ in clinical practice for the treatment of diseases and injuries of the articular cartilage.

  19. Physicomechanical properties of the extracellular matrix of a demineralized bone (United States)

    Kirilova, I. A.; Sharkeev, Yu. P.; Nikolaev, S. V.; Podorozhnaya, V. T.; Uvarkin, P. V.; Ratushnyak, A. S.; Chebodaeva, V. V.


    The article describes the results of a study of physicomechanical properties of a demineralized bone matrix of human cancellous and compact bones. A demineralized cancellous bone was shown to have the best characteristics of a porous system for colonization of matrices by cells. The ultimate stress and elasticity modulus of samples of demineralized femoral heads isolated in primary hip replacement was demonstrated to vary in wide ranges. The elasticity modulus ranged from 50 to 250 MPa, and the tensile strength varied from 1.1 to 5.5 MPa. Microhardness measurements by the recovered indentation method were not possible because of the viscoelastic properties of a bone material. To study the piezoelectric properties of samples, a measuring system was developed that comprised a measuring chamber with contact electrodes, a system for controlled sample loading, an amplifier-converter unit, and signal recording and processing software. The measurement results were used to determine the dependence of the signal amplitude on the dynamic deformation characteristics. The findings are discussed in terms of the relationship between the mechanical and electrical properties and the structure of the organic bone component.

  20. TGF-b Downregulation by RNAi Technique in ex Vivo-Expanded HSCs on 3D DBM Scaffold

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    N Amirizadeh


    Full Text Available Background: Bone Marrow Transplantations (BMT are limited by low CD34+ cell counts in umbilical cord blood (UCB and these cells need to be expanded for success in such procedures. To achieve this goal, ex vivo expansion of hematopoietic stem cells (HSCs by enhancing their self-renewal activity on demineralized bone matrix (DBM scaffold coated with mesenchymal progenitor cells (MPCs and unrestricted somatic stem cells (USSCs was recommended. TGF-b pathway is a key inhibitory factor for HSCs self-renewal. In this study ex vivo expansion and downregulation of TGF-b pathway were simultaneously performed. Methods: USSC cells were isolated from UCB and then coated on DBM scaffold as a feeder layer. UCB CD34+ cells were isolated from UCB by magnetic activated cell sorting (MACS method and were transfected by siRNA against TGFbR2 in two-dimensional (2D and three-dimensional (3D cultures by co-cultivation with USSC. TGFbR2 expression levels were evaluated by quantitative real-time PCR. Cell count and flow cytometry were performed and clonogenic activity was evaluated. Results: Ex vivo expansion of CD34+ cells was significantly enhanced (41±0.7 folds by TGFbR2 downregulation, especially in 2D than 3D cultures. Finally, 2D culture showed less TGFbR2 expression levels and higher increase in the percentage of CD34 markers by flow cytometry assay. Conclusion: The 3D siRNA delivery system would be of lower efficiency in contrast to 2D settings where the cells have less freedom and are in more contact with the feeder layer.

  1. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

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    Jung-Bo Huh


    Full Text Available Anorganic bovine bone matrix (Bio-Oss® has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2 has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter were formed in a white rabbit model and then implanted or not (controls with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6 had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6 at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration.

  2. Effect of cefazolin loaded bone matrix gelatin on repairing large segmental bone defects and preventing infection

    Institute of Scientific and Technical Information of China (English)

    游洪波; 陈安民


    Objective: To explore the possibility of repairing long segmental bone defects and preventing infection with cefazolin loaded bone matrix gelatin (C-BMG). Methods: C-BMG was made from putting cefazolin into BMG by vacuum absorption and lyophilization techniques. The sustaining period of effective drug concentration in vitro and in vivo was detected. The time of inhibiting bacteria, and the drug concentration in local tissues ( bone and muscle) and plasma after implantation of C-BMG were examined by high performance liquid chromatography.Results: The effective inhibition time to staphylococcus aureus of C-BMG was 22 days in vitro; while 14 days in vivo. The cefazolin concentration in local tissues was higher in early stage, and later it kept a stable and low drug release. C-BMG showed an excellent ability to repair segmental long bone defects.Conclusions: C-BMG can gradually release cefazolin with effective drug concentration and has excellent ability to repair segmental bone defects. It can be used to repair segmental long bone defects and prevent infection after operation.

  3. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo. (United States)

    Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu


    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

  4. Syntheses and electroluminescent properties of two europium ternary complexes Eu(DBM){sub 3}(PBO) and Eu(DBM){sub 3}(PBT)

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    Guan Min [State Key Laboratory of Rare Earth Materials Chemistry and Applications, Peking University, Beijing 100871 (China); Gao Lihua [Department of Chemistry, Beijing Normal University, Beijing 100875 (China); Wang Shanshan [State Key Laboratory of Rare Earth Materials Chemistry and Applications, Peking University, Beijing 100871 (China); Huang Chunhui [State Key Laboratory of Rare Earth Materials Chemistry and Applications, Peking University, Beijing 100871 (China)], E-mail:; Wang Kezhi [Department of Chemistry, Beijing Normal University, Beijing 100875 (China)


    Two europium complexes, Eu(DBM){sub 3}(PBO) and Eu(DBM){sub 3}(PBT) (DBM=dibenzoylmethanato, PBO=2-(2-pyridyl)benzoxazole, PBT=2-(2-pyridyl)benzothiazole), were prepared and used as emitting materials in organic electroluminescent (EL) devices. The devices with the structures ITO/TPD/Eu(DBM){sub 3}(PBO) (or Eu(DBM){sub 3}(PBT)/BCP/Alq{sub 3}/Mg:Ag/Ag emit red light originating from the europium complexes.

  5. Calcification preceding new bone formation induced by demineralized bone matrix gelatin. (United States)

    Yamashita, K; Takagi, T


    Demineralized bone matrix gelatin (BMG) was implanted into the skeletal muscle of Sprague-Dawley (S.D.) rats, and histological changes were examined 3, 5, 7, 10 and 15 days later. Before bone formation, a specific calcification process was found in most of the BMG from day 5 and 7 after implantation. The heterotopic calcified sites were not always consistent with the sites of the alkaline phosphatase activity. It was considered that this calcification progresses without any cellular components, and we distinguished this type of calcification as "acellular mineral deposition" from the calcification which occurs in new bone formation. This "acellular mineral deposition" was first observed as small spherical calcified deposits in the BMG on day 7 after implantation; these deposits then gradually grew and fused with each other. Some multinucleated cells appeared near the site of calcification on day 7 after implantation, but osteoblasts or osteoblast-like cells were scarcely observed around the calcified deposits in BMG until day 7. Vascularization was often observed near the "acellular mineral deposition" and the new bone formation. Fourier transform infrared spectroscopy showed that the calcified deposits in BMG were composed of hydroxyapatite, carbonateapatite and other calcium phosphate components, and that the first two components became prominent with time. It is believed that the "acellular mineral deposition" is due to the deposition of calcium and phosphate into the BMG by a process of heterogenic nucleation that does not involve osteoblasts or matrix vesicles. Bone formation induced by the BMG occurred after the "acellular mineral deposition." The experimental calcification shown in this paper seems a useful model for the study of biocalcification.

  6. Biomineralization of a Self-Assembled Extracellular Matrix for Bone Tissue Engineering


    Meng, Yizhi; Qin, Yi-Xian; DiMasi, Elaine; Ba, Xiaolan; Rafailovich, Miriam; Pernodet, Nadine


    Understanding how biomineralization occurs in the extracellular matrix (ECM) of bone cells is crucial to the understanding of bone formation and the development of a successfully engineered bone tissue scaffold. It is still unclear how ECM mechanical properties affect protein-mineral interactions in early stages of bone mineralization. We investigated the longitudinal mineralization properties of MC3T3-E1 cells and the elastic modulus of their ECM using shear modulation force microscopy, sync...

  7. The effect of enamel matrix proteins and deproteinized bovine bone mineral on heterotopic bone formation. (United States)

    Donos, Nikolaos; Kostopoulos, Lambros; Tonetti, Maurizio; Karring, Thorkild; Lang, Niklaus P


    To evaluate the osteoinductive potential of deproteinized bovine bone mineral (DBBM) and an enamel matrix derivative (EMD) in the muscle of rats. Sixteen rats were used in this study. The animals were divided in three groups. Group A: a pouch was created in one of the pectoralis profundis muscles of the thorax of the rats and DBBM particles (Bio-Oss) were placed into the pouch. Healing: 60 days. Group B: a small pouch was created on both pectoralis profundis muscles at each side of the thorax midline. In one side, a mixture of EMD (Emdogain) mixed with DBBM was placed into one of the pouches, whereas in the contralateral side of the thorax the pouch was implanted with DBBM mixed with the propylene glycol alginate (PGA--carrier for enamel matrix proteins of EMD). Healing: 60 days. Group C: the same procedure as group B, but with a healing period of 120 days. Qualitative histological analysis of the results was performed. At 60 days, the histological appearance of the DBBM particles implanted alone was similar to that of the particles implanted together with EMD or PGA at both 60 and 120 days. The DBBM particles were encapsulated into a connective tissue stroma and an inflammatory infiltrate. At 120 days, the DBBM particles implanted together with EMD or PGA exhibited the presence of resorption lacunae in some cases. Intramuscular bone formation was not encountered in any group. The implantation of DBBM particles alone, combined with EMD or its carrier (PGA) failed to exhibit extraskeletal, bone-inductive properties.

  8. Effects of demineralized bone matrix and a 'Ricinus communis' polymer on bone regeneration: a histological study in rabbit calvaria. (United States)

    Laureano Filho, José R; Andrade, Emanuel S S; Albergaria-Barbosa, José R; Camargo, Igor B; Garcia, Robson R


    The aim of the present study was to histologically analyze the effects of bovine and human demineralized bone matrix and a Ricinus communis polymer on the bone regeneration process. Two surgical bone defects were created in rabbit calvaria, one on the right and the other on the left side of the parietal suture. Eighteen rabbits were divided into three groups. In Group I, the experimental defect was treated with bovine demineralized bone matrix, Group II with human demineralized bone matrix, and in Group III, the experimental cavity was treated with polyurethane resin derived from Ricinus communis oil. The control defects were filled with the animals' own blood. The animals were sacrificed after 7 and 15 weeks. Histological analysis revealed that in all groups (control and experimental), bone regeneration increased with time. The least time required for bone regeneration was noted in the control group, with a substantial decrease in the thickness of the defect. All materials proved to be biologically compatible, but polyurethane resorbed more slowly and demonstrated considerably better results than the demineralized bone matrices.

  9. A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions (United States)

    Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace


    Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

  10. Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption. (United States)

    Yang, Xiao; Gandhi, Chintan; Rahman, Md Mizanur; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu


    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th day, respectively, to assess temporal changes in the number of differentiated osteoclasts, the number and size of osteoclastic resorption pits, the amount of bone resorbed, as well as the amount of matrix AGEs released in the medium by resorption. In addition, the in situ concentration of matrix AGEs at each resorption pit was also estimated based on its AGEs autofluorescent intensity. The results indicated that (1) osteoclastic resorption activities were significantly correlated with the donor age, showing larger but shallower resorption pits on the elderly bone substrates than on the younger ones; (2) osteoclast resorption activities were not significantly dependent on the in situ AGEs concentration in bone matrix, and (3) a correlation was observed between osteoclast activities and the concentration of AGEs released by the resorption. These results suggest that osteoclasts tend to migrate away from initial anchoring sites on elderly bone substrate during resorption compared to younger bone substrates. However, such behavior is not directly related to the in situ concentration of AGEs in bone matrix at the resorption sites.

  11. Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties. (United States)

    Day, J S; Ding, M; Bednarz, P; van der Linden, J C; Mashiba, T; Hirano, T; Johnston, C C; Burr, D B; Hvid, I; Sumner, D R; Weinans, H


    Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear. We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose for osteoporosis treatment. After one year, the dogs were killed, and samples from the first lumbar vertebrae were examined using a combination of micro-computed tomography, finite element modeling, and mechanical testing. By combining these methods, we examined the treatment effects on the calcified matrix and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage.

  12. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis. (United States)

    Zhu, Wei; Holmes, Benjamin; Glazer, Robert I; Zhang, Lijie Grace


    Bone is one of the most common metastatic sites of breast cancer, but the underlying mechanisms remain unclear, in part due to an absence of advanced platforms for cancer culture and study that mimic the bone microenvironment. In the present study, we integrated a novel stereolithography-based 3D printer and a unique 3D printed nano-ink consisting of hydroxyapatite nanoparticles suspended in hydrogel to create a biomimetic bone-specific environment for evaluating breast cancer bone invasion. Breast cancer cells cultured in a geometrically optimized matrix exhibited spheroid morphology and migratory characteristics. Co-culture of tumor cells with bone marrow mesenchymal stem cells increased the formation of spheroid clusters. The 3D matrix also allowed for higher drug resistance of breast cancer cells than 2D culture. These results validate that our 3D bone matrix can mimic tumor bone microenvironments, suggesting that it can serve as a tool for studying metastasis and assessing drug sensitivity. From the Clinical Editor: Cancer remains a major cause of mortality for patients in the clinical setting. For breast cancer, bone is one of the most common metastatic sites. In this intriguing article, the authors developed a bone-like environment using 3D printing technology to investigate the underlying biology of bone metastasis. Their results would also allow a new model for other researchers who work on cancer to use.

  13. Comparison of TGFbR2 down-regulation in expanded HSCs on MBA/DBM scaffolds coated by UCB stromal cells. (United States)

    Hashemi, Zahra Sadat; Moghadam, Mehdi Forouzandeh; Soleimani, Masoud


    Bone marrow transplants (BMTs) are mainly limited by a low number of CD34(+) cells. The transforming growth factor-beta (TGF-β) pathway downregulation is a key factor that increases cell self-renewal. In nature, hematopoietic stem cells (HSCs) are in a microenvironment, surrounded by cells in a three-dimensional (3D) configuration. The aim of this study is to investigate the association between a 3D culture and the delivery ratio of downregulation. Demineralized bone matrix (DBM) and mineralized bone allograft (MBA) scaffolds were coated using unrestricted somatic stem cells (USSCs) as the feeder layer. Umbilical cord blood (UCB)-CD34(+) cells were then ex vivo expanded in them and transfected by small interfering RNA (siRNA) against TGFbR2, a type 2 receptor in the TGF-β pathway. Finally, quantitative real-time PCR, flow cytometry, and clonogenic assay were performed. In a global comparison, we observed that the highest expansion ratio, lowest expression level, and the highest CD34 marker belonged to the simple 2D culture transfected group. This suggests that TGFbR2 downregulation in a 2D culture can be done more effectively. The siRNA delivery system and the transfection ratio in an ex vivo environment, which mimicks in vivo conditions, have low efficiency. Genetic modification of the cells needs free 3D spaces to enable better transfection.

  14. Gray-Level Co-occurrence Matrix Bone Fracture Detection

    Directory of Open Access Journals (Sweden)

    Hum Y. Chai


    Full Text Available Problem statement: Currently doctors in orthopedic wards inspect the bone x-ray images according to their experience and knowledge in bone fracture analysis. Manual examination of x-rays has multitude drawbacks. The process is time-consuming and subjective. Approach: Since detection of fractures is an important orthopedics and radiologic problem and therefore a Computer Aided Detection(CAD system should be developed to improve the scenario. In this study, a fracture detection CAD based on GLCM recognition could improve the current manual inspection of x-ray images system. The GLCM for fracture and non-fracture bone is computed and analysis is made. Features of Homogeneity, contrast, energy, correlation are calculated to classify the fractured bone. Results: 30 images of femur fractures have been tested, the result shows that the CAD system can differentiate the x-ray bone into fractured and nonfractured femur. The accuracy obtained from the system is 86.67. Conclusion: The CAD system is proved to be effective in classifying the digital radiograph of bone fracture. However the accuracy rate is not perfect, the performance of this system can be further improved using multiple features of GLCM and future works can be done on classifying the bone into different degree of fracture specifically.

  15. Bone regeneration with osteogenically enhanced mesenchymal stem cells and their extracellular matrix proteins. (United States)

    Clough, Bret H; McCarley, Matthew R; Krause, Ulf; Zeitouni, Suzanne; Froese, Jeremiah J; McNeill, Eoin P; Chaput, Christopher D; Sampson, H Wayne; Gregory, Carl A


    Although bone has remarkable regenerative capacity, about 10% of long bone fractures and 25% to 40% of vertebral fusion procedures fail to heal. In such instances, a scaffold is employed to bridge the lesion and accommodate osteoprogenitors. Although synthetic bone scaffolds mimic some of the characteristics of bone matrix, their effectiveness can vary because of biological incompatibility. Herein, we demonstrate that a composite prepared with osteogenically enhanced mesenchymal stem cells (OEhMSCs) and their extracellular matrix (ECM) has an unprecedented capacity for the repair of critical-sized defects of murine femora. Furthermore, OEhMSCs do not cause lymphocyte activation, and ECM/OEhMSC composites retain their in vivo efficacy after cryopreservation. Finally, we show that attachment to the ECM by OEhMSCs stimulates the production of osteogenic and angiogenic factors. These data demonstrate that composites of OEhMSCs and their ECM could be utilized in the place of autologous bone graft for complex orthopedic reconstructions.

  16. HBM Mice Have Altered Bone Matrix Composition and Improved Material Toughness. (United States)

    Ross, Ryan D; Mashiatulla, Maleeha; Acerbo, Alvin S; Almer, Jonathan D; Miller, Lisa M; Johnson, Mark L; Sumner, D Rick


    The G171V mutation in the low-density lipoprotein receptor-related protein 5 (LRP5) leads to a high bone mass (HBM) phenotype. Studies using HBM transgenic mouse models have consistently found increased bone mass and whole-bone strength, but little attention has been paid to the composition of the bone matrix. The current study sought to determine if the cortical bone matrix composition differs in HBM and wild-type mice and to determine how much of the variance in bone material properties is explained by variance in matrix composition. Consistent with previous studies, HBM mice had greater cortical area, moment of inertia, ultimate force, bending stiffness, and energy to failure than wild-type animals. The increased energy to failure was primarily caused by a large increase in post-yield behavior, with no difference in pre-yield behavior. The HBM mice had increased mineral-to-matrix and collagen cross-link ratios, and decreased crystallinity, carbonate, and acid phosphate substitution as measured by Fourier transform infrared microspectroscopy, but no differences in crystal length, intra-fibular strains, and mineral spacing compared to wild-type controls, as measured by X-ray scattering. The largest between genotype difference in material properties was a twofold increase in the modulus of toughness in HBM mice. Step-wise regression analyses showed that the specific matrix compositional parameters most closely associated with material properties varied between the wild-type and HBM genotypes. Although the mechanisms controlling the paradoxical combination of more mineralized yet tougher bone in HBM mice remain to be fully explained, the findings suggest that LRP5 represents a target to not only build bone mass but also to improve bone quality.

  17. Human Bone Matrix Changes During Deep Saturation Dives (United States)


    agreement notwithstanding, much remains unknown about its pathogenesis, prevention, and treatment . DON is currently disqualifying for U.S. Navy divers...recourse for symptomatic treatment is surgical joint replacement.7 The principal mechanism of bone injury is generally accepted to be bubble formation...urine concentrations of Ntx have been demonstrated in bone diseases such as osteoporosis, primary hyperthyroidism , and Paget’s disease. Also

  18. PTH(1-84) Administration in Hypoparathyroidism Transiently Reduces Bone Matrix Mineralization. (United States)

    Misof, Barbara M; Roschger, Paul; Dempster, David W; Zhou, Hua; Bilezikian, John P; Klaushofer, Klaus; Rubin, Mishaela R


    Patients with hypoparathyroidism have low circulating parathyroid (PTH) levels and higher cancellous bone volume and trabecular thickness. Treatment with PTH(1-84) was shown to increase abnormally low bone remodeling dynamics. In this work, we studied the effect of 1-year or 2-year PTH(1-84) treatment on cancellous and cortical bone mineralization density distribution (Cn.BMDD and Ct.BMDD) based on quantitative backscattered electron imaging (qBEI) in paired transiliac bone biopsy samples. The study cohort comprised 30 adult hypoparathyroid patients (14 treated for 1 year; 16 treated for 2 years). At baseline, Cn.BMDD was shifted to higher mineralization densities in both treatment groups (average degree of mineralization Cn.CaMean +3.9% and +2.7%, p mineralizing surface) was predictive for Cn.BMDD outcomes in the 1-year PTH(1-84) group, but not in the 2-year PTH(1-84) group. Our findings suggest higher baseline bone matrix mineralization consistent with the decreased bone turnover in hypoparathyroidism. PTH(1-84) treatment caused differential effects dependent on treatment duration that were consistent with the histomorphometric bone formation outcomes. The greater increase in bone formation during the first year of treatment was associated with a decrease in bone matrix mineralization, suggesting that PTH(1-84) exposure to the hypoparathyroid skeleton has the greatest effects on BMDD early in treatment.


    Shirvaikar, Mukul; Huang, Ning; Dong, Xuanliang Neil


    In this paper, statistical methods for the estimation of bone quality to predict the risk of fracture are reported. Bone mineral density and bone architecture properties are the main contributors of bone quality. Dual-energy X-ray Absorptiometry (DXA) is the traditional clinical measurement technique for bone mineral density, but does not include architectural information to enhance the prediction of bone fragility. Other modalities are not practical due to cost and access considerations. This study investigates statistical parameters based on the Gray Level Co-occurrence Matrix (GLCM) extracted from two-dimensional projection images and explores links with architectural properties and bone mechanics. Data analysis was conducted on Micro-CT images of 13 trabecular bones (with an in-plane spatial resolution of about 50μm). Ground truth data for bone volume fraction (BV/TV), bone strength and modulus were available based on complex 3D analysis and mechanical tests. Correlation between the statistical parameters and biomechanical test results was studied using regression analysis. The results showed Cluster-Shade was strongly correlated with the microarchitecture of the trabecular bone and related to mechanical properties. Once the principle thesis of utilizing second-order statistics is established, it can be extended to other modalities, providing cost and convenience advantages for patients and doctors.

  20. Aluminum and iron can be deposited in the calcified matrix of bone exostoses. (United States)

    Chappard, Daniel; Mabilleau, Guillaume; Moukoko, Didier; Henric, Nicolas; Steiger, Vincent; Le Nay, Patrick; Frin, Jean-Marie; De Bodman, Charlotte


    Exostosis (or osteochondroma) is the most common benign bone tumor encountered in children and adults. Exostoses may occur as solitary or multiple tumors (in the autosomal syndromes of hereditary multiple exostoses). Exostoses are composed of cortical and medullary bone covered by an overlying hyaline cartilage cap. We have searched iron (Fe) and aluminum (Al) in the matrix of cortical and trabecular bone of 30 patients with exostosis. Al(3+) and Fe(3+) are two cations which can substitute calcium in the hydroxyapatite crystals of the bone matrix. The bone samples were removed surgically and were studied undecalcified. Perls' Prussian blue staining (for Fe) and solochrome azurine B (for Al) were used on the histological sections of the tumors. Al(3+) was detected histochemically in 21/30 patients as linear bands deposited by the osteoblasts. Fe(3+) was detected in 10 out of these 21 patients as linear bands in the same locations. Fe(3+) and Al(3+) were not identified in the bone matrix of a control group of 20 osteoporotic patients. Energy X-ray Dispersive Spectrometry failed to identify Fe and Al in bone of these tumors due to the low sensitivity of the method. Wavelength Dispersive Spectrometry identified them but the concentrations were very low. Histochemistry appears a very sensitive method for Fe(3+) and Al(3+) in bone.The presence of these two metals in the exostoses advocates for a disturbed metabolism of osteoblasts which can deposit these metals into the bone matrix, similar to which is observed in case of hemochromatosis with Fe(3+).

  1. 动态压力促进骨基质支架中微血管形成的实验研究%Study of dynamic pressure to promote the angiogenesis of bone matrix

    Institute of Scientific and Technical Information of China (English)

    杨军; 周振东; 李建军; 张钦明


    Objective To observe the effects of dynamic pressure for the ability of endothelial progenitor cells (EPCs) to form blood vessels, when EPCs seeded into DBM with load. Methods Use the Ficoll density gradient centrifuge combined with difference-speed adherence screening method to separate MNCs from rat bone marrow. Identify the induced EPCs by means of immunohistochemistry and immunofluorescence. Through the organization of fixed, defatted, decalcified and other steps use of spine vertebral body,demineralized bone matrix (DBM) samples of pig were prepared in vitro. Divided scaffolds into two groups A and groups B. Induced EPCs were seeded into DBM. The cell-seeded scaffolds of groups A were dynamically loaded in compression using a sine wave at 1 Hz, 5% strain in the media-filled chamber for 4 h on days 5 of culture. and cell-seeded scaffolds of groups B were cultured directly without any load. Both of two groups were cultured two weeks. Then the ability of EPCs to form blood vessels was observed. Primer desig;Extract total RNA from cells with Trlzol; Reverse transcription reaction; PCR. Results Two groups of cells in HE staining and fluorescent staining showed the formation of vascular bundles. There were formation of blood vessels. It was obvious that the formation in group A was more than that in group B. Test the mRNA expression of vWF and Flk-1 during the EPCs differentiationby RT-PCR. Group A was significantly stronger than that of group B. Conclusion When DBM combines together with EPC, it has become organization engineering bone, then with press on it, the bone graft has been vascularized, so it has clinical application on the direction of repair bone defect.%目的 将血管内皮祖细胞(endothelial progenitor cells,EPCs)种植于体外制备的猪脱钙骨基质支架中,予适当压力干预,观察动态压力对EPCs形成血管能力的影响.方法 采用密度梯度离心法结合差速贴壁筛选法分离出骨髓单个核细胞,用条件培养液

  2. Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties

    DEFF Research Database (Denmark)

    Ding, Ming


    and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified......Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear....... We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose...

  3. Nanoporous Structure of Bone Matrix at Osteoporosis from Data of Atomic Force Microscopy and IR Spectroscopy

    Directory of Open Access Journals (Sweden)

    A. A. Gaidash


    Full Text Available It was found that in an osteoporotic bone the fraction of nanosized pores decreases, the mineral phase amorphizes, hydrated shells around mineralized particles of the bone matrix thicken, and adhesion forces increase. This contributes to the formation of water clusters similar to bulk water clusters compared to the healthy bone tissue and leads to the accumulation of more viscous liquid with increased intermolecular interaction forces in the pores of the bone matrix. Given this, the rates of chemical reactions proceeding in the water phase of ultrathin channels of general parts of collagen fibrils decrease. Ultimately, nanopores of collagen-apatite interfaces lose, to a certain extent, the capability of catalyzing the hydroxyapatite crystallization.

  4. Bone graft materials in fixation of orthopaedic implants in sheep. (United States)

    Babiker, Hassan


    Bone graft is widely used within orthopaedic surgery especially in revision joint arthroplasty and spine fusion. The early implant fixation in the revision situation of loose joint prostheses is important for the long-term survival. Bone autograft has been considered as gold standard in many orthopaedic procedures, whereas allograft is the gold standard by replacement of extensive bone loss. However, the use of autograft is associated with donor site morbidity, especially chronic pain. In addition, the limited supply is a significant clinical challenge. Limitations in the use of allograft include the risk of bacterial contamination and disease transmission as well as non-union and poor bone quality. Other bone graft and substitutes have been considered as alternative in order to improve implant fixation. Hydroxyapatite and collagen type I composite (HA/Collagen) have the potential in mimicking skeletal bones. The osteoconductive properties of the composite might be improved by adding bone marrow aspirate (BMA), which can be harvested during surgery. Other alternatives to bone graft are demineralised bone matrix (DBM) and human cancellous bone (CB). DBM is prepared by acid extraction of human bone and includes bone collagen, morphogenetic proteins and growth factors. The combination of DBM with CB and with allograft might improve the healing potential of these grafts around non-cemented orthopaedic implants and thereby the implant fixation. Study I investigates the effect of HA/Collagen composite alone and in combination with BMA on the early fixation of porous coated titanium implants. In addition, the study compares also the effect of autograft with the gold standard allograft. By using a sheep model, the implants were inserted in the trabecular bone of femoral condyles. The test biomaterials were placed in a well defined peri-implant gap. After the observation period, the bone-implant specimens were harvested and evaluated mechanically by a destructive push

  5. Ultrastructural studies on the origin and structure of matrix vesicles in bone of young rats. (United States)

    Ornoy, A; Atkin, I; Levy, J


    Tibiae of young rats were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in order to study the origin and structure of matrix vesicles in periosteal bone. SEM studies have shown that periosteal osteoblasts have elongated processes with globular structures of 0.1 micron in diameter attached to the cell surface and processes. Similar structures were found to cover the inner surface of osteoblastic lacunae. The SEM studies have further shown that in the periosteal surface (forming bone) the above-described globules once mineralized, aggregated to form larger, nonhomogeneous mineralized spherules in which, by proper treatment with NaOCl, hydroxyapatite crystals could be exposed. Endosteal osteoblasts had fewer processes, devoid of the globular structures. Similarly, osteocytic and osteoclastic processes, although elongated and numberous, were not covered by the globular structures. In the matrix, collagen fibers of forming bone were randomly orientated, while in the deeper areas of bone they formed bundles with a longitudinal orientation. TEM studies have shown that the structures found on the osteoblastic surface and in the matrix are membrane-bound matrix vesicles which seem to be formed by budding from cell processes. Preformed membrane-bound vesicles were also observed by TEM inside sections of osteoblastic processes. These vesicles resembled the extracellular matrix vesicles in size and shape, thus giving the impression that at least some of the matrix vesicles are preformed cellular structures. While comparing SEM with TEM, it can be conducted that in bone, as in cartilage, matrix vesicles which probably serve as the initial locus of calcification, are formed directly by osteoblasts.

  6. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice☆ (United States)

    Vanleene, Maximilien; Porter, Alexandra; Guillot, Pascale-Valerie; Boyde, Alan; Oyen, Michelle; Shefelbine, Sandra


    Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity. PMID:22449447

  7. Implants of polyanionic collagen matrix in bone defects of ovariectomized rats. (United States)

    Cunha, Marcelo Rodrigues; Santos, Arnaldo Rodrigues; Goissis, Gilberto; Genari, Selma C


    In recent years, there has been a great interest in the development of biomaterials that could be used in the repair of bone defects. Collagen matrix (CM) has the advantage that it can be modified chemically to improve its mechanical properties. The aim of the present study was to evaluate the effect of three-dimensional membranes of native or anionic (submitted to alkaline treatment for 48 or 96 h) collagen matrix on the consolidation of osteoporosis bone fractures resulting from the gonadal hormone alterations caused by ovariectomy in rats subjected to hormone replacement therapy. The animals received the implants 4 months after ovariectomy and were sacrificed 8 weeks after implantation of the membranes into 4-mm wide bone defects created in the distal third of the femur with a surgical bur. Macroscopic analysis revealed the absence of pathological alterations in the implanted areas, suggesting that the material was biocompatible. Microscopic analysis showed a lower amount of bone ingrowth in the areas receiving the native membrane compared to the bone defects filled with the anionic membranes. In ovariectomized animals receiving anionic membranes, a delay in bone regeneration was observed mainly in animals not subjected to hormone replacement therapy. We conclude that anionic membranes treated with alkaline solution for 48 and 96 h presented better results in terms of bone ingrowth.

  8. Utility of tricalcium phosphate and osteogenic matrix cellsheet constructs for bone defect reconstruction

    Institute of Scientific and Technical Information of China (English)


    AIM To determine the effects of transplanting osteogenicmatrix cell sheets and beta-tricalcium phosphate(TCP) constructs on bone formation in bone defects.METHODS: Osteogenic matrix cell sheets were preparedfrom bone marrow stromal cells (BMSCs), anda porous TCP ceramic was used as a scaffold. Threeexperimental groups were prepared, comprised of TCPscaffolds (1) seeded with BMSCs; (2) wrapped withosteogenic matrix cell sheets; or (3) both. Constructswere implanted into a femoral defect model in rats andbone growth was evaluated by radiography, histology,biochemistry, and mechanical testing after 8 wk.RESULTS: In bone defects, constructs implanted withcell sheets showed callus formation with segmental or continuous bone formation at 8 wk, in contrast toTCP seeded with BMSCs, which resulted in bone nonunion.Wrapping TCP constructs with osteogenic matrixcell sheets increased their osteogenic potential andresulting bone formation, compared with conventionalbone tissue engineering TCP scaffolds seeded withBMSCs. The compressive stiffness (mean ± SD) valueswere 225.0 ± 95.7, 30.0 ± 11.5, and 26.3 ± 10.6MPa for BMSC/TCP/Sheet constructs with continuousbone formation, BMSC/TCP/Sheet constructs withsegmental bone formation, and BMSC/TCP constructs,respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation wassignificantly higher than those with segmental boneformation and BMSC/TCP constructs.CONCLUSION: This technique is an improvementover current methods, such as TCP substitution, andis useful for hard tissue reconstruction and inducingearlier bone union in defects.

  9. Relationships between serum osteoprotegerin, matrix metalloproteinase-2 levels and bone metabolism in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    DAI Yi; SHEN Lin


    Background Serum osteoprotegerin (OPG) and matrix metalloproteinase-2 (MMP-2) have been shown to play a role in bone metabolism by degrading the bone matrix. The present study was undertaken to compare OPG and MMP-2 with bone mineral density and three markers (alkaline phosphatase (AKP), calcium and phosphorus) in postmenopausal women in Wuhan.Methods Serum OPG, MMP-2, and AKP of 78 Chinese postmenopausal women aged 48 to 65 were measured using enzyme-linked immunosorbent assay (ELISA). Bone mineral density was measured with dual energy X-ray absorptiometry (DEXA), and serum calcium and phosphorus were measured by auto biochemical analysis.Results Serum OPG and MMP-2 concentrations were significantly higher in postmenopausal women with osteoporosis ((127.6±6.3) ng/L; (1388±121) μg/L)) than those in age-matched normal controls ((72.3±2.4) ng/L; (1126±141) μg/L,P<0.01). Negative relationships were found between serum OPG, MMP-2 levels and bone mineral density in osteoporotic women. Adjusted by age and body mass index (BMI), the correlation of MMP-2 with bone mineral density of the neck of the femur disappeared. In osteoporotic women, negative correlations between OPG, MMP-2 levels and serum calcium were found (r=-0.216; r=-0.269, P<0.05), but positive correlations between OPG and serum AKP, serum phosphorus (r=0.235; r=0.124, P<0.05).Conclusions Significant correlations exist between serum OPG, MMP-2 levels and bone metabolism in high bone turnover of postmenopausal osteoporotic women. The concentrations of serum OPG and MMP-2 increase possibly as a concomitant event in the high bone turnover state, such as postmenopausal osteoporosis. Therefore serum OPG and MMP-2 could be used as indicators for the bone metabolism in postmenopausal osteoporotic women.

  10. Aluminum and bone: Review of new clinical circumstances associated with Al(3+) deposition in the calcified matrix of bone. (United States)

    Chappard, D; Bizot, P; Mabilleau, G; Hubert, L


    Several decades ago, aluminum encephalopathy associated with osteomalacia has been recognized as the major complication of chronic renal failure in dialyzed patients. Removal of aluminum from the dialysate has led to a disappearance of the disease. However, aluminum deposit occurs in the hydroxyapatite of the bone matrix in some clinical circumstances that are presented in this review. We have encountered aluminum in bone in patients with an increased intestinal permeability (coeliac disease), or in the case of prolonged administration of aluminum anti-acid drugs. A colocalisation of aluminum with iron was also noted in cases of hemochromatosis and sickle cell anemia. Aluminium was also identified in a series of patients with exostosis, a frequent benign bone tumor. Corrosion of prosthetic implants composed of grade V titanium (TA6V is an alloy containing 6% aluminum and 4% vanadium) was also observed in a series of hip or knee revisions. Aluminum can be identified in undecalcified bone matrix stained by solochrome azurine, a highly specific stain allowing the detection of 0.03 atomic %. Colocalization of aluminum and iron does not seem to be the fruit of chance but the cellular and molecular mechanisms are still poorly understood. Histochemistry is superior to spectroscopic analyses (EDS and WDS in scanning electron microscopy).

  11. Application of DBM tool for detection of EUV mask defect (United States)

    Yoo, Gyun; Kim, Jungchan; Park, Chanha; Lee, Taehyeong; Ji, Sunkeun; Yang, Hyunjo; Yim, Donggyu; Park, Byeongjun; Maruyama, Kotaro; Yamamoto, Masahiro


    Extreme ultraviolet lithography (EUVL) is one of the most leading lithography technologies for high volume manufacturing. The EUVL is based on reflective optic system therefore critical patterning issues are arisen from the surface of photomask. Defects below and inside of the multilayer or absorber of EUV photomask is one of the most critical issues to implement EUV lithography in mass production. It is very important to pick out and repair printable mask defects. Unfortunately, however, infrastructure for securing the defect free photomask such as inspection tool is still under development furthermore it does not seem to be ready soon. In order to overcome the lack of infrastructures for EUV mask inspection, we will discuss an alternative methodology which is based on wafer inspection results using DBM (Design Based Metrology) tool. It is very challenging for metrology to quantify real mask defect from wafer inspection result since various sources are possible contributor. One of them is random defect comes from poor CD uniformity. It is probable that those random defects are majority of a defect list including real mask defects. It is obvious that CD uniformity should be considered to pick out only a real mask defect. In this paper, the methodology to determine real mask defect from the wafer inspection results will be discussed. Experiments are carried out on contact layer and on metal layer using mask defect inspection tool, Teron(KLA6xx) and DBM (Design Based Metrology) tool, NGR2170™.

  12. The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review.

    NARCIS (Netherlands)

    Rathe, F.; Junker, R.; Chesnutt, B.C.; Jansen, J.A.


    This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic revi

  13. Changes in chemical composition of bone matrix in ovariectomized (OVX) rats detected by Raman spectroscopy and multivariate analysis (United States)

    Oshima, Yusuke; Iimura, Tadahiro; Saitou, Takashi; Imamura, Takeshi


    Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm-1 (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.

  14. Castor oil polymer induces bone formation with high matrix metalloproteinase-2 expression. (United States)

    Saran, Wallace Rocha; Chierice, Gilberto Orivaldo; da Silva, Raquel Assed Bezerra; de Queiroz, Alexandra Mussolino; Paula-Silva, Francisco Wanderley Garcia; da Silva, Léa Assed Bezerra


    The aim of this study was to evaluate the modulation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expression in newly formed bone tissue at the interface between implants derived from castor oil (Ricinus communis) polymer and the tibia medullary canal. Forty-four rabbits were assigned to either Group 1 (n = 12; control) or Group 2 (n = 30), which had the tibial medullary canals reamed bilaterally and filled with polymer. CT scans showed no space between the material surface and the bone at the implant/bone marrow interface, and the density of the tissues at this interface was similar to the density measured of other regions of the bone. At 90 days postimplantation, the interface with the polymer presented a thick layer of newly formed bone tissue rich in osteocytes. This tissue exhibited ongoing maturation at 120 and 150 days postimplantation. Overall, bone remodeling process was accompanied by positive modulation of MMP-2 and low MMP-9 expression. Differently, in control group, the internal surface close to the medullary canal was lined by osteoblasts, followed by a bone tissue zone with few lacunae filled with osteocytes. Maturation of the tissue of the medullary internal surface occurred in the inner region, with the bone being nonlamellar.

  15. How Osteoblasts Sense their Environment: Integrin-Extracellular Matrix Interactions and Mechanical Loading of Bone (United States)

    Globus, Ruth K.; Dalton, Bonnie (Technical Monitor)


    Osteoblasts are the cells responsible for forming and replacing bone throughout life. We know that mechanical stimulation through weight-bearing at I gravity on Earth is needed to maintain healthy bone, and that osteoblasts play a critical role in that process. Over the last 9 years in my laboratory at NASA ARC, we have studied the regulation of osteoblast function by interactions between the extracellular matrix and die cell. Using a cell culture approach, we defined the repertoire of adhesion receptors, called integrins, which are expressed on the osteoblast surface, as well as specific extracellular matrix proteins, which are needed for cellular differentiation and survival. We are now extending these observations to determine if integrin signaling is involved in the skeletal responses to disuse and recovery from disuse using the rodent model of hindlimb unloading by tail suspension. Together, our cell culture and animal studies are providing new insight into the regulation of osteoblast function in bone.

  16. Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna. (United States)

    Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi


    Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

  17. Different matrix evaluation for the bone regeneration of rats' femours using time domain optical coherence tomography (United States)

    Rusu, Laura-Cristina; Negrutiu, Meda Lavinia; Sinescu, Cosmin; Hoinoiu, Bogdan; Zaharia, Cristian; Ardelean, Lavinia; Duma, Virgil-Florin; Podoleanu, Adrian G.


    The osteoconductive materials are important in bone regeneration procedures. Three dimensional (3D) reconstructions were obtained from the analysis. The aim of this study is to investigate the interface between the femur rat bone and the new bone that is obtained using a method of tissue engineering that is based on two artificial matrixes inserted in previously artificially induced defects. For this study, under strict supervision 20 rats were used in conformity with ethical procedures. In all the femurs a round defect was induced by drilling with a 1 mm spherical Co-Cr surgical drill. The matrixes used were IngeniOss (for ten samples) and 4Bone(for the other ten samples). These materials were inserted into the induced defects. The femurs were investigated at 1 month, after the surgical procedures. The interfaces were examined using Time Domain (TD) Optical Coherence Tomography (OCT) combined with Confocal Microscopy (CM). The scanning procedure is similar to that used in any CM, where the fast scanning is en-face (line rate) and the scanning in depth is much slower (at the frame rate). The optical configuration uses two single mode directional couplers with a superluminiscent diode as the source centered at 1300 nm. The results showed open interfaces due to the insufficient healing process, as well as closed interfaces due to a new bone formation inside the defect. The conclusion of this study is that TD-OCT can act as a valuable tool in the investigation of the interface between the old bone and the one that has been newly created due to the osteoinductive process. The TD-OCT has proven a valuable tool for the non-invasive evaluation of the matrix bone interfaces.

  18. Histological and radiographic evaluations of demineralized bone matrix and coralline hydroxyapatite in the rabbit tibia. (United States)

    Zhukauskas, Rasa; Dodds, Robert A; Hartill, Caroline; Arola, Travis; Cobb, Ronald R; Fox, Casey


    Complex fractures resulting in bone loss or impaired fracture healing remain problematic in trauma and orthopedic surgeries. Many bone graft substitutes have been developed and are commercially available. These products differ in their osteoconductive and osteoinductive properties. Differential enhancement of these properties may optimize the performance of these products for various orthopedic and craniofacial applications. The use of bone graft substitutes offers the ability to lessen the possible morbidity of the harvest site in autografts. The objective of the present study was to compare the ability of two bone graft substitutes, BioSet RT, an allograft demineralized bone matrix formulation, and ProOsteon 500R, a coralline hydroxyapatite, in a rabbit critical tibial defect model. BioSet RT and ProOsteon 500R were implanted into a unicortical proximal metaphyseal tibial defect and evaluated for new bone formation. Samples were analyzed radiographically and histologically at 1 day, 6 weeks, 12 weeks, and 24 weeks post surgery. Both materials were biocompatible and demonstrated significant bone growth and remodeling. At 12 weeks, the BioSet RT implanted sites demonstrated significantly more defect closure and bone remodeling as determined by radiographic analyses with 10 out of 14 defects being completely healed versus 1 out of 14 being completely healed in the ProOsteon 500R implanted sites. At 24 weeks, both materials demonstrated complete closure of the defect as determined histologically. There were no statistical differences in radiographic scores between the two implanted materials. However, there was an observable trend that the BioSet RT material generated higher histological and radiographic scores, although not statistically significant. This study provides evidence that both BioSet RT and ProOsteon 500R are biocompatible and able to induce new bone formation as measured in this rabbit model. In addition, this in vivo study demonstrates the ability of

  19. The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review. (United States)

    Rathe, Florian; Junker, Rüdiger; Chesnutt, Betsy M; Jansen, John A


    This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic review. Main results of the reviewed articles were (i) guide tissue regeneration (GTR) of infrabony defects seems to result in a higher degree of bone regeneration compared to treatment with EMD; (ii) combined therapy (GTR + EMD) of infrabony defects might not lead to better results than GTR therapy alone; (iii) there seems to be no additional benefit of combined therapy (GTR + EMD) in furcation defects over GTR therapy alone; (iv) EMD seems to lead to more bone regeneration of infrabony defects compared to open flap debridement; (v) however, EMD application might result in more bone formation when applied in supporting defects compared to nonsupporting defects; and (vi) EMD does not seem to promote external jaw/parietal bone formation in the titanium capsule model. The results of one study that suggest that EMD increases the initial growth of trabecular bone around endosseous implants by new bone induction need to be confirmed by additional research.

  20. Morphological similarities between DBM and a microeconomic model of sprawl (United States)

    Caruso, Geoffrey; Vuidel, Gilles; Cavailhès, Jean; Frankhauser, Pierre; Peeters, Dominique; Thomas, Isabelle


    We present a model that simulates the growth of a metropolitan area on a 2D lattice. The model is dynamic and based on microeconomics. Households show preferences for nearby open spaces and neighbourhood density. They compete on the land market. They travel along a road network to access the CBD. A planner ensures the connectedness and maintenance of the road network. The spatial pattern of houses, green spaces and road network self-organises, emerging from agents individualistic decisions. We perform several simulations and vary residential preferences. Our results show morphologies and transition phases that are similar to Dieletric Breakdown Models (DBM). Such similarities were observed earlier by other authors, but we show here that it can be deducted from the functioning of the land market and thus explicitly connected to urban economic theory.

  1. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells (United States)


    Background Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. Materials and Methods In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Results Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Conclusion Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft. PMID:27606597

  2. Mouse basophils reside in extracellular matrix-enriched bone marrow niches which control their motility. (United States)

    Smaniotto, Salete; Schneider, Elke; Goudin, Nicolas; Bricard-Rignault, Rachel; Machavoine, François; Dardenne, Mireille; Dy, Michel; Savino, Wilson


    Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1), which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively), we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

  3. Mouse basophils reside in extracellular matrix-enriched bone marrow niches which control their motility.

    Directory of Open Access Journals (Sweden)

    Salete Smaniotto

    Full Text Available Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1, which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively, we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

  4. Mouse Basophils Reside in Extracellular Matrix-Enriched Bone Marrow Niches Which Control Their Motility


    Salete Smaniotto; Elke Schneider; Nicolas Goudin; Rachel Bricard-Rignault; François Machavoine; Mireille Dardenne; Michel Dy; Wilson Savino


    Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1), which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (...

  5. Effect of enamel matrix derivative (Emdogain) on bone defects in rabbit tibias. (United States)

    Cornelini, Roberto; Scarano, Antonio; Piattelli, Maurizio; Andreana, Sebastiano; Covani, Ugo; Quaranta, Alessandro; Piattelli, Adriano


    The aim of this study was to assess the effect of an enamel matrix derivative (Emdogain, Biora, AB, Malmö, Sweden) on bone healing. Ten New Zealand rabbits, weighing about 2.5 kg, were used. One 8-mm bone defect was created in each tibia. The defect on the right leg was filled with Emdogain, whereas the defect on the opposite leg was left unfilled as control. A total of 20 defects were created. Five rabbits each were killed at 4 and 8 weeks with an overdose of Tanax. Block sections containing the defects were retrieved and the specimens processed for light microscopy examination. The slides were stained with acid and basic fuchsin and toluidine blue. Histologically, no differences were noted in both groups at each observation period; in the test group, remnants of the implanted Emdogain were not present at 4 weeks. Newly formed bone was detectable in both groups at all observation times. At 8 weeks, both groups showed mature bone, and in the test group the material implanted was not visible. No inflammatory cells were visible in both groups. In conclusion, our results indicate that Emdogain implanted in bone defects is fully resorbed after 4 to 8 weeks and does not adversely affect bone formation.

  6. Development of biomimetic nanocomposites as bone extracellular matrix for human osteoblastic cells. (United States)

    Bhowmick, Arundhati; Mitra, Tapas; Gnanamani, Arumugam; Das, Manas; Kundu, Patit Paban


    Here, we have developed biomimetic nanocomposites containing chitosan, poly(vinyl alcohol) and nano-hydroxyapatite-zinc oxide as bone extracellular matrix for human osteoblastic cells and characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction. Scanning electron microscopy images revealed interconnected macroporous structures. Moreover, in this study, the problem related to fabricating a porous composite with good mechanical strength has been resolved by incorporating 5wt% of nano-hydroxyapatite-zinc oxide into chitosan-poly(vinyl alcohol) matrix; the present composite showed high tensile strength (20.25MPa) while maintaining appreciable porosity (65.25%). These values are similar to human cancellous bone. These nanocomposites also showed superior water uptake, antimicrobial and biodegradable properties than the previously reported results. Compatibility with human blood and pH was observed, indicating nontoxicity of these materials to the human body. Moreover, proliferation of osteoblastic MG-63 cells onto the nanocomposites was also observed without having any negative effect.

  7. Fibular Allograft and Demineralized Bone Matrix for the Treatment of Slipped Capital Femoral Epiphysis. (United States)

    Murray, Travis; Morscher, Melanie A; Krahe, Amy M; Adamczyk, Mark J; Weiner, Dennis S


    Previous studies documented the use of fibular allograft in the treatment of slipped capital femoral epiphysis (SCFE) with bone graft epiphysiodesis (BGE). This study describes the results of using a 10-mm diameter premilled fibular allograft packed with demineralized bone matrix placed across the physis in an open surgical approach under image intensification. A review identified 45 cases of BGE using fibular allograft and demineralized bone matrix in 34 patients with a diagnosis of SCFE performed by a single surgeon during an 8-year period. Thirty-four cases (25 patients) had at least 1 year of follow-up and were included in the study. Medical records were reviewed for complications, subsequent surgeries, and time to physeal closure. Of the 34 cases included, there were no cases of acute chondrolysis. Complications included 1 case of bone graft extrusion that required surgical replacement and 1 re-slip requiring surgical stabilization. Five cases of avascular necrosis (AVN) were encountered (1 unstable slip with total head AVN, and 4 stable slips with 3 total head and 1 partial head AVN). In 1 patient, small loose bony fragments were noted on postoperative radiographs that appeared outside of the articular surface of the hip and were asymptomatic. Two patients encountered wound healing issues that resolved with appropriate wound care. In light of the occurrence of AVN in stable cases, BGE with autogenous corticocancellous graft is preferable to BGE with autologous fibular graft for the treatment of SCFE. [Orthopedics. 2016; 39(3):e519-e525.].

  8. Repair of calvarial defects with human umbilical cord blood derived mesenchymal stem cells and demineralized bone matrix in athymic rats%人脐血间充质干细胞修复颅骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘广鹏; 李宇琳; 孙剑; 崔磊; 张文杰; 曹谊林


    Objective To investigate the feasibility of using human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) and demineralized bone matrix (DBM) scaffolds to repair critical-sized calvarial defects in athymic rats. Methods Human UCB-MSCs were isolated, expanded and osteogenically induced in vitro. Osteogenic differentiation of UCB-MSCs was evaluated by Alizarin Red staining and measurement of calcium content respectively, and then the cells were seeded onto DBM scaffolds. Bilateral full-thickness defects (5 mm in diameter) of parietal bone were created in an athymic rat model. The defects were either repaired with UCB-MSC/DBM constructs (experimental group) or with DBM scaffolds alone (control group). Animals were harvested at 6 and 12 weeks post-implantation respectively, and defect repair was evaluated with gross observation, micro-CT measurement and histological analysis. Results Micro-CT showed that new bone was formed in the experimental group at 6 weeks post-implantation, while no sign of new bone formation was observed in the control group. At 12 weeks post-transplantation, scaffolds had been degraded almost completely in both sides. It was shown that an average of (78.19±6.45)% of each defect volume had been repaired in experimental side; while in the control side, only limited bone formed at the periphery of the defect. Histological examination revealed that the defect was repaired by trabecular bone tissue in experimental side at 12 weeks, while only fibrous connection was observed in the control group. Conclusions Tissue-engineered bone composed of osteogenically-induced human UCB-MSCs on DBM scaffolds could successfully repair the critical-sized calvarial defects in athymic rat models.%目的 应用人脐血间充质干细胞(umbilical cord blood derived mesenchymal stem cells,UCB-MSCs)复合脱钙骨材料构建组织工程化骨,修复裸大鼠颅骨标准缺损.方法 体外扩增培养、成骨诱导人UCB-MSCs,采用Alizarin Red染色

  9. Endochondral ossification for enhancing bone regeneration: converging native extracellular matrix biomaterials and developmental engineering in vivo. (United States)

    Dennis, S Connor; Berkland, Cory J; Bonewald, Lynda F; Detamore, Michael S


    Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's "ideal" osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the "hard" or "bony" callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures and, thus, can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies which mimic the initial inflammatory or fibrocartilaginous ECM (i.e., "pro-" or "soft" callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (1) native ECM biomaterials and (2) developmental engineering, which will attempt to overcome the technical, business, and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native "raw" materials and ECM-based designs that

  10. Biomineralization of a Self-Assembled Extracellular Matrix for Bone Tissue Engineering (United States)

    Meng, Yizhi; DiMasi, Elaine; Ba, Xiaolan; Rafailovich, Miriam; Pernodet, Nadine


    Understanding how biomineralization occurs in the extracellular matrix (ECM) of bone cells is crucial to the understanding of bone formation and the development of a successfully engineered bone tissue scaffold. It is still unclear how ECM mechanical properties affect protein-mineral interactions in early stages of bone mineralization. We investigated the longitudinal mineralization properties of MC3T3-E1 cells and the elastic modulus of their ECM using shear modulation force microscopy, synchrotron grazing incidence X-ray diffraction (GIXD), scanning electron microscopy, energy dispersive X-ray spectroscopy, and confocal laser scanning microscopy (CLSM). The elastic modulus of the ECM fibers underwent significant changes for the mineralizing cells, which were not observed in the nonmineralizing cells. On substrates conducive to ECM network production, the elastic modulus of mineralizing cells increased at time points corresponding to mineral production, whereas that of the nonmineralizing cells did not vary over time. The presence of hydroxyapatite in mineralizing cells and the absence thereof in the nonmineralizing ones were confirmed by GIXD, and CLSM showed that a restructuring of actin occurred only for mineral-producing cells. These results show that the correct and complete development of the ECM network is required for osteoblasts to mineralize. This in turn requires a suitably prepared synthetic substrate for bone development to succeed in vitro. PMID:18759666

  11. Biomineralization of a Self-Assembled Extracellular Matrix for Bone Tissue Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Yizhi, M.; Yi-Xian, Q; DiMasi, E; Xiaolan, B; Rafailovich, M; Pernodet, N


    Understanding how biomineralization occurs in the extracellular matrix (ECM) of bone cells is crucial to the understanding of bone formation and the development of a successfully engineered bone tissue scaffold. It is still unclear how ECM mechanical properties affect protein-mineral interactions in early stages of bone mineralization. We investigated the longitudinal mineralization properties of MC3T3-E1 cells and the elastic modulus of their ECM using shear modulation force microscopy, synchrotron grazing incidence X-ray diffraction (GIXD), scanning electron microscopy, energy dispersive X-ray spectroscopy, and confocal laser scanning microscopy (CLSM). The elastic modulus of the ECM fibers underwent significant changes for the mineralizing cells, which were not observed in the nonmineralizing cells. On substrates conducive to ECM network production, the elastic modulus of mineralizing cells increased at time points corresponding to mineral production, whereas that of the nonmineralizing cells did not vary over time. The presence of hydroxyapatite in mineralizing cells and the absence thereof in the nonmineralizing ones were confirmed by GIXD, and CLSM showed that a restructuring of actin occurred only for mineral-producing cells. These results show that the correct and complete development of the ECM network is required for osteoblasts to mineralize. This in turn requires a suitably prepared synthetic substrate for bone development to succeed in vitro.

  12. An Osteoconductive Antibiotic Bone Eluting Putty with a Custom Polymer Matrix

    Directory of Open Access Journals (Sweden)

    John Curley


    Full Text Available With the rising tide of antibiotic resistant bacteria, extending the longevity of the current antibiotic arsenal is becoming a necessity. Developing local, controlled release antibiotic strategies, particularly for difficult to penetrate tissues such as bone, may prove to be a better alternative. Previous efforts to develop an osteoconductive local antibiotic release device for bone were created as solid molded composites; however, intimate contact with host bone was found to be critical to support host bone regrowth; thus, an osteocondconductive antibiotic releasing bone void filling putty was developed. Furthermore, a controlled releasing polymer matrix was refined using pendant-functionalized diols to provide tailorable pharmacokinetics. In vitro pharmacokinetic and bioactivity profiles were compared for a putty formulation with an analogous composition as its molded counterpart as well as four new pendant-functionalized polymers. A best-fit analysis of polymer composition in either small cylindrical disks or larger spheres revealed that the new pendant-functionalized polymers appear to release vancomycin via both diffusion and erosion regardless of the geometry of the putty. In silico simulations, a valuable technique for diffusion mediated controlled release models, will be used to confirm and optimize this property.

  13. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Directory of Open Access Journals (Sweden)

    Yang Wang


    Full Text Available The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better

  14. Effect of bone marrow stromal cell sheet on the formation of tissue-engineered bone in dogs%犬骨髓基质细胞片层在构建组织工程骨中的作用

    Institute of Scientific and Technical Information of China (English)

    王玲玲; 李宁毅; 樊功为; 卜令学; 杨学财; 高振华


    目的:探讨犬骨髓基质细胞(bone marrow stromal cells,BMSCs)细胞片层在构建组织工程骨中的价值.方法:制备犬同种异体脱钙骨基质(dermineralized bone matrix,DBM).将人重组骨形态发生蛋白-2(rhBMP-2)复合到DBM上.抽取犬髂骨骨髓,采用密度梯度离心法分离犬骨髓基质细胞(BMSCs).将经成骨诱导的第3代细胞接种于温度反应性培养皿中,制备BMSCs细胞片层.用得到的BMSCs细胞片层包裹DBM/rhBMP-2/BMSCs复合体,植入犬背阔肌血运丰富的肌筋膜下为实验侧,以无BMSCs细胞片层包裹的DBM/rhBMP-加MSCs复合体为对照侧.术后4、8、12周取材,行组织学观察,评价体内异位成骨的情况.采用SPSS13.0软件,对数据进行两样本均数差别的t检验.结果:实验侧成骨面积大于对照侧,2组差异有显著性(P<0.05).术后12周,实验侧生成大量板层骨,有哈弗系统形成,骨髓腔内有红骨髓.对照侧有板层骨形成,无哈弗系统形成,骨髓腔内无红骨髓.结论:BMSCs细胞片层可促进具有致密板层骨和哈弗系统的组织工程骨的形成.%PURPOSE: To investigate the effect of bone marrow stromal cell sheet on the formation of tissue-engineered bone in dogs. METHODS: Demineralized bone matrix (DBM) were prepared from homologous bone. DBM was constituted with recombination human bone morphogenetic protein-2(rhBMP-2). And bone marrow stromal cells(BMSCs) were isolated from iliac bone of dogs with the method of density gradient centrifugation in vitro. BMSCs induced by osteogenic DMEM at passage 3 were incubated in the temperature-responsive culture dish to form BMSCs cell sheet. BMSCs cell sheet combined with DBM/rhBMP-2/BMSCs was implanted around the vessels of latissimus dorsi muscle in the experimental side,and DBM/rhBMP-2/BMSCs without BMSCs cell sheet was implanted around the vessels of latissimus dorsi muscle in the control side. 4,8,12 weeks after operation, the ectopic bone formation was investigated by

  15. Two-Stage Revision Anterior Cruciate Ligament Reconstruction: Bone Grafting Technique Using an Allograft Bone Matrix. (United States)

    Chahla, Jorge; Dean, Chase S; Cram, Tyler R; Civitarese, David; O'Brien, Luke; Moulton, Samuel G; LaPrade, Robert F


    Outcomes of primary anterior cruciate ligament (ACL) reconstruction have been reported to be far superior to those of revision reconstruction. However, as the incidence of ACL reconstruction is rapidly increasing, so is the number of failures. The subsequent need for revision ACL reconstruction is estimated to occur in up to 13,000 patients each year in the United States. Revision ACL reconstruction can be performed in one or two stages. A two-stage approach is recommended in cases of improper placement of the original tunnels or in cases of unacceptable tunnel enlargement. The aim of this study was to describe the technique for allograft ACL tunnel bone grafting in patients requiring a two-stage revision ACL reconstruction.

  16. Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models. (United States)

    Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L; Snyder, Brian D; Rosenberg, Andrew E; Nazarian, Rosalynn M; Hrovat, Mirko I; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang


    In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization.

  17. Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix. (United States)

    Ben-David, Dror; Srouji, Samer; Shapira-Schweitzer, Keren; Kossover, Olga; Ivanir, Eran; Kuhn, Gisela; Müller, Ralph; Seliktar, Dror; Livne, Erella


    Bone repair strategies utilizing resorbable biomaterial implants aim to stimulate endogenous cells in order to gradually replace the implant with functional repair tissue. These biomaterials should therefore be biodegradable, osteoconductive, osteoinductive, and maintain their integrity until the newly formed host tissue can contribute proper function. In recent years there has been impressive clinical outcomes for this strategy when using osteoconductive hydrogel biomaterials in combination with osteoinductive growth factors such as human recombinant bone morphogenic protein (hrBMP-2). However, the success of hrBMP-2 treatments is not without risks if the factor is delivered too rapidly and at very high doses because of a suboptimal biomaterial. Therefore, the aim of this study was to evaluate the use of a PEGylated fibrinogen (PF) provisional matrix as a delivery system for low-dose hrBMP-2 treatment in a critical size maxillofacial bone defect model. PF is a semi-synthetic hydrogel material that can regulate the release of physiological doses of hrBMP-2 based on its controllable physical properties and biodegradation. hrBMP-2 release from the PF material and hrBMP-2 bioactivity were validated using in vitro assays and a subcutaneous implantation model in rats. Critical size calvarial defects in mice were treated orthotopically with PF containing 8 μg/ml hrBMP-2 to demonstrate the capacity of these bioactive implants to induce enhanced bone formation in as little as 6 weeks. Control defects treated with PF alone or left empty resulted in far less bone formation when compared to the PF/hrBMP-2 treated defects. These results demonstrate the feasibility of using a semi-synthetic biomaterial containing small doses of osteoinductive hrBMP-2 as an effective treatment for maxillofacial bone defects.

  18. Dentin extracellular matrix (ECM) proteins: comparison to bone ECM and contribution to dynamics of dentinogenesis. (United States)

    Butler, William T; Brunn, Jan C; Qin, Chunlin


    Dentinogenesis involves the initial odontoblastic synthesis of a collagen-rich extracellular matrix (ECM) and predentin that is converted to dentin when the collagen fibrils become mineralized. Since the width of predentin is rather uniform, we postulate that extracellular events regulate dentinogenesis. Similarly, osteogenesis involves an initial unmineralized osteoid that is mineralized and converted to bone. To gain insights into these two processes, we compared ECM proteins in bone with those in dentin, focusing upon the sialic acid (SA)-rich proteins. We observed qualitative similarities between the SA-rich proteins, but distinct differences in the amounts of osteopontin (OPN) and dentin sialoprotein (DSP). OPN, a predominant protein in bone, was found in much smaller amounts in dentin. Conversely, DSP was abundant in dentin ECM, but found sparingly in bone. Molecular cloning experiments indicate that coding sequences for DSP and dentin phosphoprotein (DPP) are found on the same mRNA. We believe that the initial form of the precursor protein DSPP is inactive in influencing the mineralization process and that it must be activated by cleavage of peptide bonds in conserved regions. Thus, unknown proteinases would act on DSPP, possibly at the mineralization front, and liberate active DPP, which plays an initiation and regulatory role in the formation of apatite crystals. This post-translational processing reaction would represent an important control point in dentinogenesis. Recently, we identified uncleaved DSPP in dentin extracts, which should allow us to test portions of our hypothesis.

  19. The effect of enamel matrix derivative (Emdogain®) on gene expression profiles of human primary alveolar bone cells. (United States)

    Yan, X Z; Rathe, F; Gilissen, C; van der Zande, M; Veltman, J; Junker, R; Yang, F; Jansen, J A; Walboomers, X F


    Emdogain® is frequently used in regenerative periodontal treatment. Understanding its effect on gene expression of bone cells would enable new products and pathways promoting bone formation to be established. The aim of the study was to analyse the effect of Emdogain® on expression profiles of human-derived bone cells with the help of the micro-array, and subsequent validation. Bone was harvested from non-smoking patients during dental implant surgery. After outgrowth, cells were cultured until subconfluence, treated for 24 h with either Emdogain® (100 µg/ml) or control medium, and subsequently RNA was isolated and micro-array was performed. The most important genes demonstrated by micro-array data were confirmed by qPCR and ELISA tests. Emdogain tipped the balance between genes expressed for bone formation and bone resorption towards a more anabolic effect, by interaction of the PGE2 pathway and inhibition of IL-7 production. In addition the results of the present study indicate that Emdogain possibly has an effect on gene expression for extracellular matrix formation of human bone cells, in particular on bone matrix formation and on proliferation and differentiation. With the micro-array and the subsequent validation, the genes possibly involved in Emdogain action on bone cells were identified. These results can contribute to establishing new products and pathways promoting bone formation.

  20. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Mikaël M. [Osaka Univ. (Japan). Immunology Frontier Research Center; Briquez, Priscilla S. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Maruyama, Kenta [Osaka Univ. (Japan). Immunology Frontier Research Center; Hubbell, Jeffrey A. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)


    Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of the ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.

  1. In vivo study of extracellular matrix coating enhancing fixation of the pedicle screw-bone's interface

    Institute of Scientific and Technical Information of China (English)

    LIU Guo-min; ZHANG Xing-yi; XU Chuan-jie; ZHU Xiao-min; WANG Jun; LIU Yi


    Background Based on in vivo research on the effect of the coating of the extracellular matrix composition of pedicle screws on the conduction and induction of bone formation in young sheep,the aim of this study was to investigate the application of coated pedicle screws in sheep with scoliosis whose spines are under constant development.Methods Four groups of pedicle screws were randomly implanted into bilateral L2-L5 pedicles of 2.5- to 3-month-old sheep.A static experiment was performed on one side and a loading test was performed on the other side by implanting connecting rods at the L2-L3 and L4-L5 segments.The changes in the force on the coated screws and the combination of the surface of the coated screws with the surrounding bone in the growth process of young sheep's spines with aging were observed.After 3 months,the lumbar vertebrae with the screws were removed and examined by micro-CT,histological,and biomechanical analyses.Results Under nonloading conditions,there is bone formation around the surfaces of coated screws.The bone forming on the surface of collagen/chondroitin sulfate/hydroxyapatite coating of pedicle screws is the most,the one of the collagen / chondrcitin sulfate coating and hydroxyapatite coating is followed,and no significant difference between the two groups.In terms of the trabecular bone morphology parameters of the region of interest around the surface of the pedicle screws,such as bone mineral content,bone mineral density,tissue mineral content,tissue bone mineral density,bone volume fraction,and connection density,those associated with collagen/chondroitin sulfate/hydroxyapatite coatings are largest and those unassociated with coatings are smallest.Under nonloading conditions,the pullout strength of the collagen/chondroitin sulfate/hydroxyapatite-coated screws was largest,and that of the uncoated screws was minimal (P <0.01).Under loading conditions,the maximum pullout strength of each group of pedicle screws was less than that

  2. Experimental study of bone marrow stromal cell sheet on the construction of tissue-engineered bone%应用骨髓基质细胞片层构建组织工程骨的实验研究

    Institute of Scientific and Technical Information of China (English)

    王玲玲; 李宁毅; 樊功为; 卜令学; 袁荣涛; 高振华; 邢士超


    Objective To invesligale the effecl of bone marrow slromal cell sheet on the conslruclion of tissue-engineered bone in dogs. Methods Bone marrow slromal cells ( BMSCs) were isolaled from iliac bone of dogs with the melhod of density gradienl cenlrifu galion in vitro. Demineralized bone malrix( DBM) were prepared from homologuous bone. DBM was composiled wilh recombination hu man bone morphogenelic prolein-2( rhBMP-2). BMSCs induced by osleogenic DMEM al passage 3 were incubaled in the lemperalure responsive culture dish to make the BMSCs cell sheel. BMSCs cell sheel combined wilh DBM/rhBMP-2/BMSCs was implanted around the vessels of lattisimus dorsi muscle on the left side in the experiment group, and DBM/rhBMP-2/BMSCs without BMSCs cell sheet was implanted around the vessels of lattisimus dorsi muscle on the right side in the control group. 8,12,16 weeks after operation, the bone formation was investigated by histological observation. Results Osteogenesis result was experimental group > control group. Newly formed bone tissue in two groups were significantly different( P < 0. 05). 16 weeks after operation, a large number of lamellar bone and haversian system formed in experimental group,with red bone marrow in the bone marrow cavity. Lamellar bone formed in control group without haversian system and red bone marrow. Conclusions BMSCs cell sheet could promote the formation of tissue-engineered bone with dense lamellar bone and haversian system.%目的 探讨犬骨髓基质细胞(bone marrow stromal cells,BMSCs)片层在构建组织工程骨中的价值.方法 抽取犬髂骨骨髓,采用密度梯度离心法分离犬骨髓基质细胞(BMSCs).制备犬同种异体脱钙骨基质(dermineralized bone matrix,DBM).将人重组骨形态发生蛋白-2(recombination human bone morphogenetic protein-2,rhBMP-2)复合到DBM上.将经成骨诱导的第3代细胞接种于温度反应性培养皿中,制备BMSCs细胞片层.用得到的BMSCs细胞片层包裹DBM/rhBMP-2

  3. Contribution of matrix vesicles and alkaline phosphatase to ectopic bone formation

    Directory of Open Access Journals (Sweden)

    Ciancaglini P.


    Full Text Available Endochondral calcification involves the participation of matrix vesicles (MVs, but it remains unclear whether calcification ectopically induced by implants of demineralized bone matrix also proceeds via MVs. Ectopic bone formation was induced by implanting rat demineralized diaphyseal bone matrix into the dorsal subcutaneous tissue of Wistar rats and was examined histologically and biochemically. Budding of MVs from chondrocytes was observed to serve as nucleation sites for mineralization during induced ectopic osteogenesis, presenting a diameter with Gaussian distribution with a median of 306 ± 103 nm. While the role of tissue-nonspecific alkaline phosphatase (TNAP during mineralization involves hydrolysis of inorganic pyrophosphate (PPi, it is unclear how the microenvironment of MV may affect the ability of TNAP to hydrolyze the variety of substrates present at sites of mineralization. We show that the implants contain high levels of TNAP capable of hydrolyzing p-nitrophenylphosphate (pNPP, ATP and PPi. The catalytic properties of glycosyl phosphatidylinositol-anchored, polidocanol-solubilized and phosphatidylinositol-specific phospholipase C-released TNAP were compared using pNPP, ATP and PPi as substrates. While the enzymatic efficiency (k cat/Km remained comparable between polidocanol-solubilized and membrane-bound TNAP for all three substrates, the k cat/Km for the phosphatidylinositol-specific phospholipase C-solubilized enzyme increased approximately 108-, 56-, and 556-fold for pNPP, ATP and PPi, respectively, compared to the membrane-bound enzyme. Our data are consistent with the involvement of MVs during ectopic calcification and also suggest that the location of TNAP on the membrane of MVs may play a role in determining substrate selectivity in this micro-compartment.

  4. Time domain optical coherence tomography investigation of bone matrix interface in rat femurs (United States)

    Rusu, Laura-Cristina; Negruá¹±iu, Meda-Lavinia; Sinescu, Cosmin; Hoinoiu, Bogdan; Topala, Florin-Ionel; Duma, Virgil-Florin; Rominu, Mihai; Podoleanu, Adrian G.


    The materials used to fabricate scaffolds for tissue engineering are derived from synthetic polymers, mainly from the polyester family, or from natural materials (e.g., collagen and chitosan). The mechanical properties and the structural properties of these materials can be tailored by adjusting the molecular weight, the crystalline state, and the ratio of monomers in the copolymers. Quality control and adjustment of the scaffold manufacturing process are essential to achieve high standard scaffolds. Most scaffolds are made from highly crystalline polymers, which inevitably result in their opaque appearance. Their 3-D opaque structure prevents the observation of internal uneven surface structures of the scaffolds under normal optical instruments, such as the traditional light microscope. The inability to easily monitor the inner structure of scaffolds as well as the interface with the old bone poses a major challenge for tissue engineering: it impedes the precise control and adjustment of the parameters that affect the cell growth in response to various mimicked culture conditions. The aim of this paper is to investigate the interface between the femur rat bone and the new bone that is obtained using a method of tissue engineering that is based on different artificial matrixes inserted in previously artificially induced defects. For this study, 15 rats were used in conformity with ethical procedures. In all the femurs a round defect was induced by drilling with a 1 mm spherical Co-Cr surgical drill. The matrixes used were Bioss and 4bone. These materials were inserted into the induced defects. The femurs were investigated at 1 week, 1 month, 2 month and three month after the surgical procedures. The interfaces were examined using Time Domain (TD) Optical Coherence Tomography (OCT) combined with Confocal Microscopy (CM). The optical configuration uses two single mode directional couplers with a superluminiscent diode as the source centered at 1300 nm. The scanning

  5. Demineralized bone matrix as a bone tissue engineering scaffold material%骨组织工程支架材料:脱矿骨基质

    Institute of Scientific and Technical Information of China (English)

    陈海霞; 谢志刚


    BACKGROUND:Demineralized bone matrix as bone tissue engineering biological scaffold material is more researched currently, which has osteoinductive and osteoconductive. OBTECTIVE:To summarize the development of demineralized bone matrix as bone tissue engineering scaffold material and to prospect its trend. METHODS:The relative literatures addressing demineralized bone matrix as bone tissue engineering scaffold material published between January 1965 and May 2013 in PubMed database, Chinese Biomedical Database, Wanfang Database and FMJS database were searched by the first author. The key words were“demineralized bone matrix, scaffold material, growth factor, cells, drugs”in English and Chinese. According to the inclusion criteria, repetitive researches were excluded, and final y 34 articles were included. RESULTS AND CONCLUSION:Scaffold material is the key composition of tissue engineered bone, and only demineralized bone matrix has both osteoinductive and osteoconductive properties which cannot only provide space for bone repair, but also can be combined with bioactive factors, living cells, antibiotics in vitro to construct bone graft thereby promoting healing of bone defects. However, this technique is also facing some problems to be solved such as the ratio of demineralized bone matrix and various substances, disinfection, preservation of osteogenetic activity and antigenicity elimination. Sufficiently understanding demineralized bone matrix as bone tissue engineering scaffold can provide a theoretical basis for its clinical service.%背景:脱矿骨基质是目前研究较多的具备骨诱导及骨引导的生物支架材料之一。目的:总结脱矿骨基质作为骨组织工程支架材料的研究进展,并展望其发展趋势。  方法:由第一作者检索1965年1月至2013年5月PubMed数据库、中国生物医学数据库、万方数据库及FMJS数据库有关脱矿骨基质及其作为骨组织工程支架材料的相关文

  6. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold. (United States)

    Yang, Bo; Yin, Zhanhai; Cao, Junling; Shi, Zhongli; Zhang, Zengtie; Song, Hongxing; Liu, Fuqiang; Caterson, Bruce


    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 microm) than in cortical BMG (5-15 microm), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  7. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Yang Bo; Yin Zhanhai; Cao Junling; Shi Zhongli; Zhang Zengtie; Liu Fuqiang [College of Medicine, Xi' an Jiaotong University, Yanta West Road, No 76, Yanta District, Xi' an, Shaanxi Province 710061 (China); Song Hongxing [Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Caterson, Bruce, E-mail: [Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, Biomedical Building, Museum Avenue, Cardiff, CF10 3US (United Kingdom)


    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 {mu}m) than in cortical BMG (5-15 {mu}m), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  8. Influence of mineral phase in mineralization of a biocomposite containing chitosan, demineralized bone matrix and bone ash—in vitro study

    Indian Academy of Sciences (India)

    Krithiga Gunasekaran; Santhosh Kumar Baskar; Divya Sapphire Mohan; Thotapalli P Sastry


    A resorbable composite which acts as a active barrier in guided bone regeneration was fabricated using chitosan, demineralized bone matrix and bone ash. Its potential to form bone like apatite in simulated body fluid was assessed in this study. The mechanical strength of these composites was correlated with bone ash ratios and composites with better tensile strength were studied for their acellular bioactivity by incubating in simulated body fluid for 21 days. Composites without bone ash did not show acellular bioactivity which was confirmed by thermogravimetric analysis. In case of biocomposites with bone ash, there was an increase in residual weight indicating the mineralization of the composite. The composite containing bone ash has shown the peaks related to phosphate vibrations in its Fourier-transform infrared spectrum. Scanning micrographs revealed formation of apatite like crystals on its surface. Ca/P ratio was found to be 1.7 which is nearer to that of natural bone. Thus, prepared composites can be used as resorbable biocomposite in maxillofacial and oral defects.

  9. Ridge preservation with acellular dermal matrix and anorganic bone matrix cell-binding peptide P-15 after tooth extraction in humans. A histologic and morphometric study

    Directory of Open Access Journals (Sweden)

    Arthur B. Novaes Jr


    Full Text Available Aim: The aim of this study was to analyze by histomorphometric parameters the use of acellular dermal matrix (ADM with or without anorganic bovine bone matrix (ABM / synthetic cell-binding peptide P-15 in the formation of bone in human alveoli. Materials and methods: Eighteen patients in need of extraction of maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus ABM/P-15 or the control group (ADM only. Histomorphometric measurements and histological analysis were recorded about 6 months after ridge preservation procedures in ten patients. The amount of newly formed bone, the most recently formed bone, fibrous tissue plus marrow spaces and remaining graft particles were measured and analyzed. Results: At 6 months, the new bone area parameter and the percentage of fibrous tissue plus marrow space areas showed higher values to the control group, and statistically significant differences when compared with the test group (p=0.03. Conclusion: The ADM acted as a membrane. The association of ABM/P-15 with ADM resulted in new bone formation within the alveoli, but the results were not considered relevant when used in this indication.

  10. A 10 dBm-25 dBm, 0.363 mm2 Two Stage 130 nm RF CMOS Power Amplifier

    Directory of Open Access Journals (Sweden)

    Shridhar R. Sahu


    Full Text Available This paper proposes a 2.4 GHz RF CMOS Power amplifier and variation in its main performance parameters i.e, output power, S-parameters and power added efficiency with respect to change in supply voltage and size of the power stage transistor. The supply voltage was varied form 1 V to 5 V and the range of output power at 1dB compression point was found to be from 10.684 dBm to 25.08 dBm respectively. The range of PAE is 16.65 % to 48.46 %. The width of the power stage transistor was varied from 150 µm to 500 µm to achieve output power of range 15.47 dBm to 20.338 dBm. The range of PAE obtained here is 29.085 % to 45.439 %. The total dimension of the layout comes out to be 0.714 * 0.508 mm2 .

  11. Novel biocompatible polymeric blends for bone regeneration: Material and matrix design and development (United States)

    Deng, Meng

    The first part of the work presented in this dissertation is focused on the design and development of novel miscible and biocompatible polyphosphazene-polyester blends as candidate materials for scaffold-based bone tissue engineering applications. Biodegradable polyesters such as poly(lactide-co-glycolide) (PLAGA) are among the most widely used polymeric materials for bone tissue engineering. However, acidic degradation products resulting from the bulk degradation mechanism often lead to catastrophic failure of the structure integrity, and adversely affect biocompatibility both in vitro and in vivo. One promising approach to circumvent these limitations is to blend PLAGA with other macromolecules that can buffer the acidic degradation products with a controlled degradation rate. Biodegradable polyphosphazenes (PPHOS), a new class of biomedical materials, have proved to be superior candidate materials to achieve this objective due to their unique buffering degradation products. A highly practical blending approach was adopted to develop novel biocompatible, miscible blends of these two polymers. In order to achieve this miscibility, a series of amino acid ester, alkoxy, aryloxy, and dipeptide substituted PPHOS were synthesized to promote hydrogen bonding interactions with PLAGA. Five mixed-substituent PPHOS compositions were designed and blended with PLAGA at different weight ratios producing candidate blends via a mutual solvent method. Preliminary characterization identified two specific side groups namely glycylglycine dipeptide and phenylphenoxy that resulted in improved blend miscibility and enhanced in vitro osteocompatibility. These findings led to the synthesis of a mixed-substituent polyphosphazene poly[(glycine ethyl glycinato)1(phenylphenoxy)1phosphazene] (PNGEGPhPh) for blending with PLAGA. Two dipeptide-based blends having weight ratios of PNGEGPhPh to PLAGA namely 25:75 (Matrix1) and 50:50 (Matrix2) were fabricated. Both of the blends were

  12. The effect of bone injury on extracellular matrix vesicle proliferation and mineral formation. (United States)

    Sela, J; Schwartz, Z; Amir, D; Swain, L D; Boyan, B D


    Removal of tibial bone marrow in rats is followed by primary bone formation, resorption and marrow restitution. The first week of healing is characterized by partially calcified trabeculae. After 2 weeks, a higher degree of calcification and partial resorption are observed. The third week is characterized by massive resorption of the trabeculae, which are replaced in the fourth week by new bone marrow tissue. This model was used to study primary calcification. Transmission electron micrographs of the young bone revealed osteoblasts, matrix vesicles and calcified fronts. The different vesicular types were defined as 'empty', 'amorphous', 'crystal', and 'rupture'. The vesicles were studied on days 3, 6, 8, 12, 14, 18, 21, 23 and 28 after injury. The mean diameters of most vesicles ranged between 100.3 and 121.9 nm, and their mean distance from the calcified front was less than 976.6 nm. Vesicular density, calculated as number per 10 m2, increased on the eighth day and decreased from the fourteenth day onwards. Highest diameter values were recorded on the sixth day, and decreased onward. Vesicular distance from the calcified front decreased continuously. Distribution of vesicle number, diameter, and distance in each class showed that numbers of empty and amorphous vesicles decreased and of crystal and rupture increased throughout the experiment. Distances from the calcified front and vesicular diameters varied as follows: 'rupture', 'crystal', amorphous', and 'empty', the 'rupture' type being the closest to the front and of the largest diameter. The results confirm the hypothesis that the cell is responsible for the secretion of electron lucent vesicles that accumulate Ca and Pi to form amorphous calcium phosphate complexes that convert to hydroxyapatite. Crystal growth is followed by membrane rupture.

  13. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    Directory of Open Access Journals (Sweden)

    Alison Gartland


    Full Text Available Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

  14. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    DEFF Research Database (Denmark)

    Gartland, Alison; Erler, Janine Terra; Cox, Thomas Robert


    and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview......Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating...... of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis....

  15. Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.



    BACKGROUND: Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. OBJECTIVE: To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. METHODS: 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched he...

  16. Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration. (United States)

    Spalthoff, S; Jehn, P; Zimmerer, R; Möllmann, U; Gellrich, N-C; Kokemueller, H


    We previously generated viable heterotopic bone in living animals and found that 3 months of intrinsic vascularization improved bone formation and matrix degeneration. In this study, we varied the pre-vascularization time to determine its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm-long cylindrical β-tricalcium phosphate scaffolds were filled intraoperatively with autogenous iliac crest bone marrow and implanted in the latissimus dorsi muscle in six sheep. To examine the effect of axial perfusion, one scaffold was surgically implanted with (group C) or without (group D) a central vascular bundle. All animals were sacrificed 6 months postoperatively and histomorphometric measurements were compared to previous results. All implanted scaffolds exhibited ectopic bone growth. However, bone growth was not significantly different between the 3-month (group A, 0.191±0.097 vs. group C, 0.237±0.075; P=0.345) and 6-month (group B, 0.303±0.105 vs. group D, 0.365±0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early differences between surgically and extrinsically vascularized constructs disappeared after 6 months. Here, we describe a reliable procedure for generating ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient and ceramic degradation proceeds in accordance with bone generation, supporting the hypothesis of cell-mediated resorption.

  17. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Zheng-wei Li; Min Luo; Ya-jun Li; Ke-qiang Zhang


    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some re-spects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel group, followed by the polylactic glycolic acid conduit+bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the poly-lactic glycolic acid conduit+bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve ifbers, and a completely degraded and resorbed conduit, in the polylac-tic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is ben-eifcial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the

  18. Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration. (United States)

    Pati, Falguni; Song, Tae-Ha; Rijal, Girdhari; Jang, Jinah; Kim, Sung Won; Cho, Dong-Woo


    3D printing technique is the most sophisticated technique to produce scaffolds with tailorable physical properties. But, these scaffolds often suffer from limited biological functionality as they are typically made from synthetic materials. Cell-laid mineralized ECM was shown to be potential for improving the cellular responses and drive osteogenesis of stem cells. Here, we intend to improve the biological functionality of 3D-printed synthetic scaffolds by ornamenting them with cell-laid mineralized extracellular matrix (ECM) that mimics a bony microenvironment. We developed bone graft substitutes by using 3D printed scaffolds made from a composite of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) and mineralized ECM laid by human nasal inferior turbinate tissue-derived mesenchymal stromal cells (hTMSCs). A rotary flask bioreactor was used to culture hTMSCs on the scaffolds to foster formation of mineralized ECM. A freeze/thaw cycle in hypotonic buffer was used to efficiently decellularize (97% DNA reduction) the ECM-ornamented scaffolds while preserving its main organic and inorganic components. The ECM-ornamented 3D printed scaffolds supported osteoblastic differentiation of newly-seeded hTMSCs by upregulating four typical osteoblastic genes (4-fold higher RUNX2; 3-fold higher ALP; 4-fold higher osteocalcin; and 4-fold higher osteopontin) and increasing calcium deposition compared to bare 3D printed scaffolds. In vivo, in ectopic and orthotopic models in rats, ECM-ornamented scaffolds induced greater bone formation than that of bare scaffolds. These results suggest a valuable method to produce ECM-ornamented 3D printed scaffolds as off-the-shelf bone graft substitutes that combine tunable physical properties with physiological presentation of biological signals.

  19. The Effect of an Enamel Matrix Derivative (Emdogain Combined with Bone Ceramic on Bone Formation in Mandibular Defects: A Histomorphometric and Immunohistochemical Study in the Canine

    Directory of Open Access Journals (Sweden)

    Reza Birang


    Full Text Available Background. The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD and an osteoconductive bone ceramic (BC in improving bone regeneration. Materials and Methods. Four cylindrical cavities (6×6mm were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments—filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated—and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Results. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. Conclusion. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation.

  20. Fabrication method, structure, mechanical, and biological properties of decellularized extracellular matrix for replacement of wide bone tissue defects. (United States)

    Anisimova, N Y; Kiselevsky, M V; Sukhorukova, I V; Shvindina, N V; Shtansky, D V


    The present paper was focused on the development of a new method of decellularized extracellular matrix (DECM) fabrication via a chemical treatment of a native bone tissue. Particular attention was paid to the influence of chemical treatment on the mechanical properties of native bones, sterility, and biological performance in vivo using the syngeneic heterotopic and orthotopic implantation models. The obtained data indicated that after a chemical decellularization treatment in 4% aqueous sodium chlorite, no noticeable signs of the erosion of compact cortical bone surface or destruction of trabeculae of spongy bone in spinal channel were observed. The histological studies showed that the chemical treatment resulted in the decellularization of both bone and cartilage tissues. The DECM samples demonstrated no signs of chemical and biological degradation in vivo. Thorough structural characterization revealed that after decellularization, the mineral frame retained its integrity with the organic phase; however clotting and destruction of organic molecules and fibers were observed. FTIR studies revealed several structural changes associated with the destruction of organic molecules, although all organic components typical of intact bone were preserved. The decellularization-induced structural changes in the collagen constituent resulted changed the deformation under compression mechanism: from the major fracture by crack propagation throughout the sample to the predominantly brittle fracture. Although the mechanical properties of radius bones subjected to decellularization were observed to degrade, the mechanical properties of ulna bones in compression and humerus bones in bending remained unchanged. The compressive strength of both the intact and decellularized ulna bones was 125-130 MPa and the flexural strength of humerus bones was 156 and 145 MPa for the intact and decellularized samples, respectively. These results open new avenues for the use of DECM samples as

  1. Using bone marrow matrix to analyze meprobamate for forensic toxicological purposes. (United States)

    Bévalot, F; Gustin, M P; Cartiser, N; Gaillard, Y; Le Meur, C; Fanton, L; Guitton, J; Malicier, D


    Bone marrow (BM) analysis is of forensic interest for postmortem toxicological investigations where blood samples are unavailable or unusable. Due to the lack of studies, it remains difficult to interpret concentrations of xenobiotics measured in this matrix. Based on a statistical approach published previously to interpret meprobamate concentrations in bile and vitreous humor, we propose here a diagnostic test for interpretation of BM meprobamate concentrations from analysis of 99 sets of autopsy data. The mean age was 48 years (range 18-80 years, one unknown) for males and 50 years (range 19-80 years, one unknown) for females, with a male/female ratio at 0.768. A BM concentration threshold of 11.3 μg/g was found to be statistically equivalent to that of a blood meprobamate concentration threshold of 50 μg/ml in distinguishing overdose from therapeutic use. The intrinsic qualities of this diagnostic test were good with sensitivity of 0.82 and specificity of 0.92. Compared to previous tests published with the same objective on vitreous humor and bile, this study shows that BM is a useful alternative matrix to reveal meprobamate overdose when blood, vitreous humor, and bile are not available or unusable.

  2. The tent pole splint: a bone-supported stereolithographic surgical splint for the soft tissue matrix expansion graft procedure. (United States)

    Cillo, Joseph E; Theodotou, Nicholas; Samuels, Marc; Krajekian, Joseph


    This report details the use of computer-aided planning and intraoperative stereolithographic direct-bone-contact surgical splints for the accurate extraoral placement of dental implants in the soft tissue matrix expansion (tent pole) graft of the severely resorbed mandible.

  3. Bone marrow derived cell-seeded extracellular matrix: A novel biomaterial in the field of wound management

    Directory of Open Access Journals (Sweden)

    V. Remya


    Full Text Available Aim: Extensive or irreversible damage to the skin often requires additional skin substitutes for reconstruction. Biomaterials have become critical components in the development of effective new medical therapies for wound care. Materials and Methods: In the present study, a cell matrix construct (bone marrow-derived cells (BMdc seeded extracellular matrix [ECM] was used as a biological substitute for the repair of full-thickness skin wound. ECM was developed by decellularizing fish swim bladder (FSB. Goat bone marrow-derived cells (G-BMdc were seeded over this decellularized matrix. Efficacy of this cell matrix construct in wound repair was tested by implanting it over 20 mm2 × 20 mm2 size fullthickness skin wound created over the dorsum of rat. The study was conducted in 16 clinically healthy adult rats of either sex. The animals were randomly divided into 2 equal groups of 8 animals each. In Group I, animal’s wounds were repaired with a cellular FSB matrix. In Group II, wounds were repaired with G-BMdc seeded a cellular FSB matrix. Immune response and efficacy of healing were analyzed. Results: Quality of healing and immuno tolerance to the biological substitute was significantly better in Group II than Group I. Conclusion: Seeding with BMdc increases the wound healing potency and modulates the immune response to a significantly negligible level. The BMdc seeded acellular FSB matrix was found to be a novel biomaterial for wound management.

  4. Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis aries

    Directory of Open Access Journals (Sweden)

    Adelina A. Hernandez-Hurtado


    Full Text Available Adipose-derived mesenchymal stem cells (ADMSCs are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs. This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology.

  5. Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis aries (United States)

    Hernandez-Hurtado, Adelina A.; Lara-Arias, Jorge; Romero-Diaz, Viktor J.; Abrego-Guerra, Adalberto; Vilchez-Cavazos, Jose F.; Elizondo-Riojas, Guillermo; Martinez-Rodriguez, Herminia G.; Espinoza-Juarez, Marcela A.; Mendoza Lemus, Oscar F.


    Adipose-derived mesenchymal stem cells (ADMSCs) are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs). This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM) was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology. PMID:27818692

  6. The bone matrix protein secreted phosphoprotein 24 kD (Spp24): bone metabolism regulator and starting material for biotherapeutic materials. (United States)

    Murray, Samuel S; Wang, Jeffrey C; Duarte, Maria Eugenia Leite; Zhao, Ke-Wei; Tian, Haijun; Francis, Timothy; Brochmann Murray, Elsa J


    Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that appears to be derived primarily from the liver and delivered to other tissues in a protective complex. A significant role in bone growth and turnover is suggested by genetic studies that associate the gene locus (SPP2) with bone mineral density and bone quality. The function of this protein in the normal bone environment is unknown but clues are given by the fact that Spp24, or proteolytic products of Spp24, bind cytokines of the TGF-β superfamily and also activate intracellular signaling pathways. Several potential biotherapeutics have been engineered from this protein including materials that enhance BMP-induced bone healing and, on the other hand, materials that inhibit BMPs in clinical situations where this is called for such as reducing BMP-induced inflammation and inhibiting tumors dependent on BMP autocrine systems. As understanding of the structure and function of this protein increases, more opportunities for rationally developed therapeutics will become apparent.

  7. Bone matrix calcification during embryonic and postembryonic rat calvarial development assessed by SEM-EDX spectroscopy, XRD, and FTIR spectroscopy. (United States)

    Henmi, Akiko; Okata, Hiroshi; Anada, Takahisa; Yoshinari, Mariko; Mikami, Yasuto; Suzuki, Osamu; Sasano, Yasuyuki


    Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase in the Ca/P ratio is involved in maturation of the crystal is not known. The relationships among organic components and mineral changes are also unclear. The study was designed to investigate the process of calcification during rat calvarial bone development. Calcification was evaluated by analyzing the atomic distribution and concentration of Ca, P, and C with scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Histological analysis showed that rat calvarial bone formation started around embryonic day 16. The areas of Ca and P expanded, matching the region of the developing bone matrix, whereas the area of C became localized around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like structure of the minerals at embryonic day 16 gradually transformed into poorly crystalline hydroxyapatite, whereas the proportion of mineral to protein increased until postnatal week 6. FTIR analysis also showed that crystallization of hydroxyapatite started around embryonic day 20, by which time SEM-EDX spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios had decreased significantly. The study suggests that the Ca/P molar ratio increases and the proportion of organic components such as proteins of the bone matrix decreases during the early stage of calcification, whereas crystal maturation continues throughout embryonic and postembryonic bone development.

  8. A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering. (United States)

    Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing


    A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

  9. Fiber-matrix interface studies on bioabsorbable composite materials for internal fixation of bone fractures. I. Raw material evaluation and measurement of fiber-matrix interfacial adhesion. (United States)

    Slivka, M A; Chu, C C; Adisaputro, I A


    The objective of this study was to characterize and evaluate the performance of various fiber-matrix composite systems by studying the mechanical, thermal, and physical properties of the fiber and matrix components, and by studying the fiber-matrix interface adhesion strength using both microbond and fragmentation methods. The composites studies were poly(L-lactic acid) (PLLA) matrix reinforced with continuous fibers of either nonabsorbable AS4 carbon (C), absorbable calcium phosphate (CaP), poly(glycolic acid) (PGA), or chitin. Carbon and CaP single fibers had high Young's moduli and failed in a brittle manner. PGA and chitin single fibers had relatively lower Young's moduli and relatively higher ductility. Upon in vitro hydrolysis, CaP fibers retained 17% of their tensile strength and 39% of their Young's modulus after 12 h, PCA fibers retained 10% of their tensile strength and 52% of their Young's modulus after 16 days, and chitin fibers retained 87% of their tensile strength and 130% of their Young's modulus after 25 days. PLLA films had much lower strength and Young's moduli, but much higher ductility relative to the single fibers. Using the microbond method, the initial fiber-matrix interfacial shear strength (IFSS) of C/PLLA and CaP/PLLA microcomposites was 33.9 and 12.6 MPa, respectively. Upon in vitro hydrolysis, C/PLLA retained 49% of IFSS after 15 days and CaP/PLLA retained 46% of IFSS after 6 h. Using a fiber fragmentation method, the initial IFSS of C/PLLA, CaP/PLLA, and chitin/ PLLA was 22.2, 15.6, and 28.3 MPa, respectively. The performance of carbon fibers and C/PLLA composites was superior to the other fibers and fiber/PLLA systems, but the carbon fiber was nonabsorbable. CaP had the most suitable modulus of the absorbable fibers for fixing cortical bone fracture, but its rapid deterioration of mechanical properties and loss of IFSS limits its use. PGA and chitin fibers had suitable mechanical properties and their retention for fixing cancellous

  10. Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model

    Directory of Open Access Journals (Sweden)

    Jin Wook Hwang


    Full Text Available Absorbable extracellular matrix (ECM membrane has recently been used as a barrier membrane (BM in guided tissue regeneration (GTR and guided bone regeneration (GBR. Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymes in vivo. In a previous study, to delay degradation time, collagen fibers were treated with cross-linking agents. These compounds prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit delayed tissue integration. In addition, the remaining cross-linker could induce inflammation. Here, we attempted to overcome these problems using a natural ECM membrane. The membrane consisted of freshly harvested porcine pericardium that was stripped from cells and immunoreagents by a cleaning process. Acellular porcine pericardium (APP showed a bilayer structure with a smooth upper surface and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18–0.35 mm but with excellent mechanical properties. Tensile strength of APP was 14.15±2.24 MPa. In in vivo experiments, APP was transplanted into rabbit tibia. The biocompatible material was retained for up to 3 months without the need for cross-linking. Therefore, we conclude that APP could support osteogenesis as a BM for up to 3 months.

  11. Relation between brain architecture and mathematical ability in children: a DBM study. (United States)

    Han, Zhaoying; Davis, Nicole; Fuchs, Lynn; Anderson, Adam W; Gore, John C; Dawant, Benoit M


    Population-based studies indicate that between 5 and 9 percent of US children exhibit significant deficits in mathematical reasoning, yet little is understood about the brain morphological features related to mathematical performances. In this work, deformation-based morphometry (DBM) analyses have been performed on magnetic resonance images of the brains of 79 third graders to investigate whether there is a correlation between brain morphological features and mathematical proficiency. Group comparison was also performed between Math Difficulties (MD-worst math performers) and Normal Controls (NC), where each subgroup consists of 20 age and gender matched subjects. DBM analysis is based on the analysis of the deformation fields generated by non-rigid registration algorithms, which warp the individual volumes to a common space. To evaluate the effect of registration algorithms on DBM results, five nonrigid registration algorithms have been used: (1) the Adaptive Bases Algorithm (ABA); (2) the Image Registration Toolkit (IRTK); (3) the FSL Nonlinear Image Registration Tool; (4) the Automatic Registration Tool (ART); and (5) the normalization algorithm available in SPM8. The deformation field magnitude (DFM) was used to measure the displacement at each voxel, and the Jacobian determinant (JAC) was used to quantify local volumetric changes. Results show there are no statistically significant volumetric differences between the NC and the MD groups using JAC. However, DBM analysis using DFM found statistically significant anatomical variations between the two groups around the left occipital-temporal cortex, left orbital-frontal cortex, and right insular cortex. Regions of agreement between at least two algorithms based on voxel-wise analysis were used to define Regions of Interest (ROIs) to perform an ROI-based correlation analysis on all 79 volumes. Correlations between average DFM values and standard mathematical scores over these regions were found to be significant

  12. Effect of registration on corpus callosum population differences found with DBM analysis (United States)

    Han, Zhaoying; Thornton-Wells, Tricia A.; Gore, John C.; Dawant, Benoit M.


    Deformation Based Morphometry (DBM) is a relatively new method used for characterizing anatomical differences among populations. DBM is based on the analysis of the deformation fields generated by non-rigid registration algorithms, which warp the individual volumes to one standard coordinate system. Although several studies have compared non-rigid registration algorithms for segmentation tasks, few studies have compared the effect of the registration algorithm on population differences that may be uncovered through DBM. In this study, we compared DBM results obtained with five well established non-rigid registration algorithms on the corpus callosum (CC) in thirteen subjects with Williams Syndrome (WS) and thirteen Normal Control (NC) subjects. The five non-rigid registration algorithms include: (1) The Adaptive Basis Algorithm (ABA); (2) Image Registration Toolkit (IRTK); (3) FSL Nonlinear Image Registration Tool (FSL); (4) Automatic Registration Tools (ART); and (5) the normalization algorithm available in SPM8. For each algorithm, the 3D deformation fields from all subjects to the atlas were obtained and used to calculate the Jacobian determinant (JAC) at each voxel in the mid-sagittal slice of the CC. The mean JAC maps for each group were compared quantitatively across different nonrigid registration algorithms. An ANOVA test performed on the means of the JAC over the Genu and the Splenium ROIs shows the JAC differences between nonrigid registration algorithms are statistically significant over the Genu for both groups and over the Splenium for the NC group. These results suggest that it is important to consider the effect of registration when using DBM to compute morphological differences in populations.

  13. Combination of absorbable mesh and demineralized bone matrix in orbital wall fracture for preventing herniation of orbit. (United States)

    Tak, Kyoung Seok; Jung, Min Su; Lee, Byeong Ho; Kim, Joo Hyun; Ahn, Duk Kyun; Jeong, Hii Sun; Park, Young Kyu; Suh, In Suck


    After restoration of orbit wall fracture, preventing sequelae is important. An absorbable mesh is commonly used in orbit wall fracture, yet it has limitation due to orbit sagging when bony defect is larger than the moderate size (1 × 1 cm2). In this study, the authors present a satisfactory result in treating orbit wall fracture larger than the moderate size with a combination of absorbable mesh and demineralized bone matrix.From 2009 to 2012, 63 patients with bony defect larger than the moderate size, who were treated with a combination of absorbable mesh and demineralized bone matrix, were reviewed retrospectively. The site of bony defect, size, and applied amount of demineralized bone matrix were reviewed, and a 2-year follow-up was done. Facial computed tomography scans were checked preoperative, immediate postoperative, and 2-year postoperative.Among the 63 patients, there were 52 men and 11 women. Mean age was 33.3 years. The most common cause was blunt blow (35 cases); mean defect size was 13.36 × 12.82 mm2 in inferior wall fracture and 20.69 × 14.41 mm2 in medial wall fracture. There was no complication except for 3 cases of infraorbital nerve hypoesthesia. A 2-year follow-up computed tomography showed that the surgical site preserved bony formation without herniation. In treating moderate-sized bony defect in orbit wall fracture, absorbable mesh and demineralized bone matrix can maintain structural stability through good bony formation even after degradation of absorbable mesh.

  14. Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix

    Energy Technology Data Exchange (ETDEWEB)

    Cholas, Rahmatullah, E-mail:; Kunjalukkal Padmanabhan, Sanosh, E-mail:; Gervaso, Francesca; Udayan, Gayatri; Monaco, Graziana; Sannino, Alessandro; Licciulli, Antonio


    Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6 μm, a specific surface area of 40 m{sup 2}/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16 nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200 μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15 days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales. - Highlights: • Mesoporous hydroxyapatite microsphere(mHA) synthesized by spray drying method • Porous collagen/mHA composite scaffold made by freeze

  15. Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality. (United States)

    Paschalis, E P; Gamsjaeger, S; Hassler, N; Fahrleitner-Pammer, A; Dobnig, H; Stepan, J J; Pavo, I; Eriksen, E F; Klaushofer, K


    Prospective, controlled clinical trials in postmenopausal osteoporosis typically compare effects of an active drug with placebo in addition to vitamin D and calcium supplementation in both treatment arms. While clinical benefits are documented, the effect of this supplementation in the placebo arm and in clinical practice on bone material composition properties is unknown. The purpose of the present study was to evaluate these bone quality indices (specifically mineral/matrix, nanoporosity, glycosaminoglycan content, mineral maturity/crystallinity, and pyridinoline content) in patients that either received long-term vitamin D (400-1200IU) and calcium (1.0-1.5g) supplementation, or did not. We have analyzed by Raman microspectroscopy the bone forming trabecular surfaces of iliac crest in pre-treatment samples of a teriparatide study and the endpoint biopsies of the control arm obtained from the HORIZON trial. In general, the mineral/matrix ratio and the glycosaminoglycan (GAG) content was higher while nanoporosity, (a surrogate for tissue water content), the mineral maturity/crystallinity (MMC) and the pyridinoline (Pyd) content was lower in patients without long-term supplementation. Moreover, all indices were significantly dependent on tissue age. In conclusion, vitamin D and calcium supplementation is associated with altered mineral and organic matrix properties.

  16. A-3 dBm RF transmitter front-end for 802.11g application

    Institute of Scientific and Technical Information of China (English)

    Zhao Jinxin; Yan Jun; Shi Yin


    A 2.4 GHz,direct-conversion RF transmitter front-end with an up converter and PA driver is fabricated in a 0.13 μm CMOS process for the reliable transmission of 54 Mb/s OFDM signals.The front-end output power is-3 dBm while the corresponding EVM is-27 dB which is necessary for the 802.11 g standard of EVM at-25 dB.With the adopted gain control strategy the output power changes from-14.3 to-3.7 dBm with every step 0.8 dB (20%) which covers the gain variation due to working temperature and process.A power detector indicates the output power and delivers a voltage to the baseband to control the output power.

  17. Biomimetic Mineralization on a Macroporous Cellulose-Based Matrix for Bone Regeneration



    The aim of this study is to investigate the biomimetic mineralization on a cellulose-based porous matrix with an improved biological profile. The cellulose matrix was precalcified using three methods: (i) cellulose samples were treated with a solution of calcium chloride and diammonium hydrogen phosphate; (ii) the carboxymethylated cellulose matrix was stored in a saturated calcium hydroxide solution; (iii) the cellulose matrix was mixed with a calcium silicate solution in order to introduce ...

  18. Self-assembled composite matrix in a hierarchical 3-D scaffold for bone tissue engineering

    DEFF Research Database (Denmark)

    Chen, Muwan; Le, Dang Quang Svend; Baatrup, Anette


    It is of high clinical relevance in bone tissue engineering that scaffolds promote a high seeding efficiency of cells capable of osteogenic differentiation, such as human bone marrow-derived mesenchymal stem cells (hMSCs). We evaluated the effects of a novel polycaprolactone (PCL) scaffold on h...

  19. Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix. (United States)

    Eckhardt, Bedrich L; Parker, Belinda S; van Laar, Ryan K; Restall, Christina M; Natoli, Anthony L; Tavaria, Michael D; Stanley, Kym L; Sloan, Erica K; Moseley, Jane M; Anderson, Robin L


    A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.

  20. Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone. (United States)

    Govindarajan, Parameswari; Khassawna, Thaqif; Kampschulte, Marian; Böcker, Wolfgang; Huerter, Britta; Dürselen, Lutz; Faulenbach, Miriam; Heiss, Christian


    Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid-postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized-steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below -2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could

  1. Desferrioxamine for Stimulation of Fracture Healing and Revascularization in a Bone Defect Model (United States)


    changes of 0.6N hydrochloric acid ( HCl ). The bone was then rinsed with sterile saline and titrated to a pH between 7 and 7.4 using concentrated sodium...hydroxide ( NaOH ). The DBM was then placed in 70% ethanol for 12 hours. The wet DBM was weighed and allotted into sterile micro-centrifuge tubes

  2. Development and Characterization of a Bioinspired Bone Matrix with Aligned Nanocrystalline Hydroxyapatite on Collagen Nanofibers

    Directory of Open Access Journals (Sweden)

    Hsi-Chin Wu


    Full Text Available Various kinds of three-dimensional (3D scaffolds have been designed to mimic the biological spontaneous bone formation characteristics by providing a suitable microenvironment for osteogenesis. In view of this, a natural bone-liked composite scaffold, which was combined with inorganic (hydroxyapatite, Hap and organic (type I collagen, Col phases, has been developed through a self-assembly process. This 3D porous scaffold consisting of a c-axis of Hap nanocrystals (nHap aligning along Col fibrils arrangement is similar to natural bone architecture. A significant increase in mechanical strength and elastic modulus of nHap/Col scaffold is achieved through biomimetic mineralization process when compared with simple mixture of collagen and hydroxyapatite method. It is suggested that the self-organization of Hap and Col produced in vivo could also be achieved in vitro. The oriented nHap/Col composite not only possesses bone-like microstructure and adequate mechanical properties but also enhances the regeneration and reorganization abilities of bone tissue. These results demonstrated that biomimetic nHap/Col can be successfully reconstructed as a bone graft substitute in bone tissue engineering.

  3. Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cell–collagen constructs: A three-dimensional in vitro model to study hematopoietic stem cell niche

    Directory of Open Access Journals (Sweden)

    WY Lai


    Full Text Available Mesenchymal stem/stromal cells (MSCs and osteoblasts are important niche cells for hematopoietic stem cells (HSCs in bone marrow osteoblastic niche. Here, we aim to partially reconstitute the bone marrow HSC niche in vitro using collagen microencapsulation for investigation of the interactions between HSCs and MSCs. Mouse MSCs (mMSCs microencapsulated in collagen were osteogenically differentiated to derive a bone-like matrix consisting of osteocalcin, osteopontin, and calcium deposits and secreted bone morphogenic protein 2 (BMP2. Decellularized bone-like matrix was seeded with fluorescence-labeled human MSCs and HSCs. Comparing with pure collagen scaffold, significantly more HSCs and HSC–MSC pairs per unit area were found in the decellularized bone-like matrix. Moreover, incubation with excess neutralizing antibody of BMP2 resulted in a significantly higher number of HSC per unit area than that without in the decellularized matrix. This work suggests that the osteogenic differentiated MSC–collagen microsphere is a valuable three-dimensional in vitro model to elucidate cell–cell and cell–matrix interactions in HSC niche.

  4. New collagen matrix to avoid the reduction of keratinized tissue during guided bone regeneration in postextraction sites. (United States)

    De Santis, Daniele; Cucchi, Alessandro; de Gemmis, Antonio; Nocini Pier, Francesco


    For decades, there has been an ongoing controversy regarding the need for an "adequate" width of keratinized gingiva/mucosa to preserve periodontal and implant health. Today, the presence of a certain width of keratinized tissue is recommended for achieving long-term periodontal and implant success, and therefore, a new collagen matrix has been developed to enhance the width of keratinized gingiva/mucosa. During postextraction socket preservation, guided bone regeneration techniques require complete coverage of the barrier membrane to reduce the risk of infection, occasionally causing a reduction of the width of keratinized tissue. Using the new collagen matrix, it is possible to leave the membrane intentionally uncovered, without suturing the surgical flap above it, to avoid the reduction of such tissue.

  5. Biomimetic Mineralization on a Macroporous Cellulose-Based Matrix for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Odeta Petrauskaite


    Full Text Available The aim of this study is to investigate the biomimetic mineralization on a cellulose-based porous matrix with an improved biological profile. The cellulose matrix was precalcified using three methods: (i cellulose samples were treated with a solution of calcium chloride and diammonium hydrogen phosphate; (ii the carboxymethylated cellulose matrix was stored in a saturated calcium hydroxide solution; (iii the cellulose matrix was mixed with a calcium silicate solution in order to introduce silanol groups and to combine them with calcium ions. All the methods resulted in a mineralization of the cellulose surfaces after immersion in a simulated body fluid solution. Over a period of 14 days, the matrix was completely covered with hydroxyapatite crystals. Hydroxyapatite formation depended on functional groups on the matrix surface as well as on the precalcification method. The largest hydroxyapatite crystals were obtained on the carboxymethylated cellulose matrix treated with calcium hydroxide solution. The porous cellulose matrix was not cytotoxic, allowing the adhesion and proliferation of human osteoblastic cells. Comparatively, improved cell adhesion and growth rate were achieved on the mineralized cellulose matrices.

  6. Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation. (United States)

    Eisenhauer, Peter; Chernets, Natalie; Song, You; Dobrynin, Danil; Pleshko, Nancy; Steinbeck, Marla J; Freeman, Theresa A


    The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd.

  7. The Effect of Bioceramic Composite Extracellular Matrixes Used to Repair Bone Deficiency on Relevant Blood Biochemical Indices

    Institute of Scientific and Technical Information of China (English)


    At the base of experimental animal model construction of bone defect in New Zealand rabbit, the promoting repair effect of bioactive ceramics on bone defect as well as its machanism was studied through testing body mineral elements, enzymes related to bone morphogenetic proteins and some biochemical indexes. Refering to some documents, materials of TCP, CHA and HA were combined and TCP/BMP/ TCP-β1 and CHA/BMP/ TCP-β1, HA/BMP/ TCP-β1 composite materials were made. All kinds of them were implanted into the radial defect site of rabbit, respectively. The chosen blood indexes (Ca, P, ALP, GGT, AST, ALT, TPA, BUN and Cr) were tested by colorimetry, speed rate and bromocresol green testing methods. No abnormal effects were found in any animal after operation. Serum concentrations of Ca, P and ALP were increased with the length of time in all groups of the three kinds of composite material, mixed material and pure materials. The increases in composite material groups were more significant ( P <0.05). Comparison of the three kinds of material showed TCP > CHA > HA. There was a tendency of increased TPA and decreased BUN with the length of time. There was no significant difference between the composite material groups and pure material group (P >0.05). The three kinds of bioactive ceramics composed of extracellular matrix could increase the serum concentrations of Ca and P and activity of ALP after being implanted into defect bone and showed some repairing capacity. This provided a new area of machanism study of bone defect repair by biomaterials.

  8. Bone (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  9. Construction of tissue engineering bone with bone marrow stromal cell sheets%应用骨髓基质细胞片层构建组织工程骨的实验研究

    Institute of Scientific and Technical Information of China (English)

    卜令学; 王艳辉; 李宁毅; 高振华; 陈欣; 荆恒


    目的 应用犬骨髓基质细胞片层构建组织工程骨,为临床提供组织工程骨来源.方法 分离培养传代犬骨髓基质细胞(bone marrow stromal cell,BMSC).将经成骨诱导的第3代BMSC接种于温度反应性培养皿中,制备BMSC细胞片层.制备犬同种异体脱钙骨基质(decalcification bone matrixes,DBM).实验用16只犬分为4组,每组4只,采用自身对照.将复合体BMSC片层-人重组骨形态生成蛋白2( rhBMP-2) -BMSC-DBM植入犬左侧背阔肌肌筋膜下为实验侧,同法右侧植入DBM-rhBMP-2-BMSC为对照侧.术后4、8、12、16周取材行组织学观察,评价体内异位成骨的情况.结果 实验侧成骨优于对照侧,成骨面积实验侧>对照侧,两侧差异有统计学意义(P<0.05).术后16周,实验侧板层骨连接成片,可见骨单位,骨髓腔内可见红骨髓.结论 BMSC细胞片层可促进功能性组织工程骨的形成.%Objective To construct tissue engineering bone with bone marrow stromal cell(BMSC)sheets of dogs.Methods BMSC were derived from dog bone marrow and cell sheets were prepared with temperature-responsive dishes after the cells were induced by osteogenesis.Allogeneic dogs decalcification bone matrixes(DBM) were prepared.Sixteen dogs were divided into 4 groups.The MSC cell sheets-rhBMP2-BMSC-DBM were implanted under the left latissimus dorsi myofascial as the experimental side; while the thBMP-2-BMSC-DBM were implanted in the right side as the control.Ectopic bone formation in vivo was evaluated by histological examination 4,8,12,16 weeks after operation.Results The osteogenesis in the experimental group was better than that in the control group.New bone area in the experimental side was larger than that in the control group,and the difference was significant ( P < 0.05 ).After 16 weeks,lamellar bone was connected into a film in the experimental group.Haversian system and red bone marrow could be seen.Conclusions BMSC cell sheets could promote the bone formation of

  10. Differential expression pattern of extracellular matrix molecules during chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue

    DEFF Research Database (Denmark)

    Mehlhorn, A T; Niemeyer, P; Kaiser, S;


    Adipose-derived adult stem cells (ADASCs) or bone marrow-derived mesenchymal stem cells (BMSCs) are considered as alternative cell sources for cell-based cartilage repair due to their ability to produce cartilage-specific matrix. This article addresses the differential expression pattern of extra......Adipose-derived adult stem cells (ADASCs) or bone marrow-derived mesenchymal stem cells (BMSCs) are considered as alternative cell sources for cell-based cartilage repair due to their ability to produce cartilage-specific matrix. This article addresses the differential expression pattern...... mRNA was monitored via reverse transcriptase-polymerase chain reaction (RT-PCR). Corresponding ECM synthesis was demonstrated using immunohistochemistry. After chondroinduction, expression of collagen type II, type X, COMP and aggrecan mRNA was 3-15-fold higher than in ADASCs. The type IIA splicing...... form of alpha(1)-procollagen type II was expressed in both populations, and the type IIB splicing form was exclusively detected in BMSCs. In response to TGF-beta, collagen type II and X were secreted more strongly by BMSCs than by ADASCs. BMSCs express a more mature phenotype than ADASCs after...

  11. Evolution of the vertebrate bone matrix: an expression analysis of the network forming collagen paralogues in amphibian osteoblasts. (United States)

    Aldea, Daniel; Hanna, Patricia; Munoz, David; Espinoza, Javier; Torrejon, Marcela; Sachs, Laurent; Buisine, Nicolas; Oulion, Silvan; Escriva, Hector; Marcellini, Sylvain


    The emergence of vertebrates is closely associated to the evolution of mineralized bone tissue. However, the molecular basis underlying the origin and subsequent diversification of the skeletal mineralized matrix is still poorly understood. One efficient way to tackle this issue is to compare the expression, between vertebrate species, of osteoblastic genes coding for bone matrix proteins. In this work, we have focused on the evolution of the network forming collagen family which contains the Col8a1, Col8a2, and Col10a1 genes. Both phylogeny and synteny reveal that these three paralogues are vertebrate-specific and derive from two independent duplications in the vertebrate lineage. To shed light on the evolution of this family, we have analyzed the osteoblastic expression of the network forming collagens in endochondral and intramembraneous skeletal elements of the amphibian Xenopus tropicalis. Remarkably, we find that amphibian osteoblasts express Col10a1, a gene strongly expressed in osteoblasts in actinopterygians but not in amniotes. In addition, while Col8a1 is known to be robustly expressed in mammalian osteoblasts, the expression levels of its amphibian orthologue are dramatically reduced. Our work reveals that while a skeletal expression of network forming collagen members is widespread throughout vertebrates, osteoblasts from divergent vertebrate lineages express different combinations of network forming collagen paralogues.

  12. Histologic analysis of a novel extracellullar matrix membrane for guided bone regeneration: an experimental study in rabbits. (United States)

    Al-Asfour, Adel; Tengvall, Pentti; Andersson, Lars; Dahlin, Christer


    This experiment was conducted to study the histologic feasibility and biologic impact of Ti02 impregnation of an extracellullar matrix (ECM) membrane in guided bone regeneration. Eighteen adult New Zealand White rabbits were used. Bilateral bone defects were created in edentulous areas of the maxilla. The defects were filled with demineralized freeze-dried bone (DFDB). ECM was randomly pretreated with a suspension containing saline and 3 mg Ti02 granules. A regular ECM membrane served as a control on the contralateral side. Healing periods were 2, 4, and 8 weeks. Histologic and histomorphometric analyses were performed. The parameters assessed were (1) zone of inflammatory cells adjacent to ECM membrane, (2) presence of cellullar ingrowth into ECM, and (3) presence of Ti02 particles within the ECM barrier membrane. In general, no adverse reactions toward both groups of ECM membranes could be noted. The Ti02 particles remained within the ECM after 8 weeks of healing, making histologic detection of ECM easy. Histomorphometric analysis revealed low numbers of inflammatory cells adjacent to the ECM surface and adequate preservation and integration of the barrier. Contrasting Ti02 particles impregnated into the ECM membrane can be a very useful tool for the detection of similar biologic materials in in vivo models.

  13. Effect of acemannan, an extracted polysaccharide from Aloe vera, on BMSCs proliferation, differentiation, extracellular matrix synthesis, mineralization, and bone formation in a tooth extraction model. (United States)

    Boonyagul, Sani; Banlunara, Wijit; Sangvanich, Polkit; Thunyakitpisal, Pasutha


    Aloe vera is a traditional wound healing medicine. We hypothesized acemannan, a polysaccharide extracted from Aloe vera gel, could affect bone formation. Primary rat bone marrow stromal cells (BMSCs) were treated with various concentrations of acemannan. New DNA synthesis, VEGF, BMP-2, alkaline phosphatase activity, bone sialoprotein, osteopontin expression, and mineralization were determined by [(3)H] thymidine incorporation assay, ELISA, biochemical assay, western blotting, and Alizarin Red staining, respectively. In an animal study, mandibular right incisors of male Sprague-Dawley rats were extracted and an acemannan treated sponge was placed in the socket. After 1, 2, and 4 weeks, the mandibles were dissected. Bone formation was evaluated by dual-energy X-ray absorptiometry and histopathological examination. The in vitro results revealed acemannan significantly increased BMSC proliferation, VEGF, BMP-2, alkaline phosphatase activity, bone sialoprotein and osteopontin expression, and mineralization. In-vivo results showed acemannan-treated groups had higher bone mineral density and faster bone healing compared with untreated controls. A substantial ingrowth of bone trabeculae was observed in acemannan-treated groups. These data suggest acemannan could function as a bioactive molecule inducing bone formation by stimulating BMSCs proliferation, differentiation into osteoblasts, and extracellular matrix synthesis. Acemannan could be a candidate natural biomaterial for bone regeneration.

  14. Effects of matrix metalloproteinase-1 on the myogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Zhenyang [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Leng, Yan [Department of Rehabilitation, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Zhou, Chen; Ma, Zhenyu; Zhong, Zhigang [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Shi, Xing-Ming [Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, GA 30912 (United States); Zhang, Weixi, E-mail: [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China)


    Highlights: Black-Right-Pointing-Pointer MMP-1 is a member of the zinc-dependent endopeptidase family. Black-Right-Pointing-Pointer MMP-1 has no cytotoxic effects on BMSCs. Black-Right-Pointing-Pointer MMP-1 can promote the myogenic differentiation of BMSCs. Black-Right-Pointing-Pointer MyoD and desmin were chosen as myogenic markers in this study. -- Abstract: Matrix metalloproteinase-1 (MMP-1) is a member of the family of zinc-dependent endopeptidases that are capable of degrading extracellular matrix (ECM) and certain non-matrix proteins. It has been shown that MMP-1 can enhance muscle regeneration by improving the differentiation and migration of myoblasts. However, it is still not known whether MMP-1 can promote the myogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). To address this question, we isolated BMSCs from C57BL/6J mice and investigated the effects of MMP-1 on their proliferation and myogenic differentiation. Our results showed that MMP-1 treatment, which had no cytotoxic effects on BMSCs, increased the mRNA and protein levels of MyoD and desmin in a dose-dependent manner, indicating that MMP-1 promoted myogenic differentiation of BMSCs in vitro. These results suggest that BMSCs may have a therapeutic potential for treating muscular disorders.

  15. Histologic and histomorphometric evaluation of osteogenesis induced by octacalcium phosphate (OCP combined with bone matrix gelatin (BMG in rat skull defects

    Directory of Open Access Journals (Sweden)

    Sargolzaei F.


    Full Text Available Statement of Problem: Several methods are used to enhance bone repair and new bone formation, and bone matrix gelatin (BMG is recently introduced. Purpose: The purpose of this histologic and histomorphometric study was to assess the osteogenic potential and the quantity of new trabecular bone formation after implantation of OCP and BMG alone and in combination into the cranial defects in rat. Materials and Methods: In this experimental study, 100 young male Sprague Dawley rats (5-6 weeks age and 120-150gr weight were divided into four groups randomly. A full thickness standard trephine defect 5mm in diameter was made in the rat’s parietal bone, and 5mg of OCP, BMG alone and in combination were implanted into the defects. No OCP and BMG particles were implanted in control group which was otherwise treated identically. On the 5th, 7th, 14th, 21st and 56th days after implantation, the rats were killed and bone samples collected. After processing the samples by routine histological procedures, 5µm thick sections of bone were cut and stained with Haematoxyline & Eosin (H&E and Alcian Blue and studied histologically and histomorphometrically using light microscope and eyepiece graticule. The amount of newly formed bone was quantitatively measured by the use of histomorphometric methods. Data were analyzed with SAS statistical package using ANOVA and Duncan tests. Results: In the experimental groups, the new bone formation was initiated from the margin of defects during 5-14 days after implantation. During 14-21 days after implantation, bone marrow cavities and bone marrow tissues in newly formed bone were seen. By the end of the study, the newly formed bone increased and was relatively matured and almost all of the implanted materials were absorbed. In control group, at the end of the study, a few clusters of new bone were seen near to the defect margins and host bone. The histomorphometric analysis indicated statistical significant differences in

  16. The use of beta-tricalcium phosphate and bovine bone matrix in the guided tissue regeneration treatment of deep infra-bony defects


    Luković Natalija; Zelić Obrad; Čakić Saša; Petrović Vanja


    Introduction. The primary goal of bone regeneration procedures with application of various regenerative biologic agents and biomaterials is to facilitate the formation of periodontal tissues lost as a result of periodontitis. Objective. The aim of the study was to compare clinical outcome of the guided tissue regeneration (GTR) treatment with the use of β-tricalcium phosphate and with bovine bone matrix in human deep intra-osseous defects. Methods. Twenty-one systemically healthy subjects wit...

  17. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation (United States)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.


    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  18. Pigment epithelium derived factor suppresses expression of Sost/Sclerostin by osteocytes: implication for its role in bone matrix mineralization. (United States)

    Li, Feng; Song, Na; Tombran-Tink, Joyce; Niyibizi, Christopher


    Mutations in Serpinf1 gene which encodes pigment epithelium derived factor (PEDF) lead to osteogenesis imperfecta type VI whose hallmark is defective mineralization. Mechanisms by which PEDF regulates matrix mineralization remain unknown. We examined effect of exogenous PEDF on expression of osteoblastic and osteocytic related genes and proteins in mineralizing osteoblast culture. Mineralizing human osteoblasts supplemented with exogenous PEDF for 14 days deposited 47% more mineral than cells cultured without PEDF. Analysis of selected gene expression by cells in mineralizing cultures supplemented with exogenous PEDF showed reduction in expression of Sclerostin (Sost) by 70%, matrix extracellular phosphoglycoprotein (MEPE) by 75% and dentin matrix protein (DMP-1) by 20% at day 14 of culture. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) expression was not affected. Western blotting and immunoprecipitation showed that sclerostin and MEPE synthesis by osteocytes were reduced by 50% and 60% respectively in mineralizing osteoblasts containing exogenous PEDF. Primary osteocytes exposed to PEDF also reduced synthesis of Sost/sclerostin by 50% within 24 h. For osteoblastic genes, Bone sialoprotein (BSP) was expressed at 75% higher by day 7 in cultures containing exogenous PEDF while Col1A1 expression remained high at all-time points. Total beta-catenin was increased in mineralizing osteoblastic cells suggesting increased Wnt activity. Taken together, the data indicate that PEDF suppressed expression of factors that inhibit mineralization while enhancing those that promote mineralization. The findings also suggest that PEDF may regulate Sost expression by osteocytes leading to enhanced osteoblastic differentiation and increased matrix mineralization.

  19. Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

    Directory of Open Access Journals (Sweden)

    Fanglong Song


    Full Text Available Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs and tendon cells (TCs. Methods: The effect of continuous passive motion (CPM therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

  20. Synthesis and photoluminescence of Eu(DBM)3phen/APTES-SBA-15 with morphology of pearl-like chains

    Institute of Scientific and Technical Information of China (English)

    ZHAO Chun-xia; LIU Qi; CHEN Wen; TIAN Gao; XU Ling-fang


    Novel ordered mesoporous Eu(DBM)3phen/APTES-SBA-15 (EAS) composites with reasonable photoluminescence property and interesting morphology of bundles of pearl-like chains were synthesized. The characteristics of the mesostructure and the optical properties of the prepared samples were investigated by means of XRD,FTIR,SEM,TEM,N2 adsorption-desorption and PL spectroscopy. The results indicate that the as-made EAS composites have long-distance ordered mesoporous structure. Compared with the Eu(DBM)3phen complex,it is found that the EAS composites perform a considerable photoluminescence with good color purity. It is proposed that the anchored amine from the APTES and quantum size effect of the Eu(DBM)3phen complex have great effect on the photoluminescence of the EAS composites.

  1. Comparative Environmental Performance of Two-Diesel-Fuel Oxygenates: Dibutyl Maleate (DBM) and Triproplyene Glycol Monomethyl Ether (TGME)

    Energy Technology Data Exchange (ETDEWEB)

    Layton, D.W.; Marchetti, A.A.


    Many studies have shown that the addition of oxygen bearing compounds to diesel fuel can significantly reduce particulate emissions. To assist in the evaluation of the environmental performance of diesel-fuel oxygenates, we have implemented a suite of diagnostic models for simulating the transport of compounds released to air, water, and soils/groundwater as well as regional landscapes. As a means of studying the comparative performance of DBM and TGME, we conducted a series of simulations for selected environmental media. Benzene and methyl tertiary butyl ether (MTBE) were also addressed because they represent benchmark fuel-related compounds that have been the subject of extensive environmental measurements and modeling. The simulations showed that DBM and TGME are less mobile in soil because of reduced vapor-phase transport and increased retention on soil particles. The key distinction between these two oxygenates is that DBM is predicted to have a greater potential than TGME for aerobic biodegradation, based on chemical structure.

  2. Clinical evaluation of a combined regenerative technique with enamel matrix derivative, bone grafts, and guided tissue regeneration. (United States)

    Harris, Randall J; Harris, Laura E; Harris, Christopher R; Harris, Anne J


    The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations.

  3. Promotion of Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells on Decellularized Cell-Deposited Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Hongliang He


    Full Text Available Interactions between stem cells and extracellular matrix (ECM are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimicked in vivo liver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS, bone marrow mesenchymal stem cells (BM-MSCs cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.

  4. Promotion of hepatic differentiation of bone marrow mesenchymal stem cells on decellularized cell-deposited extracellular matrix. (United States)

    He, Hongliang; Liu, Xiaozhen; Peng, Liang; Gao, Zhiliang; Ye, Yun; Su, Yujie; Zhao, Qiyi; Wang, Ke; Gong, Yihong; He, Fan


    Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimicked in vivo liver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.

  5. Autoradiographic study of the effect of 1,25-dihydroxyvitamin D/sub 3/ on bone matrix synthesis in vitamin D replete rats

    Energy Technology Data Exchange (ETDEWEB)

    Hock, J.M.; Kream, B.E.; Raisz, G.


    An autoradiographic technique using pulse labels of (/sup 3/H)proline was developed to assess the early effects of 1,25-dihydroxyvitamin D/sub 3/ (1,25(OH)/sub 2/D/sub 3/) on bone matrix synthesis in vitamin D replete rats. Rats, 7 days old, were given 0.25, 2.5, or 25 ng of 1,25(OH)/sub 2/D/sub 3/ or vehicle alone subcutaneously on days 1, 3, and 5 of the experiment. Rats received a subcutaneous injection of 100 (/sup 3/H)proline on days 2 and 6 and were killed on day 7. Calvaria and tibia were processed for autoradiography, and morphometric methods were developed to measure the rate and amount of bone matrix formed during the experimental period. When compared to control values, the amount and rate of formation of new bone matrix were both significantly decreased in rats receiving 25 ng of 1,25(OH)/sub 2/D/sub 3/ and slightly, but not significantly, decreased in rats receiving 2.5 ng. We conclude that administration of pharmacologic doses of 1,25(OH)/sub 2/D/sub 3/ to vitamin D replete rat pups impairs the formation of collagenous bone matrix.

  6. Quantitative regulation of bone-mimetic, oriented collagen/apatite matrix structure depends on the degree of osteoblast alignment on oriented collagen substrates. (United States)

    Matsugaki, Aira; Isobe, Yoshihiro; Saku, Taro; Nakano, Takayoshi


    Bone tissue has a specific anisotropic morphology derived from collagen fiber alignment and the related apatite crystal orientation as a bone quality index. However, the precise mechanism of cellular regulation of the crystallographic orientation of apatite has not been clarified. In this study, anisotropic construction of cell-produced mineralized matrix in vitro was established by initiating organized cellular alignment and subsequent oriented bone-like matrix (collagen/apatite) production. The oriented collagen substrates with three anisotropic levels were prepared by a hydrodynamic method. Primary osteoblasts were cultured on the fabricated substrates until mineralized matrix formation is confirmed. Osteoblast alignment was successfully regulated by the level of substrate collagen orientation, with preferential alignment along the direction of the collagen fibers. Notably, both fibrous orientation of newly synthesized collagen matrix and c-axis of produced apatite crystals showed preferential orientation along the cell direction. Because the degree of anisotropy of the deposited apatite crystals showed dependency on the directional distribution of osteoblasts cultured on the oriented collagen substrates, the cell orientation determines the crystallographic anisotropy of produced apatite crystals. To the best of our knowledge, this is the first report demonstrating that bone tissue anisotropy, even the alignment of apatite crystals, is controllable by varying the degree of osteoblast alignment via regulating the level of substrate orientation.

  7. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    DEFF Research Database (Denmark)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels;


    OBJECTIVES: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. METHODS: Twenty newly diagnosed patients recei...

  8. Dietary Zinc Reduces Osteoclast Resorption Activities and Increases Markers of Osteoblast Differentiation, Matrix Maturation, and Mineralization in the Long Bones of Growing Rats (United States)

    The nutritional influence of zinc (Zn) on markers of bone extracellular matrix (ECM) resorption and mineralization was investigated in growing rats. Thirty male weanling rats were randomly assigned to consume AIN-93G based diets containing 2.5, 5, 7.5, 15, or 30 µg Zn/g diet for 24 d. Femur Zn incre...

  9. Efficacy of platelet rich fibrin in the treatment of human intrabony defects with or without bone graft: A randomized controlled trial (United States)

    Chandradas, Nikhil D.; Ravindra, Shivamurthy; Rangaraju, Vivekananda M.; Jain, Sheetal; Dasappa, Shivaprasad


    Aim: To evaluate the efficacy of platelet rich fibrin (PRF) with or without bone graft [demineralized bone matrix (DBM) graft] in the treatment of intrabony defects based on clinical and radiographic parameters. Materials and Methods: Thirty six intrabony defects in 36 patients were randomly divided into three different groups and were treated with group A (PRF with DBM) or group B (PRF alone) or group C [open flap debridement (OFD)]. Clinical parameters such as plaque index (PI), gingival index (GI), probing depth (PD), relative attachment level (RAL), and gingival recession (GR) were assessed at baseline and 9 months postoperatively; radiographic parameters such as linear bone growth (LBG) and percentage in bone fill (%BF) were calculated by using the image analysis software. Comparisons of groups were analyzed using Kruskal–Wallis analysis of variance test. Pair-wise comparison of groups was done by Mann-Whitney U test. Results: Mean PD reduction and RAL gain were greater in group A (4.25 ± 1.48, 3.92 ± 0.90) and group B (3.82 ± 0.75, 3.27 ± 0.65) than control (3.00 ± 1.21, 2.25 ± 0.62). Furthermore, statistically significant improvement in LBG and %BF was found in group A (3.47 ± 0.53, 61.53 ± 4.54) compared to group B (2.55 ± 0.61, 49.60 ± 14.08) and group C (1.21 ± 0.80, 24.69 ± 15.59). Conclusions: The study demonstrated that PRF improves clinical and radiological parameters compared to OFD alone in intrabony defects. Addition of DBM enhances the effects of PRF in RAL gain and radiographic defect fill. PMID:27652249

  10. Biodegradable Thermogel as Culture Matrix of Bone Marrow Mesenchymal Stem Cells for Potential Cartilage Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Yan-bo Zhang; Jian-xun Ding; Wei-guo Xu; Jie Wu; Fei Chang; Xiu-li Zhuang; Xue-si Chen


    Poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst.The amphiphilic copolymer self-assembled into micelles in aqueous solutions,and formed hydrogels as the increase of temperature at relatively high concentrations (> 15 wt%).The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments.The good cellular and tissular compatibilities of the thermogel were demonstrated.The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEG-PLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.

  11. The NH2-terminal and COOH-terminal fragments of dentin matrix protein 1 (DMP1) localize differently in the compartments of dentin and growth plate of bone. (United States)

    Maciejewska, Izabela; Cowan, Cameron; Svoboda, Kathy; Butler, William T; D'Souza, Rena; Qin, Chunlin


    Multiple studies have shown that dentin matrix protein 1 (DMP1) is essential for bone and dentin mineralization. After post-translational proteolytic cleavage, DMP1 exists within the extracellular matrix of bone and dentin as an NH2-terminal fragment, a COOH-terminal fragment, and the proteoglycan form of the NH2-terminal fragment (DMP1-PG). To begin to assess the biological function of each fragment, we evaluated the distribution of both fragments in the rat tooth and bone using antibodies specific to the NH2-terminal and COOH-terminal regions of DMP1 and confocal microscopy. In rat first molar organs, the NH2-terminal fragment localized to predentin, whereas the COOH-terminal fragment was mainly restricted to mineralized dentin. In the growth plate of bone, the NH2-terminal fragment appeared in the proliferation and hypertrophic zones, whereas the COOH-terminal fragment occupied the ossification zone. Forster resonance energy transfer analysis showed colocalization of both fragments of DMP1 in odontoblasts and predentin, as well as hypertrophic chondrocytes within the growth plates of bone. The biochemical analysis of bovine teeth showed that predentin is rich in DMP1-PG, whereas mineralized dentin primarily contains the COOH-terminal fragment. We conclude that the differential patterns of expression of NH2-terminal and COOH-terminal fragments of DMP1 reflect their potentially distinct roles in the biomineralization of dentin and bone matrices.

  12. Designing of hydroxyapatite-gelatin based porous matrix as bone substitute: Correlation with biocompatibility aspects

    Directory of Open Access Journals (Sweden)


    Full Text Available In the present study polyacrylamide (PAm-gelatin-hydroxyapatite (HA composites have been synthesized by suspension polymerization method. The prepared composites were characterized by Fourier transform spectroscopy (FTIR which revealed the presence of functional groups in the composite. The X-ray diffraction (XRD studies indicated that HA powder was present in nano size. Thermogravimetric analysis (TGA revealed that composite is more thermally stable than the polymer matrix alone. The morphology of composite studied by optical microscopy (OPM and scanning electron microscopy (SEM suggested that pore size was between 3–20 µm. The composites showed adequately good mechanical properties as evident from the varying compressive strength and modulus in the range 31.57±8.16 MPa and 745±388 MPa, respectively. The water sorption behavior was found to be dependent on the chemical composition of the matrix and the sorption data were used to calculate network parameters. The porosity of composite varied between 4 to 30.66%.The in vitro blood compatibility indicated that the adsorption of bovine serum albumin (BSA varied from 0.11 to 0.24 mg•g–1, the percentage haemolysis was between 2.4 to 6.9% and the weight of blood clot formed on the composite surfaces were found in the range 11 to 52 mg.

  13. Comparison of osteoclastogenesis and resorption activity of human osteoclasts on tissue culture polystyrene and on natural extracellular bone matrix in 2D and 3D. (United States)

    Kleinhans, C; Schmid, F F; Schmid, F V; Kluger, P J


    Bone homeostasis is maintained by osteoblasts (bone formation) and osteoclasts (bone resorption). While there have been numerous studies investigating mesenchymal stem cells and their potential to differentiate into osteoblasts as well as their interaction with different bone substitute materials, there is only limited knowledge concerning in vitro generated osteoclasts. Due to the increasing development of degradable bone-grafting materials and the need of sophisticated in vitro test methods, it is essential to gain deeper insight into the process of osteoclastogenesis and the resorption functionality of human osteoclasts. Therefore, we focused on the comparison of osteoclastogenesis and resorption activity on tissue culture polystyrene (TCPS) and bovine extracellular bone matrices (BMs). Cortical bone slices were used as two-dimensional (2D) substrates, whereas a thermally treated cancellous bone matrix was used for three-dimensional (3D) experiments. We isolated primary human monocytes and induced osteoclastogenesis by medium supplementation. Subsequently, the expression of the vitronectin receptor (αVβ3) and cathepsin K as well as the characteristic actin formation on TCPS and the two BMs were examined. The cell area of human osteoclasts was analyzed on TCPS and on BMs, whereas significantly larger osteoclasts could be detected on BMs. Additionally, we compared the diameter of the sealing zones with the measured diameter of the resorption pits on the BMs and revealed similar diameters of the sealing zones and the resorption pits. We conclude that using TCPS as culture substrate does not affect the expression of osteoclast-specific markers. The analysis of resorption activity can successfully be conducted on cortical as well as on cancellous bone matrices. For new in vitro test systems concerning bone resorption, we suggest the establishment of a 2D assay for high throughput screening of new degradable bone substitute materials with osteoclasts.

  14. Altered composition of bone as triggered by irradiation facilitates the rapid erosion of the matrix by both cellular and physicochemical processes.

    Directory of Open Access Journals (Sweden)

    Danielle E Green

    Full Text Available Radiation rapidly undermines trabecular architecture, a destructive process which proceeds despite a devastated cell population. In addition to the 'biologically orchestrated' resorption of the matrix by osteoclasts, physicochemical processes enabled by a damaged matrix may contribute to the rapid erosion of bone quality. 8w male C57BL/6 mice exposed to 5 Gy of Cs(137 γ-irradiation were compared to age-matched control at 2d, 10d, or 8w following exposure. By 10d, irradiation had led to significant loss of trabecular bone volume fraction. Assessed by reflection-based Fourier transform infrared imaging (FTIRI, chemical composition of the irradiated matrix indicated that mineralization had diminished at 2d by -4.3±4.8%, and at 10d by -5.8±3.2%. These data suggest that irradiation facilitates the dissolution of the matrix through a change in the material itself, a conclusion supported by a 13.7±4.5% increase in the elastic modulus as measured by nanoindentation. The decline in viable cells within the marrow of irradiated mice at 2d implies that the immediate collapse of bone quality and inherent increased risk of fracture is not solely a result of an overly-active biologic process, but one fostered by alterations in the material matrix that predisposes the material to erosion.

  15. Comparison of the Ex Vivo Expansion of UCB-Derived CD34+ in 3D DBM/MBA Scaffolds with USSC as a Feeder Layer

    Directory of Open Access Journals (Sweden)

    Zahra Sadat Hashemi


    Because of acid extraction in the DBM production process, mineral materials were removed and the protein background that was more flexible was presented. Therefore these results suggest that USSC-DBM can be a suitable ex vivo mimicry niche by intensifying of surface/volume ratio and supporting the stem cell differentiation and expansion.

  16. Diffusion bonded matrix of HGMF applied for BWR condensate water purification

    Energy Technology Data Exchange (ETDEWEB)

    Soda, Fumitaka; Yukawa, Takao; Ito, Kazuyuki


    A high Gradient Magnetic Filter (HGMF) applied to the purification of power plant primary water has recently attracted much attention. In the application of HGMF to the water treatment of power plants, especially nuclear power plants, reliabillties of matrix (filtering medium) as well as removal performance for cruds (insoluble corrosion products) are considered to be important factors. To satisfy these factors, a new filtering medium named Diffision Bonded Matrix (DBM) has been developed and the test results are reported. Filtering efficiency and mechanical stiffness of DBM were examined using HGMF pilot test units consisting of 160 mm diameters x 240 mm length filter. The filtering velocity and the magnetic flux density used in this test were 800 m/h 5 kG, respectively. The filtering efficiencies and of 85-100% were obtained for artificial cruds for DBM. The DBM indicated slightly better filtering efficiency than for conventional wool matrix under the same filtering and matrix conditions. The DBM kept its original mechanical properties and very few pieces of fibers were broken off while the conventional wool matrix lost its volume elasticities and the considerable amount of fibers was broken off during the test operation. The results described here demonstrated the applicability of DBM for treatment of BWR primary water by High Gradient Magnetic Filter.

  17. A Ka-band 22 dBm GaN amplifier MMIC

    Institute of Scientific and Technical Information of China (English)

    Wang Dongfang; Chen Xiaojuan; Yuan Tingting; Wei Ke; Liu Xinyu


    A Ka-band GaN amplifier MMIC has been designed in CPW technology,and fabricated with a domestic GaN epitaxial wafer and process.This is,to the best of our knowledge,the first demonstration of domestic Kaband GaN amplifier MMICs.The single stage CPW MMIC utilizes an AIGaN/GaN HEMT with a gate-length of 0.25 μm and a gate-width of 2 × 75 μm.Under Vds =10 V,continuous-wave operating conditions,the amplifier has a 1.5 GHz operating bandwidth.It exhibits a linear gain of 6.3 dB,a maximum output power of 22 dBm and a peak PAE of 9.5% at 26.5 GHz.The output power density of the AIGaN/GaN HEMT in the MMIC reaches 1 W/mm at Ka-band under the condition of Vds =10 V.

  18. Comparison of histomorphometry and 85Sr uptake in induced heterotopic bone in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G;


    Heterotopic bone formation in the abdominal muscle of 45 male 8-week-old Wistar rats induced by implantation of 5, 10, or 15 mg demineralized bone (DBM) powder was evaluated at 4 weeks by 85Sr uptake of the implants and area histomorphometry of the induced bone. Two indices of 85Sr uptake were ca...

  19. Osteomimicry of mammary adenocarcinoma cells in vitro; increased expression of bone matrix proteins and proliferation within a 3D collagen environment.

    Directory of Open Access Journals (Sweden)

    Rachel F Cox

    Full Text Available Bone is the most common site of metastasis for breast cancer, however the reasons for this remain unclear. We hypothesise that under certain conditions mammary cells possess osteomimetic capabilities that may allow them to adapt to, and flourish within, the bone microenvironment. Mammary cells are known to calcify within breast tissue and we have recently reported a novel in vitro model of mammary mineralization using murine mammary adenocarcinoma 4T1 cells. In this study, the osteomimetic properties of the mammary adenocarcinoma cell line and the conditions required to induce mineralization were characterized extensively. It was found that exogenous organic phosphate and inorganic phosphate induce mineralization in a dose dependent manner in 4T1 cells. Ascorbic acid and dexamethasone alone have no effect. 4T1 cells also show enhanced mineralization in response to bone morphogenetic protein 2 in the presence of phosphate supplemented media. The expression of several bone matrix proteins were monitored throughout the process of mineralization and increased expression of collagen type 1 and bone sialoprotein were detected, as determined by real-time RT-PCR. In addition, we have shown for the first time that 3D collagen glycosaminoglycan scaffolds, bioengineered to represent the bone microenvironment, are capable of supporting the growth and mineralization of 4T1 adenocarcinoma cells. These 3D scaffolds represent a novel model system for the study of mammary mineralization and bone metastasis. This work demonstrates that mammary cells are capable of osteomimicry, which may ultimately contribute to their ability to preferentially metastasize to, survive within and colonize the bone microenvironment.

  20. Extracellular matrix production by nucleus pulposus and bone marrow stem cells in response to altered oxygen and glucose microenvironments. (United States)

    Naqvi, Syeda M; Buckley, Conor T


    Bone marrow (BM) stem cells may be an ideal source of cells for intervertebral disc (IVD) regeneration. However, the harsh biochemical microenvironment of the IVD may significantly influence the biological and metabolic vitality of injected stem cells and impair their repair potential. This study investigated the viability and production of key matrix proteins by nucleus pulposus (NP) and BM stem cells cultured in the typical biochemical microenvironment of the IVD consisting of altered oxygen and glucose concentrations. Culture-expanded NP cells and BM stem cells were encapsulated in 1.5% alginate and ionically crosslinked to form cylindrical hydrogel constructs. Hydrogel constructs were maintained under different glucose concentrations (1, 5 and 25 mM) and external oxygen concentrations (5 and 20%). Cell viability was measured using the Live/Dead® assay and the production of sulphated glycosaminoglycans (sGAG), and collagen was quantified biochemically and histologically. For BM stem cells, IVD-like micro-environmental conditions (5 mM glucose and 5% oxygen) increased the accumulation of sGAG and collagen. In contrast, low glucose conditions (1 mM glucose) combined with 5% external oxygen concentration promoted cell death, inhibiting proliferation and the accumulation of sGAG and collagen. NP-encapsulated alginate constructs were relatively insensitive to oxygen concentration or glucose condition in that they accumulated similar amounts of sGAG under all conditions. Under IVD-like microenvironmental conditions, NP cells were found to have a lower glucose consumption rate compared with BM cells and may in fact be more suitable to adapt and sustain the harsh microenvironmental conditions. Considering the highly specialised microenvironment of the central NP, these results indicate that IVD-like concentrations of low glucose and low oxygen are critical and influential for the survival and biological behaviour of stem cells. Such findings may promote and accelerate

  1. 表面脱钙骨基质明胶修复大块骨缺损的成骨作用研究%Osteogenesis of surface-decalcified bone matrix gelation in the repair of segmental bone defects

    Institute of Scientific and Technical Information of China (English)

    张学鹏; 伊哲; 王英兰; 徐延


    BACKGROUND: Repair of segmental bone defects is one of the difficult problems in orthopaedics. Although the therapeutic effect on bone autograft is the best, the source is limited and there is lack of suitable substitutive materials for autologous bone.OBJECTIVE: To probe into the therapeutic effects of surface-decalcified bone matrix gelation(SDBMG) and the substitutive possibility of autologous bone on repair of segmental bone defects.DESIGN: The research was designed as completely randomized controlled experiment. The clinical research was designed as pre- and post-controlled study on the basis of diagnosis.SEETING: Department of Orthopaedics, Wuhan General Hospital of Guangzhou Military Area Command.MATERLALS and PARTICIPANTS: The experiment was accomplished in Laboratory of Wuhan General Hospital of Guangzhou Military Area Command, and Testing Center of Wuhan University of Technology. Thirty-two local healthy adult male rabbits were employed as the materials in the experiment, 2.5 kg in body mass, bought from Hubei Academy of Medical Sciences. The clinical subjects were 31 patients(male 25 and female 6, a meanage of 9 years old) with segmental bone defects hospitalized in the Department of Orthopaedics, Wuhan General Hospital of Guangzhou Military Area Command during January 1991 to May 2001.METHODS: The 32 rabbits were randomized into group A and group B. The bilateral radial bones were prepared into 1-cm bone defect in both groups. In both groups, SDBMG was grafted on the left side; in Group A, wholly-decalcffied bone matrix gelatin(WDBMG) was grafted on the right side;and in Group B, the autologous bone was grafted on the right side. Human SDBMG was provided to treat 31 cases of segmental bone defects.MAIN OUTCOME MEASURES: ① Regular X-ray and histological examinations after operation in animals(Group A) and biomechanical deterruination (Group B ). ② Regular X-ray examinations after operation.RESULTS: SDBMG induced osteogenesis process "gradually" from

  2. Matrix Vesicle Enzyme Activity and Phospholipid Content in Endosteal Bone Following Implantation of Osseointegrating and Non-Osseointegrating Implant Materials. (United States)


    matrix vesicles (Schwartz et al., 1990a; Boyan et al., 1988; Peress et al., 1974) and is intimately associated with mineral formation as the principle...directly related to the process of primary mineral formation in tissues adjacent to osseointegrating and non- integrating materials. Of particular...Evans, L. 1981. Mechanisms of mineral formation by matrix vesicles. In: Matrix Vesicles, Proc. 3rd Int. Conf. Matrix Vesicles. Ascenci, A., Bonucci, D

  3. The effect of enamel matrix derivative (Emdogain(R)) on gene expression profiles of human primary alveolar bone cells

    NARCIS (Netherlands)

    Yan, X.Z.; Rathe, F.; Gilissen, C.; Zande, M. van der; Veltman, J.; Junker, R.; Yang, F.; Jansen, J.A.; Walboomers, X.F.


    Emdogain(R) is frequently used in regenerative periodontal treatment. Understanding its effect on gene expression of bone cells would enable new products and pathways promoting bone formation to be established. The aim of the study was to analyse the effect of Emdogain(R) on expression profiles of h

  4. In vitro cartilage production using an extracellular matrix-derived scaffold and bone marrow-derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yan-hong; YANG Qiang; XIA Qun; PENG Jiang; LU Shi-bi; GUO Quan-yi; MA Xin-long


    Background Cartilage repair is a challenging research area because of the limited healing capacity of adult articular cartilage.We had previously developed a natural,human cartilage extracellular matrix (ECM)-derived scaffold for in vivo cartilage tissue engineering in nude mice.However,before these scaffolds can be used in clinical applications in vivo,the in vitro effects should be further explored.Methods We produced cartilage in vitro using a natural cartilage ECM-derived scaffold.The scaffolds were fabricated by combining a decellularization procedure with a freeze-drying technique and were characterized by scanning electron microscopy (SEM),micro-computed tomography (micro-CT),histological staining,cytotoxicity assay,biochemical and biomechanical analysis.After being chondrogenically induced,the induction results of BMSCs were analyzed by histology and Immunohisto-chemistry.The attachment and viability assessment of the cells on scaffolds were analyzed using SEM and LIVE/DEAD staining.Cell-scaffold constructs cultured in vitro for 1 week and 3 weeks were analyzed using histological and immunohistochemical methods.Results SEM and micro-CT revealed a 3-D interconnected porous structure.The majority of the cartilage ECM was found in the scaffold following the removal of cellular debris,and stained positive for safranin O and collagen Ⅱ.Viability staining indicated no cytotoxic effects of the scaffold.Biochemical analysis showed that collagen content was (708.2±44.7)μg/mg,with GAG (254.7±25.9) μg/mg.Mechanical testing showed the compression moduli (E) were (1.226±0.288) and (0.052±0.007) MPa in dry and wet conditions,respectively.Isolated canine bone marrow-derived stem cells (BMSCs) were induced down a chondrogenic pathway,labeled with PKH26,and seeded onto the scaffold.Immunofluorescent staining of the cell-scaffold constructs indicated that chondrocyte-like cells were derived from seeded BMSCs and excreted ECM.The cell-scaffold constructs contained

  5. Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Kirkpatrick, Charles James [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz (Germany); Willershausen, Ines [Institute for Dental Material Sciences and Technology, University Medical Center of the Johannes Gutenberg University Mainz, Anselm-Franz-von-Bentzel-Weg 14, 55128 Mainz (Germany); Thimm, Benjamin W [Institute for Biomechanics, ETH Zuerich, Wolfgang-Pauli-Str.10, 8093 Zuerich (Switzerland); Booms, Patrick [Leeds Institute of Molecular Medicine, Section of Medicine, Surgery and Anaesthesia, University of Leeds (United Kingdom); Stuebinger, Stefan; Landes, Constantin; Sader, Robert Anton, E-mail: ghanaati@uni-mainz.d [Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Theodor-Stein-Kai 7, 60596 Frankfurt am Main (Germany)


    The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute. The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

  6. Guided bone regeneration with acellular dermal matrix as a barrier for bone defects%脱细胞真皮基质膜引导骨缺损成骨变化

    Institute of Scientific and Technical Information of China (English)

    贾仁杰; 任玉卿; 徐昊; 王维英; 弋中萍; 赵保东


    BACKGROUND:Acel ular dermal matrix has good biocompatibility and absorbability and exhibits superiority in the guided bone regeneration. OBJECTIVE:To compare the histological changes and osteogenic effects in bone defects after guided bone regeneration with acel ular dermal matrix and Bio-Gide membrane. METHODS:Mandibular second, third and fourth premolars and the first molars bilateral y were extracted from 12 beagle dogs. Three months later, four three-wal bone defect models in the mandible of each dog were made, and randomized into acel ular dermal matrix plus bone graft group (acel ular dermal matrix group), Bio-Gide plus bone graft group (Bio-Gide group), bone graft group, and blank control group (no treatment). In the former two groups, acel ular dermal matrix and Bio-Gide were used to cover the bone grafts, respectively. RESULTS AND CONCLUSION:After surgery, al the beagle dogs recovered wel . Al the groups except the control group showed dramatical improvement in histological changes and percentage of new bone area, and this improvement was more significant in the Bio-Gide and acel ular dermal matrix groups. Moreover, there was no significant difference between the Bio-Gide and acel ular dermal matrix groups. Therefore, the acel ular dermal matrix can be a candidate for bone repair instead of Bio-Gide membrane in the clinical practice.%背景:脱细胞真皮基质膜具有良好的生物相容性、可吸收性、引导骨再生性能。目的:比较脱细胞真皮基质膜和Bio-Gide膜引导骨缺损成骨的组织学变化及引导骨再生的效果的差异。  方法:12只比格犬拔除双侧下颌骨第二、三、四前磨牙及第一磨牙3个月后,在每只犬的下颌骨各建立4处标准的三壁骨缺损模型,随机分为脱细胞真皮基质膜联合骨修复材料组、Bio-Gide膜联合骨修复材料组、骨修复材料组、空白对照组。除空白对照组不做任何处理外,将骨修复材料充实于其余3组骨

  7. Homogenous demineralized dentin matrix and platelet-rich plasma for bone tissue engineering in cranioplasty of diabetic rabbits: biochemical, radiographic, and histological analysis. (United States)

    Gomes, M F; Valva, V N; Vieira, E M M; Giannasi, L C; Salgado, M A C; Vilela-Goulart, M G


    This study evaluated the effects of homogenous demineralized dentin matrix (HDDM) slices and platelet-rich plasma (PRP) in surgical defects created in the parietal bones of alloxan-induced diabetic rabbits, treated with a guided bone regeneration technique. Biochemical, radiographic, and histological analyses were performed. Sixty adult New Zealand rabbits were divided into five groups of 12: normoglycaemic (control, C), diabetic (D), diabetic with a PTFE membrane (DM), diabetic with a PTFE membrane and HDDM slices (DM-HDDM), and diabetic with PTFE membrane and PRP (DM-PRP). The quantity and quality of bone mass was greatest in the DM-HDDM group (respective radiographic and histological analyses: at 15 days, 71.70 ± 16.50 and 50.80 ± 1.52; 30 days, 62.73 ± 16.51 and 54.20 ± 1.23; 60 days, 63.03 ± 11.04 and 59.91 ± 3.32; 90 days, 103.60 ± 24.86 and 78.99 ± 1.34), followed by the DM-PRP group (respective radiographic and histological analyses: at 15 days 23.00 ± 2.74 and 20.66 ± 7.45; 30 days 31.92 ± 6.06 and 25.31 ± 5.59; 60 days 25.29 ± 16.30 and 46.73 ± 2.07; 90 days 38.10 ± 14.04 and 53.38 ± 9.20). PRP greatly enhanced vascularization during the bone repair process. Abnormal calcium metabolism was statistically significant in the DM-PRP group (P<0.001) for all four time intervals studied, especially when compared to the DM-HDDM group. Alkaline phosphatase activity was significantly higher in the DM-HDDM group (P<0.001) in comparison to the C, D, and DM-PRP groups, confirming the findings of intense osteoblastic activity and increased bone mineralization. Thus, HDDM promoted superior bone architectural microstructure in bone defects in diabetic rabbits due to its effective osteoinductive and osteoconductive activity, whereas PRP stimulated angiogenesis and red bone marrow formation.

  8. Photophysical properties of a novel organic-inorganic hybrid material: Eu(III)-β-diketone complex covalently bonded to SiO(2) /ZnO composite matrix. (United States)

    Li, Ya-Juan; Yan, Bing


    In this article, dibenzoylmethane (DBM) was first grafted with the coupling reagent 3-(triethoxysilyl)-propyl isocyanate (TESPIC) to form precursor DBM-Si, and ZnO quantum dot was modified with 3-mercaptopropyltrimethoxysilane (MPS) to form SiO(2) /ZnO nanocomposite particle. Then the precursor DBM-Si and the terminal ligand 1,10-phenthroline (phen) were coordinated to Eu(3+) ion to obtain ternary hybrid material phen-Eu-DBM-SiO(2) /ZnO after hydrolysis and copolycondensation between the tetraethoxysilane (TEOS), water molecules and the SiO(2) /ZnO network via the sol-gel process. In addition, for comparison, the binary hybrid material with SiO(2) /ZnO network and ternary hybrid material with pure Si-O network were also synthesized, denoted as Eu-DBM-SiO(2) /ZnO and phen-Eu-DBM-Si, respectively. The results reveal that hybrid material with SiO(2) /ZnO network phen-Eu-DBM-SiO(2) /ZnO exhibits the stronger red light, the longer lifetimes and higher quantum efficiency than hybrid material with pure Si-O network phen-Eu-DBM-Si, suggesting that SiO(2) /ZnO is a favorable host matrix for the luminescence of rare earth complexes.

  9. The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model. (United States)

    Zwingenberger, Stefan; Langanke, Robert; Vater, Corina; Lee, Geoffrey; Niederlohmann, Eik; Sensenschmidt, Markus; Jacobi, Angela; Bernhardt, Ricardo; Muders, Michael; Rammelt, Stefan; Knaack, Sven; Gelinsky, Michael; Günther, Klaus-Peter; Goodman, Stuart B; Stiehler, Maik


    The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.

  10. Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

    DEFF Research Database (Denmark)

    Jensen, Simon S; Chen, B; Bornstein, Michael M;


    or directly on the bone-forming cells. In addition, it is not known if the presentation of PTH by adding the amino acid sequence Arg-Gly-Asp (RGD) is essential for its osteopromotive effect. Local delivery of a bioactive substance at the right time and in the right concentration often constitutes a major...... challenge. Polyethylene glycol-based hydrogel (PEG) is a degradable vehicle developed for delivery of bioactive proteins. To enhance the mechanical stability of the PEG-bioactive substance complex, an osteoconductive bone substitute material is often needed....

  11. Effect of Emdogain enamel matrix derivative and BMP-2 on the gene expression and mineralized nodule formation of alveolar bone proper-derived stem/progenitor cells. (United States)

    Fawzy El-Sayed, Karim M; Dörfer, Christof; Ungefroren, Hendrick; Kassem, Neemat; Wiltfang, Jörg; Paris, Sebastian


    The objective of this study was to evaluate the effect of Emdogain (Enamel Matrix Derivative, EMD) and Bone Morphogenetic Protein-2 (BMP-2), either solely or in combination, on the gene expression and mineralized nodule formation of alveolar bone proper-derived stem/progenitor cells. Stem/progenitor cells were isolated from human alveolar bone proper, magnetically sorted using STRO-1 antibodies, characterized flowcytometrically for their surface markers' expression, and examined for colony formation and multilineage differentiation potential. Subsequently, cells were treated over three weeks with 100 μg/ml Emdogain (EMD-Group), or 100 ng/ml BMP-2 (BMP-Group), or a combination of 100 ng/ml BMP-2 and 100 μg/ml Emdogain (BMP/EMD-Group). Unstimulated stem/progenitor cells (MACS(+)-Group) and osteoblasts (OB-Group) served as controls. Osteogenic gene expression was analyzed using RTq-PCR after 1, 2 and 3 weeks (N = 3/group). Mineralized nodule formation was evaluated by Alizarin-Red staining. BMP and EMD up-regulated the osteogenic gene expression. The BMP Group showed significantly higher expression of Collagen-I, III, and V, Alkaline phosphatase and Osteonectin compared to MACS(+)- and OB-Group (p Emdogain and BMP-2 up-regulate the osteogenic gene expression of stem/progenitor cells. The combination of BMP-2 and Emdogain showed no additive effect and would not be recommended for a combined clinical stimulation.

  12. Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor

    DEFF Research Database (Denmark)

    Lecomte, Julie; Masset, Anne; Blacher, Silvia;


    Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes, and functions. In the present report, we have explored the contribution of bone marrow (BM)-d...

  13. SEMICONDUCTOR INTEGRATED CIRCUITS A 900 MHz, 21 dBm CMOS linear power amplifier with 35% PAE for RFID readers (United States)

    Kefeng, Han; Shengguo, Cao; Xi, Tan; Na, Yan; Junyu, Wang; Zhangwen, Tang; Hao, Min


    A two-stage differential linear power amplifier (PA) fabricated by 0.18 μm CMOS technology is presented. An output matching and harmonic termination network is exploited to enhance the output power, efficiency and harmonic performance. Measurements show that the designed PA reaches a saturated power of 21.1 dBm and the peak power added efficiency (PAE) is 35.4%, the power gain is 23.3 dB from a power supply of 1.8 V and the harmonics are well controlled. The total area with ESD protected PAD is 1.2 × 0.55 mm2. System measurements also show that this power amplifier meets the design specifications and can be applied for RFID reader.

  14. Ce(DBM)3Phen doped poly(methyl methacrylate) for three-dimensional multilayered optical memory by femtosecond laser

    Institute of Scientific and Technical Information of China (English)

    JIU; Hongfang


    The formation of submicrometer voids within Ce(DBM)3Phen doped poly(methyl methacrylate)(PMMA) was reported under multiphoton absorption excited by an infrared laser beam. The absorption spectra, photoluminescence and electron spin resonance (ESR) spectra before and after femtosecond laser irradiation were discussed. An ultrashort-pulsed laser beam with a pulse width of 200 femtosecond at a wavelength of 800 nm was focused into doped PMMA. The large changes in refractive index and the fluorescence associated with a void allowed conventional optical microscopy and reflection-type confocal microscopy to be used as detection methods. Voids could be arranged in a three-dimensional multilayered structure for high-density optical data storage. The separation of adjacent bits and layers were 4 and 16 μm, respectively.

  15. Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture (United States)


    influence the progression of osteoblast differentiation and osteogenesis, control the resorption of calcified bone, and modulate lineage determination in...low levels in all other tissues analyzed including muscle, skin, heart, kidney, fat, liver and tendon . We also determined AR-transgene expression in...0.0006 ± 0.0000 -1667 Skin 0.0006 ± 0.0002 -1667 Ear 0.0004 ± 0.0001 -2500 Liver 0.0004 ± 0.0002 -2500 Tendon 0.0003

  16. Repair of Traumatic Skeletal Muscle Injury with Bone-Marrow-Derived Mesenchymal Stem Cells Seeded on Extracellular Matrix (United States)


    Hammers D. W., Le L. N., Gokhale R., Sarathy A., Song T. J., Tierney M. T., Suggs L. J., Walters T. J., Farrar R. P., 5d. PROJECT NUMBER 5e. Bioma terials 30, 2393, 2009. 65. Beattie, A.J., et al. Chemoattraction of Progenitor Cells by Remodeling Extracellular Matrix Scaffolds

  17. A clinical evaluation of guided tissue regeneration with a bioabsorbable matrix membrane combined with an allograft bone graft. A series of case reports. (United States)

    Harris, R J


    THE PURPOSE OF THIS STUDY was to evaluate the clinical effectiveness of a surgical technique in treating periodontal defects. The technique combined tetracycline treatment of a root planed root, grafting of the osseous defect with a demineralized freeze-dried bone allograft combined with tetracycline and the placement of a bioabsorbable matrix membrane, made of polylactic acid softened with citric acid ester. Thirty defects were treated in 27 patients. Statistically significant changes, as a result of the surgical procedure, were observed in marginal recession (mean: 0.5 mm), probing depth reductions (mean: 5.7 mm), and attachment level gain (mean: 5.2 mm). No statistically significant difference existed between the results in the furcation and non-furcation groups. The defects with probing depths > or = 10 mm had a greater mean probing depth reduction (7.4 mm) and mean attachment level improvement (7.2 mm) than the defects with effective method to treat periodontal defects.

  18. Extracellular Matrix Proteins, Alkaline Phosphatase and Pyrophosphate as Molecular Determinants of Bone, Tooth, Kidney and Vascular Calcification (United States)

    McKee, Marc D.


    Progress in biomineralization research in recent years has identified, characterized and described functions for key noncollagenous extracellular matrix proteins regulating crystal growth in the skeleton and dentition. Some of these same proteins expressed in soft tissues undergoing pathologic calcification also inhibit ectopic crystal growth. In addition to extracellular matrix proteins regulating matrix mineralization, the enzyme tissue-nonspecific alkaline phosphatase—which is highly expressed by cells in mineralized tissues—cleaves pyrophosphate, an anionic small-molecule inhibitor of mineralization. Together with the required mineral ion availability necessary for crystal growth, these molecular determinants appear to function in limiting the spread of pathologic calcification seen in soft tissues such as blood vessels and kidneys. Osteopontin, in particular, is a potent calcification inhibitor that accumulates in mineralized tissues and in calcified deposits during vascular calcification and nephrolithiasis/urolithiasis. Additional research is required to establish the exact temporal sequence in which the molecular determinants of pathologic calcification appear relative to mineral crystal growth in different tissues, and to establish their relationship (if any) to the activation of osteogenic differentiation programs.

  19. [Effect of laminar shear stress on the expression of matrix metalloproteinases-9 in rat bone marrow-derived mesenchymal stem cells]. (United States)

    Chen, Longju; Sun, Xiaodong; Tang, Jie; Ding, Yan; Li, Jing; Li, Wenchun; Gong, Jian; Wang, Hanqin


    This paper was designed to investigate the effect of laminar shear stress on matrix metalloproteinase -9 (MMP-9) expression in rat bone marrow-derived mesenchymal stem cells (MSCs), and the possible signal transduction mechanism involved. Rat bone marrow MSCs were isolated and cultured, then, exposed to laminar shear stress at indicated strengths such as low (5dyne/cm2), medium (15 dyne/cm2) and high (30 dyne/cm2) via parallel plate flow chamber. RT-PCR was used to analyze the expression of MMP-9. The signaling inhibitors such as Wortmannin (PI3K specific inhabitor), SB202190 (p38MAPK specific inhabitor), and PD98059 (ERK1/2 specific inhabitor) were used to investigate the possible mechanical signal transduction pathway. The results showed: (1) The expression of MMP-9 was weak in static state, however, MMP-9 expression increased when MSCs were exposed to 15 dyne/cm2 shear stress for 2 hours, and MMP-9 expression increased with the extension of stimulating time, and it reached the peak at 24 h; (2) MSCs were stimulated by shear stress for 2 hours at different strengths (5 dyne/cm2, 15 dyne/cm2, 30 dyne/cm2), and under all these conditions, the expression of MMP-9 increased, and reached the peak at 15 dyne/cm2; (3) After MSCs were pretreated by three kinds of signal pathway inhibitors, the expression of MMP-9 did not change obviously in Wortmannin group and PD98059 group, but it was significantly inhibited in SB202190 group. This study demonstrated that shear stress could induce the expression of MMP-9 in rat bone marrow-derived mesenchymal stem cells; the amount of MMP-9 expression was closely related to stimulating time and the strengths of shear stress; and p38MAPK signal pathway played a critical role during the process.

  20. Characterization of partially hydrolyzed OCP crystals deposited in a gelatin matrix as a scaffold for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Ezoe, Yushi [Tohoku University Graduate School of Dentistry, Division of Oral and Maxillofacial Surgery (Japan); Anada, Takahisa [Tohoku University Graduate School of Dentistry, Division of Craniofacial Function Engineering (Japan); Yamazaki, Hajime [The Forsyth Institute, Department of Applied Oral Sciences, Center for Biomineralization (United States); Handa, Takuto; Kobayashi, Kazuhito; Takahashi, Tetsu [Tohoku University Graduate School of Dentistry, Division of Oral and Maxillofacial Surgery (Japan); Suzuki, Osamu, E-mail: [Tohoku University Graduate School of Dentistry, Division of Craniofacial Function Engineering (Japan)


    The present study was designed to investigate how hydrolysis of octacalcium phosphate (OCP) into hydroxyapatite is affected by the presence of gelatin (Gel) molecules and how osteoblastic cells respond to the resultant OCP hydrolyzate/Gel composites as the hydrolysis advances. OCP was prepared from a solution containing calcium and phosphate ions and Gel molecules, having a composition to produce a 40 wt% OCP as a final co-precipitate as the OCP/Gel. The precipitate was further incubated up to 40 h to advance the hydrolysis of OCP. These precipitates were processed to mold OCP/Gel sponges through lyophilization and dehydrothermal treatment. Chemical analysis, X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and selected area electron diffraction revealed that the hydrolysis of OCP/Gel composite in hot water advanced in a time-dependent manner and faster than hydrolysis of OCP alone. The effect of Gel on the OCP hydrolysis was further examined in the presence of distinct concentrations of Gel molecules in hot water, showing that the Gel enhanced the hydrolysis as the concentration increased. Proliferation and differentiation of mouse bone marrow stromal ST-2 cells on the hydrolyzed OCP/Gel composites were compatible with Gel sponge alone after 21 days of culture, suggesting that these composites could be a candidate as a scaffold in bone tissue engineering.

  1. 硫酸钙/骨基质明胶复合人工骨修复骨缺损%Calcium sulphate/bone matrix gelatin composite biomaterial for repair of bone defects

    Institute of Scientific and Technical Information of China (English)

    陈建民; 刘方刚; 金大地


    .OBJECTIVE: To verify the potential ofCS/bone matrix gelatin (BMG) composite biomaterial in the repair of segmental bone defects.DESIGN, TIME AND SETTING: An in vivo multi-dimensional observation was performed in the Laboratory Animal Center, Nanfang Hospital, Southern Medical University between December 2004 and April 2006.MATERIALS: Twenty-one healthy adult New Zealand rabbits, weighing 2.5-3.5 kg, were included. The segmental ulnar defects of 15 mm were created bilaterally. CS and BMG were self-prepared.METHODS: CS and BMG were composited at 2:1 and then implanted into 15-mm rabbit ulnar bone defect. The present study consisted of 3 groups: CS/BMG group, defects were filled with CS/BMG; CS group, defects were filled with CS; and blank control group, untreated control defects.MAIN OUTCOME MEASURES: At weeks 4, 8, and 12 post-surgery, repair of bone defect was observed by gross observation, radiographic, histomorphological and tetracycline tracing analysis.RESULTS: Surgical incisions all primarily healed. No inflammatory or foreign reaction was found around all the defects. Both CS/BMG and CS were almost completely absorbed at week 8 post-surgery. In the CS/BMG group, newly formed bone was found throughout the defects after 4 weeks; all defects were repaired with a well-organized trabecular pattern and a thit neocortex after 12 weeks. In the CS group, mass of new bone tissue formed at the periphery of the defect at week 4 post-surgery, but the development of new bone in the center of defect was latter compared with the CS/BMG group: at 12 weeks, all defects were bridged by newly formed bone tissue with little adjacent medullary bone. In the blank control group, slight new bone was found at the periphery of the defect region, and the defects were filled with fibrous tissue.CONCLUSION: CS/BMG composite is totally bioresorbable and biocompatible. The composite can repair bone defects effectively as a bone graft substitute.

  2. Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor

    DEFF Research Database (Denmark)

    Lecomte, Julie; Masset, Anne; Blacher, Silvia;


    )-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13) and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. We......producing cells were exclusively α-SMA(+) cells and derived from GFP(+) BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs) from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained...... from MMP13-deficient mice failed to. Our data support the concept of fibroblast subset specialization with BM-derived α-SMA(+) cells being the main source of MMP13, a stromal mediator of cancer cell invasion....

  3. Synth esis and characterization of collagen-based artificial bone matrix based on typeⅠ collagen%以Ⅰ型胶原制备的胶原基人工骨基质理化性能研究

    Institute of Scientific and Technical Information of China (English)

    汤祥忠; 孙小莉; 谢磊; 汤晓阳; 刘向辉; 周静


    目的:研究采用仿生原理制备的胶原基人工骨基质的理化性能。方法用Ⅰ型胶原、饱和二水氯化钙制备胶原基人工骨基质。采用扫描电子显微镜、金相显微镜、傅里叶变换红外光谱(FT-IR)分析、差热-热重(TG-DTG)分析、X射线衍射(XRD)分析、X射线能谱仪(EDS)等分析测试手段对其形貌、组成、结晶度和Ca/P等进行详细的研究。结果采用扫描电子显微镜和金相显微镜观察,胶原基人工骨基质无机钙盐均匀沉积在自组装的胶原模板上,有清晰的孔隙,呈梯度分布,并且具有类似天然骨的内连孔结构;孔隙直径为50~500μm;孔隙率为(68±5)%。 FT-IR分析,胶原基人工骨基质与天然骨的红外图谱基本吻合,胶原基人工骨基质的872 cm -1为HPO42-的吸收峰。TG-DTG分析证明有羟基磷灰石。XRD、EDS分析,无机相主要为羟基磷灰石,与天然骨的衍射峰位置、数量相似。结晶度和Ca/P分别为49.3%、1.64。结论仿生原理制备的胶原基人工骨基质与人骨基质相似。%Objective To investigate the physicochemical properties of the collagen-based artificial bone matrix prepared ac-cording to bionic principle. Methods The collagen based artificial bone matrix was synthesized by type Ⅰcollagen and satu-rated calcium chloride dihydrate. The morphology, composition, crystallinity and Ca/P of the collagen-based artificial bone ma-trix were characterized by scanning electron microscope (SEM), metallographic microscope, Fourier transform infrared spec-troscopy(FT-IR), differential thermal gravimetric analysis(TG-DTG), X-ray diffraction(XRD), X-ray energy dispersive analysis (EDS). Results SEM and metallographic microscope analysis result showed that the collagen-based artificial bone matrix ’s inorganic calcium salt uniformly deposited on the self-assembled collagen template and the bone porosity of the collagen-based artificial bone

  4. Tissue inhibitor of matrix metalloproteinase-1 suppresses apoptosis of mouse bone marrow stromal cell line MBA-1. (United States)

    Guo, L-J; Luo, X-H; Xie, H; Zhou, H-D; Yuan, L-Q; Wang, M; Liao, E-Y


    We investigated the action of tissue inhibitor of metalloproteinase-1 (TIMP-1) on apoptosis and differentiation of mouse bone marrow stromal cell line MBA-1. TIMP-1 did not affect alkaline phosphatase (ALP) activity, suggesting that it is not involved in osteoblastic differentiation in MBA-1 cells. However, TIMP-1 inhibited MBA-1 apoptosis induced by serum deprivation in a dose-dependent manner. Our study also showed increased Bcl-2 protein expression and decreased Bax protein expression with TIMP-1 treatment. TIMP-1 decreased cytochrome c release and caspase-3 activation in MBA-1 cells. TIMP-1 activated phosphatidylinositol 3-kinase (PI3-kinase) and c-Jun N-terminal kinase (JNK), and the PI3-kinase inhibitor LY294002 or the JNK inhibitor SP600125 abolished its antiapoptotic activity. To investigate whether antiapoptotic action of TIMP-1 was mediated through its inhibition on MMP activities, we constructed mutant TIMP-1 by side-directed mutagenesis, which abolished the inhibitory activity of MMPs by deletion of Cys1 to Ala4. Wild-type TIMP-1 and mutant TIMP-1 expression plasmids were transfected in MBA-1 cells, and results showed that mutant TIMP-1 still protected the induced MBA-1 cell against apoptosis. These data suggest that TIMP-1 antiapoptotic actions are mediated via the PI3-kinase and JNK signaling pathways and independent of TIMP-1 inhibition of MMP activities.

  5. GS/DBM/PLA porous composite biomaterial for the treatment of infective femoral condyle defect in rats


    Liu, Xiaoming; Yang, Lin; Li, Jing; Zhang, Yuming; Xu, Weijun; Ren, Yan; LIU, BIWANG; Yang, Biao; LI, BAOXING


    A bone defect resulting from open bone trauma may easily become infected; however, the administration of efficacious systemic antibiotics cannot be performed at safe levels. Previous studies have investigated anti-infective biomaterials that incorporate into bone and facilitate the direct application of high-concentration local antibiotics. In the present study, the effect of a novel porous composite with gentamicin sulfate (GS) in treating infected femoral condyle defects was investigated us...

  6. Boron Induces Early Matrix Mineralization via Calcium Deposition and Elevation of Alkaline Phosphatase Activity in Differentiated Rat Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Bent-al-hoda Movahedi Najafabadi


    Full Text Available Objective: Boron (B is essential for plant development and might be an essential micronutrient for animals and humans. This study was conducted to characterize the impact of boric acid (BA on the cellular and molecular nature of differentiated rat bone marrow mesenchymal stem cells (BMSCs. Materials and Methods: In this experimental study, BMSCs were extracted and expanded to the 3rd passage, then cultured in Dulbecco’s Modified Eagle’s Medium (DMEM complemented with osteogenic media as well as 6 ng/ml and 6 μg/ml of BA. After 5, 10, 15 and 21 days the viability and the level of mineralization was determined using MTT assay and alizarin red respectively. In addition, the morphology, nuclear diameter and cytoplasmic area of the cells were studied with the help of fluorescent dye. The concentration of calcium, activity of alanine transaminase (ALT, aspartate transaminase (AST, lactate dehydrogenase (LDH and alkaline phosphatase (ALP as well as sodium and potassium levels were also evaluated using commercial kits and a flame photometer respectively. Results: Although 6 μg/ml of BA was found to be toxic, a concentration of 6 ng/ml increased the osteogenic ability of the cell significantly throughout the treatment. In addition it was observed that B treatment caused the early induction of matrix mineralization compared to controls. Conclusion: Although more investigation is required, we suggest the prescription of a very low concentration of B in the form of BA or foods containing BA, in groups at high risk of osteoporosis or in the case of bone fracture.

  7. The use of beta-tricalcium phosphate and bovine bone matrix in the guided tissue regeneration treatment of deep infra-bony defects

    Directory of Open Access Journals (Sweden)

    Luković Natalija


    Full Text Available Introduction. The primary goal of bone regeneration procedures with application of various regenerative biologic agents and biomaterials is to facilitate the formation of periodontal tissues lost as a result of periodontitis. Objective. The aim of the study was to compare clinical outcome of the guided tissue regeneration (GTR treatment with the use of β-tricalcium phosphate and with bovine bone matrix in human deep intra-osseous defects. Methods. Twenty-one systemically healthy subjects with moderate to advanced periodontitis, between 30 and 56 years of age, 11 females and 10 males, were selected. Patients having two similar inter-proximal defects with pocket probing depths following initial therapy greater than 5 mm were recruited for the study. Experimental sites were grafted with pure β-tricalcium phosphate biomaterial (Cerasorb® and a biomembrane, while control sites were treated with bovine-bone hydroxiapatite xenograft (Bio-oss® and a biomembrane. Immediately before surgery and 12 months after surgery, pocket probing depth (PPD, epithelial attachment level (EAL and gingival recession (GR were evaluated. Results. In the experimental group PPD amounted to 6.76±0.83 mm before surgery, and decreased significantly to 2.67±0.48 mm 12 months following surgery, while in the control group PPD significantly decreased from 7.14±0.65 mm presurgically to 2.85±0.57 mm postsurgically. After one year, EAL gain was 2.76±0.99 mm in the experimental group, and 3.24±0.16 mm in the control group. After twelve months postoperatively GR amounted to 1.33±0.79 mm in the experimental group and to 1.05±0.80 mm in the control group. No statistically significant differences for PPD reduction, EAL gain and GR increase were detected between the groups. Conclusion. Results from the present study indicate that GTR treatment of deep intra-osseous defects with Bio-oss® and Cerasorb® resulted in clinically and statistically significant improvement of EAL gain

  8. 人纳米脱钙骨基质复合物的理化性质和安全性%Physicochemical property and safety of nanometer human demineralized bone matrix composite

    Institute of Scientific and Technical Information of China (English)

    房雷; 陈雄生; 黄凯; 周盛源; 朱巍; 王辉; 邵将; 贾连顺


    背景:脱钙骨基质和骨形态发生蛋白已被证实具有良好的骨诱导性,但有关纳米脱钙骨基质的研究较少,其理化性质和生物安全性尚不明确。  目的:在前期实验制备人纳米脱钙骨基质的基础上加载重组人骨形态发生蛋白2,分析人纳米脱钙骨基质复合重组人骨形态发生蛋白2的理化性质及生物安全性。  方法:采用改良Urist法制备人脱钙骨基质,并进行纳米化处理,再将骨形态发生蛋白2与其按特定比例混合,冻干塑型行以下实验:①热源实验:将材料浸提液经耳静脉注入兔体内。②毒性实验:将材料浸提液与生理盐水分别经尾静脉注入小白鼠体内。③植入实验:在兔两侧后肢肌肉内分别植入实验材料和β-磷酸三钙。  结果与结论:冻干塑型后,纳米人脱钙骨基质材料表面致密,孔隙直径100-400μm,孔隙分布欠均匀,孔隙率小于30%,以碳、氧和氮为主要元素组成。人纳米脱钙骨基质复合重组人骨形态发生蛋白2材料无热源效应,注射后未见兔体温有明显波动。急性全身毒性实验结果表明人纳米脱钙骨基质复合重组人骨形态发生蛋白2材料符合国家相关规定,注射后未见小鼠出现明显毒性反应。人纳米脱钙骨基质复合重组人骨形态发生蛋白2材料植入兔体内的炎症反应明显轻于β-磷酸三钙植入后的反应。结果表明人纳米脱钙骨基质复合重组人骨形态发生蛋白2是一种无毒、组织相容性好、生物利用度高、炎症反应轻的纳米同种异体骨移植替代物。%BACKGROUND: Demineralized bone matrix and bone morphogenetic protein have been shown to have good bone induction, but less studies concerned nanometer demineralized bone matrix. Its physical and chemical properties and biological security are not yet clear. OBJECTIVE:On the basis of preparing the nanometer human demineralized bone

  9. Short bouts of mechanical loading are as effective as dexamethasone at inducing matrix production by human bone marrow Mesenchymal stem cell

    Directory of Open Access Journals (Sweden)

    A Sittichokechaiwut


    Full Text Available Dexamethasone (Dex is used widely to induce differentiation in human mesenchymal stem cells (hMSCs; however, using a pharmaceutical agent to stimulate hMSC differentiation is not the best choice for engineered tissue transplantation due to potential side-effects. The goal of the present study was to investigate the effects of dynamic compressive loading on differentiation and mineralized matrix production of hMSCs in 3D polyurethane scaffolds, using a loading regimen previously shown to stimulate mineralised matrix production of mature bone cells (MLO-A5. hMSCs were seeded in polyurethane scaffolds and cultured in standard culture media with or without Dex. Cell-seeded scaffolds were compressed at 5% global strain for 2 h on day 9 and then every 5 days in a media-filled sterile chamber. Samples were tested for mRNA expression of alkaline phosphatase (ALP, osteopontin (OPN, collagen type 1 (col 1 and runt-related transcription factor-2 (RUNX-212 h after the first loading, cell viability by MTS assay and alkaline phosphatase activity at day 12 of culture and cell viability, collagen content by Sirius red and calcium content by alizarin red at day 24 of culture. Neither Dex nor loading had significant effects on cell viability. Collagen content was significantly higher (p<0.01 in the loaded group compared with the non-loaded group in all conditions. There was no difference in ALP activity or the amount of collagen and calcium produced between the non-loaded group supplemented with Dex and the loaded group without Dex. We conclude that dynamic loading has the ability to stimulate osteogenic differentiation of hMSC in the absence of glucocorticoids.


    Directory of Open Access Journals (Sweden)

    Asmamaw Tegegne


    Full Text Available These days cost of building materials are continuously increasing and the conventional construction materials for this particular purpose become low and low. The weight of conventional construction materials particularly building block is heavy and costly due to particularly cement. Thus, the objective of this paper is to develop an alternative light weight, high strength and relatively cost effective building material that satisfy the quality standard used in the country. A bio-based polymer matrix composite material for residential construction was experimentally developed. Sugar cane bagasse, thermoplastics (polyethylene g roup sand and red ash were used as materials alternatively. Mixing of the additives,melting of the hermoplastics, molding and curing (dryingwere the common methods used on the forming process of the samples. Mechanical behavior evaluation (testing of the product was carried out. Totally 45 specimens were produced and three replicate tests were performed per each test type. Quality analysis was carried out for group B material using Ishikawa diagram. The tensile strength of group A specimen was approximately 3 times greater than that of group B specimens. The compression strength of group A specimens were nearly 2 times greater than group B. Comparing to the conventional building materials(concert block and agrostoneproduced in the country, which the compression strength is 7Mpa and 16Mpa respectively, the newly produced materials show much better results in which Group A is 25.66 Mpa and group B is 16.66 Mpa. energy absorption capacity of group A specimens was approximately 3 times better than that of group B. Water absorption test was carried out for both groups and both showed excellent resistivity. Group A composite material specimens, showed better results in all parameters.

  11. ATLAS DBM Module Qualification

    Energy Technology Data Exchange (ETDEWEB)

    Soha, Aria [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Gorisek, Andrej [J. Stefan Inst., Ljubljana (Slovenia); Zavrtanik, Marko [J. Stefan Inst., Ljubljana (Slovenia); Sokhranyi, Grygorii [J. Stefan Inst., Ljubljana (Slovenia); McGoldrick, Garrin [Univ. of Toronto, ON (Canada); Cerv, Matevz [European Organization for Nuclear Research (CERN), Geneva (Switzerland)


    This is a technical scope of work (TSW) between the Fermi National Accelerator Laboratory (Fermilab) and the experimenters of Jozef Stefan Institute, CERN, and University of Toronto who have committed to participate in beam tests to be carried out during the 2014 Fermilab Test Beam Facility program. Chemical Vapour Deposition (CVD) diamond has a number of properties that make it attractive for high energy physics detector applications. Its large band-gap (5.5 eV) and large displacement energy (42 eV/atom) make it a material that is inherently radiation tolerant with very low leakage currents and high thermal conductivity. CVD diamond is being investigated by the RD42 Collaboration for use very close to LHC interaction regions, where the most extreme radiation conditions are found. This document builds on that work and proposes a highly spatially segmented diamond based luminosity monitor to complement the time segmented ATLAS Beam Conditions Monitor (BCM) so that when Minimum Bias Trigger Scintillators (MTBS) and LUCID (LUminosity measurement using a Cherenkov Integrating Detector) have difficulty functioning the ATLAS luminosity measurement is not compromised.

  12. ATLAS DBM Module Qualification

    Energy Technology Data Exchange (ETDEWEB)

    Soha, Aria [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Gorisek, Andrej [J. Stefan Inst., Ljubljana (Slovenia); Zavrtanik, Marko [J. Stefan Inst., Ljubljana (Slovenia); Sokhranyi, Grygorii [J. Stefan Inst., Ljubljana (Slovenia); McGoldrick, Garrin [Univ. of Toronto, ON (Canada); Cerv, Matevz [European Organization for Nuclear Research (CERN), Geneva (Switzerland)


    This is a technical scope of work (TSW) between the Fermi National Accelerator Laboratory (Fermilab) and the experimenters of Jozef Stefan Institute, CERN, and University of Toronto who have committed to participate in beam tests to be carried out during the 2014 Fermilab Test Beam Facility program. Chemical Vapour Deposition (CVD) diamond has a number of properties that make it attractive for high energy physics detector applications. Its large band-gap (5.5 eV) and large displacement energy (42 eV/atom) make it a material that is inherently radiation tolerant with very low leakage currents and high thermal conductivity. CVD diamond is being investigated by the RD42 Collaboration for use very close to LHC interaction regions, where the most extreme radiation conditions are found. This document builds on that work and proposes a highly spatially segmented diamond-based luminosity monitor to complement the time-segmented ATLAS Beam Conditions Monitor (BCM) so that, when Minimum Bias Trigger Scintillators (MTBS) and LUCID (LUminosity measurement using a Cherenkov Integrating Detector) have difficulty functioning, the ATLAS luminosity measurement is not compromised.

  13. [Actin cytoskeleton organization and spreading of bone marrow stromal cells and cartilage cells during their combined and independent cultivation on different extracellular matrix proteins]. (United States)

    Sakhenberg, E I; Nikolaenko, N S; Pinaev, G P


    To clarify the mutual influence of bone marrow stromal cells (BMSCs) and cartilage cells we studied the organization of their actin cytoskeleton and cell spreading on different extracellular matrix proteins--laminin 2/4, collagen type I or fibronectin. It has been shown that the most pronounced difference in morphological characteristics of the cells such as their form, size and actin cytoskeleton organization occur in the case of interaction with fibronectin. So, after separate brief incubation of both cell types on fibronectin, the average area of BMSCs spreading was about 4 times greater than the area of the cartilage cell spreading. However, in the co-culture of these cells in a ratio of 1:1, the average jointed spreading area on fibronctin was nearly 1.5 times less than the theoretically calculated. To determine the nature of exposure of the cells to each other we have studied spreading of these cells in the media conditioned by another cell type. We have found that the area of BMSC's spreading in the medium conditioned by cartilage cells is markedly smaller than the area of spreading of the same cells in the control medium. These data suggest that the cartilage cells secrete factors that reduce BMSC's spreading.

  14. The application of acellular dermal matrix combined with coralline hydroxyapatite in guided bone regeneration%异种脱细胞真皮基质联合珊瑚羟基磷灰石在GBR术中的应用

    Institute of Scientific and Technical Information of China (English)

    汪竹红; 康博; 黄达鸿; 管红雨; 温玉洁; 林天赐; 林丽娥


    Objective: To evaluate the clinical effectiveness of acellular dermal matrix combined with coralline hydroxyapatite for guided bone regeneration. Methods: 17 patients with 27 lost teeth were included in this study. 10 anterior lost teeth area with the alveolar bone thickness about 4mm was placed ankylos implants using bone condensing technique followed by guided bone generation. The other lost teeth area with bone defect was placed ankylos implants using routine method followed by GBR. 6-8 months later, the second-stage operation was performed and the condition of the new bone was observed. Results: All implants showed good osseointegration and were covered by alveolar bone except one implant whose labial neck about 1.5mm height wasn't covered by bone. Conclusion:Acellular dermal matrix combined with coralline hydroxyapatite can achieve good bone formation in guided bone regeneration.%目的:评价异种脱细胞真皮基质联合珊瑚羟基磷灰石在引导骨组织再生术中的应用效果。方法:17例共27颗牙缺失患者作为研究对象,其中10颗上前牙牙槽骨宽度约4mm的延期种植先行骨挤压术植入种植体再行GBR术,其余12颗延期即刻种植上前牙及5颗环状骨缺损后牙常规植入种植体后行GBR术。6-8m后观察成骨效果。结果:除一例患者右上侧切牙植体颈部唇侧暴露约1.5mm左右,其余患者植体均被新生骨包绕,成骨效果显著。结论:异种脱细胞真皮基质联合珊瑚羟基磷灰石在牙种植术中引导骨组织再生效果良好。

  15. Xeno-free culture condition for human bone marrow and umbilical cord matrix-derived mesenchymal stem/stromal cells using human umbilical cord blood serum (United States)

    Esmaeli, Azadeh; Moshrefi, Mojgan; Shamsara, Ali; Eftekhar-vaghefi, Seyed Hasan; Nematollahi-mahani, Seyed Noureddin


    Background: Fetal bovine serum (FBS) is widely used in cell culture laboratories, risk of zoonotic infections and allergic side effects create obstacles for its use in clinical trials. Therefore, an alternative supplement with proper inherent growth-promoting activities is demanded. Objective: To find FBS substitute, we tested human umbilical cord blood serum (hUCS) for proliferation of human umbilical cord matrix derived mesenchymal stem cells (hUC-MSCs) and human bone marrow-derived mesenchymal cells (hBM-MSCs). Materials and Methods: Umbilical cord blood of healthy neonates, delivered by Caesarian section, was collected and the serum was separated. hUC-MSCs and hBM-MSCs were isolated and characterized by assessment of cell surface antigens by flow cytometry, alkaline phosphatase activity and osteogenic/adipogenic differentiation potential. The cells were then cultured in Iscove's Modified Dulbecco's Medium (IMDM) by conventional methods in three preparations: 1- with hUCS, 2- with FBS, and 3- without serum supplements. Cell proliferation was measured using WST-1 assay, and cell viability was assessed by trypan blue staining. Results: The cells cultured in hUCS and FBS exhibited similar morphology and mesenchymal stem cells properties. WST-1 proliferation assay data showed no significant difference between the proliferation rate of either cells following hUCS and FBS supplementation. Trypan blue exclusion dye test also revealed no significant difference for viability between hUCS and FBS groups. A significant difference was detected between the proliferation rate of stem cells cultured in serum-supplemented medium compared with serum-free medium. Conclusion: Our results indicate that human umbilical cord serum can effectively support proliferation of hBM-MSCS and hUC-MSCs in vitro and can be used as an appropriate substitute for FBS, especially in clinical studies. PMID:27738658

  16. Evaluation of the effectiveness of enamel matrix derivative, bone grafts, and membrane in the treatment of mandibular Class II furcation defects. (United States)

    Jaiswal, Ritika; Deo, Vikas


    The combination of osseous graft with barrier membrane and enamel matrix protein derivative (EMD) has the potential to result in a synergistic effect. Therefore, the aim of this study was to evaluate the effectiveness of EMD in combination with demineralized freeze-dried bone allograft (BG) and bioresorbable membrane (Biomesh) in the treatment of human mandibular Class II furcation defects over a period of 12 months. Thirty patients with chronic periodontitis and a single Class II furcation defect on the buccal or lingual surface of mandibular teeth were included. The clinical parameters evaluated were probing pocket depth (PPD), horizontal probing depth (HPD), vertical relative attachment level (V-RAL), and relative gingival margin level (RGML). three groups were created based on treatment method: EMD + BG + guided tissue regeneration (GTR), BG + GTR, and open flap debridement (OFD). All three groups showed a statistically significant PPD reduction of 1.74 ± 1.00 mm, 0.81 ± 0.31 mm, and 0.46 ± 0.52 mm at 12 months postsurgery. EMD + BG + GTR showed a significantly greater PPD reduction compared with BG + GTR, as well as OFD. EMD + BG + GTR showed a statistically significant vertical clinical attachment gain of 2.12 ± 1.07 mm at 12 months compared with BG + GTR as well as OFD. Significant reductions in mean HPD were observed for EMD + BG + GTR (2.10 mm) as well as BG + GTR (1.5 mm). The number of Class II furcation defects that closed or converted to Class I was greatest for EMD + BG + GTR. It can be concluded that EMD + BG + GTR resulted in a statistically significant reduction of PPD, V-RAL gain, and a nonsignificantly greater reduction of HPD compared to BG + GTR.

  17. Bone tumor (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  18. Increased serum and bone matrix levels of transforming growth factor {beta}1 in patients with GH deficiency in response to GH treatment

    DEFF Research Database (Denmark)

    Ueland, Thor; Lekva, Tove; Otterdal, Kari


    Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1 in vivo...

  19. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells.

    Directory of Open Access Journals (Sweden)

    Zhenya Gao

    Full Text Available All-trans retinoic acid (ATRA plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2 and matrix metalloproteinase 2 (MMP-2 and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19 cells.The effects of ATRA (concentrations from 10-9 to 10-5 mol/l on the expression of retinoic acid receptors (RARs in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10-9 to 10-5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR and enzyme-linked immunosorbent assay (ELISA. The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ.RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10-9 to 10-5 mol/l with a maximum effect observed at 10-6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10-6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135.ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated these cells to secrete BMP-2 and MMP-2.

  20. 应用99m锝-亚锡亚甲基二磷酸盐骨显像研究微波诱导高温对狗股骨缺损修复作用%99mTc-MDP Bone Scintigraphy for Study on Repair of Femoral Eefect Caused by Microwave-induced Hyperthermia in Dogs

    Institute of Scientific and Technical Information of China (English)

    赵廷宝; 范清宇; 张殿忠; 裘秀春; 文艳华


    Objective To investigated the biological procedure of allograft decalcified bone matrix(DBM)and bone cement(BC)combined with bovine bone morphogenetic protein (bBMP)used for the repair of femoral defect caused by microwave- induced hyperthermia in dogsby 99mTc- MDP bone scintigraphy.Method The canine femoral defect(length 25mm,width 10mm)was caused by microwave- induced hyperthermia(50℃ ,20minutes)and the composite material was implanted .Then the canine femurs were examined by 99mTc- MDP bone scintigraphy respectively at different postoperative time and the results were compared with that of X- ray photography and histological observation.Bone cement was implanted in the other femur as a contrast.Results It could be observed at the first and the second month that the radioisotope was gathered in the place where the composite material was implanted and the amount of radioisotope gathered in was the most abundant at the third month and it was lasted to the fourth month. That of the sixth month was decreased to that of the second month.The radiation count of the first, the second, the third the fourth and the sixth month were 93.9± 12.7, 110.7± 16.4,222.1± 24.0,201.3± 26.9 and 111.6± 20.7 respectively,and the count of the third month and the fourth month were more than that of the first, the second and the sixth month(P<0.01).Conclusion The composite material could be remodeled easily and the new bone could be formed by the induction of bBMP. So it could be merged with the normal bone.While the 99mTc- MDP bone scintigraphy is the object and reliable index to determine the biological procedure of the composite material in dogs.

  1. Bone graft materials in fixation of orthopaedic implants in sheep

    DEFF Research Database (Denmark)

    Babiker, Hassan


    Bone graft is widely used within orthopaedic surgery especially in revision joint arthroplasty and spine fusion. The early implant fixation in the revision situation of loose joint prostheses is important for the long-term survival. Bone autograft has been considered as gold standard in many...... the risk of bacterial contamination and disease transmission as well as non-union and poor bone quality. Other bone graft and substitutes have been considered as alternative in order to improve implant fixation. Hydroxyapatite and collagen type I composite (HA/Collagen) have the potential in mimicking...... bone and includes bone collagen, morphogenetic proteins and growth factors. The combination of DBM with CB and with allograft might improve the healing potential of these grafts around non-cemented orthopaedic implants and thereby the implant fixation. Study I investigates the effect of HA...

  2. Clinical evaluation of the efficacy of a GTR membrane (HEALIGUIDE® and demineralised bone matrix (OSSEOGRAFT® as a space maintainer in the treatment of Miller′s Class I gingival recession

    Directory of Open Access Journals (Sweden)

    S Nanditha


    Full Text Available Background: Periodontal plastic surgical procedures aimed at coverage of exposed root surface have evolved into routine treatment modalities. The present study was designed to evaluate the effectiveness and predictability of using a collagen barrier along with a demineralized bone matrix in the treatment of recession defects in a single surgical procedure. Materials and Methods: Seventeen patients with Miller′s class I recession were treated with a combination of a collagen barrier used along with a bone graft and coronally advanced flap technique. Clinical parameters were recorded at baseline, 3 months, 6 months, and 9 months. Results: The study showed a highly significant reduction in the recession depth (70.29 ± 21.96% at the end of the study. This study showed that the use of this technique for recession coverage is highly predictable and highly esthetic root coverage can be obtained.

  3. Area-Efficient 60 GHz +18.9 dBm Power Amplifier with On-Chip Four-Way Parallel Power Combiner in 65-nm CMOS (United States)

    Farahabadi, Payam Masoumi; Basaligheh, Ali; Saffari, Parvaneh; Moez, Kambiz


    This paper presents a compact 60-GHz power amplifier utilizing a four-way on-chip parallel power combiner and splitter. The proposed topology provides the capability of combining the output power of four individual power amplifier cores in a compact die area. Each power amplifier core consists of a three-stage common-source amplifier with transformer-coupled impedance matching networks. Fabricated in 65-nm CMOS process, the measured gain of the 0.19-mm2 power amplifier at 60 GHz is 18.8 and 15 dB utilizing 1.4 and 1.0 V supply. Three-decibel band width of 4 GHz and P1dB of 16.9 dBm is measured while consuming 424 mW from a 1.4-V supply. A maximum saturated output power of 18.3 dBm is measured with the 15.9% peak power added efficiency at 60 GHz. The measured insertion loss is 1.9 dB at 60 GHz. The proposed power amplifier achieves the highest power density (power/area) compared to the reported 60-GHz CMOS power amplifiers in 65 nm or older CMOS technologies.

  4. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination. (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G


    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  5. Species identification by analysis of bone collagen using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. (United States)

    Buckley, Michael; Collins, Matthew; Thomas-Oates, Jane; Wilson, Julie C


    Species identification of fragmentary bone, such as in rendered meat and bone meal or from archaeological sites, is often difficult in the absence of clear morphological markers. Here we present a robust method of analysing genus-specific collagen peptides by mass spectrometry simply by using solid-phase extraction (a C18 ZipTip) for peptide purification, rather than liquid chromatography/mass spectrometry (LC/MS). Analysis of the collagen from 32 different mammal species identified a total of 92 peptide markers that could be used for species identification, for example, in processed food and animal feed. A set of ancient (>100 ka@10 degrees C) bone samples was also analysed to show that the proposed method has applications to archaeological bone identification.

  6. Platelet-rich plasma diminishes calvarial bone repair associated with alterations in collagen matrix composition and elevated CD34+ cell prevalence. (United States)

    Giovanini, Allan Fernando; Deliberador, Tatiana Miranda; Gonzaga, Carla Castiglia; de Oliveira Filho, Marco Antonio; Göhringer, Isabella; Kuczera, Juliane; Zielak, João Cesar; de Andrade Urban, Cícero


    The interaction between platelets and both type I and III collagens plays an important role in modulating platelet adhesion and aggregation, also contributing to the chemotaxis of CD34+ cells. The interaction with type III collagen can maintain high levels of collagen and alter the biology of bone repair when the PRP is used. The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) and autograft on the presence of type III and type I collagens, the ratio between them, as well as the presence of CD34+ progenitor cells, while comparing these results by means of a histomorphometric analysis of the bone tissue. Four bone defects (8.0mm in diameter and 2.0mm in depth) were produced on the calvarium of 23 rabbits. The surgical defects were treated with either autogenous bone grafts, autogenous bone grafts with PRP and PRP alone. Animals were euthanized at 2, 4 or 6 weeks post-surgery. Histological, histomorphometric and immunohistochemical analyses were performed to assess repair time, as well as the expression of type I and III collagens, and number of progenitor CD34+ cells. Data were analyzed using the ANOVA and Student-Newman-Keuls test (alpha=5%). An enlarged granulation and medullary tissue areas in the PRP groups were observed. The use of PRP in this study hindered bone deposition, also enhanced type III to type I collagen ratio and the chemotaxis of CD34+ progenitor cells, similarly to a thrombogenic effect.

  7. 引导种植牙区骨再生的异种脱细胞真皮基质%Acellular dermal matrix used for guiding bone regeneration in the dental implant area

    Institute of Scientific and Technical Information of China (English)

    周静; 邓蔡; 张进锋


      BACKGROUND: Acel ular dermal matrix is a kind of prosthodontics membrane material which has been widely used due to the good biocompatibility. OBJECTIVE: To evaluate the effect of acel ular dermal matrix in guiding bone regeneration in the dental implant area. METHODS: Immunohistochemical staining was performed, and the microscope was used to observe the microstructure and cel compatibility of acel ular dermal matrix, in order to evaluate the feasibility of acel ular dermal matrix in guiding bone regeneration. The dental implantation patients who received bone regeneration with acel ular dermal matrix were fol owed-up to evaluate the osteogenesis effect and the effect on soft tissue defects. Then, the effects of Bio-Gide membrane and Bot medical col agen membrane on guiding bone regeneration were compared. RESULTS AND CONCLUSION: The microstructure of acel ular dermal matrix showed there was basement membrane surface and tissue surface. The stylode-like structure and hair fol icle could be observed on the basement membrane surface and the tissue surface was scaly structure, and acel ular dermal matrix had no influence on the proliferation activity osteoblast-like cel s and the alkaline phosphatase activity, but had good cel compatibility. The clinical researches showed that acel ular dermal matrix used in dental implantation was effective for bone regeneration, and there was no significant difference in the effect on guiding bone regeneration when compared with Bio-Gide membrane and Bot medical col agen membrane. The acel ular dermal matrix had good bone regeneration effect in repairing soft tissue deficiencies after bone augmentation.%  背景:异种脱细胞真皮基质属于口腔修复膜材料,因具有良好的生物相容性而被广泛应用。目的:评价异种脱细胞真皮基质在牙区引导牙种植骨再生的效果。方法:以免疫组化染色后显微镜观察异种脱细胞真皮基质的显微结构和细胞相容性,评


    Institute of Scientific and Technical Information of China (English)

    张育敏; 李晶; 牛晓军; 刘建春; 王珏; 高岚


    目的 探讨超临界CO2法制备的聚乳酸(poly lactic acid,PLA)/骨基质明胶(bone matrix gelatin, BMG)多孔复合材料的生物相容性,为其下一步骨缺损修复奠定基础.方法 取小鼠成骨前体细胞MCT3T-E1细胞,分别与PLA/BMG多孔复合材料和PLA材料的浸提液培养7d,每天采用MTT法测定细胞增殖率并进行细胞毒性分级.将PLA/BMG多孔复合材料与MC3T3-E1细胞复合培养,1、3、5d于倒置相差显微镜下观察细胞生长及与材料贴附情况,5d时取材行扫描电镜观察细胞贴附情况.将PLA材料(PLA组)及PLA/BMG多孔复合材料(PLA/BMG组)分别植于15只Wistar大鼠背部两侧皮下,术后大体观察大鼠一般情况,2、4、8周取材行组织学观察,测量包膜厚度、炎性细胞数及血管面积.结果 体外细胞毒性检测示,培养1 ~7 d PLA/BMG组细胞增殖率均达100%以上,细胞毒性均为0级;而PLA组除1、3、5、6d细胞毒性为0级外,2、4、7d细胞增殖率均低于100%,细胞毒性级为1级.PLA/BMG多孔复合材料与细胞复合培养,可见随时间延长细胞逐渐长入材料孔隙内,细胞形态良好.材料皮下植入后,大鼠均存活至实验完成,切口愈合良好;PLA组材料被纤维结缔组织所包裹,周围组织及材料内含有较多炎性细胞,结缔组织向材料内部生长缓慢;PLA/BMG组纤维组织包裹不明显,结缔组织易于向材料中心长入且其中炎性细胞少见.两组各时间点包膜厚度差异无统计学意义(P>0.05).PLA/BMG组2、4、8周炎性细胞数均显著低于PLA组(P<0.05),8周血管面积高于PLA组(P<0.05).结论 超临界CO2法制备的PLA/BMG多孔复合材料具有良好的细胞和组织相容性.

  9. Comparação histológica entre o osso desmineralizado e polímero de mamona sobre a regeneração óssea Histological comparison of demineralized bone matrix and the Ricinus communis polymer on bone regeneration

    Directory of Open Access Journals (Sweden)

    José Rodrigues Laureano Filho


    Full Text Available O presente estudo tem por objetivo analisar histologicamente o efeito de uma matriz óssea desmineralizada de origem humana e de uma resina poliuretana derivada do óleo da mamona sobre o processo de reparação óssea. MATERIAIS E MÉTODOS: Foram utilizados 24 coelhos e em cada calvária foram preparadas duas cavidades cirúrgicas, sendo uma do lado direito e a outra do lado esquerdo da sutura parietal. Os animais foram divididos em dois grupos. No grupo I, a cavidade experimental (lado direito foi preenchida com a matriz óssea desmineralizada de origem humana, enquanto no grupo II a cavidade experimental foi preenchida com a poliuretana derivada do óleo de mamona. As cavidades de controle foram preenchidas apenas com o sangue do animal. Os animais foram sacrificados nos períodos pós-operatórios de 4, 7 e 15 semanas. RESULTADOS: A análise histológica revelou que tanto o grupo controle quanto os grupos I e II apresentaram um aumento na neoformação óssea ao longo do tempo, sendo que esta reparação se deu mais rapidamente no grupo controle, mesmo mostrando diminuição importante na espessura. CONCLUSÕES: Ambos os materiais apresentaram-se biocompatíveis, sendo a poliuretana reabsorvida mais tardiamente e considerada de melhor resultado em relação ao outro material empregado.Aim the aim of the present study is to make a histologic analysis the effects of a human demineralized bone matrix and a polyurethane resin derived from the Ricinus communis, on bone regeneration process. MATERIALS AND METHODS: For this, 24 rabbits were submitted to two surgical calvaria bone defects, one on the right and another on the left side of the parietal suture. The animals were divided in two groups. In group I the experimental defect (right side was treated with a human demineralized bone matrix, while in group II the experimental cavity was treated with the polyurethane resin derived from Ricinus communis. The control defects were filled with the

  10. Tumores ósseos benignos e lesões ósseas Pseudotumorais: tratamento atual e novas tendências Benign bone tumors and tumor-like bone lesions: treatment update and new trends

    Directory of Open Access Journals (Sweden)

    José Marcos Nogueira Drumond


    , which have ossified bone lesions caused by fibrous dysplasia. Aneurismal bone cyst has been treated with sclerosing agents by percutaneous injection, yielding good results. Adjuvants allow joint salvage, maintenance of movements and function, with low rates of recurrence. Among them, the most used ones are bone cement (PMMA, phenol, nitrogen-based cryotherapy, hydrogen peroxide, ethanol and radiotherapy. New methods of treatment include thermal ablation with radiofrequency and laser, mainly utilized for treating osteoid osteoma. Arthroscopy allows resection of benign intra-joint lesions and assists the surgery of subchondral tumors. A great advance is the utilization of synthetic bone substitutes, which are a mixture of osteoinductive growth factors and osteoconductive ceramics, and have presented comparable results to autogenous bone grafts. There is a recent trend for closed treatments, with percutaneous injection of demineralized bone matrix (DBM and calcium sulfate. Autogenous cancellous bone graft remains as the gold standard. Vascularized fibula graft, on the other hand, incorporates faster in the treatment of large destructive lesions. Also, allogenic cortical support allows structural augmentation for aggressive tumors. Freeze-dried allografts are used to fill contained defects and as expanders of autografts. Joint endoprosthesis may be used in large destructive lesions of the distal femur, hip and shoulder.

  11. Detection of irradiated ingredients included in low quantity in non-irradiated food matrix. 1. Extraction and ESR analysis of bones from mechanically recovered poultry meat. (United States)

    Marchioni, Eric; Horvatovich, Péter; Charon, Helène; Kuntz, Florent


    Protocol EN 1786 for the detection of irradiated food by electron spin resonance (ESR) spectroscopy was not conceived for the detection of irradiated bone-containing ingredients included in low concentration in non-irradiated food. An enzymatic hydrolysis method, realized at 55 degrees C, has been developed for the extraction of the bone fraction. When followed by a purification of the extracts by an aqueous solution of sodium polytungstate, this method made possible the detection of irradiated mechanically recovered poultry meat at very low inclusions (0.5%, wt/wt by ESR) in various meals (quenelles and precooked meals).

  12. Clinical application of heterogeneous acellular dermal matrix used in alveolar bone grafting%异种脱细胞真皮基质膜在齿槽裂植骨术中的临床应用

    Institute of Scientific and Technical Information of China (English)

    李可兴; 刘曙光


    Objective To observe the effect of bone repair and evaluate its esthetic outcome with heterogeneous acellular dermal matrix cover the alveolar cleft bone grafting area in the alveolar cleft operation.Methods In 67 cases,unilateral cleft palate,were treated by alveolar cleft conventional surgical method.Cancellous iliac bone grafting were control group,heterogeneous acellular dermal matrix cover the alveolar cleft bone grafting area were treatment group.Radiographs was taken at 1 st,3 rd,6 th,12 th,18 th,24 th month postoperatively to observe the bone regeneration alveolar cleft zone.Results The alveolar cleft graft area new bone formation with Ⅰ,Ⅱ,Ⅲ,Ⅳ grade after 6 months in control group was 15,11,9,6 cases and in treatment group was 13,9,3,1 case.The graft survival rate and success rate (97.8%,84.3%) of treatment group were higher than that of control group (84.5%,63.7%),the difference was statistically significant (P < 0.05).Conclusion The successful rate of operation could be warranted,by the joint application of autogenous iliac bone grafts and heterogeneous acellular dermal matrix in the alveolar cleft operation.%目的 在齿槽裂手术中,将异种脱细胞真皮基质膜覆盖齿槽裂植骨区,观察新骨形成状况,评价植骨修复效果.方法 选择67例单侧齿槽裂患者,按治疗方法不同分为对照组和试验组.对照组单纯应用髂骨骨松质移植41例,试验组应用异种脱细胞真皮基质膜加髂骨骨松质移植26例.术后1,3,6,12,18,24个月随访,X线片观察齿槽裂植骨区新骨生成情况.结果 对照组病例术后6个月齿槽裂植骨区新骨形成Ⅰ,Ⅱ,Ⅲ,Ⅳ级分别为15,11,9,6例,齿槽裂植骨成活率为84.5%,临床成功率为63.7%.而试验组病例植骨区新骨形成Ⅰ,Ⅱ,Ⅲ,Ⅳ级分别为13,9,3,1例.齿槽裂植骨成活率为97.8%,临床成功率为84.3%.两组植骨成活率、临床成功率比较差异有统计学意义(P<0.05).结论 自体髂骨加异

  13. Bone scintiscanning updated. (United States)

    Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I


    Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

  14. Synthesis and characterization of a nanostructured matrix hydroxyapatite ceramic bone reconstruction; Sintese e caracterizacao de uma matriz ceramica nanoestruturada de hidroxiapatita para reconstituicao ossea

    Energy Technology Data Exchange (ETDEWEB)

    Correa, P.; Camargo, N.H.A.; Silva, D.F. [Universidade do Estado de Santa Catarina (PGCEM/UDESC), SC (Brazil). Programa de Pos-Graduacao em Ciencia e Engenharia de Materiais


    The nanostructured ceramics have been shown promise as biomaterials for bone reconstruction. Among calcium phosphates, hydroxyapatite Ca/P ratio = 1.67 mol stands out because of its crystallographic similarity with the mineral bone phase and biocompatibility. This work was based on synthesis and characterization of a nanostructured hydroxyapatite for use in reconstituting bone tissue. The synthesis method for obtaining the bioceramic powder occurred at process of dissolution/precipitation, involving CaO solid/liquid and phosphoric acid required for forming the composition of Ca/P = 1.67 mole. The material recovered from the synthesis was calcined at 900 ° C/2h, providing the hydroxyapatite powder nanometer. This was subjected to mechanical fragmentation process in mill attritor, providing a hydroxyapatite with modified surface morphology. The results presented relate to morphological characterization studies (SEM), mineralogical (XRD), chemical (FTIR) and particle size distribution, using the laser particle size analysis method. Such results showed the formation of hydroxyapatite phase and morphology satisfactory for use in reconstituting bone tissue.

  15. Old age and the associated impairment of bones' adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle. (United States)

    Galea, Gabriel L; Meakin, Lee B; Harris, Marie A; Delisser, Peter J; Lanyon, Lance E; Harris, Stephen E; Price, Joanna S


    In old animals, bone's ability to adapt its mass and architecture to functional load-bearing requirements is diminished, resulting in bone loss characteristic of osteoporosis. Here we investigate transcriptomic changes associated with this impaired adaptive response. Young adult (19-week-old) and aged (19-month-old) female mice were subjected to unilateral axial tibial loading and their cortical shells harvested for microarray analysis between 1h and 24h following loading (36 mice per age group, 6 mice per loading group at 6 time points). In non-loaded aged bones, down-regulated genes are enriched for MAPK, Wnt and cell cycle components, including E2F1. E2F1 is the transcription factor most closely associated with genes down-regulated by ageing and is down-regulated at the protein level in osteocytes. Genes up-regulated in aged bone are enriched for carbohydrate metabolism, TNFα and TGFβ superfamily components. Loading stimulates rapid and sustained transcriptional responses in both age groups. However, genes related to proliferation are predominantly up-regulated in the young and down-regulated in the aged following loading, whereas those implicated in bioenergetics are down-regulated in the young and up-regulated in the aged. Networks of inter-related transcription factors regulated by E2F1 are loading-responsive in both age groups. Loading regulates genes involved in similar signalling cascades in both age groups, but these responses are more sustained in the young than aged. From this we conclude that cells in aged bone retain the capability to sense and transduce loading-related stimuli, but their ability to translate acute responses into functionally relevant outcomes is diminished.

  16. Function of osteocytes in bone. (United States)

    Aarden, E M; Burger, E H; Nijweide, P J


    Although the structural design of cellular bone (i.e., bone containing osteocytes that are regularly spaced throughout the bone matrix) dates back to the first occurrence of bone as a tissue in evolution, and although osteocytes represent the most abundant cell type of bone, we know as yet little about the role of the osteocyte in bone metabolism. Osteocytes descend from osteoblasts. They are formed by the incorporation of osteoblasts into the bone matrix. Osteocytes remain in contact with each other and with cells on the bone surface via gap junction-coupled cell processes passing through the matrix via small channels, the canaliculi, that connect the cell body-containing lacunae with each other and with the outside world. During differentiation from osteoblasts to mature osteocyte the cells lose a large part of their cell organelles. Their cell processes are packed with microfilaments. In this review we discuss the various theories on osteocyte function that have taken in consideration these special features of osteocytes. These are 1) osteocytes are actively involved in bone turnover; 2) the osteocyte network is through its large cell-matrix contact surface involved in ion exchange; and 3) osteocytes are the mechanosensory cells of bone and play a pivotal role in functional adaptation of bone. In our opinion, especially the last theory offers an exciting concept for which some biomechanical, biochemical, and cell biological evidence is already available and which fully warrants further investigations.

  17. Crystal structure and luminescence spectra of Eu(DBM)3 4,4’-BIPY complex

    Institute of Scientific and Technical Information of China (English)

    王明昭; 金林培; 王哲民; 蔡冠梁; 张家骅


    The title complex,C55H41O6N2Eu,Mr=979.91,crystallizes in the monoclinic space group C2/cwith a=2.0413(4),b=2.5556(5),c=0.8926(3)nm,β=104.64(2)°,μ=14.44cm-1,T=295K and the finalR=0.043.The structure was solved by the heavy-atom method and refined by the full-matrix least-squarestechnique for 64 non-hydrogen atoms anisotropicaUy for 2180 reflections with I≥3σ(I).The title complexforms one-dimensional chains through C-C bonds between pyridine rings of 4,4’-bipyridine.The centralEu(Ⅲ)ion is coordinated to six oxygen atoms and two nitrogen atoms and its polyhedron is a distorted squareantiprism.The high resolution laser excited excitation and luminescence spectra show that the complex pos-sesses two Eu(Ⅲ)sites with the energy difference 39 cm-1of 5D0 levels in excited state.The radiationless energytransfer to a great extent between the two Eu(Ⅲ)sites and the dominant luminescence of Eu(Ⅲ)site withlower energy as the complex was excited have been supported by the selectively excited luminescence spectra,time-resolved luminescence spectra and selectively excited luminescence decay curves.

  18. Bone Biopsy (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging ... the limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided ...

  19. Guide bone regeneration with acellular dermal matrix in the maxillary anterior region%脱细胞真皮基质在上前牙GBR种植术中的临床研究

    Institute of Scientific and Technical Information of China (English)

    董强; 夏茜; 马洪; 王小玲; 杨红; 周成菊; 毛久凤


    目的:研究采用脱细胞真皮基质进行引导骨组织再生技术(GBR)并同期种植体植入的短期临床效果。方法29例上前牙脱细胞真皮基质进行 GBR并同期植入种植体,经软组织塑形后,完成最终上部结构。随访3~9个月,对种植体周围软硬组织进行评价。结果29例均获得良好骨整合,种植体无松动脱落。种植体周围软硬组织状态良好,美学效果满意。结论采用脱细胞真皮基质进行上前牙 GBR并同期植入种植体,短期内可获得较满意的临床效果。%Objective To evaluate the clinical and aesthetic results of guide bone regeneration(GBR)with acellular dermal matrix and implant placement in the maxillary anterior region.Methods 29 cases in the maxillary anterior region were selected carefully, GBR with acellular dermal matrix were processed and the implants were placed immediately.Impressions were taken after soft tis-sue development with provisional implant restorations and the definitive restorations were finished.The follow-up time was 3 to 9 months.The evaluated indexes involved marginal bone level at mesial and distal aspects of the implants,the interproximal papilla in-dex score of Jemt′s classification and the level of the labial soft-tissue margin.Results 29 cases were good bone integration,implant without mobility.Hard and soft tissue around implants in good condition,aesthetic effect was satisfied.Conclusion Using acellular dermal matrix to come forward to tooth GBR and implanted implant during this period,can obtain satisfactory clinical effect in the short term.

  20. Comparison of Demineralized Dentin and Demineralized Freeze Dried Bone as Carriers for Enamel Matrix Proteins in a Rat Critical Size Defect (United States)


    usually requires resorption prior to the formation of new bone. At this early two weeks stage it is possible that there was insufficient time for the... resorptive and formative processes to be completed. At eight weeks the mean RIDIT values for all groups were greater than 0.5, 49 indicating that the...non-collageous proteins of rat incisors dentin. Calcified Tissue Research 1978;25:169-178. Finkelman R., Mohan S., Jennings J., Taylor A., Jepsen S

  1. Microdamage induced calcium efflux from bone matrix activates intracellular calcium signaling in osteoblasts via L-type and T-type voltage-gated calcium channels. (United States)

    Jung, Hyungjin; Best, Makenzie; Akkus, Ozan


    Mechanisms by which bone microdamage triggers repair response are not completely understood. It has been shown that calcium efflux ([Ca(2+)]E) occurs from regions of bone undergoing microdamage. Such efflux has also been shown to trigger intracellular calcium signaling ([Ca(2+)]I) in MC3T3-E1 cells local to damaged regions. Voltage-gated calcium channels (VGCCs) are implicated in the entry of [Ca(2+)]E to the cytoplasm. We investigated the involvement of VGCC in the extracellular calcium induced intracellular calcium response (ECIICR). MC3T3-E1 cells were subjected to one dimensional calcium efflux from their basal aspect which results in an increase in [Ca(2+)]I. This increase was concomitant with membrane depolarization and it was significantly reduced in the presence of Bepridil, a non-selective VGCC inhibitor. To identify specific type(s) of VGCC in ECIICR, the cells were treated with selective inhibitors for different types of VGCC. Significant changes in the peak intensity and the number of [Ca(2+)]I oscillations were observed when L-type and T-type specific VGCC inhibitors (Verapamil and NNC55-0396, respectively) were used. So as to confirm the involvement of L- and T-type VGCC in the context of microdamage, cells were seeded on devitalized notched bone specimen, which were loaded to induce microdamage in the presence and absence of Verapamil and NNC55-0396. The results showed significant decrease in [Ca(2+)]I activity of cells in the microdamaged regions of bone when L- and T-type blockers were applied. This study demonstrated that extracellular calcium increase in association with damage depolarizes the cell membrane and the calcium ions enter the cell cytoplasm by L- and T-type VGCCs.

  2. In vitro fibrocartilage construction with bone marrow-derived mesenchymal stem cells-fully demineralized bone matrix%完全脱钙骨基质与骨髓间充质干细胞体外诱导构建组织工程纤维软骨

    Institute of Scientific and Technical Information of China (English)

    王鹏; 崔一民; 陈晓东


    背景:含有骨形态发生蛋白的完全脱钙骨基质可使骨髓间充质干细胞向软骨细胞分化并维持其软骨细胞的特性,在软骨发生过程中发挥重要作用.目的:将骨髓间充质干细胞与完全脱钙骨基质在体外诱导培养成纤维软骨组织以及观察培养体系与支架材料对细胞凋亡的影响.方法:采用全骨髓培养法分离培养猪骨髓间充质干细胞,取第1代骨髓间充质干细胞均匀接种到完全脱钙骨基质上,以含有转化生长因子β1、胰岛素样生长因子、地塞米松、抗坏血酸及体积分数10%FBS的高糖DMEM诱导培养液培养作为实验组,将单层诱导培养、单层基础培养的骨髓间充质干细胞、空白完全脱钙骨基质作为对照,于培养第1,2,3,4周进行大体形态观察以及Ⅰ、Ⅱ型胶原及聚集蛋白聚糖的RT-PCR定性检测;培养4周进行细胞凋亡检测.结果与结论:实验组可检测到Ⅰ型胶原的持续表达,Ⅱ型胶原及聚集蛋白聚糖表达逐渐增加.单层诱导培养组可检测到Ⅱ型胶原、聚集蛋白聚糖的表达及Ⅰ型胶原的持续表达,但表达量远低于实验组;实验组细胞凋亡率高于单层诱导培养组、单层基础培养组.说明转化生长因子β1、胰岛素样生长因子1体外诱导培养的骨髓间充质干细胞-完全脱钙骨基质可以表达特异性软骨基质,三维环境培养细胞外基质的表达量明显高于单层诱导培养;静态培养系统对三维培养的细胞凋亡有影响.%BACKGROUND:The fully demineralized bone matrix containing bone morphogenetic protein can induce bone marrow-derived mesenchymal stem cells (BMSCs) differentiate into cartilage cells, and keep it characteristics of cartilage cells. It plays an important role in the process of chondrogenesis.OBJECTIVE:To observe the complexes of BMSCs and fully demineralized bone matrix induced into the cartilage tissue in vitro and to detect the effects on cell apoptosis of

  3. Chondrogenic co-culture of allogenic decalcified bone matrix and bone marrow mesenchymal stem cells in the joint cavity:comparison of cartilage traits in the same joint cavity%同种异体脱钙骨与骨髓间充质干细胞关节腔内共培养:与同腔软骨性状的对比

    Institute of Scientific and Technical Information of China (English)

    徐斌; 周亮; 王英明; 钱三祥


    BACKGROUND:Loose bodies in the knee are found to survive for a long term and maintain certain histophysiological properties of cartilage tissue. Therefore, a bold hypothesis is proposed that the joint cavity may be a preferred environment for chondrocyte growth and development, supporting the concept of “intracavitary culture and intracavitary transplantation”. OBJECTIVE:To observe the trait difference of chondrogenic culture with alogenic decalcified bone matrix and bone marrow mesenchymal stem cels in the joint cavity orin vitro versus cartilage in the same cavity. METHODS:There were three groups in this experiment: inin vitro culture group, bone marrow mesenchymal stem cels from newborn rabbits undergoing chondrogenic culture were co-cultured with decalcified bone matrix from adult rabbitsin vitro; in intracavitary culture group, bone marrow mesenchymal stem cels from newborn rabbits undergoing chondrogenic culture were co-cultured with decalcified bone matrix from adult rabbits in the joint cavity; normal cartilage in the same cavity served as control group. RESULTS AND CONCLUSION: (1) After 12 weeks of culture, in the in vitro culture group, hematoxylin-eosin staining showed a smal amount of chondrocytes proliferated, with blue-stained nuclei; toluidine blue staining showed chondrocytes arranged disorderly, surrounded by a smal amount of matrix; Masson staining showed a smal positive area and irregular cellarrangement; type II colagen immunohistochemistry staining showed a few of yelow particles in the cytoplasm and extracelular matrix. (2) After 12 weeks of culture, in the intracavitary culture group, hematoxylin-eosin staining showed proliferation of chondrocytes with blue-stained nuclei; toluidine blue staining showed cluster-shaped arrangement of chondrocytes surrounded by the matrix with lacuna formation; Masson staining showed there were many positive cels with blue-stained matrix that arranged in a certain stress direction; immunohistochemical

  4. Bone Densitometry (Bone Density Scan) (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

  5. Biomechanical Evaluation of Rat Skull Defects, 1, 3, and 6 Months after Implantation with Osteopromotive Substances

    DEFF Research Database (Denmark)

    Jones, Leigh Robert; Thomsen, Jesper Skovhus; Mosekilde, Lis;


    Purpose: To compare the mechanical strength of surgically created and healed rat calvarial defects having been filled with three different osteopromotive substances: hydroxyapatite, intramembraneous demineralised bone matrix (DBM), and autogenous bone chips. Material: Sixty adult male Wistar rats...

  6. Matrix metalloproteinase-12 (MMP-12) in osteoclasts

    DEFF Research Database (Denmark)

    Hou, Peng; Troen, Tine; Ovejero, Maria C


    bone show MMP-12 expression in osteoclasts in calvariae and long bones. We also demonstrate that recombinant MMP-12 cleaves the putative functional domains of osteopontin and bone sialoprotein, two bone matrix proteins that strongly influence osteoclast activities, such as attachment, spreading......Osteoclasts require matrix metalloproteinase (MMP) activity and cathepsin K to resorb bone, but the critical MMP has not been identified. Osteoclasts express MMP-9 and MMP-14, which do not appear limiting for resorption, and the expression of additional MMPs is not clear. MMP-12, also called...

  7. Mechanisms of cancer metastasis to the bone

    Institute of Scientific and Technical Information of China (English)

    Juan Juan YIN; Claire B. POLLOCK; Kathleen KELLY


    Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecular components and mechanisms that are responsible for those interactions.

  8. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail:; Chapman, S


    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  9. TGF-β in cancer and bone: implications for treatment of bone metastases. (United States)

    Juárez, Patricia; Guise, Theresa A


    Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.

  10. Nanoscale deformation mechanisms in bone. (United States)

    Gupta, Himadri S; Wagermaier, Wolfgang; Zickler, Gerald A; Raz-Ben Aroush, D; Funari, Sérgio S; Roschger, Paul; Wagner, H Daniel; Fratzl, Peter


    Deformation mechanisms in bone matrix at the nanoscale control its exceptional mechanical properties, but the detailed nature of these processes is as yet unknown. In situ tensile testing with synchrotron X-ray scattering allowed us to study directly and quantitatively the deformation mechanisms at the nanometer level. We find that bone deformation is not homogeneous but distributed between a tensile deformation of the fibrils and a shearing in the interfibrillar matrix between them.

  11. Comparison of histomorphometry and [sup 85]Sr uptake in induced heterotopic bone in rats

    Energy Technology Data Exchange (ETDEWEB)

    Solheim, E.; Pinholt, E.M. (Institute for Surgical Research, Rikshospitalet, University of Oslo (Norway)); Bang, G. (Department of Oral Pathology and Forensic Odontology, University of Bergen (Norway)); Sudmann, E. (Hagavik Orthopedic Hospital, University of Bergen (Norway))


    Heterotopic bone formation in the abdominal muscle of 45 male 8-week-old Wistar rats induced by implantation of 5, 10, or 15 mg demineralized bone (DBM) powder was evaluated at 4 weeks by [sup 85]Sr uptake of the implants and area histomorphometry of the induced bone. Two indices of [sup 85]Sr uptake were calculated: the osteogenic index [(counts/min/mg implant)/(counts/min/mg os ilium)] and an index that we have called the osteoquantum index in which the weight of the implant is disregarded [(counts/min implant)/(counts/min/mg os ilium)]. The osteoquantum index showed a linear relationship to the area of the induced bone with a correlation coefficient (r) of 0.90. Only weak linear relationships were found between the osteogenic index and the area of the bone (r = 0.32) and between the osteogenic index and the osteoquantum index (r = 0.33). The osteoquantum index and the area of the induced bone both increased with increasing mass of implanted DBM, whereas the osteogenic index did not change. (au).

  12. Bone regeneration with cultured human bone grafts

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, T.; Nakajima, H. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology; Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Ohgushi, H.; Ueda, Y.; Takakura, Y. [Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Uemura, T.; Tateishi, T. [National Inst. for Advanced Interdisciplinary Research (NAIR), Ibaraki (Japan). Tsukuba Research Center; Enomoto, Y.; Ichijima, K. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology


    From 73 year old female patient, 3 ml of bone marrow was collected from the ilium. The marrow was cultured to concentrate and expand the marrow mesenchymal cells on a culture dish. The cultured cells were then subculturedeither on another culture dish or in porous areas of hydroxyapatite ceramics in the presence of dexamethasone and beta-glycerophosphate (osteo genic medium). The subculturedtissues on the dishes were analyzed by scanning electron microscopy (SEM), and subculturedtissues in the ceramics were implanted intraperitoneally into athymic nude mice. Vigorous growth of spindle-shaped cells and a marked formation of bone matrix beneath the cell layers was observed on the subculture dishes by SEM. The intraperitoneally implanted ceramics with cultured tissues revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the ceramics after 8 weeks. The in vitro bone formations on the culture dishes and in vivo bone formation in porous ceramics were detected. These results indicate that we can assemble an in vitro bone/ceramic construct, and due to the porous framework of the ceramic, the construct has osteogenic potential similar to that of autologous cancellous bone. A significant benefit of this method is that the construct can be made with only a small amount of aspirated marrow cells from aged patients with little host morbidity. (orig.)

  13. Immobilization of cross linked Col-I–OPN bone matrix protein on aminolysed PCL surfaces enhances initial biocompatibility of human adipogenic mesenchymal stem cells (hADMSC)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-Hee; Jyoti, Md. Anirban; Song, Ho-Yeon, E-mail:


    In bone tissue engineering surface modification is considered as one of the important ways of fabricating successful biocompatible material. Addition of biologically active functionality on the surfaces has been tried for improving the overall biocompatibility of the system. In this study poly-ε-caprolactone film surfaces have been modified through aminolysis and immobilization process. Collagen type I (COL-I) and osteopontin (OPN), which play an important role in osteogenesis, was immobilized onto PCL films followed by aminolysis treatment using 1,6-hexanediamine. Characterization of animolysed and immobilized surfaces were done by a number techniques using scanning electron microscopy (SEM), FT-IR, XPS, ninhydrin staining, SDS-PAGE and confocal microscopy and compared between the modified and un-modified surfaces. Results of the successive experiments showed that aminolysis treatment was homogeneously achieved which helped to entrap or immobilize Col-I–OPN proteins on surfaces of PCL film. In vitro studies with human adipogenic mesenchymal stem cells (hADMSC) also confirmed the attachment and proliferation of cells was better in modified PCL surfaces than the unmodified surfaces. SEM, confocal microscopy and MTT assay showed a significant increase in cell spreading, attachment and proliferations on the biofunctionalized surfaces compared to the unmodified PCL surfaces at all-time points indicating the success of surface biofunctionalization.

  14. 异种脱细胞真皮基质联合Bio-oss Collagen修复牙槽骨缺损的临床研究%Clinical application of acellular dermal matrix combined with Bio-oss Collagen to repair alveolar bone defects

    Institute of Scientific and Technical Information of China (English)

    杨春羚; 林良缘; 庄亮亮; 曾金表


    Objective: To investigate the effect of guided bone regeneration of acellular dermal matrix (ADM) combined with Bio -oss Collagen in alveolar defect. Method: 18 cases patients with severe alveolar bone resorption or damage were included.Bone defect after teeth extraction were very serious and the residual height and width of the alveolar bone were very limited in all these cases. Bio-oss Collagen was delivered into the sockets immediately after tooth extraction and covered with acellular dermal matrix membrane.Suture was removed 2 weeks postop.and the alveolar bone was regularly examined at the 3rd month. Result:New bone was found to form well in both physical examination and X-ray examination in all the 18 cases in the 3rd month.The height and width of the alveolar bone were significantly increased, providing a good bone condition for later FPD prosthetic treatment. Conclusion: Acellular dermal matrix combined with Bio-oss Collagen can improve the bone condition before restoration in clinical.%目的:通过引导骨再生(GBR)技术评估异种脱细胞真皮基质(acellular dermal matrix,ADM)与Bio-oss Collagen联合应用在修复牙槽骨缺损中的作用.方法:选择拔牙术后牙槽骨缺损严重的病例18例,拔牙同期在拔牙创植入Bio-oss Collagen并覆盖异种脱细胞真皮基质(海奥生物膜),术后2周拆线,3个月复诊并拍摄X线片.结果:术后经临床检查和X线检查,18例患者植骨区新骨形成良好,牙槽骨高度与丰满度明显改善,术区骨生成良好.结论:临床上异种脱细胞真皮基质与Bio-oss Collagen联合应用能有效修复牙槽骨缺损,改善修复前的骨条件.

  15. Exogenic Acellular Dermal Matrix in Guided Bone Regeneration of Dental Implant%异种脱细胞真皮基质在牙种植中引导骨再生的临床观察

    Institute of Scientific and Technical Information of China (English)

    韦丽萍; 左陈启; 王远勤


    Objective: To identify the clinical effect of a homemade exogenic acelluar dermal matrix as a barrier membrane in guide bone regeneration (GBR) of dental implants. Methods: Seventy eight dental implants/cases with limited bone-bed were divided into 2 groups, and treated by GBR technology with different barrier membrane. Experiment group (38 cases) used homemade exogenic acelluar dermal matrix, while in the control group (40 cases) Bio-Gide biofilm was used. Results: The difference of bone harvested in two groups was not statistically significant (P>0.05). All patients were healed with first intention and the healing rate of 2 groups were all 100%. One case complicated with facial swelling in control group, which was cured after anti-inflammatory and symptomatic treatment. There was no statistically significant between two groups in the demographic basic information, such as, adverse events, healing of incision, bone growth effect,and the like. Conclusion: This alternative homemade material should be considered in GBR by practitioners.%目的:观察国产异种脱细胞真皮基质修复膜作为屏障膜,在牙种植的引导骨再生中应用的临床效果.方法:78例需要引导骨再生的种植病例,均为前牙区或前磨牙区单牙或连续多牙位(3牙)缺失;其中前牙52颗,前磨牙26颗.缺牙区牙槽嵴主要为唇颊侧垂直性吸收,牙槽嵴顶宽度约1~3 mm,牙槽嵴水平吸收量在2 mm以内.分为2组,一组采用国产异种脱细胞真皮基质修复膜作为GBR技术的屏蔽膜(38例),另一组采用Bio-Gide生物膜作为对照(40例),比较二者的临床效果.结果:2组在骨生长效果之间的差异无统计学意义(P>0.05).2组患者切口均甲级愈合,切口愈合率均为100%.术后3 d,对照组有1例发生面部肿胀,经抗感染治疗和对症处理后缓解.本研究的其他病例均未出现感染等不良事件.结论:使用国产异种脱细胞真皮基质修复膜在牙种植术中进行骨引

  16. Sorption and degradation of selected organic UV filters (BM-DBM, 4-MBC, and OD-PABA) in laboratory water-sediment systems. (United States)

    Li, Sheng; Lu, Guanghua; Xie, Zhengxin; Ding, Jiannan; Liu, Jianchao; Li, Yi


    Organic UV filters that have been widely used in sunscreens and other personal care products have drawn much public concern because of their widespread contamination in the environment and their potential ecological risks to ecosystems. We selected three UV filters with high frequency of detection in the environment, namely butyl methoxy dibenzoylmethane (BM-DBM), ethylhexyl dimethyl p-aminobenzoate (OD-PABA), and 4-methylbenzylidene camphor (4-MBC), to investigate the sorption and degradation behaviors of these compounds in lab-scale water-sediment systems set up with natural water and sediment samples collected from different rivers and lakes (i.e., Yangtze River, Qinhuai River, Xuanwu Lake, and Mochou Lake) in Nanjing, East China. The sorption isotherms of these UV filters were well described by the Freundlich equation (C s   = K f  × C w (n) ). The sorption of three UV filters in four sediments was all linear or close to it, with n values between 0.92 and 1.13. A moderate to strong sorption affinity was observed for these compounds, and the sorption appears to be irreversible. For the combined sorption and degradation studies, sorption was found to be a primary mechanism for the disappearance of these UV filters from the water phase, and biotransformation appears to be the predominant factor for the degradation of the target compounds in the water-sediment systems. All three UV filters were found to be slightly resistant to the microbes in these systems, with DT50total and DT90total values-the disappearance time (DT) describes the time in which the initial total mass of the UV filters in the whole system is reduced by 50 and 90 %-ranging between 18 and 31 days and 68 and 101 days, respectively.

  17. Matriz óssea homóloga desmineralizada associada à medula óssea autógena fresca na artrodese vertebral dorsolateral lombar em coelhos Homologous demineralized bone matrix associated to autologous bone marrow in a rabbit dorsolateral lumbar vertebral fusion

    Directory of Open Access Journals (Sweden)

    D. Rizzo


    Full Text Available Foi avaliada a matriz óssea homóloga desmineralizada (MOD, associada à medula óssea autógena fresca (MO, na artrodese vertebral dorsolateral lombar em 24 coelhos (grupo 1, depositada sobre os processos transversos de L5-L6 previamente descorticados. Em outros nove coelhos (grupo-controle, foi realizada apenas a descorticação dos processos transversos e nas diferentes avaliações, foi observada insignificante reação periosteal local, sem união óssea. No grupo 1, às cinco semanas de pós-operatório, 87,5% dos animais apresentaram união (artrodese à palpação, seguido por 75 e 100% às sete e nove semanas, respectivamente. Os índices de artrodese aos RX foram de 50%, 62% e 75%, no mesmo período de avaliação. Histologicamente, às cinco semanas havia características de osteointegração da MOD com os processos transversos descorticados, de onde partiram os vasos sangüíneos que penetraram a matriz, e presença de ilhas de cartilagem no centro do enxerto. Nas semanas seguintes, a ossificação endocondral evoluiu e a MOD foi quase totalmente substituída por tecido ósseo trabecular, formando uma ponte de osso maduro entre e sobre os processos transversos adjacentes, propiciando ao segmento operado maior resistência mecânica em comparação aos segmentos adjacentes. A associação da MOD com a MO mostrou-se uma opção exeqüível e de baixo custo na artrodese vertebral dorsolateral lombar em coelhos.It was evaluated the homologous demineralized bone matrix (HDBM, associated with the fresh autogenous bone marrow (FABM, in the vertebral dorsolateral lumbar union in 24 rabbits (group 1, that was placed on the transverse processes of previously decorticated L5-L6 vertebrae. In other nine rabbits (control group, it was just accomplished the decortications of the transverse processes, which showed insignificant local periostial reaction, without bone union after different evaluations. In the group 1, after five weeks of

  18. 脱细胞真皮基质对骨质疏松大鼠骨缺损愈合影响%Effect of acellular dermal matrix on osteoporosis rats bone defect healing

    Institute of Scientific and Technical Information of China (English)

    王晓晗; 赵志国; 王智明; 王文茉; 张力平


    Objective To observe the characteristics and capabilities of acellular dermal matrix( ADM) in osteoporosis rats cranial parietal bone defect repair guided bone regeneration( GBR) ,to explore the biocompatibility and effects on bone re-generation. Methods A total of 26 SD female rats were randomly divided into the control group(Sham group:n=13)and the ovariectomized group(VOX group:n=13). Conventional breeding for 3 months after the surgery,after the success of the building,in skull of rats,there were 2 defective holes with 5 mm preparation on both sides of central line,one side was cov-ered with ADM,the other side was control blank( CK) . In Sham group,the CK side was Group A,the ADM cover side was Group B. In the CK side in OVX group was Group C,the ADM cover side was Group D. In 6 and 12 weeks postoperatively, the clinical features such as the bone defect healing,bone tissue HE and masson trichromatic dyeing,new bone lengths were compared,the mineralization rate,immunohistochemical method was to detect callus osteocalcin expression in different peri-ods. Results Among the gross observation experimental animals,there were 2 deaths caused by bowel bilges gas in. Other animals healed within a week without infection and wound dehiscence,visible sutures were not fallen off. 6 weeks after sur-gery,the blank defects naked eye obvious difference between the two groups,the defect area was covered with transparency, defect edge was clear. ADM cover side was with visible white ADM,defect edge was clear. After 12 weeks,there was no na-ked eye obvious difference between two groups of blank defect,the defect area was covered with transparency,defect edge was clear. ADM cover side with visible white ADM film was thinner,harder to hit,defect edge was obtuse. The tissue mor-phology observation 6 weeks when two groups of new bone gap defect was not obvious,the broken end by fibrous tissue pack-age. Sham group of bone defect end osteogenesis was dense, ADM retained membrane

  19. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice. (United States)

    Colnot, C; Huang, S; Helms, J


    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  20. Bone Material Properties in Osteogenesis Imperfecta. (United States)

    Bishop, Nick


    Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density-the quantity of mineral in relation to the quantity of matrix within a specific bone volume-and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment-largely improved architecture and possibly some macroscale toughening-and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales.

  1. Study of building an integrated annulus fibrosus-nucleus pulposus biphasic scaffold based on bone matrix gelatin and cartilage matrix%以骨基质明胶及软骨基质构建一体化纤维环-髓核双相支架的实验研究

    Institute of Scientific and Technical Information of China (English)

    伍耀宏; 徐宝山; 杨强; 马信龙; 夏群; 李秀兰; 胡永成; 张杨; 张春秋


    Objective To fabricate an integrated annulus fibrosus-nucleus pulposus biphasic scaffolds based on bone matrix gelatin and acellular cartilage matrix,and to detect its property and cell compatibility.Methods An integrated annulus fibrosus-nucleus pulposus biphasic scaffold was fabricated by the following steps: preparing the hollow bone matrix gelatin ring,injecting the acellular cartilage homogenate into the center of the bone matrix gelatin ring,and freeze drying.Sample slices were stained with Hoechst 33258,picrosirius and HE.The internal structure of the scaffold was observed under a scanning electron microscope.The porosity and water absorption of the scaffold were also evaluated.Compressive mechanical property under wet situation was tested.The annulus fibrosus and nucleus pulposus cells were isolated from sheep disc and separately implanted into the corresponding sites of the scaffold,and biocompatibility of the scaffold was evaluated by scanning electron microscope and live/dead cell staining.Results Hoechst 33258 staining showed no residual cells,picrosirius staining was positive,and HE staining showed two parts linked closely.Under scanning electron microscope,the scaffold had porous structure,and the average pore size was 401.4±13.1 μm for annulus fibrosus,and 112.4±21.8 μm for nucleus pulposus.The porosity and water absorption of the scaffold was 73.37%±2.56% and 655.7%±78.6%,respectively.The average compressive elastic modulus of the scaffold (49.06 ±15.57) kpa was smaller than that of the native disc (135.9±28.9) kPa.Scanning electron microscope showed cells adhered on the scaffold surface,with secreted matrix around them,and live/dead cells staining showed cells with good activity on scaffolds.Conclusion The integrated annulus fibrosus-nucleus pulposus scaffold based on bone matrix gelatin and cartilage matrix is an ideal artificial disc material,in view of well pore size,closely linked boundary,and good biocompatibility.%目的 以

  2. MKP1-dependent PTH modulation of bone matrix mineralization in female mice is osteoblast maturation stage specific and involves P-ERK and P-p38 MAPKs. (United States)

    Mahalingam, Chandrika D; Sampathi, Bharat Reddy; Sharma, Sonali; Datta, Tanuka; Das, Varsha; Abou-Samra, Abdul B; Datta, Nabanita S


    Limited information is available on the role of MAPK phosphatase 1 (MKP1) signaling in osteoblasts. We have recently reported distinct roles for MKP1 during osteoblast proliferation, differentiation, and skeletal responsiveness to parathyroid hormone (PTH). As MKP1 regulates the phosphorylation status of MAPKs, we investigated the involvement of P-ERK and P-p38 MAPKs in MKP1 knockout (KO) early and mature osteoblasts with respect to mineralization and PTH response. Calvarial osteoblasts from 9-14-week-old WT and MKP1 KO male and female mice were examined. Western blot analysis revealed downregulation and sustained expressions of P-ERK and P-p38 with PTH treatment in differentiated osteoblasts derived from KO males and females respectively. Exposure of early osteoblasts to p38 inhibitor, SB203580 (S), markedly inhibited mineralization in WT and KO osteoblasts from both genders as determined by von Kossa assay. In osteoblasts from males, ERK inhibitor U0126 (U), not p38 inhibitor (S), prevented the inhibitory effects of PTH on mineralization in early or mature osteoblasts. In osteoblasts from KO females, PTH sustained mineralization in early osteoblasts and decreased mineralization in mature cells. This effect of PTH was attenuated by S in early osteoblasts and by U in mature KO cells. Changes in matrix Gla protein expression with PTH in KO osteoblasts did not correlate with mineralization, indicative of MKP1-dependent additional mechanisms essential for PTH action on osteoblast mineralization. We conclude that PTH regulation of osteoblast mineralization in female mice is maturation stage specific and involves MKP1 modulation of P-ERK and P-p38 MAPKs.

  3. Bone scintigraphy in chondroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Humphry, A.; Gilday, D.L.; Brown, R.G.


    Scintigraphy in 3 patients with chondroblastoma showed that the tumors were hyperemic and avidly accumulated the radionuclide. These changes were also present in adjacent normal bone, but to a lesser degree. This suggests that radionuclide uptake in chondroblastoma is a function of the blood supply to the tumor rather than primary matrix extraction.

  4. Comparison of autologous ilium spongy bone combined with human decalcified dentinal matrix in alveolar process cleft bone grafting%脱钙人牙基质材料联合髂骨与单纯髂骨移植修复牙槽突裂的对比性研究

    Institute of Scientific and Technical Information of China (English)

    霍永力; 张雷; 王建华; 李华; 邢建峰; 孙志干; 陆立本; 刘英华


    group (13.3%), 1 case(2 sides) in class 4 group(6.7%). The overall survival rate of ABGR was 93.3%, and the clinical success rate was 80%. Conclusion: Ilium spongy bone combined with DDM is good for alveolar process cleft bone grafting. It is better to use decalcified dentinal matrix of human than autologous ilium spongy bone.

  5. Bone Markers (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  6. Bone scan (United States)

    ... legs, or spine fractures) Diagnose a bone infection (osteomyelitis) Diagnose or determine the cause of bone pain, ... 2015:chap 43. Read More Broken bone Metabolism Osteomyelitis Review Date 12/10/2015 Updated by: Jatin ...

  7. Bone Cancer (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  8. Bone Diseases (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  9. Altered matrix mineralization in a case of a sclerosing osteosarcoma. (United States)

    Hofstaetter, Jochen G; Roschger, Andreas; Puchner, Stephan E; Dominkus, Martin; Sulzbacher, Irene; Windhager, Reinhard; Klaushofer, Klaus; Roschger, Paul


    Little is known about the tumor matrix mineralization of highly sclerotic osteosarcoma. We used quantitative backscattered electron imaging (qBEI) to determine the Bone mineralization density distribution (BMDD) of a highly sclerosing osteosarcoma of the proximal tibia as well as adjacent normal bone of a 10-year-old girl following chemotherapy according to the EURAMOS-1 protocol. Data were compared to recently published normative reference data for young individuals. Backscattered electron imaging of the tumor region revealed a dense accumulation of mineralized tumor bone matrix (up to 90% of the medullar space). The BMDD was shifted tremendously towards higher matrix mineralization (CaMean +18.5%, CaPeak +22.5%, CaHigh +100 fold) compared to normal bone. Additionally the BMDD became much wider, indicating a higher heterogeneity in mineralization (CaWidth +40%). In contrast to lamellar bone, which mineralizes via a mineralization front, the mineralization of the tumor matrix starts by randomly distributed spots of mineral clusters fusing together to a highly mineralized non-lamellar bone matrix. We also found an altered BMDD of the patient's normal bone when compared with the reference BMDD of young individuals. In conclusion this high radiodensity region of the sclerosing sarcoma is not only due to the high amount of tumor matrix but also to its high mineralization density. Chemotherapy may lead to altered matrix mineralization of normal bone due to suppression of bone turnover. The mechanism of matrix mineralization in a sclerosing osteosarcoma warrants further studies.

  10. Transcutaneous Raman Spectroscopy of Bone (United States)

    Maher, Jason R.

    Clinical diagnoses of bone health and fracture risk typically rely upon measurements of bone density or structure, but the strength of a bone is also dependent upon its chemical composition. One technology that has been used extensively in ex vivo, exposed-bone studies to measure the chemical composition of bone is Raman spectroscopy. This spectroscopic technique provides chemical information about a sample by probing its molecular vibrations. In the case of bone tissue, Raman spectra provide chemical information about both the inorganic mineral and organic matrix components, which each contribute to bone strength. To explore the relationship between bone strength and chemical composition, our laboratory has contributed to ex vivo, exposed-bone animal studies of rheumatoid arthritis, glucocorticoid-induced osteoporosis, and prolonged lead exposure. All of these studies suggest that Raman-based predictions of biomechanical strength may be more accurate than those produced by the clinically-used parameter of bone mineral density. The utility of Raman spectroscopy in ex vivo, exposed-bone studies has inspired attempts to perform bone spectroscopy transcutaneously. Although the results are promising, further advancements are necessary to make non-invasive, in vivo measurements of bone that are of sufficient quality to generate accurate predictions of fracture risk. In order to separate the signals from bone and soft tissue that contribute to a transcutaneous measurement, we developed an overconstrained extraction algorithm that is based upon fitting with spectral libraries derived from separately-acquired measurements of the underlying tissue components. This approach allows for accurate spectral unmixing despite the fact that similar chemical components (e.g., type I collagen) are present in both soft tissue and bone and was applied to experimental data in order to transcutaneously detect, to our knowledge for the first time, age- and disease-related spectral

  11. 松质骨基质作为细胞载体应用于牙周组织工程的实验研究%A study on periodontal tissue engineering with cancellous bone matrix as the cell scaffold

    Institute of Scientific and Technical Information of China (English)

    鲁红; 田宇; 吴织芬


    目的 研究评价松质骨基质(CBM)作为细胞载体应用于牙周组织工程的可行性及意义.方法 将体外培养的犬自体牙周膜细胞(PDLCs)接种到CBM三维支架上,扫描电镜观察PDLCs在CBM支架上的生长、附着情况;同时,将PDLCs/CBM复合植入动物牙周组织缺损,以空白组及仅植入CBM组为对照组,术后8周观察评价其牙周组织的再生情况.结果 扫描电镜显示PDLCs在CBM上伸展充分,生长旺盛,而CBM具有良好的多孔网状结构.动物实验结果可见PDLCJs/CBM复合植入组较对照组有更多的新生牙骨质、新生牙周膜和新生牙槽骨生成,缺损处牙周组织几近完全再生,且未见上皮长人.结论 CBM可作为细胞载体用于牙周组织工程研究,有望用作牙周组织工程的支架材料.%Objective To estimate the feasibility of applying cancellous bone matrix (CBM) as the cell scaffold for periodontal tissue engineering. Methods Dog autogenous periodontal ligament cells (PDLCs) cultured in vitro were collected and seeded on the three-dimensional scaffolds of CBM, The growth of cells on the scaffolds was observed with scanning electronic microscope. Then the PDLCs/ CBM composites were transplanted into man-made periodontal defects,and the groups filled with nothing or filled with only CBM were the controls. The dogs were sacrificed 8 weeks later and the periodontium regeneration was observed histologically. Results Scanning electronic microscope showed the flourishing growth of cells on the CBM scaffolds which were in porous structure. The histological observation showed that the PDLCs/CBM group exhibited more new bone,new periodontal ligament and new cementum occupying the majority of the defects than the control groups,and epitheliums were not observed. Conclusions The study proves that CBM can be used as the cell scaffolds for periodontal tissue engineering.

  12. Parallel mechanisms suppress cochlear bone remodeling to protect hearing. (United States)

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara


    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  13. Experimental study on peri-implant bone regeneration by bone marrow stromal cells with Osx gene activated matrix%骨髓基质干细胞复合Osx基因活化材料促进种植体周围骨再生的实验研究

    Institute of Scientific and Technical Information of China (English)

    李大鲁; 黄国倩; 李肇元


    导作用,与不含Osx基质的对照组相比成骨速度更快,新生骨量更多,明显促进了骨组织再生。%Objective: To build the beagle dog peri-implant bone defect model, and construct Gene Activated Matrix (GAM)containing plasmid pcDNA3.1 flag-Osx and mixed with autologous Bone Marrow Stromal Cells (BMSC);to evaluate the effect of Osx gene activation technology on bone formation and minerali-zation. Methods: With the marrow extracted prior to operation, bone marrow stromal cells were culti-vated and plasmid pcDNA3.1 flag-Osx amplified. Fifteen male beagle dogs were randomly whilst evenly divided into three groups, with group 1 being a four-week group, group 2 as an eight-week group and group 3 a twelve-week group. The left mandibular 2nd and 4th premolar and the rihgt mandibular 2nd premolar were extracted, based on which the operations of trapezoidal incisions and bone defects were made. Each of the three bone defects was implanted with an OSSTEM GSII, and filled respectively with:Category A, Perioglas;Category B, Perioglas+BMSCs+empty vector pcDNA3.1flag;and Category C, Perioglas+BMSCs+pcDNA3.1flag-Osx. Each material was covered with Bio-Gide collagen membrane via Guided Bone Regeneration (GBR) technique. Finally in 4, 8, and 12 weeks after the operation, ani-mals in group 1, 2 and 3 were killed respectively to obtain the specimens. The specimens were analyzed by comparison with the control group utilizing histological, imageological, and histomorphometric mea-surements. Each index is weighted by Mean ±Standard deviation (X ±s). The index differences between groups at each time sample are analyzed using the statistical package SPSS 17.0 by one way analysis of variance (ANOVA). P<0.05 were considered statistically significant. Results:1. Sclerous tissue exami-nation. Newly formed bone appeared at every bone defect under tests, among which Group C has the richest new bones, Group B has less and Group A has the least. 2.Results from Micro

  14. 釉基质蛋白对猪骨髓基质细胞生物学特性的影响%Effects of Enamel Matrix Proteins on the Biological Activity of Porcine Bone Marrow Stromal Cells in Vitro

    Institute of Scientific and Technical Information of China (English)

    宋爱梅; 束蓉; 蒋欣泉; 张秀丽; 刘晓峰; 张文


    目的 研究釉基质蛋白(enamel matrix proteins,EMPs)对体外培养的猪骨髓基质细胞(bone marrow stromal cells,BMSCs)生物学特性的影响.方法 抽取猪髂骨骨髓,全血培养法获得骨髓基质细胞.培养液中EMPs的浓度分别为25、50、100、200ug/ml,以不加EMPs为对照.用比色法检测不同浓度EMPs对BMSCs粘附性的影响.通过计数预定视野中伸展的细胞数,计算BMSCs在1h、3.5h、6.5h的伸展率.MTT法测定各组细胞的增殖活性.结果 猪BMSCs在含有EMPs的培养液中生长良好.对照组以及不同浓度EMPs对细胞粘附性的影响无统计学差异.在1h、3.5h、6.5h,各组细胞的伸展率无显著不同.EMPs对BMSCs的促增殖作用呈浓度和时间依赖性,200ug/ml浓度的EMPs从实验的第三天开始显著促进猪BMSCs的增殖.结论 EMPs对体外培养的猪BMSCs的粘附性和伸展率无影响,200ug/ml浓度的EMPs可显著促进猪BMSCs增殖,提示可尝试联合应用EMPs和BMSCs修复牙周组织缺损.

  15. Determination of osteocalcin in meat and bone meal of bovine and porcine origin using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and high-resolution hybrid mass spectrometry. (United States)

    Balizs, Gabor; Weise, Christoph; Rozycki, Christel; Opialla, Tobias; Sawada, Stefanie; Zagon, Jutta; Lampen, Alfonso


    A method has been developed for determining the origin of meat and bone meal (MBM) by detecting species-specific osteocalcin (OC) using matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) and high-resolution hybrid mass spectrometry (HR-Q/TOF MS). The analysis is based on the detection of typical species-specific OC and its tryptic peptide fragments which differ in mass due to differences in the amino-acid sequences between species. After dissolving the MBM samples in EDTA buffer, purification after ultrafiltration was performed using two methods: solid-phase extraction using Zip-Tip C(18) or size exclusion coupled with reverse-phase chromatography. Fractions containing partially purified intact OC were analyzed using LC-Q/TOF and MALDI/TOF mass spectrometry. Species-specific OC was detected at the typical protonated and doubly protonated molecular ions. Furthermore, typical porcine- and bovine-derived tryptic fragments from MBM were detected after enzymatic digestion. In order to determine the underlying amino-acid sequences and to confirm the assignment to OC-derived peptides, MS/MS analysis was carried out. In conclusion, we were able to detect OC in bovine and porcine MBM with high sensitivity and the MS-based method described here by which total OC mass and marker peptides of digested OC are recorded can be used as an alternative approach to detect genus-specific differences in MBM and can be applied as a confirmatory method to mainly immunological osteocalcin screening methods.

  16. Determination of osteocalcin in meat and bone meal of bovine and porcine origin using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and high-resolution hybrid mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Balizs, Gabor, E-mail: [Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin (Germany); Weise, Christoph [Freie Universitaet Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, D-14195 Berlin (Germany); Rozycki, Christel; Opialla, Tobias; Sawada, Stefanie; Zagon, Jutta; Lampen, Alfonso [Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin (Germany)


    A method has been developed for determining the origin of meat and bone meal (MBM) by detecting species-specific osteocalcin (OC) using matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) and high-resolution hybrid mass spectrometry (HR-Q/TOF MS). The analysis is based on the detection of typical species-specific OC and its tryptic peptide fragments which differ in mass due to differences in the amino-acid sequences between species. After dissolving the MBM samples in EDTA buffer, purification after ultrafiltration was performed using two methods: solid-phase extraction using Zip-Tip C{sub 18} or size exclusion coupled with reverse-phase chromatography. Fractions containing partially purified intact OC were analyzed using LC-Q/TOF and MALDI/TOF mass spectrometry. Species-specific OC was detected at the typical protonated and doubly protonated molecular ions. Furthermore, typical porcine- and bovine-derived tryptic fragments from MBM were detected after enzymatic digestion. In order to determine the underlying amino-acid sequences and to confirm the assignment to OC-derived peptides, MS/MS analysis was carried out. In conclusion, we were able to detect OC in bovine and porcine MBM with high sensitivity and the MS-based method described here by which total OC mass and marker peptides of digested OC are recorded can be used as an alternative approach to detect genus-specific differences in MBM and can be applied as a confirmatory method to mainly immunological osteocalcin screening methods.

  17. Avaliação das metaloproteinases de matriz -2 e -9 em gatos com desmineralização óssea secundária à tirotoxicose induzida Evaluation of matrix metalloproteinases -2 and -9 in cats under bone demineralization secondary to induced thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    F.S. Costa


    Full Text Available Observou-se significativo aumento de atividade das formas ativas das metaloproteinases -2 e -9 em gatos com tirotoxicose induzida e desmineralização óssea. As formas pró e intermediária da metaloproteinase -2 elevaram-se com 14 dias de administração hormonal, porém, posteriormente, houve uma tendência de queda. Observou-se correlação negativa entre a forma ativa das metaloproteinases de matriz -2 e -9 e a densidade mineral óssea da extremidade distal do rádio. Os resultados sugerem aumento da degradação da matriz colágena secundária com a elevação dos hormônios tiroidianos.Significant increase of activity of active forms of matrix metalloproteinases -2 and -9 in cats under induced thyrotoxicosis and bone demineralization was observed. Pro and intermediated forms of matrix metalloproteinases -2 and -9 increased at 14 days of hormonal treatment, followed by decrease tendency. A negative correlation between active forms of matrix metalloproteinases -2 and -9 and bone mineral density of radius distal extremity was also observed. The results suggest an increase of collagen matrix degradation secondary to high levels of thyroid hormones.

  18. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to expressions of c-fos and c-jun products and bone matrix proteins: a clinicopathologic review and immunohistochemical study of c-fos, c-jun, type I collagen, osteonectin, osteopontin, and osteocalcin. (United States)

    Sakamoto, A; Oda, Y; Iwamoto, Y; Tsuneyoshi, M


    Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. We retrospectively studied clinicopathologic findings in 62 cases of fibrous dysplasia and 20 cases of osteofibrous dysplasia with regard to their anatomic location and histological appearance. From among these cases, the immunohistochemical expressions of c-fos and c-jun proto-oncogene products and bone matrix proteins of type I collagen, osteonectin, osteopontin, and osteocalcin were evaluated in 20 typical fibrous dysplasias and 17 osteofibrous dysplasias using paraffin sections, and these expressions were then assessed semiquantitatively. Microscopically, fibrous dysplasia showed various secondary changes, such as hyalinization, hemorrhage, xanthomatous reaction, and cystic change in 22 of the 62 cases (35%). This was a higher incidence than in osteofibrous dysplasia, in which only 2 of the 20 cases (10%) showed such changes. In the elderly fibrous dysplasia cases, the cellularity of fibroblast-like cells was rather low, and those cases were hyalinized. Almost all of the cases of fibrous dysplasia and osteofibrous dysplasia showed positive expressions of c-fos and c-jun products. The expressions of type I collagen and osteopontin showed no difference between fibrous dysplasia and osteofibrous dysplasia. Immunoreactivity for osteonectin in bone matrix was detected in only 1 case of fibrous dysplasia (1 of 20), whereas it was recognized in 14 of the 17 cases of osteofibrous dysplasia. Furthermore, the immunoreactivity for osteocalcin in bone matrix and fibroblast-like cells was higher in fibrous dysplasia than it was in osteofibrous dysplasia, semiquantitatively. Our immunohistochemical results regarding osteonectin and osteocalcin suggest that the bone matrix of fibrous dysplasia is

  19. Synthetic matrix metalloproteinase inhibitors inhibit growth of established breast cancer osteolytic lesions and prolong survival in mice

    DEFF Research Database (Denmark)

    Winding, Bent; NicAmhlaoibh, Róisín; Misander, Henriette;


    PURPOSE: Breast cancer frequently leads to incurable bone metastasis. Essential requirements for the development of bone metastasis are cell-cell and cell-matrix interactions, release of bioactive growth factors and cytokines, and removal of large amounts of bone matrix. Matrix metalloproteinases...

  20. Bone Densitometry (Bone Density Scan) (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  1. Bone marrow aspiration (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  2. Matrix calculus

    CERN Document Server

    Bodewig, E


    Matrix Calculus, Second Revised and Enlarged Edition focuses on systematic calculation with the building blocks of a matrix and rows and columns, shunning the use of individual elements. The publication first offers information on vectors, matrices, further applications, measures of the magnitude of a matrix, and forms. The text then examines eigenvalues and exact solutions, including the characteristic equation, eigenrows, extremum properties of the eigenvalues, bounds for the eigenvalues, elementary divisors, and bounds for the determinant. The text ponders on approximate solutions, as well

  3. Estudio comparativo del uso de la matriz ósea desmineralizada de origen humana y de la poliuretana derivada del aceite de mamona sobre el proceso de regeneración ósea: Estudio histométrico en calota de conejos A comparative study on the use of demineralized bone matrix of human origin and polyurethane derived from castor oil in bone regeneration processes: A histometric study on rabbit calvaria

    Directory of Open Access Journals (Sweden)

    J. Rodrigues Laureano Filho


    Full Text Available Objetivo. Analizar histométricamente el efecto de la matriz ósea desmineralizada de origen humana y de la resina poliuretana derivada del aceite de mamona, sobre el proceso de regeneración ósea. Diseño del estudio: fueron utilizados 24 conejos y en cada calota craniana fueron preparadas dos cavidades quirúrgicas, siendo una a cada lado de la sutura parietal. Los animales fueron divididos en dos grupos. En el grupo I la cavidad experimental (lado derecho fue rellenada con la poliuretana derivada del aceite de mamona, mientras que en el grupo II la cavidad experimental fue rellenada con la matriz ósea desmineralizada de origen humano. Las cavidades de control fueron rellenadas solo con la sangre del animal. Los animales fueron sacrificados en los períodos postoperatorios de 04, 07 y 15 semanas. Resultados. El análisis estadístico, realizado en base de los datos de la histometría, mostró una mayor neoformación ósea de los grupos I y II en relación al grupo control, no existiendo diferencia estadística cuando los grupos experimentales fueron comparados. Conclusiones. El uso de poliuretana derivada del aceite de mamona y matriz ósea desmineralizada de origen humano mejoran el proceso de regeneración cuando lo comparamos a la regeneración ósea normal resultando que entre ambos materiales tuvieron un comportamiento similar sin diferencias estadísticas significantes entre sí.Objective. The present study was aimed at carrying out a histological and histometric analysis on the effect of human demineralized bone matrix and a polyurethane resin, derived of the castor bean oil, on the bone regeneration process. Design: For this, 24 rabbits were used and in each calvarium two surgical bone defect were prepared, one on the right side and another on the left side of the parietal suture. The animals were divided into two groups. In group I the experimental defect (right side was filled with polyurethane derived from oil of the castor oil

  4. 人工骨支撑棒结合脱钙骨基质治疗股骨头缺血性坏死的临床观察%Clinical observation of artificial bone rod combined with decalcified bone matrix for the treatment of osteonecrosis of the femoral head

    Institute of Scientific and Technical Information of China (English)

    王金龙; 杨述华; 叶树楠; 王晶; 刘先哲


    Objective To evaluate the clinical outcome associated with the core decompression in combination with the nano-hydroxyapatite/collagen composite rod combined with decalcified bone matrix in a consecutive series of patients with osteonecrosis of femoral head,especially the prevention of collapse of femoral head and its predisposing factors.Methods From August,2012 to May,2013,46 pationts (50 hips) who had undergone core decompression in combination with nano-hydroxyapatite/collagen composite rod insertion in corporated with decalcified bone matrix in our hospital were involved in this study.Postoperative care consisted of prophylactic intravenous antibiotic and anticoagulation therapy.Patients were instructed to be non-weight-bearing for 3 weeks,to partial weight-bear for the next 3 weeks,and to weight bear as tolerated thereafter.All patients were evaluated both clinically and radiographically.The primary clinical outcome of this study was functional improvement assessed with the Harris hip score.Serial radiograms of the pelvis were taken at 1,3,6,12 months post-operatively to analyze the process of osteonecrosis.Results All patients followed up for 12 months,no one suffer complications.The mean Harris score pre-operation was 65.6 ± 10.6,post-operation score was 87.5 ± 15.3,with a mean improvement of 21.8 ± 13.2 (P < 0.05).According to Harris hip score system,excellent for 30 hips,good for 14 hips,fair for 2 hip and poor for 4 hips.Refer to the Kaplan-Meier survivorship curve,the success rate at 12 months post-operatively was 92%.Radiological changes coincided with clinical changes.Conclusion Core decompressionin combination with nano-hydroxyapatite/ collagen composite rod insertion in corporated with decalcified bone matrix provided a minimally invasive surgical treatment option to treat early stage osteonecrotic hips(stage Ⅰ and Ⅱ) and to prevent femoral heads from collapsing,with clinical outcomes and success rates priorto other commonly used surgical

  5. Development of an injectable pseudo-bone thermo-gel for application in small bone fractures. (United States)

    Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness


    A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures.

  6. Evidence that Resorption of Bone by Rat Peritoneal Macrophages Occurs in an Acidic Environment (United States)

    Blair, H. C.


    Skeletal loss in space, like any form of osteoporosis, reflects a relative imbalance of the activities of cells resorbing (degrading) or forming bone. Consequently, prevention of weightlessness induced bone loss may theoretically be accomplished by (1) stimulating bone formation or (2) inhibiting bone resorption. This approach, however, requires fundamental understanding of the mechanisms by which cells form or degrade bone, information not yet at hand. An issue central to bone resorption is the pH at which resorption takes place. The pH dependent spectral shift of a fluorescent dye (fluorescein isothiocyanate) conjugated to bone matrix was used to determine the pH at the resorptive cell bone matrix interface. Devitalized rat bone was used as the substrate, and rat peritoneal macrophages were used as the bone resorbing cells. The results suggest that bone resorption is the result of generation of an acidic microenvironment at the cell matrix junction.

  7. Mechanism of mineral formation in bone. (United States)

    Anderson, H C


    The mechanism of mineral formation in bone is seen best where active new bone formation is occurring, e.g., in newly forming subperiosteal bone of the embryo, in the growing bone of young animals, and in healing rickets where the calcification process in osteoid is reactivated. A large body of ultrastructural evidence, using conventional and anhydrous methods for tissue preparation, has shown convincingly that extracellular matrix vesicles are present at or near the mineralization front in all of the above, and that these vesicles are the initial site of apatite mineral deposition. Thus bone resembles growth plate cartilage, predentin, and turkey tendon in having calcification initiated by matrix vesicles. Once the calcification cascade is begun, matrix vesicles are no longer needed to support mineralization and are consumed by the advancing mineralization front in which performed crystals serve as nuclei for the formation of new crystals. The rate of crystal proliferation is promoted by the availability of Ca2+, PO4(3-), and the presence of collagen, and retarded by naturally occurring inhibitors of mineralization such as proteoglycans and several noncollagenous calcium-binding proteins of bone including bone-Gla protein (osteocalcin), phosphoproteins, osteonectin, and alpha-2HS-glycoproteins. New electron microscopic immunocytochemical findings in our laboratory suggest that the origin of alkaline phosphatase-positive bone matrix vesicles is polarized to the mineral-facing side of osteoblasts and may be concentrated near the intercellular junctions of human embryonic osteoblasts.

  8. Matrix Thermalization

    CERN Document Server

    Craps, Ben; Nguyen, Kévin


    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  9. Synthetic matrix metalloproteinase inhibitors inhibit growth of established breast cancer osteolytic lesions and prolong survival in mice

    DEFF Research Database (Denmark)

    Winding, Bent; NicAmhlaoibh, Róisín; Misander, Henriette;


    Breast cancer frequently leads to incurable bone metastasis. Essential requirements for the development of bone metastasis are cell-cell and cell-matrix interactions, release of bioactive growth factors and cytokines, and removal of large amounts of bone matrix. Matrix metalloproteinases (MMPs) p......) play an important role in all of these processes, but the possibility of using synthetic MMP inhibitors to decrease bone metastasis has received little attention....

  10. Degradation of the organic phase of bone by osteoclasts

    DEFF Research Database (Denmark)

    Henriksen, Kim; Sørensen, Mette G; Nielsen, Rasmus H


    Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matri...

  11. Neutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury

    NARCIS (Netherlands)

    Bastian, Okan W.; Koenderman, Leo; Alblas, Jacqueline; Leenen, Luke P H; Blokhuis, Taco J.


    The role of inflammatory cells in bone regeneration remains unclear. We hypothesize that leukocytes contribute to fracture healing by rapidly synthesizing an "emergency extracellular matrix (ECM)" before stromal cells infiltrate the fracture hematoma (FH) and synthesize the eventual collagenous bone

  12. Bone cutting. (United States)

    Giraud, J Y; Villemin, S; Darmana, R; Cahuzac, J P; Autefage, A; Morucci, J P


    Bone cutting has always been a problem for surgeons because bone is a hard living material, and many osteotomes are still very crude tools. Technical improvement of these surgical tools has first been their motorization. Studies of the bone cutting process have indicated better features for conventional tools. Several non-conventional osteotomes, particularly ultrasonic osteotomes are described. Some studies on the possible use of lasers for bone cutting are also reported. Use of a pressurised water jet is also briefly examined. Despite their advantages, non-conventional tools still require improvement if they are to be used by surgeons.

  13. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent;


    A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide...... support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces...

  14. Organ printing: the future of bone regeneration? (United States)

    Fedorovich, Natalja E; Alblas, Jacqueline; Hennink, Wim E; Oner, F Cumhur; Dhert, Wouter J A


    In engineered bone grafts, the combined actions of bone-forming cells, matrix and bioactive stimuli determine the eventual performance of the implant. The current notion is that well-built 3D constructs include the biological elements that recapitulate native bone tissue structure to achieve bone formation once implanted. The relatively new technology of organ/tissue printing now enables the accurate 3D organization of the components that are important for bone formation and also addresses issues, such as graft porosity and vascularization. Bone printing is seen as a great promise, because it combines rapid prototyping technology to produce a scaffold of the desired shape and internal structure with incorporation of multiple living cell types that can form the bone tissue once implanted.

  15. Matrix inequalities

    CERN Document Server

    Zhan, Xingzhi


    The main purpose of this monograph is to report on recent developments in the field of matrix inequalities, with emphasis on useful techniques and ingenious ideas. Among other results this book contains the affirmative solutions of eight conjectures. Many theorems unify or sharpen previous inequalities. The author's aim is to streamline the ideas in the literature. The book can be read by research workers, graduate students and advanced undergraduates.

  16. Effect of Physical Forces on the Metastatic Bone Microenvironment (United States)


    of the extracellular matrix. MMPs are known to be secreted from cells during bone remodeling [7]. Furthermore, MMPs are known to be important for...Rodan et al., 1987; Czekanska et al., 2012]. However, due to their presence in the bone and bone- remodeling ability, it is plausible that OCy may also...persist, but it is plausible that these are primarily lytic lesions masked by the normal bone architecture . OCys do not secrete components of

  17. Impairment of osteoclastic bone resorption in rapidly growing female p47phox knockout mice (United States)

    Bone formation is dependent on the activity and differentiation of osteoblasts; whereas resorption of preexisting mineralized bone matrix by osteoclasts is necessary not only for bone development but also for regeneration and remodeling. Bone remodeling is a process in which osteoblasts and osteocla...

  18. Bone x-ray (United States)

    ... or broken bone Bone tumors Degenerative bone conditions Osteomyelitis (inflammation of the bone caused by an infection) ... Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Osteomyelitis Paget disease of the bone Rickets X-ray ...

  19. Matrix analysis

    CERN Document Server

    Bhatia, Rajendra


    A good part of matrix theory is functional analytic in spirit. This statement can be turned around. There are many problems in operator theory, where most of the complexities and subtleties are present in the finite-dimensional case. My purpose in writing this book is to present a systematic treatment of methods that are useful in the study of such problems. This book is intended for use as a text for upper division and gradu­ ate courses. Courses based on parts of the material have been given by me at the Indian Statistical Institute and at the University of Toronto (in collaboration with Chandler Davis). The book should also be useful as a reference for research workers in linear algebra, operator theory, mathe­ matical physics and numerical analysis. A possible subtitle of this book could be Matrix Inequalities. A reader who works through the book should expect to become proficient in the art of deriving such inequalities. Other authors have compared this art to that of cutting diamonds. One first has to...

  20. Microscopic and radiographic analysis of the effect of particle size of demineralized bovine cancellous bone matrix on the repair of bone defects in femurs of rabbits Análise microscópica e radiográfica do efeito do tamanho das partículas de matriz de osso medular bovino desmineralizado na reparação de defeito ósseo em fêmures de coelhos

    Directory of Open Access Journals (Sweden)

    Everdan Carneiro


    Full Text Available The bone tissue has a great regenerative potential, with ability to completely restore its structure and original functions. In some situations, though, bone defects cannot be self-repaired, thus requiring the use of grafts for a correct treatment and good prognosis. This work aimed at microscopically analyzing the effect of the particle size of demineralized bovine cancellous bone matrix in micro and macrogranular forms on the repair of bone defects in femurs of rabbits, with blood clot used as control. At 1, 3 and 6 months after implantation of the materials, the animals were killed and the anatomic specimens were removed. A foreign body-type granulomatous reaction containing macrophages and multinucleated giant cells in contact with the implanted particles was observed. These results suggest a failure in demineralization and/or interruption of the antigenic potential during production of the biomaterial. It is concluded that the size of the particles did not influence the evolution of the repair process of bone defects, acting only as bone-filler substances, and that the material implanted should be improved by quality control during production, since it may represent a good alternative for bone graft.O tecido ósseo possui grande potencial regenerativo com capacidade para restaurar completamente sua estrutura e função originais. Há situações em que os defeitos ósseos não conseguem por si só obter o reparo, casos em que se fazem necessários o uso de enxertos, para um correto tratamento e bom prognóstico. Este experimento teve o propósito de analisar microscopicamente o efeito do tamanho das partículas de matriz de osso medular bovino desmineralizado, nas formas micro e macrogranular, na reparação de defeito ósseo em fêmures de coelhos, tendo como controle o coágulo sanguíneo. Após 1,3 e 6 meses da implantação dos materiais, os animais foram mortos e as peças anatômicas removidas. Uma reação granulomatosa tipo corpo

  1. Matrix pentagons

    CERN Document Server

    Belitsky, A V


    The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang-Mills theory runs systematically in terms of multiparticle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unravelled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4) matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  2. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie


    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  3. Bone graft (United States)

    ... around the area. The bone graft can be held in place with pins, plates, or screws. Why ... Orthopaedic Surgery, San Francosco, CA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  4. A physical mechanism for coupling bone resorption and formation in adult human bone

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Sondergaard, Teis Esben; Skorzynska, Katarzyna Ewa


    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone...... within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation...... that osteoclasts and osteoblasts on the bone surface were always covered by a canopy of flat cells expressing osteoblast markers. In contrast, in biopsies in which this canopy was disrupted, bone formation was deficient. Three-dimensional visualizations revealed that this canopy covered the entire remodeling site...

  5. Low Bone Density (United States)

    ... Information › Bone Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your ... compared to people with normal bone density. Detecting Low Bone Density A bone density test will determine ...

  6. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

    Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A


    (OPG) and RANKL revealed increased levels of OPG and decreased levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn deficiency protects against increased trabecular bone turnover and bone loss in response to estrogen depletion, supporting the concept that bgn has dual roles......Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response...... to biglycan deficiency. INTRODUCTION: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan...

  7. Effects of demineralized dentin matrix on the odontogenic differentiation potential of bone marrow mesenchymal stem cells in vitro%脱矿牙本质基质诱导骨髓间充质干细胞向成牙本质样细胞分化的体外实验研究

    Institute of Scientific and Technical Information of China (English)

    张红梅; 张晓梅; 闫志伟; 王江; 荀文兴; 李蓉; 庞楠; 杨海珍; 金岩


    AIM; To observe the adhesion and growth of rat bone marrow mesenehymal stem ceils (rBMSCs)seeded on demineralized dentin matrix (DDM) in vitro and the odontogenic induction of DDM. METHODS; BMSCs were successfully isolated and cultured. The compatibility of the biomaterial was evaluated by MTT assay. The odontogenic differentiation of BMSCs induced by DDM was measured using Alizarin red staining, the alkaline phosphatase (ALP) activity and reverse transcription-polymerase chain reaction (RT-PCR) assay. RESULTS; The proliferation of BMSCs in DDM groups was obviously higher than that in the control groups. The higher levels of ALP activity and larger mineralizing nodes were also detected in the experiment groups. RT-PCR demonstrated mRNA expression of dentin sialophospho-protein ( DSPP ) and dentin matrix proteinl ( DMP-1) in BMSCs induced by DDM. CONCLUSION; DDM possesses a good cellular compatibility with BMSCs. It can induce the odontogenic differentiation of BMSCs.%目的:观察脱矿牙本质基质(demineralized dentin matrix,DDM)与大鼠骨髓间充质干细胞(rat bone marrow mesenehymal stem ceils,rBMSCs)的生物相容性及其作为支架材料对BMSCs的牙向诱导作用.方法:分离培养BMSCs,分别用四唑盐比色法(MTS)、茜素红染色法、碱性磷酸酶(alkaline phosphatase,ALP)和逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)方法观察DDM生物材料对BMSCs增殖活性和牙向分化能力的影响.结果:DDM能显著促进体外培养的BMSCs的增殖、诱导细胞的矿化和提高细胞ALP活性;同时还能诱导BMSCs在mRNA水平表达牙本质涎磷蛋白(dentin sialophosphoprotein,DSPP)和牙本质基质蛋白(dentin matrix proteinl,DMP-1).结论:体外培养条件下,DDM与BMSCs有良好的生物相容性,能够诱导BMSCs牙向分化.

  8. The Role of Anisotropic Exchange in Single Molecule Magnets: A CASSCF/NEVPT2 Study of the Fe4 SMM Building Block [Fe2(OCH32(dbm4] Dimer

    Directory of Open Access Journals (Sweden)

    Alessandro Lunghi


    Full Text Available The rationalisation of single molecule magnets’ (SMMs magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III dimer [Fe 2 (OCH 3 2 (dbm 4 ]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe 4 RC(CH 2 O 3 2 (dpm 6 ] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining, for the first time, the extremely rapidly changing nature of the anisotropic exchange coupling.

  9. Bone marrow transplant (United States)

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  10. Vitamin D and Bone Disease

    Directory of Open Access Journals (Sweden)

    S. Christodoulou


    Full Text Available Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a “good bone health” guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.

  11. High-strength mineralized collagen artificial bone (United States)

    Qiu, Zhi-Ye; Tao, Chun-Sheng; Cui, Helen; Wang, Chang-Ming; Cui, Fu-Zhai


    Mineralized collagen (MC) is a biomimetic material that mimics natural bone matrix in terms of both chemical composition and microstructure. The biomimetic MC possesses good biocompatibility and osteogenic activity, and is capable of guiding bone regeneration as being used for bone defect repair. However, mechanical strength of existing MC artificial bone is too low to provide effective support at human load-bearing sites, so it can only be used for the repair at non-load-bearing sites, such as bone defect filling, bone graft augmentation, and so on. In the present study, a high strength MC artificial bone material was developed by using collagen as the template for the biomimetic mineralization of the calcium phosphate, and then followed by a cold compression molding process with a certain pressure. The appearance and density of the dense MC were similar to those of natural cortical bone, and the phase composition was in conformity with that of animal's cortical bone demonstrated by XRD. Mechanical properties were tested and results showed that the compressive strength was comparable to human cortical bone, while the compressive modulus was as low as human cancellous bone. Such high strength was able to provide effective mechanical support for bone defect repair at human load-bearing sites, and the low compressive modulus can help avoid stress shielding in the application of bone regeneration. Both in vitro cell experiments and in vivo implantation assay demonstrated good biocompatibility of the material, and in vivo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load-bearing sites.

  12. Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling. (United States)

    Hambli, Ridha


    Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone

  13. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.


    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  14. [Bone transplant]. (United States)

    San Julián, M; Valentí, A


    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands.

  15. Bone biopsy (image) (United States)

    A bone biopsy is performed by making a small incision into the skin. A biopsy needle retrieves a sample of bone and it ... examination. The most common reasons for bone lesion biopsy are to distinguish between benign and malignant bone ...

  16. Bone lesion biopsy (United States)

    Bone biopsy; Biopsy - bone ... needle is gently pushed and twisted into the bone. Once the sample is obtained, the needle is ... sample is sent to a lab for examination. Bone biopsy may also be done under general anesthesia ...

  17. Facts about Broken Bones (United States)

    ... Room? What Happens in the Operating Room? Broken Bones KidsHealth > For Kids > Broken Bones Print A A ... sticking through the skin . What Happens When a Bone Breaks? It hurts to break a bone! It's ...

  18. Calcium and bones (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  19. Broken Bones (For Parents) (United States)

    ... Feeding Your 1- to 2-Year-Old Broken Bones KidsHealth > For Parents > Broken Bones Print A A ... bone fragments in place. When Will a Broken Bone Heal? Fractures heal at different rates, depending upon ...

  20. Riemann Zeta Matrix Function


    Kargın, Levent; Kurt, Veli


    In this study, obtaining the matrix analog of the Euler's reflection formula for the classical gamma function we expand the domain of the gamma matrix function and give a infinite product expansion of sinπxP.  Furthermore we define Riemann zeta matrix function and evaluate some other matrix integrals. We prove a functional equation for Riemann zeta matrix function.

  1. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A


    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone...

  2. Carbon dioxide (CO2) absorption behavior of mixed matrix polymer composites containing a flexible coordination polymer. (United States)

    Culp, Jeffrey T; Sui, Lang; Goodman, Angela; Luebke, David


    Mixed matrix membranes (MMMs) comprised of metal organic frameworks (MOFs) dispersed in organic polymers are popular materials under study for potential applications in gas separations. However, research on MMMs containing structurally dynamic sorbents known as flexible MOFs has only very recently appeared in the literature. The thermodynamic requirements of the structure transition between the low porosity and high porosity phases of flexible MOFs may provide a mechanism for high adsorption selectivity in these materials. A fundamental question in MMMs containing flexible MOFs is how the constraint of the polymer matrix on the intrinsic expansion of the flexible MOF particles that occurs during gas adsorption might affect the thermodynamics of this structural phase transition and influence the gas adsorption properties of the embedded MOF. To investigate the fundamental nature of this flexible MOF-polymer interface, thin films of ~20 um thickness were prepared using the flexible linear chain coordination polymer catena-bis(dibenzoylmethanato)-(4,4'bipyridyl)nickel(II) "Ni(Bpy)(DBM)(2)" embedded as 35 wt% dispersions in Matrimid®, polystyrene, and polysulfone. The adsorption of CO(2) in the polymers and embedded particles was studied using in situ ATR-FTIR spectroscopy and variable temperature volumetric CO(2) adsorption/desorption isotherms. Interestingly, no effect of the polymer matrix on the gas adsorption behavior of the embedded Ni(Bpy)(DBM)(2) particles was observed. The composite samples all showed the same threshold pressures for CO(2) absorption and desorption hysteresis associated with the structural phase change in the polymer embedded Ni(Bpy)(DBM)(2) particles as was observed in the pristine polycrystalline sample. The current results contrast those recently reported for a MMM containing the flexible MOF "NH(2)-MIL-53" where a significant increase in the threshold pressure for CO(2) adsorption associated with the structural phase change of the MOF was

  3. Bone Proteoglycan Changes During Skeletal Unloading (United States)

    Yamauchi, M.; Uzawa, K.; Pornprasertsuk, S.; Arnaud, S.; Grindeland, R.; Grzesik, W.


    Skeletal adaptability to mechanical loads is well known since the last century. Disuse osteopenia due to the microgravity environment is one of the major concerns for space travelers. Several studies have indicated that a retardation of the mineralization process and a delay in matrix maturation occur during the space flight. Mineralizing fibrillar type I collagen possesses distinct cross-linking chemistries and their dynamic changes during mineralization correlate well with its function as a mineral organizer. Our previous studies suggested that a certain group of matrix proteoglycans in bone play an inhibitory role in the mineralization process through their interaction with collagen. Based on these studies, we hypothesized that the altered mineralization during spaceflight is due in part to changes in matrix components secreted by cells in response to microgravity. In this study, we employed hindlimb elevation (tail suspension) rat model to study the effects of skeletal unloading on matrix proteoglycans in bone.

  4. Development of electrospun bone-mimetic matrices for bone regenerative applications (United States)

    Phipps, Matthew Christopher

    Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater

  5. Quantitative evaluation of regularized phase retrieval algorithms on bone scaffolds seeded with bone cells (United States)

    Weber, L.; Langer, M.; Tavella, S.; Ruggiu, A.; Peyrin, F.


    In the field of regenerative medicine, there has been a growing interest in studying the combination of bone scaffolds and cells that can maximize newly formed bone. In-line phase-contrast x-ray tomography was used to image porous bone scaffolds (Skelite©), seeded with bone forming cells. This technique allows the quantification of both mineralized and soft tissue, unlike with classical x-ray micro-computed tomography. Phase contrast images were acquired at four distances. The reconstruction is typically performed in two successive steps: phase retrieval and tomographic reconstruction. In this work, different regularization methods were applied to the phase retrieval process. The application of a priori terms for heterogeneous objects enables quantitative 3D imaging of not only bone morphology, mineralization, and soft tissue formation, but also cells trapped in the pre-bone matrix. A statistical study was performed to derive statistically significant information on the different culture conditions.

  6. Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis. (United States)

    Cox, L G E; van Donkelaar, C C; van Rietbergen, B; Emans, P J; Ito, K


    For many years, pharmaceutical therapies for osteoarthritis (OA) were focused on cartilage. However, it has been theorized that bone changes such as increased bone volume fraction and decreased bone matrix mineralization may play an important role in the initiation and pathogenesis of OA as well. The mechanisms behind the bone changes are subject of debate, and a better understanding may help in the development of bone-targeting OA therapies. In the literature, the increase in bone volume fraction has been hypothesized to result from mechanoregulated bone adaptation in response to decreased mineralization. Furthermore, both changes in bone volume fraction and mineralization have been reported to be highest close to the cartilage, and bone volume fraction has been reported to be correlated with cartilage degeneration. These data indicate that cartilage degeneration, bone volume fraction, and bone matrix mineralization may be related in OA. In the current study, we aimed to investigate the relationships between cartilage degeneration, bone matrix mineralization and bone volume fraction at a local level. With microCT, we determined bone matrix mineralization and bone volume fraction as a function of distance from the cartilage in osteochondral plugs from human OA tibia plateaus with varying degrees of cartilage degeneration. In addition, we evaluated whether mechanoregulated bone adaptation in response to decreased bone matrix mineralization may be responsible for the increase in bone volume fraction observed in OA. For this purpose, we used the experimentally obtained mineralization data as input for bone adaptation simulations. We simulated the effect of mechanoregulated bone adaptation in response to different degrees of mineralization, and compared the simulation results to the experimental data. We found that local changes in subchondral bone mineralization and bone volume fraction only occurred underneath severely degenerated cartilage, indicating that bone

  7. Anabolic actions of Notch on mature bone (United States)

    Liu, Peng; Ping, Yilin; Ma, Meng; Zhang, Demao; Liu, Connie; Zaidi, Samir; Gao, Song; Ji, Yaoting; Lou, Feng; Yu, Fanyuan; Lu, Ping; Stachnik, Agnes; Bai, Mingru; Wei, Chengguo; Zhang, Liaoran; Wang, Ke; Chen, Rong; New, Maria I.; Rowe, David W.; Yuen, Tony; Sun, Li; Zaidi, Mone


    Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response. PMID:27036007

  8. New laboratory tools in the assessment of bone quality. (United States)

    Chappard, D; Baslé, M F; Legrand, E; Audran, M


    Bone quality is a complex set of intricated and interdependent factors that influence bone strength. A number of methods have emerged to measure bone quality, taking into account the organic or the mineral phase of the bone matrix, in the laboratory. Bone quality is a complex set of different factors that are interdependent. The bone matrix organization can be described at five different levels of anatomical organization: nature (organic and mineral), texture (woven or lamellar), structure (osteons in the cortices and arch-like packets in trabecular bone), microarchitecture, and macroarchitecture. Any change in one of these levels can alter bone quality. An altered bone remodeling can affect bone quality by influencing one or more of these factors. We have reviewed here the main methods that can be used in the laboratory to explore bone quality on bone samples. Bone remodeling can be evaluated by histomorphometry; microarchitecture is explored in 2D on histological sections and in 3D by microCT or synchrotron. Microradiography and scanning electron microscopy in the backscattered electron mode can measure the mineral distribution; Raman and Fourier-transformed infra-red spectroscopy and imaging can simultaneously explore the organic and mineral phase of the matrix on multispectral images; scanning acoustic microscopy and nanoindentation provide biomechanical information on individual trabeculae. Finally, some histological methods (polarization, surface staining, fluorescence, osteocyte staining) may also be of interest in the understanding of quality as a component of bone fragility. A growing number of laboratory techniques are now available. Some of them have been described many years ago and can find a new youth; others having benefited from improvements in physical and computer techniques are now available.

  9. Effects of atorvastatin on the expression levels of tissue inhibitor of metalloproteinases timps/matrix metalloproteinases in bone tissues of femoral head necrosis induced by glucocorticoid%阿托伐他汀对糖皮质激素性股骨头坏死骨组织MMP/TIMP系统的影响

    Institute of Scientific and Technical Information of China (English)

    王建忠; 武永刚; 董慧珍


    .02,0.15±0.05和0.18±0.04;TIMP-2在3组中的表达分别为0.45±0.15,0.73±0.08和0.69±0.19。激素组与对照组比较,MMP-2、MMP-9 mRNA表达增高,TIMP-1、TIMP-2 mRNA的表达降低,差异有统计学意义( P<0.05);阿托伐他汀组与对照组比较,除 MMP-9差异有统计学意义外,其余差异无统计学意义;阿托伐他汀组与激素组比较,MMP-2、MMP-9 mRNA表达降低,TIMP-1、TIMP-2mRNA表达增高,差异有统计学意义(P<0.05)。结论醋酸泼尼松龙上调大鼠骨组织中MMP-2、MMP-9 mRNA的表达水平,下调TIMP-1、TIMP-2的表达水平,使MMPs/TIMPs比值升高。阿托伐他汀可以拮抗皮质激素对MMPs/TIMPs系统的调控。%Objective To investigate the effects of atorvastatin on the mRNA expressions of matrix metalloproteinase-2 ( MMP-2 ), matrix metalloproteinase-9 ( MMP-9 ), tissue inhibitor of matrix metalloproteinases-1 ( TIMP-1 ) and tissue inhibitor of matrix metalloproteinases-2 ( TIMP-2 ) in bone tissues of the rats receiving glucocorticoid for a long time, and to discuss the effects and mechanism of atorvastatin in preventing glucocorticoid-induced femoral head necrosis ( FHN ).Methods A total of 30 healthy adult Sprague-Dawley ( SD ) rats were randomly divided into 3 groups, including glucocorticoid group, atorvastatin group and control group with 10 rats in each group. The rats in the glucocorticoid group and atorvastatin group were treated by intramuscular injection of 12.5 mg / kg prednisolone twice a week. The rats in the atorvastatin group were treated by intragastric administration with 1 mg / kg atorvastatin once a week. The maximum dose was 60 mg each day for experimental animals whose maximum weight was 60 kg. The rats in the control group were treated only by intramuscular injection of the same volume sodium chloride. After 4 weeks’ intervention, the parafifn-embedded osteonecrosis of the left femoral head was detected by HE stain, to identify osteoporosis and

  10. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

    Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A;


    Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response to...

  11. Assessment of bone mineral status in children with Marfan syndrome (United States)

    Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ßeta, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone minerali...

  12. A supra-cellular model for coupling of bone resorption to formation during remodeling

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L


    by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow......The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released...

  13. Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis. (United States)

    Sun, Yao; Weng, Yuteng; Zhang, Chenyang; Liu, Yi; Kang, Chen; Liu, Zhongshuang; Jing, Bo; Zhang, Qi; Wang, Zuolin


    Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser(89) is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S(89) was substituted with G(89) (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.

  14. The effect of Emdogain on the growth and differentiation of rat bone marrow cells.

    NARCIS (Netherlands)

    Dolder, J. van den; Vloon, A.P.; Jansen, J.A.


    BACKGROUND AND OBJECTIVE: The major extracellular matrix (ECM) proteins in developing enamel can induce and maintain the formation and mineralization of other skeletal hard tissue, such as bone. Therefore, dental matrix proteins are ideal therapeutic agents when direct formation of functional bone i

  15. Calcium phosphate cement delivering zoledronate decreases bone turnover rate and restores bone architecture in ovariectomized rats. (United States)

    Wu, Chang-Chin; Wang, Chen-Chie; Lu, Dai-Hua; Hsu, Li-Ho; Yang, Kai-Chiang; Lin, Feng-Huei


    Patients sustaining bony fractures frequently require the application of bone graft substitutes to fill the bone defects. In the meantime, anti-osteoporosis drugs may be added in bone fillers to treat osteoporosis, especially in postmenopausal women and the elderly. The effects of zoledronate-impregnated calcium phosphate cement (ZLN/CPC) on ovariectomized (OVX) rats were evaluated. OVX rats were implanted with ZLN/CPC, containing 0.025 mg ZLN in the greater omentum. Afterward the clinical sign of toxicity was recorded for eight weeks. The rats were sacrificed and blood samples were collected for hematology and serum bone turnover markers analyses. The four limbs of the rats were harvested and micro-computer tomography (micro-CT) scanning and bone ash analyses were performed. No clinical toxicity was observed in the treated rats. Compared to the OVX rats, levels of bone resorption markers (fragments of C-telopeptides of type I collagen) and bone formation markers (alkaline phosphatase and osteocalcin) decreased significantly in the treated rats. Osteopontin, which mediates the anchoring of osteoclasts to the mineral matrix of bones, also decreased significantly. Micro-CT scanning and histologic examinations of the distal femoral metaphyses showed that the cancellous bone architectures were restored, with a concomitant decrease in bone porosity. The bone mineral content in the bone ashes also increased significantly. This study indicates that ZLN-impregnated CPC reduces bone turnover rate and restores bone architecture in OVX rats. CPC may be an appropriate carrier to deliver drugs to treat osteoporosis, and this approach may also reduce rates of post-dosing symptoms for intravenous ZLN delivery.

  16. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry

    Directory of Open Access Journals (Sweden)

    Takashi Matsuura


    Full Text Available Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  17. Selenoprotein P is the essential selenium transporter for bones. (United States)

    Pietschmann, Nicole; Rijntjes, Eddy; Hoeg, Antonia; Stoedter, Mette; Schweizer, Ulrich; Seemann, Petra; Schomburg, Lutz


    Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations.

  18. [Bone Cell Biology Assessed by Microscopic Approach. Micro- and nanomechanical analysis of bone]. (United States)

    Saito, Masami; Hongo, Hiromi


    For Stiffness, we have several ways, Vicker's, Nano Indentor and NanoIndentation with AFM. Recent study needs several nm, tens of nm scale lateral resolution. For this request, AFM supply new technology, PeakForce QNM®, is only way to measure sub molecular level modulus mapping. In this article, introduce several data and specially talk about bone modulus near osteocytic lacunae treated with PTH which is considering to resolve bone matrix around the osteocytic lacunae.

  19. Antibodies to Staphylococcus aureus Bone Sialoprotein-Binding Protein Indicate Infectious Osteomyelitis▿


    Persson, Lena; Johansson, Christian; Rydén, Cecilia


    Discrimination of soft tissue infection from osteomyelitis in diabetic foot infections is a common clinical problem. Staphylococcus aureus isolates from patients with osteomyelitis express bone sialoprotein-binding protein (Bbp) that binds the bone matrix protein bone sialoprotein. The serological assay with Bbp discriminated cases of osteomyelitis from soft tissue infections in patients with diabetic foot ulcers.

  20. Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin


    Ishijima, Muneaki; Rittling, Susan R.; Yamashita, Teruhito; Tsuji, Kunikazu; Kurosawa, Hisashi; Nifuji, Akira; Denhardt, David T.; Noda, Masaki


    Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investi...

  1. Dating of cremated bones

    NARCIS (Netherlands)

    Lanting, JN; Aerts-Bijma, AT; van der Plicht, J; Boaretto, E.; Carmi, I.


    When dating unburnt bone, bone collagen, the organic fraction of the bone, is used. Collagen does not survive the heat of the cremation pyre, so dating of cremated bone has been considered impossible. Structural carbonate in the mineral fraction of the bone, however, survives the cremation process.

  2. New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

    Energy Technology Data Exchange (ETDEWEB)

    Herlin, Maria, E-mail: [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)


    Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation

  3. Brown Tumor Shown Flare Phenomenon On Bone Scan After Parathyroidectomy

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwang Ho; Park, Seol Hoon; Baek, So Ra; Chae, Sun Young; Koh, Jung Min; Kim, Jae Seung; Moon, Dae Hyuk; Ryu, Jin Sook [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)


    Brown tumor is the benign bone lesion consists of woven bone and fibrous tissue without matrix, which develop due to chronic excessive osteoclastic activity such as hyperparathyroidism. Usually they appear with normal uptake or occasionally focally increased uptake on bone scan. We present a case with brown tumor shown more increased uptake and more number of lesions on bone scan after parathyroidectomy, and lesser increased uptake on serial bone scans without any other treatment through several months. This finding is thought to be similar to 'flare phenomenon' which is occasionally seen after treatment of metastatic bone lesions of malignant cancer, and may represent curative process of brown tumor with rapid normal bone formation.

  4. Smoking and Bone Health (United States)

    ... supported by your browser. Home Bone Basics Lifestyle Smoking and Bone Health Publication available in: PDF (85 ... late to adopt new habits for healthy bones. Smoking and Osteoporosis Cigarette smoking was first identified as ...

  5. A Numerically Subdominant CD8 T Cell Response to Matrix Protein of Respiratory Syncytial Virus Controls Infection with Limited Immunopathology.

    Directory of Open Access Journals (Sweden)

    Jie Liu


    Full Text Available CD8 T cells are involved in pathogen clearance and infection-induced pathology in respiratory syncytial virus (RSV infection. Studying bulk responses masks the contribution of individual CD8 T cell subsets to protective immunity and immunopathology. In particular, the roles of subdominant responses that are potentially beneficial to the host are rarely appreciated when the focus is on magnitude instead of quality of response. Here, by evaluating CD8 T cell responses in CB6F1 hybrid mice, in which multiple epitopes are recognized, we found that a numerically subdominant CD8 T cell response against DbM187 epitope of the virus matrix protein expressed high avidity TCR and enhanced signaling pathways associated with CD8 T cell effector functions. Each DbM187 T effector cell lysed more infected targets on a per cell basis than the numerically dominant KdM282 T cells, and controlled virus replication more efficiently with less pulmonary inflammation and illness than the previously well-characterized KdM282 T cell response. Our data suggest that the clinical outcome of viral infections is determined by the integrated functional properties of a variety of responding CD8 T cells, and that the highest magnitude response may not necessarily be the best in terms of benefit to the host. Understanding how to induce highly efficient and functional T cells would inform strategies for designing vaccines intended to provide T cell-mediated immunity.

  6. Photosensized Controlling Benzyl Methacrylate-Based Matrix Enhanced Eu3+ Narrow-Band Emission for Fluorescence Applications

    Directory of Open Access Journals (Sweden)

    Mei-Hsiang Lin


    Full Text Available This study synthesized a europium (Eu3+ complex Eu(DBM3Cl-MIP (DBM = dibenzoyl methane; Cl-MIP = 2-(2-chlorophenyl-1-methyl-1H-imidazo[4,5-f][1,10]phenanthroline dispersed in a benzyl methacrylate (BMA monomer and treated with ultraviolet (UV light for polymerization. Spectral results showed that the europium complex containing an antenna, Cl-MIP, which had higher triplet energy into the Eu3+ energy level, was an energetically enhanced europium emission. Typical stacking behaviors of π–π interactions between the ligands and the Eu3+-ion were analyzed using single crystal X-ray diffraction. Regarding the luminescence performance of this europium composite, the ligand/defect emission was suppressed by dispersion in a poly-BMA (PBMA matrix. The underlying mechanism of the effective enhancement of the pure Eu3+ emission was attributed to the combined effects of structural modifications, defect emissions, and carrier charge transfer. Fluorescence spectra were compared to the composite of optimized Eu3+ emission where they were subsequently chelated to four metal ions via carboxylate groups on the BMA unit. The optical enhanced europium composite clearly demonstrated highly efficient optical responses and is, therefore a promising application as an optical detection material.

  7. Influence of in vitro biomimicked stem cell 'niche' for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontaneous stem cell transformation enhanced by the matrix environment. (United States)

    Kim, Jae Hyung; Shin, Sang-Hyun; Li, Tian Zhu; Suh, Hwal


    Niche appears important for preventing the spontaneous differentiation or senescence that cells undergo during in vitro expansion. In the present study, it was revealed that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) undergo senescence-related differentiation into the myocardial lineage in vitro without any induction treatment. This phenomenon occurred over the whole population of MCSs, much different from conventional differentiation with limited frequency of occurrence, and was accompanied by a change of morphology into large, flat cells with impeded proliferation, which are the representative indications of MSC senescence. By culturing MSCs under several culture conditions, it was determined that induction treatment with 5-azacytidine was not associated with the phenomenon, but the serum-starvation condition, under which proliferation is severely hampered, caused senescence progression and upregulation of cardiac markers. Nevertheless, MSCs gradually developed a myocardial phenotype under normal culture conditions over a prolonged culture period and heterogeneous populations were formed. In perspectives of clinical applications, this must be prevented for fair and consistent outcomes. Hence, the biomimetic 'niche' was constituted for hBM-MSCs by cultivating on a conventionally available extracellular matrix (ECM). Consequently, cells on ECM regained a spindle-shape morphology, increased in proliferation rate by two-fold and showed decreased expression of cardiac markers at both the mRNA and protein levels. In conclusion, the outcome indicates that progression of MSC senescence may occur via myocardial differentiation during in vitro polystyrene culture, and this can be overcome by employing appropriate ECM culture techniques.

  8. Effect of Calcitonin on Bone Matrix Metalloproteinase 1,3 and 13 in Rabbits%降钙素对兔骨关节炎软骨基质金属蛋白酶1、3、13的影响

    Institute of Scientific and Technical Information of China (English)

    吕伟; 时剑辉; 崔巍; 单静


    目的:研究降钙素对兔骨关节炎软骨基质金属蛋白酶1、3、13的影响。方法60只日本大白兔被随机分为对照组(ACLT)、降钙素(CT)干预组,各30只。结果 CT组MMP-1、3、13的含量低于ACLT组(P<0.01)。结论降钙素对MMP-1、3、13的分泌有着一定的抑制作用,进而对骨关节炎进程有着相应的干预,使得骨关节炎的进展得以缓解和延缓。%Objective To study the effect of calcitonin on the matrix metaloproteinase 1,3 and 13 in rabbit osteoarthrit is.MethodsSixty Japanese white rabbits were randomly divided into control group(ACLT)and CTintervention group,each of which was divided into 30 groups.Results MMP-1,3 and 13 inCT group were much lower than that in ACLT group(P< 0.01). Conclusion Calcitonin can inhibit the process of MMP-1,3 and -13 in the process of bone arthritis,and delay the development of osteoarthritis.

  9. Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects (United States)


    also suggests that the lymphatics play a critical role in fracture repair. With normal healing of tibial fracture, foci of ossification are...Effectiveness in segmental tibial defects in rats. Tissue Eng 12:489–497. Finkemeier CG. 2002. Bone-grafting and bone-graft substitutes. J Bone Joint...Vogelin E, Brekke JH, Jones NF. 2000. Heterotopic and orthotopic bone formation with a vascularized periosteal flap, a matrix and rh-BMP- 2 (bone

  10. Mathematical model for bone mineralization

    Directory of Open Access Journals (Sweden)

    Svetlana V Komarova


    Full Text Available Defective bone mineralization has serious clinical manifestations, including deformities and fractures, but the regulation of this extracellular process is not fully understood. We have developed a mathematical model consisting of ordinary differential equations that describe collagen maturation, production and degradation of inhibitors, and mineral nucleation and growth. We examined the roles of individual processes in generating normal and abnormal mineralization patterns characterized using two outcome measures: mineralization lag time and degree of mineralization. Model parameters describing the formation of hydroxyapatite mineral on the nucleating centers most potently affected the degree of mineralization, while the parameters describing inhibitor homeostasis most effectively changed the mineralization lag time. Of interest, a parameter describing the rate of matrix maturation emerged as being capable of counter-intuitively increasing both the mineralization lag time and the degree of mineralization. We validated the accuracy of model predictions using known diseases of bone mineralization such as osteogenesis imperfecta and X-linked hypophosphatemia. The model successfully describes the highly non-linear mineralization dynamics, which includes an initial lag phase when osteoid is present but no mineralization is evident, then fast primary mineralization, followed by secondary mineralization characterized by a continuous slow increase in bone mineral content. The developed model can potentially predict the function for a mutated protein based on the histology of pathologic bone samples from mineralization disorders of unknown etiology.

  11. An update on the Application of Nanotechnology in Bone Tissue Engineering (United States)

    Griffin, MF; Kalaskar, DM; Seifalian, A.; Butler, PE


    Background: Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. Methods: This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Results: Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Conclusion: Future studies to improve the application of nanomaterials for bone tissue engineering are needed. PMID:28217209

  12. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures.

    Directory of Open Access Journals (Sweden)

    Chiara Gardin

    Full Text Available The combination of bone grafting materials with guided bone regeneration (GBR membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM. In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications.

  13. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures. (United States)

    Gardin, Chiara; Ricci, Sara; Ferroni, Letizia; Guazzo, Riccardo; Sbricoli, Luca; De Benedictis, Giulia; Finotti, Luca; Isola, Maurizio; Bressan, Eriberto; Zavan, Barbara


    The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications.

  14. Dentin matrix degradation by host Matrix Metalloproteinases: inhibition and clinical perspectives towards regeneration.

    Directory of Open Access Journals (Sweden)

    Catherine eChaussain


    Full Text Available Bacterial enzymes have long been considered solely accountable for the degradation of the dentin matrix during the carious process. However, the emerging literature suggests that host-derived enzymes, and in particular the matrix metalloproteinases (MMPs contained in dentin and saliva can play a major role in this process by their ability to degrade the dentin matrix from within. These findings are important since they open new therapeutic options for caries prevention and treatment. The possibility of using MMP inhibitors to interfere with dentin caries progression is discussed. Furthermore, the potential release of bioactive peptides by the enzymatic cleavage of dentin matrix proteins by MMPs during the carious process is discussed. These peptides, once identified, may constitute promising therapeutical tools for tooth and bone regeneration.

  15. Osteoblast Differentiation and Bone: Relevant proteins, regulatory processes and the vascular connection



    textabstractBone is a highly specialized form of connective tissue present in most vertebrate animals as part of the endoskeleton. Structurally speaking, bone is mainly constituted by an organic extracellular matrix (ECM) hardened by deposited mineral. The blending between the organic and inorganic parts originates two main types of osseous tissue. The outer part of the tissue, the cortex, is hard compact bone and surrounds the inner trabecular bone, a spongy-like structure. In terms of funct...

  16. The Matrix Cookbook

    DEFF Research Database (Denmark)

    Petersen, Kaare Brandt; Pedersen, Michael Syskind

    Matrix identities, relations and approximations. A desktop reference for quick overview of mathematics of matrices.......Matrix identities, relations and approximations. A desktop reference for quick overview of mathematics of matrices....

  17. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.


    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram...... lambs were randomly assigned to two weight-matched groups at birth. During the first 14 days of life AKG was administered orally to the experimental group (n=12) at the dosage of 0.1 g/kg body weight per day, while the control group (n=11) received an equal dose of the vehicle. Lambs were slaughtered...... has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development...

  18. Pre-osteoblastic MC3T3-E1 promote breast cancer cell growth in bone in a murine xenograft model (United States)

    The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cance...

  19. Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Daniel S. [University of Kentucky, Lexington; Pienkowski, David [University of Kentucky, Lexington; Faugere, Marie-Claude [Albert B. Chandler Medical Center; Malluche, Hartmut H. [Albert B. Chandler Medical Center


    Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bone with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.

  20. Matrix with Prescribed Eigenvectors (United States)

    Ahmad, Faiz


    It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…

  1. Biological Events in Periodontal Ligament and Alveolar Bone Associated with Application of Orthodontic Forces

    Directory of Open Access Journals (Sweden)

    L. Feller


    Full Text Available Orthodontic force-induced stresses cause dynamic alterations within the extracellular matrix and within the cytoskeleton of cells in the periodontal ligament and alveolar bone, mediating bone remodelling, ultimately enabling orthodontic tooth movement. In the periodontal ligament and alveolar bone, the mechanically induced tensile strains upregulate the expression of osteogenic genes resulting in bone formation, while mechanically induced compressive strains mediate predominantly catabolic tissue changes and bone resorption. In this review article we summarize some of the currently known biological events occurring in the periodontal ligament and in the alveolar bone in response to application of orthodontic forces and how these facilitate tooth movement.

  2. A Bone Glue with Sustained Adhesion under Wet Conditions. (United States)

    Wistlich, Laura; Rücker, Anja; Schamel, Martha; Kübler, Alexander C; Gbureck, Uwe; Groll, Jürgen


    Bone glues often suffer from low adhesion to bone under wet conditions. This study aims to improve wet adhesiveness of a bone glue based on a photocurable poly(ethylene glycol) dimethacrylate matrix through in situ interpenetrating network formation by addition of six-armed isocyanate functional star-shaped prepolymers (NCO-sP(EO-stat-PO)). Biodegradable ceramic fillers are added to adjust the paste workability. The 3-point bending strength of the bone glues is in the range of 3.5-5.5 MPa and not significantly affected by the addition of NCO-sP(EO-stat-PO). Storage in phosphate buffered saline (PBS) decreases the bending strength of all formulations to approximately 1 MPa but the adhesion to cortical bone increases from 0.15-0.2 to 0.3-0.5 MPa after adding 20-40 wt% NCO-sP(EO-stat-PO) to the matrix. Bone glues without the NCO-sP(EO-stat-PO) additive lose their adhesiveness to bone after aging in PBS for 7 days, whereas modified glues maintain a shear strength of 0.18-0.25 MPa demonstrating the efficacy of the approach. Scanning electron microscopy and energy-dispersive X-ray spectroscopy investigations of the fracture surfaces prove a high amount of residual adhesive on the bone surface indicating that adhesion to the bone under wet conditions is stronger than cohesion.

  3. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi


    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  4. Orchestration of bone remodeling

    NARCIS (Netherlands)

    Moester, Martiene Johanna Catharina


    In healthy individuals, a balance exists between bone formation and resorption. Disruption of this balance can lead to higher or lower bone mass, and disease such as osteoporosis. Treatment for osteoporosis generally inhibits bone resorption, but does not rebuild bone to a healthy strength. More kno

  5. Bone grafts in dentistry

    Directory of Open Access Journals (Sweden)

    Prasanna Kumar


    Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

  6. Bone Marrow Diseases (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  7. Bone Health and Osteoporosis. (United States)

    Lupsa, Beatrice C; Insogna, Karl


    Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to decreased bone strength and an increased risk of low-energy fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. Bone loss is an inevitable consequence of the decrease in estrogen levels during and following menopause, but additional risk factors for bone loss can also contribute to osteoporosis in older women. A well-balanced diet, exercise, and smoking cessation are key to maintaining bone health as women age. Pharmacologic agents should be recommended in patients at high risk for fracture.

  8. Organ and tissue level properties are more sensitive to age than osteocyte lacunar characteristics in rat cortical bone

    DEFF Research Database (Denmark)

    Wittig, Nina; Bach-Gansmo, Fiona Linnea; Birkbak, Mie Elholm;


    of bone on the organ and tissue level, whereas features on the nano- and micrometer scale are much less explored. We investigated the age-related development of organ and tissue level bone properties such as bone volume, bone mineral density, and load to fracture and correlated these with osteocyte...... orientation with animal age. Hence, the evolution of organ and tissue level properties with age in rat cortical bone is not accompanied by related changes in osteocyte lacunar properties. This suggests that bone microstructure and bone matrix material properties and not the geometric properties...

  9. Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats. (United States)

    El Khassawna, Thaqif; Böcker, Wolfgang; Brodsky, Katharina; Weisweiler, David; Govindarajan, Parameswari; Kampschulte, Marian; Thormann, Ulrich; Henss, Anja; Rohnke, Marcus; Bauer, Natali; Müller, Robert; Deutsch, Andreas; Ignatius, Anita; Dürselen, Lutz; Langheinrich, Alexander; Lips, Katrin S; Schnettler, Reinhard; Heiss, Christian


    Bone loss is a symptom related to disease and age, which reflects on bone cells and ECM. Discrepant regulation affects cell proliferation and ECM localization. Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at young and old ages. Biophysical, histological and molecular techniques were implemented to examine the underlying cellular and extracellular matrix changes and to assess the mechanisms contributing to bone loss in the context of aging and the widely used osteoporotic models in rats. Bone loss exhibited a compromised function of bone cells and infiltration of adipocytes into bone marrow. However, the expression of genes regulating collagen catabolic process and adipogenesis was chronologically shifted in diseased bone in comparison with aged bone. The data showed the involvement of Wnt signaling inhibition in adipogenesis and bone loss due to over-expression of SOST in both diseased and aged bone. Further, in the OVX animals, an integrin-mediated ERK activation indicated the role of MAPK in osteoblastogenesis and adipogenesis. The increased PTH levels due to calcium and estrogen deficiency activated osteoblastogenesis. Thusly, RANKL-mediated osteoclastogenesis was initiated. Interestingly, the data show the role of MEPE regulating osteoclast-mediated resorption at late stages in osteoporotic bone. The interplay between ECM and bone cells change tissue microstructure and properties. The involvement of Wnt and MAPK pathways in activating cell proliferation has intriguing similarities to oncogenesis and myeloma. The study indicates the importance of targeting both pathways simultaneously to remedy metabolic bone diseases and age-related bone loss.


    Directory of Open Access Journals (Sweden)



    Full Text Available Osteopetrosis, a generalized developmental bone disease due to genetic disturbances, characterized by failure of bone re sorption and continuous bone formation making the bone hard, dense and brittle. Bones of intramembranous ossification and enchondrial ossification are affected genetically and symmetrically. During the process of disease the excess bone formation obliterates the cranial foramina and presses the optic, auditory and facial nerves resulting in defective vision, impaired hearing and facial paralysis. The bone formation in osteopetrosis affects bone marrow function leading to severe anemia and deficient of blood cells. The bone devoid of blood supply due to compression of blood vessels by excess formation of bone are prone to osteomyelitic changes with suppuration and pathological fracture if exposed to infection. Though the condition is chronic progressive, it produces changes leading to fatal condition, it should be studied thoroughly by everyone and hence this article presents a classical case of osteopetrosis with detailed description and discussion for the benefit of readers

  11. Multiscale Modeling of Bone (United States)


    DISEASE Both age and disease can affect the structure of bone, the effects of which are often similar. The most common bone disease is osteoporosis ... Osteoporosis is a disease that results in reduced bone mass and density. This reduction of bone mass and density has a greater impact on trabecular...Bone loss in females is linked to a decrease in estrogen ; the decrease of estrogen associated with menopause increases osteoclast activity [89]. This

  12. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Yibin Kang


    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  13. Assessment of Bonelike (registered) graft with a resorbable matrix using an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, J.V. [CHVNG-Servico de Estomatologia, Centro Hospitalar de Vila Nova de Gaia (Portugal); ICBAS-Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto (Portugal); CECA/ICETA-Centro de Estudos de Ciencia Animal, Instituto de Ciencias e Tecnologias Agrarias e Agro-Alimentares, Campus Agrario de Vairao, Rua Padre Armando Quintas, 4485-661 Vairao (Portugal); Hussain, N. Sooraj [INEB-Instituto de Engenharia Biomedica, Laboratorio de Biomateriais, Rua Campo Alegre, 823, 4150-180, Porto (Portugal); FEUP-Faculdade de Engenharia da Universidade do Porto, DEMM, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Botelho, C.M. [INEB-Instituto de Engenharia Biomedica, Laboratorio de Biomateriais, Rua Campo Alegre, 823, 4150-180, Porto (Portugal); FEUP-Faculdade de Engenharia da Universidade do Porto, DEMM, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Mauricio, A.C. [ICBAS-Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto (Portugal); CECA/ICETA-Centro de Estudos de Ciencia Animal, Instituto de Ciencias e Tecnologias Agrarias e Agro-Alimentares, Campus Agrario de Vairao, Rua Padre Armando Quintas, 4485-661 Vairao (Portugal); Afonso, A. [FMDUP-Faculdade de Medicina Dentaria da Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto (Portugal); Ali, N. [Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Santos, J.D. [INEB-Instituto de Engenharia Biomedica, Laboratorio de Biomateriais, Rua Campo Alegre, 823, 4150-180, Porto (Portugal) and FEUP-Faculdade de Engenharia da Universidade do Porto, DEMM, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal)]. E-mail:


    Synthetic bone grafts have been developed to provide an alternative to autografts and allografts. Bonelike (registered) is a patented synthetic osteoconductive bone graft that mimics the mineral composition of natural bone. In the present preliminary animal studies a user-friendly version of synthetic bone graft Bonelike (registered) have been developed by using a resorbable matrix, Floseal (registered) , as a vehicle and raloxifene hydrochloride as a therapeutic molecule, that is known to decrease osteoclast activity and therefore enhanced bone formation. From histological and scanning electron microscopy evaluations, the use of Bonelike (registered) associated with Floseal (registered) and raloxifene hydrochloride showed that new bone was rapidly apposed on implanted granules and also that the presence of the matrix and therapeutic molecule does not alter the proven highly osteoconductivity properties of Bonelike (registered) . Therefore, this association may be one step-forward for the clinical applications of Bonelike (registered) scaffolds since it is much more easy-to-handle when compared to granular materials.

  14. Bioreactor cultivation of anatomically shaped human bone grafts. (United States)

    Temple, Joshua P; Yeager, Keith; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana; Grayson, Warren L


    In this chapter, we describe a method for engineering bone grafts in vitro with the specific geometry of the temporomandibular joint (TMJ) condyle. The anatomical geometry of the bone grafts was segmented from computed tomography (CT) scans, converted to G-code, and used to machine decellularized trabecular bone scaffolds into the identical shape of the condyle. These scaffolds were seeded with human bone marrow-derived mesenchymal stem cells (MSCs) using spinner flasks and cultivated for up to 5 weeks in vitro using a custom-designed perfusion bioreactor system. The flow patterns through the complex geometry were modeled using the FloWorks module of SolidWorks to optimize bioreactor design. The perfused scaffolds exhibited significantly higher cellular content, better matrix production, and increased bone mineral deposition relative to non-perfused (static) controls after 5 weeks of in vitro cultivation. This technology is broadly applicable for creating patient-specific bone grafts of varying shapes and sizes.

  15. Molecular packing in bone collagen fibrils prior to mineralization (United States)

    Hsiao, Benjamin; Zhou, Hong-Wen; Burger, Christian; Chu, Benjamin; Glimcher, Melvin J.


    The three-dimensional packing of collagen molecules in bone collagen fibrils has been largely unknown because even in moderately mineralized bone tissues, the organic matrix structure is severely perturbed by the deposition of mineral crystals. During the past decades, the structure of tendon collagen (e.g. rat tail) --- a tissue that cannot mineralize in vivo, has been assumed to be representative for bone collagen fibrils. Small-angle X-ray diffraction analysis of the native, uncalcified intramuscular fish bone has revealed a new molecular packing scheme, significantly different from the quasi-hexagonal arrangement often found in tendons. The deduced structure in bone collagen fibrils indicates the presence of spatially discrete microfibrils, and an arrangement of intrafibrillar space to form ``channels'', which could accommodate crystals with dimensions typically found in bone apatite.

  16. Bone cysts: unicameral and aneurysmal bone cyst. (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K


    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

  17. 松质骨骨基质明胶负载软骨细胞移植修复兔膝关节软骨缺损%Cancellous bone matrix gelatin engineered chondrocyte transplantation for the repair of rabbit articular cartilage defects

    Institute of Scientific and Technical Information of China (English)

    宋红星; 沈惠良; 王民; 刘淼; 曹峻岭; 郭雄


    目的应用松质骨骨基质明胶(bone matrix gelatin,BMG)负载兔软骨细胞移植修复同种异体关节软骨缺损.方法 BMG负载软骨细胞,体外培养12 d后植入同种异体新西兰兔膝关节软骨缺损.对照组植入BMG或不作任何植入.移植前用胰蛋白酶处理关节软骨缺损.术后2、4、8、12、24周行解剖显微镜、组织学、电镜观察和免疫组织化学染色.结果 BMG术后8周降解.实验组术后24周关节软骨缺损以软骨组织修复,与周围软骨及软骨下骨愈合良好.Safranin-O、免疫组织化学染色证实其基质有蛋白多糖和Ⅱ型胶原,电镜观察表明修复组织软骨细胞及基质与正常关节软骨一致.BMG对照组以部分软骨组织修复,空白对照组以纤维组织修复.结论松质骨BMG可作为软骨组织工程的天然细胞支架,其负载软骨细胞移植能修复同种异体兔关节软骨缺损.

  18. Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model. (United States)

    Chen, Guobao; Yang, Li; Lv, Yonggang


    To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing.

  19. Characterizing the inorganic/organic interface in cancer bone metastasis (United States)

    Wu, Fei

    Bone metastasis frequently occurs in patients with advanced breast cancer and remains a major source of mortality. At the molecular level, bone is a nanocomposite composed of inorganic bone mineral deposited within an organic extracellular matrix (ECM). Although the exact mechanisms of bone metastasis remain unclear, the nanoscale materials properties of bone mineral have been implicated in this process. Bone apatite is closely related to synthetic hydroxyapatite (HAP, Ca10(PO4)6(OH)2) in terms of structural and mechanical properties. Additionally, although the primary protein content of bone is collagen I, the glycoprotein fibronectin (Fn) is essential in maintaining the overall integrity of the bone matrix. Importantly, in vivo, neither breast cancer cells nor normal bone cells interact directly with the bone mineral but rather with the protein film adsorbed onto the mineral surface. Therefore, we hypothesized that breast cancer cell functions were regulated by differential fibronectin adsorption onto hydroxyapatite, which led to pathological remodeling of the bone matrix and sustained bone metastasis. Three model systems containing HAP and Fn were developed for this thesis. In model system I, a library of synthetic HAP nanoparticles were utilized to investigate the effect of mineral size, shape, and crystallinity on Fn conformation, using Forster resonance energy transfer (FRET) spectroscopy. In model system II, Fn-functionalized large geologic HAP crystals were used instead of HAP nanoparticles to avoid cellular uptake when investigating subsequent cell functions. Overall our FRET analysis (models I and II) revealed that Fn conformation depended on size, surface chemistry, and roughness of underlying HAP. When breast cancer cells were seeded on the Fn-coated HAP crystal facets (model II), our data indicated high secretion levels of proangiogenic and proinflammatory factors associated with the presence of unfolded Fn conformations, likely caused by differential

  20. Interactions between inorganic and organic phases in bone tissue as a source of inspiration for design of novel nanocomposites

    NARCIS (Netherlands)

    Farbod, K.; Nejadnik, M.R.; Jansen, J.A.; Leeuwenburgh, S.C.G.


    Mimicking the nanostructure of bone and understanding the interactions between the nanoscale inorganic and organic components of the extracellular bone matrix are crucial for the design of biomaterials with structural properties and a functionality similar to the natural bone tissue. Generally, thes

  1. Application of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold on tissue engineering cartilage in vitro%自体骨髓间质干细胞外基质支架在体外软骨组织工程中的应用

    Institute of Scientific and Technical Information of China (English)

    唐成; 徐燕; 王黎明; 苗登顺; 裴璇; 魏波; 杜小涛; 金成哲


    Objective To evaluate the feasibility of the formation of tissue engineering cartilage in vitro by using autologous bone marrow mesenchymal stem cell-derived extracellular matrix (aBMSC-dECM)scaffold.Methods The autologous bone marrow mesenchymal stem cells were harvested from 5 New Zealand white rabbits which are two weeks old.The extracellular matrix was collected after 4 weeks culture and fabricated into aBMSC-dECM scaffold.The scaffold was investigated by a scanning electron microscope and HE staining.The autologous articular chondrocytes were isolated,cultured and seeded into the aBMSC-dECM scaffold.Live-Dead staining was analyzed 48 h after seeding.Gross morphological and volume measurement,HE staining,Safranin-O staining and type Ⅱ collagen immunohistochemistry staining,RT-PCRassay,and compression strength test were operated for the cell-scaffold composite at 1,2,4,and 6 weeks after the cultivation respectively.Atelocollagen scaffold was used as the control group.Results The aBMSC-dECM scaffold was three-dimensional and spongy.The engineered cartilage in aBMSC-dECM scaffold group appeared milk white in color with smooth and glossy surface.Compared with the atelocollagen scaffold group,the volume of engineered cartilage in aBMSC-dECM scaffold group significantly grew with time,the chondrocyte,proteoglycan and type Ⅱ collagen were gradually accumulated,the mRNA of type Ⅱ collage and Aggrecan were constantly expressed,and the compressive strength significantly increased with time.Conclusion The aBMSC-dECM scaffold could enhance the viability and biological function of chondrocytes,and promote engineered cartilage regeneration.It could be a novel candidate scaffold for cartilage tissue engineering.%目的 探讨利用自体骨髓间质干细胞外基质(autologous bone marrow mesenchymal stemcell-derived extracellular matrix,aBMSC-dECM)支架体外制备组织工程软骨的可行性.方法 取2周龄新西兰大白兔5只,分离、培养骨

  2. Microfibrous {beta}-TCP/collagen scaffolds mimic woven bone in structure and composition

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Shen; Zhang Xin; Cai Qing; Yang Xiaoping [Key Laboratory of Beijing City on Preparation and Processing of Novel Polymer Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Wang Bo; Deng Xuliang, E-mail: [Department of VIP Dental Service, School and Hospital of Stomatology, Peking University, Beijing 100081 (China)


    Woven bone, as the initial form of bone tissue, is always found in developing and repairing bone. It is thought of as a temporary scaffold for the deposition of osteogenic cells and the laying down of lamellar bone. Thus, we hypothesize that a matrix which resembles the architecture and components of woven bone can provide an osteoblastic microenvironment for bone cell growth and new bone formation. In this study, woven-bone-like beta-tricalcium phosphate ({beta}-TCP)/collagen scaffolds were fabricated by sol-gel electrospinning and impregnating methods. Optimization studies on sol-gel synthesis and electrospinning process were conducted respectively to prepare pure {beta}-TCP fibers with dimensions close to mineralized collagen fibrils in woven bone. The collagen-coating layer prepared by impregnation had an adhesive role that held the {beta}-TCP fibers together, and resulted in rapid degradation and matrix mineralization in in vitro tests. MG63 osteoblast-like cells seeded on the resultant scaffolds showed three-dimensional (3D) morphologies, and merged into multicellular layers after 7 days culture. Cytotoxicity test further revealed that extracts from the resultant scaffolds could promote the proliferation of MG63 cells. Therefore, the woven-bone-like matrix that we constructed favored the attachment and proliferation of MG63 cells in three dimensions. It has great potential ability to shorten the time of formation of new bone.

  3. Parallelism in matrix computations

    CERN Document Server

    Gallopoulos, Efstratios; Sameh, Ahmed H


    This book is primarily intended as a research monograph that could also be used in graduate courses for the design of parallel algorithms in matrix computations. It assumes general but not extensive knowledge of numerical linear algebra, parallel architectures, and parallel programming paradigms. The book consists of four parts: (I) Basics; (II) Dense and Special Matrix Computations; (III) Sparse Matrix Computations; and (IV) Matrix functions and characteristics. Part I deals with parallel programming paradigms and fundamental kernels, including reordering schemes for sparse matrices. Part II is devoted to dense matrix computations such as parallel algorithms for solving linear systems, linear least squares, the symmetric algebraic eigenvalue problem, and the singular-value decomposition. It also deals with the development of parallel algorithms for special linear systems such as banded ,Vandermonde ,Toeplitz ,and block Toeplitz systems. Part III addresses sparse matrix computations: (a) the development of pa...

  4. Regulation of Bone Metabolism. (United States)

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi


    Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation, and bone homeostasis are controlled by various markers and signaling pathways. Bone needs to be remodeled to maintain integrity with osteoblasts, which are bone-forming cells, and osteoclasts, which are bone-degrading cells.In this review we considered the major factors and signaling pathways in bone formation; these include fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), wingless-type (Wnt) genes, runt-related transcription factor 2 (RUNX2) and osteoblast-specific transcription factor (osterix or OSX).

  5. Regulation of Bone Metabolism (United States)

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi


    Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation, and bone homeostasis are controlled by various markers and signaling pathways. Bone needs to be remodeled to maintain integrity with osteoblasts, which are bone-forming cells, and osteoclasts, which are bone-degrading cells.In this review we considered the major factors and signaling pathways in bone formation; these include fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), wingless-type (Wnt) genes, runt-related transcription factor 2 (RUNX2) and osteoblast-specific transcription factor (osterix or OSX). PMID:28367467

  6. Phosphine in various matrixes

    Institute of Scientific and Technical Information of China (English)


    Matrix-bound phosphine was determined in the Jiaozhou Bay coastal sediment, in prawn-pond bottom soil, in the eutrophic lake Wulongtan, in the sewage sludge and in paddy soil as well. Results showed that matrix-bound phosphine levels in freshwater and coastal sediment, as well as in sewage sludge, are significantly higher than that in paddy soil. The correlation between matrix bound phosphine concentrations and organic phosphorus contents in sediment samples is discussed.

  7. Technical aspects of bone scintigraphy. (United States)

    Brown, M L; O'Connor, M K; Hung, J C; Hayostek, R J


    Optimal bone scintigraphy is obtained by using a current generation gamma camera with a high-resolution collimator, minimizing the patient-to-collimator distance, using scatter reduction techniques where possible, and obtaining a 500,000 to 1 million count image for 40-cm field of view camera. Hard copy images from an analog or digital formatter should be optimized to display all intensities either on the same images or, when necessary, to display the low count information on one image and the high count information on another. Additional images using different collimators, such as converging or pinhole collimators, and oblique and lateral views should be obtained when necessary to demonstrate or define the pathologic area. To optimize SPECT imaging, the following parameters should be used: a high-resolution collimator, a 128 x 128 acquisition matrix, and minimum separation between the patient and the collimator, which may require the use of an elliptic orbit. Between 64 and 128 views should be obtained, and depending on preference, the planar data should be prefiltered with a Butterworth, order 8-12 and a cutoff at 0.5 Nyquist. The data should then be reconstructed using a simple ramp filter. This method provides a good technique when one is first beginning to perform bone SPECT. Attenuation correction is not generally beneficial for SPECT bone studies, although sometimes weighted backprojection may improve image contrast and resolution. Finally, the use of volume rendering may help clarify the location of suspect lesions.

  8. Mixed matrix membrane development. (United States)

    Kulprathipanja, Santi


    Two types of mixed matrix membranes were developed by UOP in the late 1980s. The first type includes adsorbent polymers, such as silicalite-cellulose acetate (CA), NaX-CA, and AgX-CA mixed matrix membranes. The silicalite-CA has a CO(2)/H(2) selectivity of 5.15 +/- 2.2. In contrast, the CA membrane has a CO(2)/H(2) selectivity of 0.77 +/- 0.06. The second type of mixed matrix membrane is PEG-silicone rubber. The PEG-silicone rubber mixed matrix membrane has high selectivity for polar gases, such as SO(2), NH(3), and H(2)S.

  9. Microspectroscopic evidence of cretaceous bone proteins.

    Directory of Open Access Journals (Sweden)

    Johan Lindgren

    Full Text Available Low concentrations of the structural protein collagen have recently been reported in dinosaur fossils based primarily on mass spectrometric analyses of whole bone extracts. However, direct spectroscopic characterization of isolated fibrous bone tissues, a crucial test of hypotheses of biomolecular preservation over deep time, has not been performed. Here, we demonstrate that endogenous proteinaceous molecules are retained in a humerus from a Late Cretaceous mosasaur (an extinct giant marine lizard. In situ immunofluorescence of demineralized bone extracts shows reactivity to antibodies raised against type I collagen, and amino acid analyses of soluble proteins extracted from the bone exhibit a composition indicative of structural proteins or their breakdown products. These data are corroborated by synchrotron radiation-based infrared microspectroscopic studies demonstrating that amino acid containing matter is located in bone matrix fibrils that express imprints of the characteristic 67 nm D-periodicity typical of collagen. Moreover, the fibrils differ significantly in spectral signature from those of potential modern bacterial contaminants, such as biofilms and collagen-like proteins. Thus, the preservation of primary soft tissues and biomolecules is not limited to large-sized bones buried in fluvial sandstone environments, but also occurs in relatively small-sized skeletal elements deposited in marine sediments.

  10. The materials used in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Tereshchenko, V. P., E-mail:; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M. [Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk (Russian Federation)


    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  11. Chondroblastoma with secondary aneurysmal bone cyst of the capitate. (United States)

    Sato, Eiichi; Ichikawa, Jiro; Ando, Takashi; Sato, Nobutaka; Kawasaki, Tomonori; Haro, Hirotaka


    Chondroblastoma is a benign tumor that typically arises in the epiphysis of a long bone. There have been only 2 reported cases of chondroblastoma involving the capitate. This is the first report of chondroblastoma with secondary aneurysmal bone cyst involving the capitate. A 33-year-old man presented with a 3-year history of pain and swelling of the right wrist. Radiography as well as computed tomography showed a radiolucent area and no matrix calcification within the capitate. Magnetic resonance imaging revealed a homogeneous signal that was low on T1-weighted images and high on T2-weighted images and showed only slight enhancement. On the basis of imaging findings, the authors chose excisional biopsy. The bone tumor in the capitate was explored through a dorsal approach by dividing the extensor tendons. After repeated curettages, bone graft substitute using allograft bone was packed into the capitate. Histologically, the authors diagnosed this tumor as a chondroblastoma with a secondary aneurysmal bone cyst. At the final 2-year follow-up, there was evidence of bone union, full range of motion, and recovery and no evidence of recurrence. Although the recurrence of chondroblastoma is occasionally reported, the principal treatment is intralesional curettage and bone graft. High-speed burring, phenol, bone cement, and cryosurgery have been reported to reduce local recurrence. Complete excision of the carpal bone seems to be overtreatment.

  12. Detection of drugs of forensic importance in postmortem bone. (United States)

    McGrath, Kelly K; Jenkins, Amanda J


    There is a paucity of literature detailing the disposition of drugs in bone and bone marrow. Infrequently, in deaths involving skeletonized remains, fragmentation, decomposition, and exsanguination, traditional specimens may be unavailable for toxicological testing. This study examined the utility of bone for the detection of benzodiazepines, opiates, cocaine and metabolites, and basic drugs in 39 cases. Cases were identified on the basis of a positive blood result. After specimen preparation, samples were assayed by liquid-liquid or solid phase extraction with gas chromatographic and gas chromatographic mass spectrometric detection. The majority of decedents were white males with 28% of individuals between the ages of 41 to 50 years. The cause of death was drug intoxication in 22 cases. The most prevalent drugs detected in the blood males and females were opiates and bases. Morphine, codeine, and oxycodone were detected in bone, whereas 6-acetylmorphine and hydrocodone were absent. For alkaline extractable drugs, in only 57% of blood positive specimens, the corresponding bone was also positive. These included antidepressants and antihistamines. Diazepam and nordiazepam were detected in the bone of all blood positive cases. Bone concentrations were higher than blood levels. Benzoylecgonine was the most common cocaine analyte detected in bone. These data demonstrated that drugs may be detected in bone using current technologies and that in general concentrations were higher than those observed in corresponding blood specimens. A negative result in bone, however, should be interpreted with caution because multiple factors determine the deposition of a drug in this matrix.

  13. Solid aneurysmal bone cyst in the humerus

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Tetsuji; Marui, Takashi; Akisue, Toshihiro; Mizuno, Kosaku [Dept. of Orthopaedic Surgery, Kobe University School of Medicine, Chuo-Ku (Japan)


    We report on a 69-year-old woman with a solid variant of aneurysmal bone cyst (solid ABC) in the left humerus with a pathological fracture. Radiographically, the lesion exhibited a relatively well-defined osteolytic lesion in the diaphysis of the left humerus. On magnetic resonance (MR) imaging, the medullary lesion exhibited a homogeneous signal intensity isointense with surrounding normal muscles on the T1-weighted images and a mixture of low and high signal intensity on the T2-weighted images. Contrast-enhanced T1-weighted images revealed diffuse enhancement of the entire lesion. The pathological study showed a proliferation of fibroblasts, histiocytes, chronic inflammatory cells and numerous multinucleated giant cells in a collagenous matrix. Abundant osteoid formation in the matrix was observed, but the cells were devoid of nuclear atypia. Aneurysmal cystic cavities were absent. A review of the English literature found 22 cases of solid ABC of the long bones. (orig.)

  14. Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

    Directory of Open Access Journals (Sweden)

    F Shapiro


    Full Text Available Bone development occurs by two mechanisms: intramembranous bone formation and endochondral bone formation. Bone tissue forms by eventual differentiation of osteoprogenitor cells into either mesenchymal osteoblasts (MOBL, which synthesize woven bone in random orientation, or surface osteoblasts (SOBL, which synthesize bone on surfaces in a well oriented lamellar array. Bone repair uses the same formation patterns as bone development but the specific mechanism of repair is determined by the biomechanical environment provided. Bone synthesis and maintenance are highly dependent on the blood supply of bone and on cell-cell communication via the lacunar-canalicular system. Recent investigations highlight the molecular cascades leading to cell differentiation, the components of the structural proteins such as the various collagens, and tissue vascularization. The patterning of bone matrix from an initial woven to an eventual lamellar orientation is essential for bone to develop its maximum strength. This review demonstrates the repetitive nature of woven to lamellar bone formation as mediated by MOBLs and SOBLs in both normal vertebrate bones and bone repair. Repair, using endochondral, primary, direct and distraction osteogenesis mechanisms, is reviewed along with the associated molecular, vascular, and biophysical features.

  15. A nano-hydroxyapatite--pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering. (United States)

    Fricain, Jean Christophe; Schlaubitz, Silke; Le Visage, Catherine; Arnault, Isabelle; Derkaoui, Sidi Mohammed; Siadous, Robin; Catros, Sylvain; Lalande, Charlotte; Bareille, Reine; Renard, Martine; Fabre, Thierry; Cornet, Sandro; Durand, Marlène; Léonard, Alain; Sahraoui, Nouredine; Letourneur, Didier; Amédée, Joëlle


    Research in bone tissue engineering is focused on the development of alternatives to allogenic and autologous bone grafts that can stimulate bone healing. Here, we present scaffolds composed of the natural hydrophilic polysaccharides pullulan and dextran, supplemented or not with nanocrystalline hydroxyapatite particles (nHA). In vitro studies revealed that these matrices induced the formation of multicellular aggregates and expression of early and late bone specific markers with human bone marrow stromal cells in medium deprived of osteoinductive factors. In absence of any seeded cells, heterotopic implantation in mice and goat, revealed that only the composite macroporous scaffold (Matrix + nHA) (i) retained subcutaneously local growth factors, including Bone Morphogenetic Protein 2 (BMP2) and VEGF165, (ii) induced the deposition of a biological apatite layer, (iii) favored the formation of a dense mineralized tissue subcutaneously in mice, as well osteoid tissue after intramuscular implantation in goat. The composite scaffold was thereafter implanted in orthotopic preclinical models of critical size defects, in small and large animals, in three different bony sites, i.e. the femoral condyle of rat, a transversal mandibular defect and a tibial osteotomy in goat. The Matrix + nHA induced a highly mineralized tissue in the three models whatever the site of implantation, as well as osteoid tissue and bone tissue regeneration in direct contact to the matrix. We therefore propose this composite matrix as a material for stimulating bone cell differentiation of host mesenchymal stem cells and bone formation for orthopedic and maxillofacial surgical applications.

  16. Selective retention of bone marrow-derived cells to enhance spinal fusion. (United States)

    Muschler, George F; Matsukura, Yoichi; Nitto, Hironori; Boehm, Cynthia A; Valdevit, Antonio D; Kambic, Helen E; Davros, William J; Easley, Kirk A; Powell, Kimerly A


    Connective tissue progenitors can be concentrated rapidly from fresh bone marrow aspirates using some porous matrices as a surface for cell attachment and selective retention, and for creating a cellular graft that is enriched with respect to the number of progenitor cells. We evaluated the potential value of this method using demineralized cortical bone powder as the matrix. Matrix alone, matrix plus marrow, and matrix enriched with marrow cells were compared in an established canine spinal fusion model. Fusions were compared based on union score, fusion mass, fusion volume, and by mechanical testing. Enriched matrix grafts delivered a mean of 2.3 times more cells and approximately 5.6 times more progenitors than matrix mixed with bone marrow. The union score with enriched matrix was superior to matrix alone and matrix plus marrow. Fusion volume and fusion area also were greater with the enriched matrix. These data suggest that the strategy of selective retention provides a rapid, simple, and effective method for concentration and delivery of marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting procedures in various clinical settings.

  17. Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

    DEFF Research Database (Denmark)

    Delaissé, Jean-Marie; Andersen, Thomas L; Engsig, Michael T;


    is based on a model of osteoclast recruitment in primitive long bones, an assay of osteoclast invasion through collagen gel, and the effect of proteinase inhibitors/knockouts in these models. Furthermore, we mention observations indicating a role of MMPs in initiation of bone resorption. Finally, we......The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute...

  18. Patience of matrix games

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Ibsen-Jensen, Rasmus; Podolskii, Vladimir V.;


    For matrix games we study how small nonzero probability must be used in optimal strategies. We show that for image win–lose–draw games (i.e. image matrix games) nonzero probabilities smaller than image are never needed. We also construct an explicit image win–lose game such that the unique optimal...

  19. What Is Bone Cancer? (United States)

    ... start in bone, muscle, fibrous tissue, blood vessels, fat tissue, as well as some other tissues. They can develop anywhere in the body. There are several different types of bone tumors. Their names are based on ...

  20. Osteochondroma (Bone Tumor) (United States)

    ... to be the most common benign bone tumor, accounting for 35% to 40% of all benign bone ... imaging scans. Doctors may also request computed tomography (CT) scans or magnetic resonance imaging (MRI) scans to ...

  1. What causes bone loss? (United States)

    ... bone biology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier; 2016:chap 29. Maes C, Kronenberg HM. Bone development and remodeling. In: Jameson JL, ...

  2. Bone mineral density test (United States)

    BMD test; Bone density test; Bone densitometry; DEXA scan; DXA; Dual-energy x-ray absorptiometry; p-DEXA; Osteoporosis-BMD ... need to undress. This scan is the best test to predict your risk of fractures. Peripheral DEXA ( ...

  3. Androgens and bone. (United States)

    Vanderschueren, Dirk; Vandenput, Liesbeth; Boonen, Steven; Lindberg, Marie K; Bouillon, Roger; Ohlsson, Claes


    Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs. Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and

  4. Gracile bone dysplasias

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, Kazimierz [Department of Medical Imaging, The Children' s Hospital at Westmead, Locked Bag 4001, Westmead 2145, NSW (Australia); Masel, John [Department of Radiology, Royal Children' s Hospital, Brisbane (Australia); Sillence, David O. [Department of Paediatrics and Child Health, The University of Sydney (Australia); Arbuckle, Susan [Department of Anatomical Pathology, The Children' s Hospital at Westmead, NSW (Australia); Juttnerova, Vera [Oddeleni Lekarske Genetiky, Hradec Kralove (Czech Republic)


    Gracile bone dysplasias constitute a group of disorders characterised by extremely slender bones with or without fractures. We report four newborns, two of whom showed multiple fractures. Two babies had osteocraniostenosis and one had features of oligohydramnios sequence. The diagnosis in the fourth newborn, which showed thin long bones and clavicles and extremely thin, poorly ossified ribs, is uncertain. Exact diagnosis of a gracile bone dysplasia is important for genetic counselling and medico-legal reasons. (orig.)

  5. Matrix Metalloproteinases as Regulators of Periodontal Inflammation (United States)

    Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández


    Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

  6. The critical role of bisphosphonates to target bone cancer metastasis: an overview. (United States)

    Singh, Tejinder; Kaur, Veerpal; Kumar, Manish; Kaur, Prabhjot; Murthy, R S R; Rawal, Ravindra K


    Cancer becomes the leading cause of deaths worldwide, including breast cancer, prostate cancer and lung cancer that preferentially metastasize to bone and bone marrow. Bisphosphonates (BPs) have been used successfully for many years to reduce the skeletal complications related with the benign and malignant bone diseases that are characterized by enhanced osteoclastic bone resorption. Nitrogen-containing bisphosphonates (N-BPs) have also been demonstrated to exhibit direct anti-tumour effects. BPs binds avidly to the bone matrix, and released from matrix during bone resorption process, BPs are internalized by the osteoclasts where they interfere with biochemical pathways and induce osteoclast apoptosis. BPs also antagonizes the production of osteoclast and promotes the osteoblasts proliferation. Currently, Zoledronic acid is widely used as one of the BP having high bone specificity and potential to inhibit the osteoclast-mediated bone resorption. In addition to inhibition of cell multiplication and initiation of apoptosis in cultured cancer cells, they also interfere with adhesion of cancer cells to the bone matrix and inhibit cell migration and invasion. Pathophysiology and current target therapies like conjugate of BPs with liposomes, nanoparticle used for the treatment of bone cancer is reviewed in this article along with the use of different BPs.

  7. Enzymatic maceration of bone

    DEFF Research Database (Denmark)

    Uhre, Marie-Louise; Eriksen, Anne Marie; Simonsen, Kim Pilkjær;


    the bones. The DNA analysis showed that DNA was preserved on all the pieces of bones which were examined. Finally, the investigation suggests that enzyme maceration could be gentler on the bones, as the edges appeared less frayed. The enzyme maceration was also a quicker method; it took three hours compared...

  8. Simulation of fracture of the bone implant with the porous structure (United States)

    Korobenkov, M. V.; Kulkov, S. N.


    Different approaches to bone defects reconstruction with the use of ceramic materials have been developed recently. Ceramics are identical with bone matrix, provide biomedical compatibility with bone tissue and possess high strength. But with an overall high strength ceramic implants destruct in dynamic mode. The paper presents a study of the effect of the porosity gradient on the destruction of the bone implants under dynamic loading. It is shown that the fracture behavior of the bone implants is changed with increasing levels of the gradient of porosity.

  9. Characteristics of alveolar bone associated with physiological movement of molar in mice: a histological and histochemical study. (United States)

    Matsuda, Kie; Haga-Tsujimura, Maiko; Yoshie, Sumio; Shimomura-Kuroki, Junko


    Mouse molars undergo distal movement, during which new bone is formed at the mesial side of the tooth root whereas the preexisting bone is resorbed at the distal side of the root. However, there is little detailed information available regarding which of the bones that surround the tooth root are involved in physiological tooth movement. In the present study, we therefore aimed to investigate the precise morphological differences of the alveolar bone between the bone formation side of the tooth root, using routine histological procedures including silver impregnation, as well as by immunohistochemical analysis of alkaline phosphatase and tartrate-resistant acid phosphatase activity, and immunohistochemical analysis of the expression of the osteocyte markers dentin matrix protein 1, sclerostin, and fibroblast growth factor 23. Histochemical analysis indicated that bone formation by osteoblasts and bone resorption by osteoclasts occurred at the bone formation side and the bone resorption side, respectively. Osteocyte marker immunoreactivity of osteocytes at the surface of the bone close to the periodontal ligament differed at the bone formation and bone resorption sides. We also showed different specific features of osteocytic lacunar canalicular systems at the bone formation and bone resorption sides by using silver staining. This study suggests that the alveolar bone is different in the osteocyte nature between the bone formation side and the bone resorption side due to physiological distal movement of the mouse molar.

  10. Improved Matrix Uncertainty Selector

    CERN Document Server

    Rosenbaum, Mathieu


    We consider the regression model with observation error in the design: y=X\\theta* + e, Z=X+N. Here the random vector y in R^n and the random n*p matrix Z are observed, the n*p matrix X is unknown, N is an n*p random noise matrix, e in R^n is a random noise vector, and \\theta* is a vector of unknown parameters to be estimated. We consider the setting where the dimension p can be much larger than the sample size n and \\theta* is sparse. Because of the presence of the noise matrix N, the commonly used Lasso and Dantzig selector are unstable. An alternative procedure called the Matrix Uncertainty (MU) selector has been proposed in Rosenbaum and Tsybakov (2010) in order to account for the noise. The properties of the MU selector have been studied in Rosenbaum and Tsybakov (2010) for sparse \\theta* under the assumption that the noise matrix N is deterministic and its values are small. In this paper, we propose a modification of the MU selector when N is a random matrix with zero-mean entries having the variances th...

  11. Growth and differentiation of a long bone in limb development, repair and regeneration. (United States)

    Egawa, Shiro; Miura, Shinichirou; Yokoyama, Hitoshi; Endo, Tetsuya; Tamura, Koji


    Repair from traumatic bone fracture is a complex process that includes mechanisms of bone development and bone homeostasis. Thus, elucidation of the cellular/molecular basis of bone formation in skeletal development would provide valuable information on fracture repair and would lead to successful skeletal regeneration after limb amputation, which never occurs in mammals. Elucidation of the basis of epimorphic limb regeneration in amphibians would also provide insights into skeletal regeneration in mammals, since the epimorphic regeneration enables an amputated limb to re-develop the three-dimensional structure of bones. In the processes of bone development, repair and regeneration, growth of the bone is achieved through several events including not only cell proliferation but also aggregation of mesenchymal cells, enlargement of cells, deposition and accumulation of extracellular matrix, and bone remodeling.

  12. Oxytocin and bone (United States)

    Sun, Li; Zaidi, Mone; Zallone, Alberta


    One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR−/− mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

  13. Relation Between Bone Matrix Proteins and Monocyte Chemoattractant Protein-1 in Renal Small Artery in Diabetic Nephropathy Rats%糖尿病肾病大鼠肾小动脉骨基质蛋白表达及其与MCP-1的关系

    Institute of Scientific and Technical Information of China (English)

    赵安菊; 黄颂敏; 欧三桃; 刘芳; 陈泽君; 胡章学; 唐万欣


    of bone matrix proteins and monocyte chemoattractant protein-1 ((MCP-1) in the renal arteriole of diabetic nephropathy CDN) rats and analyze their correlations and roles in diabetic nephropathy. Methods Adult Sprague-Dawley male rats were used to establish the animal model of diabetic nephropathy induced by peritoneal injection of 55 mg/kg of streptozocin. Calcium deposit around the renal arteriole was observed by alizarin red staining. The protein and mRNA levels of core-bind factor alpha 1 (cbfα1), bone morphogenetic protein 2 (BMP-2) and matrix Gla protein (MGP) in renal arteriole of DN rats were detected by immunohistochemistry, in-situ hybridization and real-time PCR. The biochemical indices were detected by routine test. Results ①Blood glucose and Urine protein of 24 h were significantly increased in the renal arteriole of DN rats vs. the control rats (P<0. 05),serum creatinine (SCr) and phosphorus were significantly increased from 12 weeks. ② Little deposit of calcium salt was observed in the renal arteriole of DN rats at the 4th week and a large amount of deposit was observed at 24th week, but no calcium deposit was observed in control rats. ③Cbfal and BMP-2 expressions were significantly increased in the renal arteriole of DN rats from 4 to 24 weeks vs. the control rats. MGP mRNA expression in the renal arteriole of DN rats was significantly decreased from 4 to 24 weeks. MCP-1 expression was obviously upregulated in the renal arteriole of DN rats at 24th week vs. that at 4th and 12th week. No MCP-1 expression was observed in the renal arterioles of control rats. ④MCP-1 were positively correlated with the expression of cbfα1 and BMP-2. Conclusion bone matrix proteins has already expressed in renal arteriole before the formation of vascular calcification. MCP-1 can affect the expression of cbfα1,BMP-2 ;Cbfα1. BMP-2, MGP and MCP-1 may be involved in the formation of vascular lesions of DN.

  14. Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice. (United States)

    Hankenson, K D; James, I E; Apone, S; Stroup, G B; Blake, S M; Liang, X; Lark, M W; Bornstein, P


    Although bone is composed primarily of extracellular matrix (ECM), the dynamic role that the ECM plays in regulating bone remodeling secondary to estrogen loss is relatively unexplored. Previous studies have shown that mice deficient in the matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone; thus, we postulated that enhanced bone formation in TSP2-null mice could protect against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a significant loss of both midfemoral endocortical and proximal tibial trabecular bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed an increase in bone formation, as indicated by a 70% increase in serum osteocalcin two weeks post OVX and a two-fold increase in bone formation rate (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR at five weeks. This increase in bone formation in TSP2-null OVX mice was accompanied by a three-fold increase in osteoprogenitor number. Although these results provide a partial explanation for the maintenance of bone geometry post-OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level of bone resorption than OVX WT mice, as determined by serum levels of the amino-terminal telopeptide of type I collagen (NTx). We conclude that the absence of TSP2 protects against OVX-induced bone loss by two complementary processes: increased formation and decreased resorption.

  15. Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

    Directory of Open Access Journals (Sweden)

    PPY Lui


    Full Text Available Peri-tunnel bone loss after anterior cruciate ligament (ACL reconstruction is commonly observed, both clinically and experimentally. We aimed to study the effect and mechanisms of different doses of alendronate in the reduction of peri-tunnel bone loss and promotion of graft-bone tunnel healing in ACL reconstruction. Eighty-four ACL-reconstructed rats were divided into 4 groups. Alendronate at different dosages, or saline, were injected subcutaneously weekly, for 2 or 6 weeks post-reconstruction, for vivaCT (computed tomography imaging, biomechanical tests, histology and immunohistochemistry. Alendronate significantly increased bone mass and density of tissue inside bone tunnels except at the epiphyseal region of tibial tunnel. The femoral tunnel diameter decreased significantly in the mid-dose and high-dose alendronate groups compared to that in the saline group at week 6. Alendronate significantly increased the peri-tunnel bone mass and density along all tunnel regions at week 6. Better graft-bone tunnel integration and intra-tunnel graft integrity were observed in the alendronate groups. The ultimate load was significantly higher in the mid-dose and high-dose alendronate groups at week 2, but not at week 6. There was a reduction in matrix metalloprotein (MMP1, MMP13 and CD68-positive cells at the peri-tunnel region and graft-bone interface in the alendronate-treated group compared to the saline group. Alendronate reduced peri-tunnel bone resorption, increased mineralised tissue inside bone tunnel as well as histologically and biomechanically promoted graft-bone tunnel healing, probably by reducing the expression of MMP1, MMP13 and CD68-positive cells. Alendronate might be used for reducing peri-tunnel bone loss and promoting graft-bone tunnel healing at early stage post-ACL reconstruction.

  16. Elementary matrix theory

    CERN Document Server

    Eves, Howard


    The usefulness of matrix theory as a tool in disciplines ranging from quantum mechanics to psychometrics is widely recognized, and courses in matrix theory are increasingly a standard part of the undergraduate curriculum.This outstanding text offers an unusual introduction to matrix theory at the undergraduate level. Unlike most texts dealing with the topic, which tend to remain on an abstract level, Dr. Eves' book employs a concrete elementary approach, avoiding abstraction until the final chapter. This practical method renders the text especially accessible to students of physics, engineeri

  17. Rheocasting Al matrix composites

    Energy Technology Data Exchange (ETDEWEB)

    Girot, F.A.; Albingre, L.; Quenisset, J.M.; Naslain, R.


    A development status account is given for the rheocasting method of Al-alloy matrix/SiC-whisker composites, which involves the incorporation and homogeneous distribution of 8-15 vol pct of whiskers through the stirring of the semisolid matrix melt while retaining sufficient fluidity for casting. Both 1-, 3-, and 6-mm fibers of Nicalon SiC and and SiC whisker reinforcements have been experimentally investigated, with attention to the characterization of the resulting microstructures and the effects of fiber-matrix interactions. A thin silica layer is found at the whisker surface. 7 references.

  18. The reversal phase of the bone-remodeling cycle

    DEFF Research Database (Denmark)

    Delaisse, Jean-Marie


    for the cells leading to osteogenesis during the reversal phase. This review aims at creating awareness of these cells and their activities in adult cancellous bone. It relates cell events (i) on the bone surface, (ii) in the mesenchymal envelope surrounding the bone marrow and appearing as a canopy above...... under the osteogenic influence of capillaries and osteoclasts, whereas bone surface cells become exposed to the eroded matrix and other osteoclast products. In several diverse pathophysiological situations, including osteoporosis, a decreased availability of osteoprogenitors from these local reservoirs...... coincides with decreased osteoblast recruitment and impaired initiation of bone formation, that is, uncoupling. Overall, this review stresses that coupling does not only depend on molecules able to activate osteogenesis, but that it also demands the presence of osteoprogenitors and ordered cell...

  19. [Bone marrow stromal damage mediated by immune response activity]. (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H


    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  20. Giant cell reparative granuloma of the sphenoid bone. (United States)

    Aralasmak, A; Aygun, N; Westra, W H; Yousem, D M


    We present 2 patients with giant cell reparative granuloma (GCRG) of the sphenoid bone. The first patient is an 8-year-old boy with involvement of the greater wing, and the second is a 53- year-old man with a lateral pterygoid plate mass. Both patients presented with rapid expansion of lytic bone lesions, which had solid and cystic components and lacked matrix calcification. Biopsies were indeterminate for definitive diagnoses. The radiologic appearance, location, and incidence of the lesions, and the patient's age and medical history are helpful aids in narrowing the differential diagnosis of sphenoid bone lesions. However, the imaging and, occasionally, even the histologic findings may not suggest the specific diagnosis of GCRG, which must be added into the differential diagnosis of rapidly enlarging cystic bone lesions of the sphenoid bone.

  1. Intracystic negative pressure may promote bone formation around jaw cysts

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yi; HAN Qi-bing; LIU Bing


    The growth and enlargement of jaw cysts are associated with raised intracystic pressure and bone resorption surrounding the cysts. The major bone-resorbing cells are the osteoclasts. They are acting under the influence of local bone-resorbing factors: prostaglandins, proteinases and cytokines. It was found that positive pressure enhanced the expression of IL-1αmRNA and protein in epithelial cells of odontogenic keratocyst, and increased the secretion of matrix metalloproteinase and PGE in a co-culture of odontogenic keratocyst fibroblasts and epithelial cells. However, the signal intensities for IL-1α mRNA and protein in the epithelium were significantly decreased after marsupialization which relived intracystic pressure. Experimental study indicated that intermittent negative pressure could promote osteogenesis in human bone marrow-derived stroma cells (BMSCs) in vitro. We propose a hypothesis that bone formation around the cyst of the jaws would be stimulated by intracystic negative pressure.

  2. Laminin on urinary bladder matrix promotes proliferation of bone marrow mesenchymal stem cells and differentiation into smooth muscle cells%UBM材料上的Laminin蛋白促进负载骨髓间充质干细胞增殖和平滑肌分化

    Institute of Scientific and Technical Information of China (English)

    魏桂枝; 刘晶霞; 徐萍萍; 倪兵; 刘禄斌; 梁志清


    目的 探讨猪膀胱细胞外基质(urinary bladder matrix,UBM)上的Laminin蛋白对大鼠骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)增殖和向平滑肌分化的影响.方法 采用机械分离法、酶消化法及冷冻干燥法等方法对新鲜猪膀胱进行脱细胞处理,采用蛋白与支架共孵育,制备出UBM+Laminin及UBM+Anti-Laminin复合支架.采用贴壁法培养BMSCs,流式细胞仪鉴定BMSCs.采用P3代BMSCs,分别接种于UBM+Laminin、UBM及UBM+Anti-Laminin上.采用CCK-8检测、HE染色观察及免疫组化鉴定等方法检测Laminin蛋白对BMSCs增殖、迁移和分化的影响.结果 流式细胞仪鉴定BMSCs CD29阳性表达率为98%,CD31阳性表达率为4.56%,CD34阳性率为3.30%.3种材料均能支持BMSCs生长,且随共孵育时间的延长,D(450)值逐渐升高,其中UBM+Laminin复合材料组细胞D(450)最高(P<0.01).HE染色结果显示UBM+ Laminin组细胞接种第3天形成黏附层,并向深部迁移,第14天可达材料致密层;UBM组第7天仅少许细胞向深层迁移,第14天未达基底层;UBM+Anti-Laminin组仅在支架表层生长.免疫组化检测显示UBM+Laminin组、UBM组、UBM+ Anti-Laminin组细胞α-SMA表达分别呈阳性、弱阳性和阴性.结论 UBM材料上Laminin蛋白能促进负载BMSCs增殖、迁移、并有诱导其向平滑肌方向分化的作用.

  3. Asymptomatic Paget's disease of bone presenting with complete atrioventricular block

    Institute of Scientific and Technical Information of China (English)

    A.Rauoof Malik; Nazir A.Lone; Hilal A.Rather; Vicar M Jan; Javid A.Malik; Khursheed A.Khan; S.Jalal


    @@ Paget's disease of bone is a deforming bone disease (osteitis deformans) characterized by increased bone remodeling,bone hypertrophy,and abnormal bone structure,leading to bone expansion,deformities,easy fractures,and occasionally,neoplastic transformation.It is the second most common bone disorder after osteoporosis.1 The disease is relatively rare in Asia but is common in Europe and North America,affecting approximately 2% of the population over 50 years,although lately,a decline in the prevalence has been reported.2 Paget's disease commonly affects people in or past their middle age and is slightly more common in men than in women.1 The exact cause of Paget's disease is not known.Environmental agents,particularly paramyxoviral infections (measles and canine distemper viruses) have been postulated as potential etiological factors.3 Recently,a strong genetic component has been described,with candidate loci suggested at 18q,5q35-QTER,and particularly,the squestosome 1/p62.2,3 The pathological process in Paget's disease consists of one or more areas of aggressive and relentless osteoclastic activity,coupled with deposition of structurally abnormal excessive bone and matrix tissues.1,4 Most of the cases involve only one (monostotic) or few bones,particularly skull,vertebrae,pelvis,femur,and tibia.

  4. Osteocyte regulation of bone mineral: a little give and take. (United States)

    Atkins, G J; Findlay, D M


    Osteocytes actively participate in almost every phase of mineral handling by bone. They regulate the mineralisation of osteoid during bone formation, and they are also a major RANKL-producing cell. Osteocytes are thus able to liberate bone mineral by regulating osteoclast differentiation and activity in response to a range of stimuli, including bone matrix damage, bone disuse and mechanical unloading, oestrogen deficiency, high-dose glucocorticoid and chemotherapeutic agents. At least some of these activities may be regulated by the osteocyte-secreted product, sclerostin. There is also mounting evidence that in addition to regulating phosphate homeostasis systemically, osteocytes contribute directly to calcium homeostasis in the mature skeleton. Osteocyte cell death and the local loss of control of bone mineralisation may be the cause of focal hypermineralisation of bone and osteopetrosis, as seen in aging and pathology. The sheer number of osteocytes in bone means that "a little give and take" in terms of regulation of bone mineral content translates into a powerful whole organism effect.


    Directory of Open Access Journals (Sweden)

    Wijianto Wijianto


    Full Text Available This paper discuss about ceramics in application as bone implant. Bioceramics for instance Hydroxyapatite, usually is abbreviated with HA or HAp, is a mineral that is very good physical properties as bone replacement in human body. To produce Hydroxyapatite, coating process is used which have good potential as they can exploit the biocompatible and bone bonding properties of the ceramic. There are many advantages and disadvantages of bioceramics as bone implant. Advantages of hydroxyapatite as bone implant are rapidly integrated into the human body, and is most interesting property that will bond to bone forming indistinguishable unions. On contrary, disadvantages of hydroxyapatite as bone implant are poor mechanical properties (in particular fatigue properties mean that hydroxyapatite cannot be used in bulk form for load bearing applications such as orthopaedics and poor adhesion between the calcium phosphate coating and the material implant will occur.

  6. Modified Laminar Bone in Ampelosaurus atacis and Other Titanosaurs (Sauropoda): Implications for Life History and Physiology (United States)

    Klein, Nicole; Sander, P. Martin; Stein, Koen; Le Loeuff, Jean; Carballido, Jose L.; Buffetaut, Eric


    Background Long bone histology of the most derived Sauropoda, the Titanosauria suggests that titanosaurian long bone histology differs from the uniform bone histology of basal Sauropoda. Here we describe the long bone histology of the titanosaur Ampelosaurus atacis and compare it to that of basal neosauropods and other titanosaurs to clarify if a special titanosaur bone histology exists. Methodology/Principal Findings Ampelosaurus retains the laminar vascular organization of basal Sauropoda, but throughout most of cortical growth, the scaffolding of the fibrolamellar bone, which usually is laid down as matrix of woven bone, is laid down as parallel-fibered or lamellar bone matrix instead. The remodeling process by secondary osteons is very extensive and overruns the periosteal bone deposition before skeletal maturity is reached. Thus, no EFS is identifiable. Compared to the atypical bone histology of Ampelosaurus, the large titanosaur Alamosaurus shows typical laminar fibrolamellar bone. The titanosaurs Phuwiangosaurus, Lirainosaurus, and Magyarosaurus, although differing in certain features, all show this same low amount or absence of woven bone from the scaffolding of the fibrolamellar bone, indicating a clear reduction in growth rate resulting in a higher bone tissue organization. To describe the peculiar primary cortical bone tissue of Phuwiangosaurus, Ampelosaurus, Lirainosaurus, and Magyarosaurus, we here introduce a new term, “modified laminar bone” (MLB). Conclusions/Significance Importantly, MLB is as yet not known from extant animals. At least in Lirainosaurus and Magyarosaurus the reduction of growth rate indicated by MLB is coupled with a drastic body size reduction and maybe also a reduction in metabolic rate, interpreted as a result of dwarfing on the European islands during the Late Cretaceous. Phuwiangosaurus and Ampelosaurus both show a similar reduction in growth rate but not in body size, possibly indicating also a reduced metabolic rate. The

  7. Matrix theory of gravitation

    CERN Document Server

    Koehler, Wolfgang


    A new classical theory of gravitation within the framework of general relativity is presented. It is based on a matrix formulation of four-dimensional Riemann-spaces and uses no artificial fields or adjustable parameters. The geometrical stress-energy tensor is derived from a matrix-trace Lagrangian, which is not equivalent to the curvature scalar R. To enable a direct comparison with the Einstein-theory a tetrad formalism is utilized, which shows similarities to teleparallel gravitation theories, but uses complex tetrads. Matrix theory might solve a 27-year-old, fundamental problem of those theories (sec. 4.1). For the standard test cases (PPN scheme, Schwarzschild-solution) no differences to the Einstein-theory are found. However, the matrix theory exhibits novel, interesting vacuum solutions.

  8. Pesticide-Exposure Matrix (United States)

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  9. Matrix comparison, Part 2

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Borlund, Pia


    The present two-part article introduces matrix comparison as a formal means for evaluation purposes in informetric studies such as cocitation analysis. In the first part, the motivation behind introducing matrix comparison to informetric studies, as well as two important issues influencing...... such comparisons, matrix generation, and the composition of proximity measures, are introduced and discussed. In this second part, the authors introduce and thoroughly demonstrate two related matrix comparison techniques the Mantel test and Procrustes analysis, respectively. These techniques can compare...... important. Alternatively, or as a supplement, Procrustes analysis compares the actual ordination results without investigating the underlying proximity measures, by matching two configurations of the same objects in a multidimensional space. An advantage of the Procrustes analysis though, is the graphical...

  10. In vitro short term cartilage tissue engineering with oriented cartilage extracellular matrix scaffolds and bone marrow mesenchymal stem cells%软骨细胞外基质源性取向支架与骨髓基质干细胞体外软骨组织工程的初步研究

    Institute of Scientific and Technical Information of China (English)

    姚军; 卢世璧; 彭江; 郭全义; 张莉; 黄靖香; 汪嗳媛; 许文静


    Objective To fabricate cartilage extracellular matrix (ECM) oriented scaffolds and investigate the attachment, proliferation, distribution and orientation of bone marrow mesenchymal stem cells (BMSCs) cultured within the scaffolds in vitro. Methods Cartilage slices were shattered in sterile phosphate-buffered saline (PBS) and the suspension were differentially centrifugated untill the micro- fiber of the cartilage extracellular matrix was disassociated from the residue cartilage fragments. At last the supernatant were centrifugated, the precipitation were collected and were made into 2%-3% suspension. Using unidirectional solidification as a freezing process and freeze-dried method, the cartilage extracellular matrix derived oriented scaffolds was fabricated. The scaffolds were then cross-linked by exposure to ultraviolet radiation and immersion in a carbodiimide solution. By light microscope and scan electron microscope (SEM) observation, histological staining, and biomechanical test, the traits of scaffolds were studied. After being labelled with PKH26 fluorescent dye, rabbit BMSCs were seeded onto the scaffolds. The attachment, proliferation and differentiation of the cells were analyzed using inverted fluorescent microscope. Results The histological staining showed that toluidine blue, safranin O, alcian blue and anti-collagen Ⅱ immunohistochemistry staining of the scaffolds were positive. A perpendicular pore-channel structures which has a diameter of 100 μm were verified by light microscope and SEM analysis. The cell-free scaffolds showed the compression moduli were (2.02±0.02) MPa in the mechanical testing. Inverted fluorescent microscope showed that most of the cells attached to the scaffold. Cells were found to be widely distributed within the scaffold, which acted as a columnar arrangement. The formation of a surface cells layer was found on the surface of the scaffolds which resembled natural cartilage. Coclusion The cartilage extracellular matrix

  11. Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone


    Starup-Linde, Jakob


    Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone marker...

  12. The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report (United States)

    Pennline, James; Mulugeta, Lealem


    changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise

  13. Sunlight activated lanthanide complex for luminescent solar collector applications: effect of waveguide matrix (United States)

    Shahi, Praveen Kumar; Singh, Priyam; Bahadur Rai, Shyam


    The performance of Eu(DBM)3Phen complex (EDP) dispersed in PMMA poly-(methyl methacrylate) polymer matrix, as simple planner luminescent solar collectors (LSCs) is demonstrated using spectroscopic and photovoltaic (PV) measurements. The organic ligands absorb ultra-violet-blue (UV-blue) radiation (220–450 nm) very efficiently and transfer its energy to the Eu3+ ion, which gives an intense red emission even in sunlight exposure. The excellent optical properties of EDP in PMMA permit its coating on the front surface of c-Si solar cell (10  ×  10 cm2) for PV measurements. The PV characterizations reveal the improvement in the short circuit current density (J sc) of PV cell and maximum improvement is found to be 4.6% for 2.5 wt% EDP concentration in PMMA matrix. The efficiency of solar cell increases from 17.22% to 18.33% for bare and 2.5% EDP in PMMA. At a higher concentration of EDP, the thin film starts losing its transparency and hence PV efficiency decreases. These results illustrate that a EDP complex combined with a PV cell could work as a prototype of a new generation solar cell.

  14. The Matrix Organization Revisited

    DEFF Research Database (Denmark)

    Gattiker, Urs E.; Ulhøi, John Parm


    This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively).......This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively)....

  15. Matrix fractional systems (United States)

    Tenreiro Machado, J. A.


    This paper addresses the matrix representation of dynamical systems in the perspective of fractional calculus. Fractional elements and fractional systems are interpreted under the light of the classical Cole-Cole, Davidson-Cole, and Havriliak-Negami heuristic models. Numerical simulations for an electrical circuit enlighten the results for matrix based models and high fractional orders. The conclusions clarify the distinction between fractional elements and fractional systems.

  16. Correlating the nanoscale mechanical and chemical properties of knockout mice bones (United States)

    Kavukcuoglu, Nadire Beril

    Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2

  17. Osteoblast Differentiation and Bone: Relevant proteins, regulatory processes and the vascular connection

    NARCIS (Netherlands)

    R.D.A.M. Alves (Rodrigo)


    textabstractBone is a highly specialized form of connective tissue present in most vertebrate animals as part of the endoskeleton. Structurally speaking, bone is mainly constituted by an organic extracellular matrix (ECM) hardened by deposited mineral. The blending between the organic and inorganic

  18. Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival

    DEFF Research Database (Denmark)

    Nielsen, Rasmus H; Karsdal, Morten A; Sørensen, Mette G;


    Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased os...

  19. Regulation of Osteoblast Survival by the Extracellular Matrix and Gravity (United States)

    Globus. Ruth K.; Almeida, Eduardo A. C.; Searby, Nancy D.; Bowley, Susan M. (Technical Monitor)


    Spaceflight adversely affects the skeleton, posing a substantial risk to astronaut's health during long duration missions. The reduced bone mass observed in growing animals following spaceflight is due at least in part to inadequate bone formation by osteoblasts. Thus, it is of central importance to identify basic cellular mechanisms underlying normal bone formation. The fundamental ideas underlying our research are that interactions between extracellular matrix proteins, integrin adhesion receptors, cytoplasmic signaling and cytoskeletal proteins are key ingredients for the proper functioning of osteoblasts, and that gravity impacts these interactions. As an in vitro model system we used primary fetal rat calvarial cells which faithfully recapitulate osteoblast differentiation characteristically observed in vivo. We showed that specific integrin receptors ((alpha)3(beta)1), ((alpha)5(beta)1), ((alpha)8(betal)1) and extracellular matrix proteins (fibronectin, laminin) were needed for the differentiation of immature osteoblasts. In the course of maturation, cultured osteoblasts switched from depending on fibronectin and laminin for differentiation to depending on these proteins for their very survival. Furthermore, we found that manipulating the gravity vector using ground-based models resulted in activation of key intracellular survival signals generated by integrin/extracellular matrix interactions. We are currently testing the in vivo relevance of some of these observations using targeted transgenic technology. In conclusion, mechanical factors including gravity may participate in regulating survival via cellular interactions with the extracellular matrix. This leads us to speculate that microgravity adversely affects the survival of osteoblasts and contributes to spaceflight-induced osteoporosis.

  20. Current trends and future perspectives of bone substitute materials - from space holders to innovative biomaterials. (United States)

    Kolk, Andreas; Handschel, Jörg; Drescher, Wolf; Rothamel, Daniel; Kloss, Frank; Blessmann, Marco; Heiland, Max; Wolff, Klaus-Dietrich; Smeets, Ralf


    An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging.

  1. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties. (United States)

    Finnilä, Mikko A J; Zioupos, Peter; Herlin, Maria; Miettinen, Hanna M; Simanainen, Ulla; Håkansson, Helen; Tuukkanen, Juha; Viluksela, Matti; Jämsä, Timo


    Dioxins are known to decrease bone strength, architecture and density. However, their detailed effects on bone material properties are unknown. Here we used nanoindentation methods to characterize the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on nanomechanical behaviour of bone matrix. Pregnant rats were treated with a single intragastric dose of TCDD (1 microg/kg) or vehicle on gestational day 11. Tibias of female offspring were sampled on postnatal day (PND) 35 or 70, scanned at mid-diaphysis with pQCT, and evaluated by three-point bending and nanoindentation. TCDD treatment decreased bone mineralization (p<0.05), tibial length (p<0.01), cross-sectional geometry (p<0.05) and bending strength (p<0.05). Controls showed normal maturation pattern between PND 35 and 70 with decreased plasticity by 5.3% and increased dynamic hardness, storage and complex moduli by 26%, 13% and 12% respectively (p<0.05), while similar maturation was not observed in TCDD-exposed pups. In conclusion, for the first time, we demonstrate retardation of bone matrix maturation process in TCDD-exposed animals. In addition, the study confirms that developmental TCDD exposure has adverse effects on bone size, strength and mineralization. The current results in conjunction with macromechanical behaviour suggest that reduced bone strength caused by TCDD is more associated with the mineralization and altered geometry of bones than with changes at the bone matrix level.

  2. Pathological fracture of the femur in a patient with Paget's disease of bone: a case report. (United States)

    Petrescu, Pompiliu HoraŢiu; Izvernariu, Dragoş Andrei; Iancu, Cătălina; Dinu, Gabriel Ovidiu; Berceanu-Văduva, Marcel Mihai; Crişan, Dan; Iacob, Mihaela; Bucur, Venera Margareta; RăuŢia, Ion Călin; Prejbeanu, Ion Radu; Dema, Sorin; DuŢă, Ciprian Constantin


    Paget's disease of bone is a benign disease characterized by exaggerated remodeling of the bone matrix after osteoclast-mediated bone destruction. Its etiology is still unknown, despite the fact that it was discovered and described in 1877, but genetic factors and environmental triggers were shown to play their part in the pathogenesis of the disease. The main clinical presentations of the disease are related to bone pain and deformities. Radiological diagnosis is the main detection tool, though many monostotic Paget's disease cases may remain undiagnosed. We present the case of an 81-year-old male patient admitted to the Clinic of Orthopedics, Emergency County Hospital, Timisoara, Romania, with intense pain and deformity of the upper left thigh. Radiological examination performed shows a complete fracture of the upper third diaphysis of the left femur with suggestive signs for Paget's disease of the bone therefore a biopsy was taken and the patient was treated by surgical realignment with favorable evolution. He was discharged 13 days after surgery. The biopsy of the bone revealed extensive bone remodeling with numerous osteoclasts and extensive bone matrix deposition, unevenly stained and unevenly mineralized and reverse cement lines, which are consistent with the diagnosis of Paget's disease of the bone. Histomorphometric analysis show intense matrix deposition with a highly active remodeling process. Computed tomography (CT) scans were performed three years later and show the extension of the disease into the lower half of the left femur.

  3. Strain energy density gradients in bone marrow predict osteoblast and osteoclast activity: a finite element study. (United States)

    Webster, Duncan; Schulte, Friederike A; Lambers, Floor M; Kuhn, Gisela; Müller, Ralph


    Huiskes et al. hypothesized that mechanical strains sensed by osteocytes residing in trabecular bone dictate the magnitude of load-induced bone formation. More recently, the mechanical environment in bone marrow has also been implicated in bone׳s response to mechanical stimulation. In this study, we hypothesize that trabecular load-induced bone formation can be predicted by mechanical signals derived from an integrative µFE model, incorporating a description of both the bone and marrow phase. Using the mouse tail loading model in combination with in vivo micro-computed tomography (µCT) we tracked load induced changes in the sixth caudal vertebrae of C57BL/6 mice to quantify the amount of newly mineralized and eroded bone volumes. To identify the mechanical signals responsible for adaptation, local morphometric changes were compared to micro-finite element (µFE) models of vertebrae prior to loading. The mechanical parameters calculated were strain energy density (SED) on trabeculae at bone forming and resorbing surfaces, SED in the marrow at the boundary between bone forming and resorbing surfaces, along with SED in the trabecular bone and marrow volumes. The gradients of each parameter were also calculated. Simple regression analysis showed mean SED gradients in the trabecular bone matrix to significantly correlate with newly mineralized and eroded bone volumes R(2)=0.57 and 0.41, respectively, pbone marrow plays a significant role in determining osteoblast and osteoclast activity.

  4. Delivery Systems for Bone Morphogenetic Protein (BMP) for Repair of Battle Incurred Bone Injuries. (United States)


    infections, congenital malformations that fail to heal are eligible for BMP treatment. I (my child/my ward) will be one of 50 patients to be treated with...Fusions in Dogs 6. Craniotomy Defects in Sheep t0 7. Craniotomy Defects in Monkeys 10 8. BMP Delivery System of Bone Matrix Non Collagenous 11 Proteins...effects. The most important and indispensptle substitutes for experiments in human beings are adult mongrel dogs, monkeys, and sheep . Experimental .S

  5. Matrix Information Geometry

    CERN Document Server

    Bhatia, Rajendra


    This book is an outcome of the Indo-French Workshop on Matrix Information Geometries (MIG): Applications in Sensor and Cognitive Systems Engineering, which was held in Ecole Polytechnique and Thales Research and Technology Center, Palaiseau, France, in February 23-25, 2011. The workshop was generously funded by the Indo-French Centre for the Promotion of Advanced Research (IFCPAR).  During the event, 22 renowned invited french or indian speakers gave lectures on their areas of expertise within the field of matrix analysis or processing. From these talks, a total of 17 original contribution or state-of-the-art chapters have been assembled in this volume. All articles were thoroughly peer-reviewed and improved, according to the suggestions of the international referees. The 17 contributions presented  are organized in three parts: (1) State-of-the-art surveys & original matrix theory work, (2) Advanced matrix theory for radar processing, and (3) Matrix-based signal processing applications.  

  6. Bone building with bortezomib (United States)

    Roodman, G. David


    In this issue of the JCI, Mukherjee et al. report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells (MSCs) — rather than mature osteoprogenitor cells — into osteoblasts, resulting in new bone formation (see the related article beginning on page 491). These results were observed when MSCs were implanted subcutaneously in mice or were used to treat a mouse model of postmenopausal bone loss. Others have reported that immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These results reflect the utility of targeting endogenous MSCs for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease. PMID:18219395

  7. A biocomposite of collagen nanofibers and nanohydroxyapatite for bone regeneration

    NARCIS (Netherlands)

    Ribeiro, N.; Sousa, S.R.; Blitterswijk, van C.A.; Moroni, L.; Monteiro, F.J.


    This work aims to design a synthetic construct that mimics the natural bone extracellular matrix through innovative approaches based on simultaneous type I collagen electrospinning and nanophased hydroxyapatite (nanoHA) electrospraying using non-denaturating conditions and non-toxic reagents. The mo

  8. Fabrication of bioactive composite scaffolds by electrospinning for bone regeneration

    NARCIS (Netherlands)

    Nandakumar, Anandkumar; Fernandes, Hugo; Boer, de Jan; Moroni, Lorenzo; Habibovic, Pamela; Blitterswijk, van Clemens A.


    Electrospun scaffolds are widely used for various biomedical applications. In this study, we prepared electrospun bioactive composite scaffolds combining hydroxyapatite, collagen (Col) and a synthetic polymer—PolyActive™—to mimic naturally occurring extracellular matrix for in situ bone regeneration

  9. Adrenal gland and bone. (United States)

    Hardy, Rowan; Cooper, Mark S


    The adrenal gland synthesizes steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. Both cortisol and adrenal androgens can have powerful effects on bone. The overproduction of cortisol in Cushing's disease leads to a dramatic reduction in bone density and an increase risk of fracture. Overproduction of adrenal androgens in congenital adrenal hyperplasia (CAH) leads to marked changes in bone growth and development with early growth acceleration but ultimately a significant reduction in final adult height. The role of more physiological levels of glucocorticoids and androgens on bone metabolism is less clear. Cortisol levels measured in elderly individuals show a weak correlation with measures of bone density and change in bone density over time with a high cortisol level associated with lower bone density and more rapid bone loss. Cortisol levels and the dynamics of cortisol secretion change with age which could also explain some age related changes in bone physiology. It is also now clear that adrenal steroids can be metabolized within bone tissue itself. Local synthesis of cortisol within bone from its inactive precursor cortisone has been demonstrated and the amount of cortisol produced within osteoblasts appears to increase with age. With regard to adrenal androgens there is a dramatic reduction in levels with aging and several studies have examined the impact that restoration of these levels back to those seen in younger individuals has on bone health. Most of these studies show small positive effects in women, not men, but the skeletal sites where benefits are seen varies from study to study.

  10. Bone scanning in otolaryngology. (United States)

    Noyek, A M


    Modern radionuclide bone scanning has introduced a new concept in physiologic and anatomic diagnostic imaging to general medicine. As otolaryngologists must diagnose and treat disease in relation to the bony and/or cartilaginous supporting structures of the neurocranium and upper airway, this modality should be included in the otolaryngologist's diagnostic armamentarium. It is the purpose of this manuscript to study the specific applications of bone scanning to our specialty at this time, based on clinical experience over the past three years. This thesis describes the development of bone scanning in general (history of nuclear medicine and nuclear physics; history of bone scanning in particular). General concepts in nuclear medicine are then presented; these include a discussion of nuclear semantics, principles of radioactive emmissions, the properties 99mTc as a radionuclide, and the tracer principle. On the basis of these general concepts, specific concepts in bone scanning are then brought forth. The physiology of bone and the action of the bone scan agents is presented. Further discussion considers the availability and production of the bone scan agent, patient factors, the gamma camera, the triphasic bone scan and the ultimate diagnostic principle of the bone scan. Clinical applications of bone scanning in otolaryngology are then presented in three sections. Proven areas of application include the evaluation of malignant tumors of the head and neck, the diagnosis of temporomandibular joint disorders, the diagnosis of facial fractures, the evaluation of osteomyelitis, nuclear medicine imaging of the larynx, and the assessment of systemic disease. Areas of adjunctive or supplementary value are also noted, such as diagnostic imaging of meningioma. Finally, areas of marginal value in the application of bone scanning are described.

  11. Enamel matrix proteins; old molecules for new applications. (United States)

    Lyngstadaas, S P; Wohlfahrt, J C; Brookes, S J; Paine, M L; Snead, M L; Reseland, J E


    Emdogain (enamel matrix derivative, EMD) is well recognized in periodontology, where it is used as a local adjunct to periodontal surgery to stimulate regeneration of periodontal tissues lost to periodontal disease. The biological effect of EMD is through stimulation of local growth factor secretion and cytokine expression in the treated tissues, inducing a regenerative process that mimics odontogenesis. The major (>95%) component of EMD is Amelogenins (Amel). No other active components have so far been isolated from EMD, and several studies have shown that purified amelogenins can induce the same effect as the complete EMD. Amelogenins comprise a family of highly conserved extracellular matrix proteins derived from one gene. Amelogenin structure and function is evolutionary well conserved, suggesting a profound role in biomineralization and hard tissue formation. A special feature of amelogenins is that under physiological conditions the proteins self-assembles into nanospheres that constitute an extracellular matrix. In the body, this matrix is slowly digested by specific extracellular proteolytic enzymes (matrix metalloproteinase) in a controlled process, releasing bioactive peptides to the surrounding tissues for weeks after application. Based on clinical and experimental observations in periodontology indicating that amelogenins can have a significant positive influence on wound healing, bone formation and root resorption, several new applications for amelogenins have been suggested. New experiments now confirm that amelogenins have potential for being used also in the fields of endodontics, bone regeneration, implantology, traumatology, and wound care.

  12. Localized tissue mineralization regulated by bone remodelling: A computational approach (United States)

    Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel


    Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

  13. Effects of microgravity on rat bone, cartlage and connective tissues (United States)

    Doty, S.


    The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

  14. Extracellular matrix structure. (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K


    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

  15. Ceramic Matrix Composites .

    Directory of Open Access Journals (Sweden)

    J. Mukerji


    Full Text Available The present state of the knowledge of ceramic-matrix composites have been reviewed. The fracture toughness of present structural ceramics are not enough to permit design of high performance machines with ceramic parts. They also fail by catastrophic brittle fracture. It is generally believed that further improvement of fracture toughness is only possible by making composites of ceramics with ceramic fibre, particulate or platelets. Only ceramic-matrix composites capable of working above 1000 degree centigrade has been dealt with keeping reinforced plastics and metal-reinforced ceramics outside the purview. The author has discussed the basic mechanisms of toughening and fabrication of composites and the difficulties involved. Properties of available fibres and whiskers have been given. The best results obtained so far have been indicated. The limitations of improvement in properties of ceramic-matrix composites have been discussed.

  16. Matrix interdiction problem

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Feng [Los Alamos National Laboratory; Kasiviswanathan, Shiva [Los Alamos National Laboratory


    In the matrix interdiction problem, a real-valued matrix and an integer k is given. The objective is to remove k columns such that the sum over all rows of the maximum entry in each row is minimized. This combinatorial problem is closely related to bipartite network interdiction problem which can be applied to prioritize the border checkpoints in order to minimize the probability that an adversary can successfully cross the border. After introducing the matrix interdiction problem, we will prove the problem is NP-hard, and even NP-hard to approximate with an additive n{gamma} factor for a fixed constant {gamma}. We also present an algorithm for this problem that achieves a factor of (n-k) mUltiplicative approximation ratio.

  17. Finite Temperature Matrix Theory

    CERN Document Server

    Meana, M L; Peñalba, J P; Meana, Marco Laucelli; Peñalba, Jesús Puente


    We present the way the Lorentz invariant canonical partition function for Matrix Theory as a light-cone formulation of M-theory can be computed. We explicitly show how when the eleventh dimension is decompactified, the N=1 eleven dimensional SUGRA partition function appears. From this particular analysis we also clarify the question about the discernibility problem when making statistics with supergravitons (the N! problem) in Matrix black hole configurations. We also provide a high temperature expansion which captures some structure of the canonical partition function when interactions amongst D-particles are on. The connection with the semi-classical computations thermalizing the open superstrings attached to a D-particle is also clarified through a Born-Oppenheimer approximation. Some ideas about how Matrix Theory would describe the complementary degrees of freedom of the massless content of eleven dimensional SUGRA are also discussed.

  18. Hypercalciuric Bone Disease (United States)

    Favus, Murray J.


    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

  19. Glutamate signalling in bone.

    Directory of Open Access Journals (Sweden)

    Karen eBrakspear


    Full Text Available Mechanical loading plays a key role in the physiology of bone, allowing bone to functionally adapt to its environment, however characterisation of the signalling events linking load to bone formation is incomplete. A screen for genes associated with mechanical load-induced bone formation identified the glutamate transporter GLAST, implicating the excitatory amino acid, glutamate, in the mechanoresponse. When an osteogenic load (10N, 10Hz was externally applied to the rat ulna, GLAST (EAAT1 mRNA, was significantly down-regulated in osteocytes in the loaded limb. Functional components from each stage of the glutamate signalling pathway have since been identified within bone, including proteins necessary for calcium-mediated glutamate exocytosis, receptors, transporters and signal propagation. Activation of ionotropic glutamate receptors has been shown to regulate the phenotype of osteoblasts and osteoclasts in vitro and bone mass in vivo. Furthermore, glutamatergic nerves have been identified in the vicinity of bone cells expressing glutamate receptors in vivo. However, it is not yet known how a glutamate signalling event is initiated in bone or its physiological significance. This review will examine the role of the glutamate signalling pathway in bone, with emphasis on the functions of glutamate transporters in osteoblasts.

  20. Blood: bone equilibrium

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, M.W.


    The conundrum of blood undersaturation with respect to bone mineralization and its supersaturation with respect to bone's homeostatic function has acquired a new equation. On the supply side, Ca/sup 2 +/ is pumped in across bone cells to provide the needed Ca/sup 2 +/ x P/sub i/ for brushite precipitation. On the demand side, blood is in equilibrium with bone fluid, which is in equilibrium with a mineral more soluble than apatite. The function of potassium in this equation is yet to be found.

  1. Olecranon bone graft: revisited. (United States)

    Mersa, Berkan; Ozcelik, Ismail Bulent; Kabakas, Fatih; Sacak, Bulent; Aydin, Atakan


    Autogenous bone grafts are frequently in use in the field of reconstructive upper extremity surgery. Cancellous bone grafts are applied to traumatic osseous defects, nonunions, defects after the resection of benign bone tumors, arthrodesis, and osteotomy procedures. Cancellous bone grafts do not only have benefits such as rapid revascularization, but they also have mechanical advantages. Despite the proximity to the primary surgical field, cancellous olecranon grafts have not gained the popularity they deserve in the field of reconstructive hand surgery. In this study, the properties, advantages, and technical details of harvesting cancellous olecranon grafts are discussed.

  2. Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus. (United States)

    Farlay, Delphine; Armas, Laura A G; Gineyts, Evelyne; Akhter, Mohammed P; Recker, Robert R; Boivin, Georges


    Low-energy fractures are frequent complications in type 1 diabetes mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced glycation end products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and nonfracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and nonfracturing T1DM versus CTL. We analyzed iliac crest bone biopsies from 5 fracturing T1DM patients, 5 nonfracturing T1DM patients, and 5 healthy subjects, all age- and sex-matched. AGEs (pentosidine) in bone matrix was measured by high-performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Trabecular bone from fracturing T1DM exhibited significantly higher levels of pentosidine than CTL (p = 0.04) and was more mineralized than nonfracturing T1DM (p = 0.04) and CTL (p = 0.04). Trabecular bone was not significantly different in pentosidine between nonfracturing T1DM and CTL. Cortical bone from nonfracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and pentosidine (r' = 0.79, p < 0.003) and between HbA1c and DMB (r' = 0.64, p < 0.02). Both modifications could lead to less flexible bone (reduced modulus of elasticity) and a tendency toward low-energy fractures in T1DM patients.

  3. Matrixed business support comparison study.

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, Josh D.


    The Matrixed Business Support Comparison Study reviewed the current matrixed Chief Financial Officer (CFO) division staff models at Sandia National Laboratories. There were two primary drivers of this analysis: (1) the increasing number of financial staff matrixed to mission customers and (2) the desire to further understand the matrix process and the opportunities and challenges it creates.

  4. Reduced Google matrix

    CERN Document Server

    Frahm, K M


    Using parallels with the quantum scattering theory, developed for processes in nuclear and mesoscopic physics and quantum chaos, we construct a reduced Google matrix $G_R$ which describes the properties and interactions of a certain subset of selected nodes belonging to a much larger directed network. The matrix $G_R$ takes into account effective interactions between subset nodes by all their indirect links via the whole network. We argue that this approach gives new possibilities to analyze effective interactions in a group of nodes embedded in a large directed networks. Possible efficient numerical methods for the practical computation of $G_R$ are also described.

  5. IIB Matrix Model

    CERN Document Server

    Aoki, H; Kawai, H; Kitazawa, Y; Tada, T; Tsuchiya, A


    We review our proposal for a constructive definition of superstring, type IIB matrix model. The IIB matrix model is a manifestly covariant model for space-time and matter which possesses N=2 supersymmetry in ten dimensions. We refine our arguments to reproduce string perturbation theory based on the loop equations. We emphasize that the space-time is dynamically determined from the eigenvalue distributions of the matrices. We also explain how matter, gauge fields and gravitation appear as fluctuations around dynamically determined space-time.

  6. Little IIB Matrix Model

    CERN Document Server

    Kitazawa, Y; Saito, O; Kitazawa, Yoshihisa; Mizoguchi, Shun'ya; Saito, Osamu


    We study the zero-dimensional reduced model of D=6 pure super Yang-Mills theory and argue that the large N limit describes the (2,0) Little String Theory. The one-loop effective action shows that the force exerted between two diagonal blocks of matrices behaves as 1/r^4, implying a six-dimensional spacetime. We also observe that it is due to non-gravitational interactions. We construct wave functions and vertex operators which realize the D=6, (2,0) tensor representation. We also comment on other "little" analogues of the IIB matrix model and Matrix Theory with less supercharges.

  7. Density matrix perturbation theory. (United States)

    Niklasson, Anders M N; Challacombe, Matt


    An orbital-free quantum perturbation theory is proposed. It gives the response of the density matrix upon variation of the Hamiltonian by quadratically convergent recursions based on perturbed projections. The technique allows treatment of embedded quantum subsystems with a computational cost scaling linearly with the size of the perturbed region, O(N(pert.)), and as O(1) with the total system size. The method allows efficient high order perturbation expansions, as demonstrated with an example involving a 10th order expansion. Density matrix analogs of Wigner's 2n+1 rule are also presented.

  8. Rheocasting Al Matrix Composites (United States)

    Girot, F. A.; Albingre, L.; Quenisset, J. M.; Naslain, R.


    Aluminum alloy matrix composites reinforced by SiC short fibers (or whiskers) can be prepared by rheocasting, a process which consists of the incorporation and homogeneous distribution of the reinforcement by stirring within a semi-solid alloy. Using this technique, composites containing fiber volume fractions in the range of 8-15%, have been obtained for various fibers lengths (i.e., 1 mm, 3 mm and 6 mm for SiC fibers). This paper attempts to delineate the best compocasting conditions for aluminum matrix composites reinforced by short SiC (e.g Nicalon) or SiC whiskers (e.g., Tokamax) and characterize the resulting microstructures.

  9. Elementary matrix algebra

    CERN Document Server

    Hohn, Franz E


    This complete and coherent exposition, complemented by numerous illustrative examples, offers readers a text that can teach by itself. Fully rigorous in its treatment, it offers a mathematically sound sequencing of topics. The work starts with the most basic laws of matrix algebra and progresses to the sweep-out process for obtaining the complete solution of any given system of linear equations - homogeneous or nonhomogeneous - and the role of matrix algebra in the presentation of useful geometric ideas, techniques, and terminology.Other subjects include the complete treatment of the structur

  10. Building bone tissue: matrices and scaffolds in physiology and biotechnology

    Directory of Open Access Journals (Sweden)

    Riminucci M.


    Full Text Available Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies.

  11. Determinants of microdamage in elderly human vertebral trabecular bone.

    Directory of Open Access Journals (Sweden)

    Hélène Follet

    Full Text Available Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53 from donors 54-95 years of age (22 men and 30 women, 1 unknown and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types.

  12. Phase field approaches of bone remodeling based on TIP (United States)

    Ganghoffer, Jean-François; Rahouadj, Rachid; Boisse, Julien; Forest, Samuel


    The process of bone remodeling includes a cycle of repair, renewal, and optimization. This adaptation process, in response to variations in external loads and chemical driving factors, involves three main types of bone cells: osteoclasts, which remove the old pre-existing bone; osteoblasts, which form the new bone in a second phase; osteocytes, which are sensing cells embedded into the bone matrix, trigger the aforementioned sequence of events. The remodeling process involves mineralization of the bone in the diffuse interface separating the marrow, which contains all specialized cells, from the newly formed bone. The main objective advocated in this contribution is the setting up of a modeling and simulation framework relying on the phase field method to capture the evolution of the diffuse interface between the new bone and the marrow at the scale of individual trabeculae. The phase field describes the degree of mineralization of this diffuse interface; it varies continuously between the lower value (no mineral) and unity (fully mineralized phase, e.g. new bone), allowing the consideration of a diffuse moving interface. The modeling framework is the theory of continuous media, for which field equations for the mechanical, chemical, and interfacial phenomena are written, based on the thermodynamics of irreversible processes. Additional models for the cellular activity are formulated to describe the coupling of the cell activity responsible for bone production/resorption to the kinetics of the internal variables. Kinetic equations for the internal variables are obtained from a pseudo-potential of dissipation. The combination of the balance equations for the microforce associated to the phase field and the kinetic equations lead to the Ginzburg-Landau equation satisfied by the phase field with a source term accounting for the dissipative microforce. Simulations illustrating the proposed framework are performed in a one-dimensional situation showing the evolution of

  13. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis. (United States)

    Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha


    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  14. Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-A knockout mice. (United States)

    Seto, Jong; Busse, Björn; Gupta, Himadri S; Schäfer, Cora; Krauss, Stefanie; Dunlop, John W C; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catalá-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter; Jahnen-Dechent, Willi


    The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix--a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.

  15. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. (United States)

    Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A; Schense, Jason C


    Regenerative medicine requires innovative therapeutic designs to accommodate high morphogen concentrations in local depots, provide their sustained presence, and enhance cellular invasion and directed differentiation. Here we present an example for inducing local bone regeneration with a matrix-bound engineered active fragment of human parathyroid hormone (PTH(1-34)), linked to a transglutaminase substrate for binding to fibrin as a delivery and cell-invasion matrix with an intervening plasmin-sensitive link (TGplPTH(1-34)). The precursor form displays very little activity and signaling to osteoblasts, whereas the plasmin cleavage product, as it would be induced under the enzymatic influence of cells remodeling the matrix, was highly active. In vivo animal bone-defect experiments showed dose-dependent bone formation using the PTH-fibrin matrix, with evidence of both osteoconductive and osteoinductive bone-healing mechanisms. Results showed that this PTH-derivatized matrix may have potential utility in humans as a replacement for bone grafts or to repair bone defects.


    Institute of Scientific and Technical Information of China (English)

    张育敏; 李宝兴; 李冀; 马绍英; 赵