Bone Defects (bone + defect)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Bone Defects

  • calvarial bone defect
  • large bone defect
  • segmental bone defect

  • Selected Abstracts

    Reconstruction of a Rabbit Ulna Bone Defect Using Bone Marrow Stromal Cells and a PLA/, -TCP Composite by a Novel Sintering Method,

    Youngmee Jung
    We developed PLA/, -TCP composites with a novel sintering method in order to enhance cellular interaction with matrices for bone regeneration. Thereafter, we confirmed the superior bone-forming characteristics of PLA/, -TCP cell-composite constructs resulting from greater surface exposure of the , -TCP particles, which may yield higher osteogenic and osteoconductive properties. [source]

    Photocrosslinkable Chitosan Hydrogel Can Prevent Bone Formation in Both Rat Skull and Fibula Bone Defects

    ARTIFICIAL ORGANS, Issue 1 2009
    Yoshifumi Tsuda
    Abstract UV light irradiation to a photocrosslinkable chitosan (Az-CH-LA) resulted in an insoluble and flexible hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinkable chitosan to inhibit bone formation in the bone defects. A 5-mm-diameter defect was made in the rat calvarium, and then photocrosslinkable chitosan was implanted and irradiated with UV for 30 s. Furthermore, a 2-mm defect was made in the fibula of a rat hind leg, and then photocrosslinkable chitosan was implanted and irradiated with UV. Bone formations in the rat skull and fibula defects with photocrosslinkable chitosan hydrogel were significantly prevented for 8 weeks. Thus, the chitosan hydrogel has an inhibitory effect on bone formation. [source]

    Biodegradation and Cytocompatibility Studies of a Triphasic Ceramic-Coated Porous Hydroxyapatite for Bone Substitute Applications

    Annie John
    Bone defects due to trauma or disease have led to the need for biomaterials as substitutes for tissue regeneration and repair. Herein, we introduce a porous triphasic ceramic-coated hydroxyapatite scaffold (HASi) for such applications. Interestingly, in the degradation experiments with isotonic buffer, HASi showed a significant release of silica with the disappearance of the tricalcium phosphate phase. Furthermore, the material also exhibited cytocompatibility with cultured bone marrow-derived mesenchymal stem cells of human origin. The material chemistry, together with the favorable cellular characteristics, indicates HASi as a promising candidate for critical-size bony defects, which still remains a formidable clinical challenge in the orthopedic scenario. [source]

    Polymer-assisted regeneration therapy with Atrisorb® barriers in human periodontal intrabony defects

    Lein-Tuan Hou
    Abstract Aim: This study compared clinical results of 40 periodontal osseous defects treated by two types of absorbable barrier materials. Material and Methods: Thirty patients (23 males and seven females) suffering from moderate to advanced periodontitis (with comparable osseous defects) were randomly assigned to receive either Atrisorb® barrier (n=22; group A) or Resolut XT® barrier (n=18; group B) therapy. Periodontal phase I treatment and oral hygiene instruction were performed before periodontal surgery. Papillary preservation, partial thickness flap, citric acid root conditioning, and decortication procedures were applied during the operation. Bone defects were filled with demineralized freeze-dried bone allograft and minocycline mixture (4:1 ratio). Postoperative care included 0.10% chlorhexidine rinse daily and antibiotic medication for 2 weeks. Clinical assessments including probing depth (PD), clinical attachment level (CAL), gingival recession (GR), plaque index (PlI), gingival index (GI), and radiographic examinations were taken at the baseline, preoperatively and at 3 and 6 months after regenerative surgery. Results: Six months following therapy, both Atrisorb® and Resolut XT® groups had achieved comparable clinical improvement in pocket reduction (3.9 versus 4.4 mm), attachment tissue gain (clinical attachment gain; 3.5 versus 3.6 mm), and reduction in the GI and in the PlI. Within-group comparisons showed significant attachment gain and pocket reduction between baseline data and those at both 3 and 6 months postoperatively (p<0.01). There were no statistically significant differences in any measured data between groups A and B. Conclusions: The results of this study indicate that a comparable and favorable regeneration of periodontal defects can be achieved with both Atrisorb® and Resolut XT® barriers. Further long-term study and histologic observations of tissue healing are needed to evaluate whether Atrisorb® is promising for clinical use. [source]

    Subacute reconstruction of lower leg and foot defects due to high velocity-high energy injuries caused by gunshots, missiles, and land mines

    MICROSURGERY, Issue 1 2005
    Bahattin Çeliköz M.D.
    The present study reviews 215 male patients suffering high velocity-high energy injuries of the lower leg or foot caused by war weapons such as missiles, gunshots, and land mines. They were treated in the Department of Plastic and Reconstructive Surgery at Gülhane Military Medical Academy (Ankara, Turkey) between November 1993,January 2001. Severe soft-tissue defects requiring flap coverage and associated open bone fractures that were treated 7,21 days (mean, 9.6 days) after the injury were included in the study. Twenty-three of 226 extremities (10.2%) underwent primary below-knee amputation. The number of debridements prior to definitive treatment was between 1,3 (mean, 1.9). Gustilo type III open tibia fractures accompanied 104 of 126 soft-tissue defects of the lower leg. Sixty-four bone defects accompanied 83 soft-tissue defects of the feet. Eighteen local pedicled muscle flaps and 208 free muscle flaps (latissimus dorsi, rectus abdominis, and gracilis) were used in soft-tissue coverage of 209 defects. Overall, the free muscle flap success rate was 91.3%. Bone defects were restored with 106 bone grafts, 25 free fibula flaps, and 14 distraction osteogenesis procedures. Osseous and soft-tissue defects were reconstructed simultaneously at the first definitive treatment in 94% of cases. The mean follow-up after definitive treatment was 25 (range, 9,47) months. The average full weight-bearing times for lower leg and feet injuries were 8.4 months and 4 months, respectively. Early, aggressive, and serial debridement of osseous and soft tissue, early restoration of bone and soft-tissue defects at the same stage, intensive rehabilitation, and patient education were the key points in the management of high velocity-high energy injuries of the lower leg and foot. © 2005 Wiley-Liss, Inc. Microsurgery 25:3,15, 2005. [source]

    Tissue-engineered injectable bone regeneration for osseointegrated dental implants

    Yoichi Yamada
    Abstract: The present study investigated a correlation between osseointegration in dental implants and an injectable tissue-engineered bone, using mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). Initially, the teeth in the mandible region were extracted and the healing period was 1 month. Bone defects on both sides of the mandible were prepared with a trephine bar. The defects were implanted with graft materials as follows: PRP, dog MSCs (dMSCs), and PRP, autogenous particulate cancellous bone and marrow (PCBM), and control (defect only). Two months later, the animals were evaluated by histology, and at the same time dental implants were installed. Two months later, the animals were sacrificed and nondecalcified sections were evaluated histologically and histometrically. According to the histological observations, the dMSCs/PRP group had well-formed mature bone and neovascularization, compared with the control (defect only) and PRP groups, as was the same for the PCBM group. A higher marginal bone level was observed around implants with PRP, PCBM, and dMSCs/PRP compared with the control. Furthermore, the values describing the amount of bone,implant contact (BIC) at the bone/implant interface were significantly different between the PRP, PCBM, dMSCs/PRP, and control groups. Significant differences were also found between the dMSCs/PRP and control groups in bone density. The findings of this experimental study indicate that the use of a mixture of dMSCs/PRP results in good results such as the amount of BIC and bone density comparable with that achieved by PCBM. Résumé L'étude présente a analysé une corrélation entre l'ostéïntégration d'implants dentaires et un os injectable traité en utilisant des cellules souches mésenchymateuses (MSC) et du plasma riche en plaquette (PRP). Initialement, les dents de la région mandibulaire ont été avulsées et la période de guérison a été d'un mois. Les lésions osseuses des deux côtés de la mandibule ont été préparées avec un trépan. Les lésions ont été traitées avec les matériaux de greffe suivants : PRP, MSC canin (dMSC) et PRP, moelle l'os spongieux en petites particules autogènes (PCBM) et contrôle (lésion seulement). Deux mois plus tard, les animaux ont étéévalués et en même temps les implants dentaires ont été placés. Deux mois plus tard, les animaux ont été euthanasiés et des coupes non-décalcifiées ont étéévaluées histologiquement et histométriquement. Suivant les observations histologiques, le groupe dMSC/PRP avait de l'os mûr bien formé et une néovascularisation comparé au contrôle et aux groupes PRP, comme pour le groupe PCBM. Un niveau osseux marginal plus important a été observé autour des implants avec PRP, PCBM et dMSC/PRP comparé au contrôle. De plus les valeurs décrivant la quantité de contact os/implant à l'interface os/implant étaient significativement différentes entre les groupes PRP, PCBM, dMSC/PRP et contrôles. Des différences significatives étaient aussi trouvées entre les groupes dMSC/PRP et contrôle en ce qui concernait la densité osseuse. Ces découvertes indiquent que l'utilisation d'un mélange dMSC/PRP résulte en de bons résultats tels que la quantité de contact os-implant et la densité osseuse comparéà ce qui se passe après l'utilisation du PCBM. Zusammenfassung Gewebemanipulierte injizierbare Knochenregenerate für osseointegrierte dentale Implantate Die vorliegende Studie untersuchte eine Korrelation zwischen der Osseointegration bei dentalen Implantaten und einem injizierbaren gewebemanipulierten Knochenregenerat aus mesenchymalen Stammzellen (MSCs) und plättchenreichem Plasma (PRP). Zuerst wurden die Zähne im Unterkiefer extrahiert. Darauf folgte eine Heilungsperiode von 1 Monat. Auf beiden Seiten der Unterkiefer wurden mit einer Hohlfräse Knochendefekte präpariert. Die Defekte wurden mit folgenden Transplantatmaterialien aufgefüllt: PRP, Hunde MSCs (dMSCs) und PRP, autologer zerkleinerter Knochen und Knochenmark (PCBM) und kein Füllmaterial (Kontrolle). Zwei Monate später wurden die Tiere histologisch untersucht und es wurden dentale Implantate eingesetzt. Nach weiteren zwei Monaten wurden die Tiere geopfert und nicht entkalkte Schnitte wurden histologisch und histometrisch ausgewertet. Gemäss der histologischen Beobachtungen zeigten die dMSCs/PRP Gruppe im Vergleich zur Kontrollgruppe und zur PRP Gruppe gut ausgebildeten reifen Knochen und neue Gefässe. Das Selbe galt für die PCBM Gruppe. Bei den Implantaten mit PRP, PCBM und dMSCs/PRP konnte im Vergleich zur Kontrollgruppe ein höheres marginales Knocheniveau beobachtet werden. Zudem waren die Werte, welche das Ausmass an Knochen-Implantat-Kontakt an der Kochen/Implantat Berührungsfläche beschreiben, zwischen den PRP, PCBM, dMSCs/PRP und der Kontrollgruppe signifikant verschieden. Signifikante Unterschiede wurden auch bezüglich Knochendichte zwischen der dMSCs/PRP und der Kontrollgruppe gefunden. Die Ergebnisse dieser experimentellen Studie zeigen, dass die Anwendung eines Gemisches aus dMSCs/PRP zu guten Resultaten bezüglich Ausmass an Knochen-Implantat-Kontakt und Knochendichte führt. Die erzielten Resultate sind mit den mit PCBM erreichten vergleichbar. Resumen El presente estudio investigó la correlación entre osteointegración en implantes dentales y un tejido-elaborado óseo inyectable, usando células madre mesenquimales (MSCs) y plasma rico en plaquetas (PRP). Inicialmente, se extrajeron los dientes de la mandíbula y el periodo de cicatrización fue de un mes. Se prepararon defectos óseos en ambos lados de la mandíbula con una fresa trépano. Los defectos se implantaron con material de injerto de la siguiente manera: PRP, MSCs de perro (dMSCs) y PRP, partículas de hueso esponjoso y médula autógenos (PCBM), y control (defecto solo). Dos meses mas tarde, los animales se evaluaron por histología, al mismo tiempo se instalaron implantes dentales. Dos meses mas tarde se sacrificaron los animales y se evaluaron secciones no descalcificadas histológica e histometricamente. De acuerdo con las observaciones histológicas, el grupo dMSCs/PRP había formado bien un hueso maduro y una neovascularización, comparado con el control (defecto solo) y grupos PRP, también fue igual para el grupo PCBM. Se observó un nivel óseo marginal mas alto alrededor de los implantes con PRP, PCBM, y dMSCs/PRP comparados con el control. Mas aun, los valores que describen la cantidad de contacto hueso-implante en la interfase hueso/implante fueron significativamente diferentes entre los grupos PRP, PCBM, dMSCs/PRP, y de control en la densidad ósea. Estos hallazgos de este estudio experimental indican que el uso de una mezcla de dMSCs/PRP resulta en buenos resultados tales como la cantidad de contacto hueso-implante y densidad ósea comparable a aquella lograda por PCBM. [source]

    Stimulation of intramembranous bone repair in rats by ghrelin

    Feilong Deng
    Researchers in our laboratory have previously shown that ghrelin, a gastric peptide hormone, may regulate mesenchymal cell differentiation into adipocytes and myocytes. Here we show that ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defects in rats. Rats with a 9 mm full-thickness calvarial bone defect received either Bio-Oss® (control group) or Bio-Oss® mixed with 20 ,g ghrelin (treatment group), followed by local administration of saline or ghrelin (10 ,g), respectively, on days 5, 10 and 15. After 6 and 12 weeks, new bone formation was assessed. Animals treated with ghrelin showed a significant increase in new bone formation as demonstrated by an increment in bone mineral density and fluorescence labelling of tetracycline relative to the control group. At 6 weeks, bone mineral density increased from 54 ± 7 (control group) to 78 ± 9 mg cm,2 in the treatment group, while the tetracycline fluorescence labelling increased by 61 ± 15%. A similar increment was observed at 12 weeks. Quantitative reverse transcriptase-polymerase chain reaction showed that expression of alkaline phosphatase (ALP), osteocalcin and collagen type I was elevated. Relative to the control animals, mRNAs for ALP, osteocalcin and collagen type I increased 2.4 ± 0.4-, 4.7 ± 1.9- and 4.0 ± 1.7-fold, respectively, in animals treated with ghrelin for 6 weeks (P < 0.05). At 12 weeks, mRNA levels of ALP, osteocalcin and collagen type I showed a decline relative to levels at 6 weeks but still remained significantly higher than in the control group, with fold changes of 2.4 ± 0.8, 2.4 ± 1.2 and 2.1 ± 0.7, respectively (P < 0.05). This study demonstrated that ghrelin stimulates intramembranous osteogenesis. [source]

    Erythema multiforme-like lesions associated with lesional infiltration of tumor cells occurring with adult T-cell lymphoma/leukemia

    Tomoyuki Ohtani MD
    A 66-year-old Japanese woman visited our hospital with a complaint of multiple papules on her trunk and extremities. She had a past medical history of appendicitis and blood transfusion 40 years earlier. For the last 10 years, she had noticed multiple, gradually enlarging papulonodular lesions with surrounding erythema on her trunk and extremities. ,Physical examination revealed multiple, violaceous papules or nodules, less than 10 mm in diameter, with surrounding erythema on her trunk and extremities (Fig. 1). The results of routine laboratory examinations, including blood count, liver function, renal function, serum calcium, and lactate dehydrogenase, were within the normal range. The peripheral blood picture showed a small population of atypical lymphocytes below 1% of the total white blood cells. Human T-cell lymphotropic virus type I (HTLV-I) serology was positive. A microscopic examination of a biopsy specimen from a nodule on the abdomen demonstrated diffuse infiltration of large pleomorphic T cells in the upper and middle dermis, although highly atypical lymphocytes, so-called flower cells, could not be recognized. Infiltrating lymphocytes were positive for CD2, CD3, CD4, CD5, CD7, and CD45, but negative for CD8 and CD20, immunohistologically. Bone marrow biopsy also demonstrated the infiltration of lymphocytes expressing CD2, CD3, CD4, CD5, and CD7, but not CD25. Southern blot analysis of the infiltrating cells in the skin revealed an integration of HTLV-I proviral DNA in T cells. Clonal T-cell receptor , gene rearrangement was detected in skin and bone marrow biopsies. No abnormal mass or bone defect was detected by chest or abdominal computed tomographic scanning, systemic gallium-67 citrate scintigraphy, or chest radiography. On the basis of these data, the patient was diagnosed with smouldering-type adult T-cell lymphoma/leukemia. Figure 1. Clinical features of adult T-cell lymphoma/leukemia (ATL) skin lesions. Crusted, target-like, dark-red plaques on the lower legs ,The patient was started on topical steroid and electron beam radiation therapy (27 Gy/14 days). Five days after the start of irradiation, she noticed multiple patches of edematous erythema appearing on the trunk and extremities (Fig. 2). As it was initially suspected that these newly emerging erythema multiforme or toxic eruptions were caused by irradiation, therapy was interrupted. Anti-herpes simplex virus antibody was not checked because no typical herpes simplex lesions were noticed. The patient was not taking any systemic drugs. A skin biopsy was taken from a representative lesion on the chest. The pathologic specimen showed epidermotropism, liquefaction degeneration in the basal layer, marked edema, and dense infiltration of mononuclear cells in the upper dermis. Infiltrating cells possessed abundant cytoplasm and large pleomorphic nuclei with distinct nucleoli (Fig. 3). These findings were consistent with the histopathologic findings of erythema multiforme, except for the atypical lymphoid cell infiltration. Immunohistochemical staining demonstrated that the phenotype of the skin-infiltrating cells was identical to that of the atypical cells in the initial lesions. As the eruptions did not disappear in spite of the interruption of radiation, total skin irradiation was restarted. After completion of therapy, both the erythema multiforme-like lesions and the initial adult T-cell lymphoma/leukemia nodules on the trunk and extremities had resolved, leaving brown pigmentation. The patient has been free of any recurrence of skin lesions or systemic symptoms for 6 years after the completion of total skin irradiation. Figure 2. Appearance of erythema multiforme (EM)-like lesions. Edematous red plaques involving the breast Figure 3. Microscopic examination of a biopsy specimen from (EM)-like lesions on the chest (hematoxylin and eosin staining). (a) Epidermotropism, liquefaction degeneration in the basal layer, and dense infiltration of mononuclear cells and severe edema in the upper dermis (×100). (b) High-power magnification revealed that the dermal infiltration included atypical lymphoid cells with abundant cytoplasm, convoluted large nuclei, and distinct nucleoli (×400) [source]

    Hydroxyapatite fiber material with BMP-2 gene induces ectopic bone formation

    Mitsumasa Oda
    Abstract Collagen containing bone morphogenetic protein-2 (BMP-2) expression vector, which is called "gene-activated matrix," promotes bone regeneration when transplanted to the bone defect. We speculated that hydroxyapatite fiber (HF) would be an ideal matrix for "gene-activated matrix" especially for bone regeneration, because it is oseteoconductive and has high affinity to DNA. The purpose of this study is to clarify whether HF containing BMP-2 expression vector induces ectopic bone formation. We prepared HF containing 0, 10, 50, and 100 ,g BMP-2 expression vector. Wistar male rats (8 weeks) were used and each rat received two HF implants in the left and right dorsal muscle. The rats were sacrificed 4, 8, and 12 weeks after the operation, and implants were analyzed radiographically by softex, dual-energy X-ray absorptiometry, and they were histologically examined. At 4 weeks, HF containing 50 or 100 ,g BMP-2 expression vector showed high bone mineral contents and large radiopaque volume compared to the other implants. At 8 and 12 weeks, HF containing 50 ,g BMP-2 expression vector exerted the highest values in the radiographic analyses. Bonelike tissue was histologically observed in HF containing 50 and 100 ,g BMP-2 expression vector groups but not detected in the other implants. The present results suggest that HF is potential as a matrix for "gene-activated matrix" for bone tissue engineering. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source]

    Understanding the pathology and mechanisms of type I diabetic bone loss

    *Article first published online: 1 NOV 200, Laura R. McCabe
    Abstract Type I (T1) diabetes, also called insulin dependent diabetes mellitus (IDDM), is characterized by little or no insulin production and hyperglycemia. One of the less well known complications of T1-diabetes is bone loss which occurs in humans and animal models. This complication is receiving increased attention because T1-diabetics are living longer due to better therapeutics, and are faced with their existing health concerns being compounded by complications associated with aging, such as osteoporosis. Both male and female, endochondrial and intra-membranous, and axial and appendicular bones are susceptible to T1-diabetic bone loss. Exact mechanisms accounting for T1-diabetic bone loss are not known. Existing data indicate that the bone defect in T1-diabetes is anabolic rather than catabolic, suggesting that anabolic therapeutics may be more effective in preventing bone loss. Potential contributors to T1-diabetic suppression of bone formation are discussed in this review and include: increased marrow adiposity, hyperlipidemia, reduced insulin signaling, hyperglycemia, inflammation, altered adipokine and endocrine factors, increased cell death, and altered metabolism. Differences between T1-diabetic- and age-associated bone loss underlie the importance of condition specific, individualized treatments for osteoporosis. Optimizing therapies that prevent bone loss or restore bone density will allow T1-diabetic patients to live longer with strong healthy bones. J. Cell. Biochem. 102: 1343,1357, 2007. © 2007 Wiley-Liss, Inc. [source]

    Bone healing around implants placed in a jaw defect augmented with Bio-Oss®

    An experimental study in dogs
    Abstract The present experiment was carried out to study some tissue reactions around implants that were placed in an edentulous ridge which had been augmented with deproteinized natural bovine cancellous bone mineral. In 4 male beagle dogs, the premolars in the right side of the mandible were extracted and a large buccal ridge defect was created by mechanical means. The bone plate at the lingual aspect of the defect was left intact. 5 months later, the distal 2/3 of the defect area was augmented with Bio-Oss® (Geistlich Sons Ltd, Wolhusen, Switzerland) mixed with a fibrin sealer (Tisseel®, Immuno AG, Vienna, Austria). After 3 months of healing, 3 fixtures (Astra Tech AB, Mölndal, Sweden; TiO-blast; 8×3.5 mm) were installed in the mandible; 2 were placed in the augmented portion and 1 was placed in the non-augmented portion of the defect. After a healing period of 3 months, abutment connection was performed and a plaque control period initiated. 4 months later, the dogs were sacrificed and each implant region was dissected. The tissue samples were dehydrated, embedded in plastic, sectioned in the bucco-lingual plane and examined in the light microscope. It was observed that osseointegration failed to occur to implant surfaces within an alveolar ridge portion previously augmented with Bio-Oss®. In the augmented portion of the crest, the graft particles were separated from the host tissue as well as from the implant by a well-defined connective tissue capsule. Although the lingual aspect of all fixtures (test and control) was in contact with hard tissue at the time of installation, after 4 months of function, a deep vertical bone defect frequently had formed at the lingual surface of the implants. It was concluded that in this model (i) Bio-Oss® failed to integrate with the host bone tissue and (ii) no osseointegration occurred to the implants within the augmented portion of the crest. [source]

    Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

    G Low
    Summary The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings. [source]

    Stem cell-mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury

    Sheen-Woo Lee
    Abstract Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [18F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [18F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMC's traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p,<,0.05). Systemically administered ADMC's traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:295,302, 2009 [source]

    Effect of cell-based VEGF gene therapy on healing of a segmental bone defect

    Ru Li
    Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0,×,106 fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n,=,9); control groups were treated with fibroblasts (Group 2) (n,=,7), or saline (Group 3) (n,=,7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p,<,0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:8,14, 2009 [source]

    Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis

    C. A. Lill
    Abstract Current methods for fracture treatment in osteoporosis are not always sufficient. To develop new fixation strategies (both mechanical and biological) requires pre-clinical testing utilizing appropriate models. The aim of this study was to apply a recently developed sheep model of osteoporosis to the study of healing in a non-critical long bone defect. A standardized transverse mid-shaft tibial osteotomy (with a fracture gap of 3 mm) was performed in seven osteoporotic and seven normal sheep and stabilized with a special external fixator for 8 weeks. The fixator was used for weekly in vivo bending stiffness measurements. Ex vivo bending stiffness and torsional stiffness of the callus zone were also determined. Callus area, callus density, and osteoporosis status were determined at 0, 4, and 8 weeks using peripheral quantitative computed tomography. The increase of in vivo bending stiffness of the callus was delayed approximately 2 weeks in osteoporotic animals. A significant difference (33%) in torsional stiffness was found between the osteotomized and contralateral intact tibia in osteoporotic animals, but no significant difference occurred in normal sheep (2%). In osteoporotic animals, ex vivo bending stiffness was reduced 21% (p = 0.05). Bending stiffness was correlated with callus density (r = 0.76, r = 0.53); torsional stiffness was correlated with callus area (r = 0.60) and to a lesser extent with callus density (r = 0.53). This study demonstrated a delay of fracture healing in osteoporotic sheep tibiae with respect to callus formation, mineralization, and mechanical properties. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]

    Induction of a neoarthrosis by precisely controlled motion in an experimental mid-femoral defect

    Dennis M. Cullinane
    Bone regeneration during fracture healing has been demonstrated repeatedly, yet the regeneration of articular cartilage and joints has not yet been achieved. It has been recognized however that the mechanical environment during fracture healing can be correlated to the contributions of either the endochondral or intramembranous processes of bone formation, and to resultant tissue architecture. Using this information, the goal of this study was to test the hypothesis that induced motion can directly regulate osteogenic and chondrogenic tissue formation in a rat mid-femoral bone defect and thereby influence the anatomical result. Sixteen male Sprague Dawley rats (400 ± 20 g) underwent production of a mid-diaphyseal, non-critical sized 3.0 mm segmental femoral defect with rigid external fixation using a custom designed four pin fixator. One group of eight animals represented the controls and underwent surgery and constant rigid fixation. In the treatment group the custom external fixator was used to introduce daily interfragmentary bending strain in the eight treatment animals (12°s angular excursion), with a hypothetical symmetrical bending load centered within the gap. The eight animals in the treatment group received motion at 1.0 Hz, for 10 min a day, with a 3 days on, one day off loading protocol for the first two weeks, and 2 days on, one day off for the remaining three weeks. Data collection included histological and immunohistological identification of tissue types, and mean collagen fiber angles and angular conformity between individual fibers in superficial, intermediate, and deep zones within the cartilage. These parameters were compared between the treatment group, rat knee articular cartilage, and the control group as a structural outcome assessment. After 35 days the control animals demonstrated varying degrees of osseous union of the defect with some animals showing partial union. In every individual within the mechanical treatment group the defect completely failed to unite. Bony arcades developed in the experimental group, capping the termini of the bone segments on both sides of the defect in four out of six animals completing the study. These new structures were typically covered with cartilage, as identified by specific histological staining for Type II collagen and proteoglycans. The distribution of collagen within analogous superficial, intermediate, and deep zones of the newly formed cartilage tissue demonstrated preferred fiber angles consistent with those seen in articular cartilage. Although not resulting in complete joint development, these neoarthroses show that the induced motion selectively controlled the formation of cartilage and bone during fracture repair, and that it can be specifically directed. They further demonstrate that the spatial organization of molecular components within the newly formed tissue, at both microanatomical and gross levels, are influenced by their local mechanical environment, confirming previous theoretical models. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]

    Enhancement of bone healing using non-glycosylated rhBMP-2 released from a fibrin matrix in dogs and cats

    H. G. Schmoekel
    Objectives: To test a non-glycosylated recombinant human bone morphogenetic protein-2 (ngly-rhBMP-2)/fibrin composite, which has been shown experimentally to enhance healing of bone defects in rodents, in a clinical case series of dogs and cats undergoing treatment for fracture non-unions and arthrodesis. Methods: A ngly-rhBMP-2/fibrin composite was applied in 41 sites in 38 dogs and cats for which a cancellous bone autograft was indicated, replacing the graft. Results: Bridging of the bone defect with functional bone healing was achieved in 90 per cent of the arthrodesis and fracture nonunions treated in this manner. Clinical Significance: This prospective clinical study demonstrates the beneficial effects of ngly-rhBMP-2 in a specially designed fibrin matrix on the treatment of bone defects, and validates the use of this composite as an alternative to bone autografts in dogs and cats. [source]

    Reconstruction of anterior through and through oromandibular defects following oncological resections,

    MICROSURGERY, Issue 2 2010
    Bernardo Bianchi M.D.
    Background: Resections of oromandibular squamous cell carcinoma involving anterior mandible, floor of the mouth, and the skin, lead to composite oromandibular defects that can be approached in several ways depending on the extension of the bone defect, of the soft tissue and cutaneous resection, the patient's general status, and the prognosis. Methods: A retrospective evaluation of 27 patients has been performed. The techniques described included single osseous or soft tissues free flap reconstruction, two free flaps or free and locoregional flap association. Results: Postoperative follow-up ranged from 12 to 120 months. Final results were evaluated with regards to deglutition, speech, oral competence, and esthetic outcome. Conclusion: Reconstruction of the anterior mandible is strongly indicated whenever possible. When the defect involves the tongue, the best results are provided by the association of two free flaps. Finally, the association of free and locoregional flaps ia a good option for external coverage reconstruction. © 2009 Wiley-Liss, Inc. Microsurgery, 2010. [source]

    Reconstruction of large posttraumatic skeletal defects of the forearm by vascularized free fibular graft,

    MICROSURGERY, Issue 6 2004
    Roberto Adani M.D.
    Vascularized bone graft is most commonly applied for reconstruction of the lower extremity; indications for its use in the reconstruction of the upper extremity have expanded in recent years. Between 1993,2000, 12 patients with segmental bone defects following forearm trauma were managed with vascularized fibular grafts: 6 males and 6 females, aged 39 years on average (range, 16,65 years). The reconstructed site was the radius in 8 patients and the ulna in 4. The length of bone defect ranged from 6,13 cm. In 4 cases, the fibular graft was harvested and used as a vascularized fibula osteoseptocutaneous flap. To achieve fixation of the grafted fibula, plates were used in 10 cases, and screws and Kirschner wires in 2. In the latter 2 cases, an external skeletal fixator was applied to ensure immobilization of the extremity. The follow-up period ranged from 10,93 months. Eleven grafts were successful. The mean period to obtain radiographic bone union was 4.8 months (range, 2.5,8 months). Fibular grafts allow the use of a segment of diaphyseal bone which is structurally similar to the radius and ulna and of sufficient length to reconstruct most skeletal defects of the forearm. The vascularized fibular graft is indicated in patients with intractable nonunions where conventional bone grafting has failed or large bone defects, exceeding 6 cm, are observed in the radius or ulna. © 2004 Wiley-Liss, Inc. Microsurgery 24:423,429, 2004. [source]

    Monitoring angiogenesis in soft-tissue engineered constructs for calvarium bone regeneration: an in vivo longitudinal DCE-MRI study

    NMR IN BIOMEDICINE, Issue 1 2010
    Marine Beaumont
    Abstract Tissue engineering is a promising technique for bone repair and can overcome the major drawbacks of conventional autogenous bone grafting. In this in vivo longitudinal study, we proposed a new tissue-engineering paradigm: inserting a biological soft-tissue construct within the bone defect to enhance angiogenesis for improved bone regeneration. The construct acts as a resorbable scaffold to support desired angiogenesis and cellular activity and as a vector of vascular endothelial growth factor, known to promote both vessel and bone growth. Dynamic contrast- enhanced magnetic resonance imaging was performed to investigate and characterize angiogenesis necessary for bone formation following the proposed paradigm of inserting a VEGF-impregnated tissue-engineered construct within the critical-sized calvarial defect in the membranous parietal bone of the rabbit. Results show that a model-free quantitative approach, the normalized initial area under the curve metric, provides sensitive and reproducible measures of vascularity that is consistent with known temporal evolution of angiogenesis during bone regeneration. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Repair of mandible defect with tissue engineering bone in rabbits

    ANZ JOURNAL OF SURGERY, Issue 11 2005
    Zhi Li
    Background: The aim of the present study was to investigate the effect of tissue engineering bone composed of bone marrow-derived osteoblasts and demineralized bone in repairing mandible defect. Methods: Bone marrow-derived osteoblasts of 20 rabbits were cultured and seeded into scaffold of allogeneic demineralized bone to construct tissue engineering bone graft in vitro, which was used to repair the 10 × 5-mm bone defect made in the same rabbit mandible edge. Implant of demineralized bone alone was as the control. Rabbits were killed according to the schedule: five after 2 weeks, five after 4 weeks, five after 8 weeks, five after 12 weeks, and the implants were harvested for gross, radiographic, and histological observation. Results: New bone formation at the margin region of defect and osteogenesis at the centre were observed in the implant of tissue engineering bone, and the bone formation pattern included osteogenesis, osteoconduction, and osteoinduction. In the implant of demineralized bone alone, the major bone formation pattern was ,creeping substitute'. Conclusions: The tissue engineering bone graft constructed by autogenous bone marrow-derived osteoblasts and allogeneic demineralized bone was better than demineralized bone alone in bone formation capability, which might be an ideal graft for bone defect repair. [source]

    Efficacy of Bone Marrow Mononuclear Cells to Promote Bone Regeneration Compared With Isolated CD34+ Cells From the Same Volume of Aspirate

    ARTIFICIAL ORGANS, Issue 7 2010
    Shinji Yasuhara
    Abstract Autologous bone marrow mononuclear cell (BMMNC) transplantation is currently an emerging clinical treatment in the orthopedic as well as cardiovascular fields. It is believed that the therapeutic effect of the BMMNCs is due to neovascularization enhanced by the CD34+ cells contained therein, which include endothelial progenitor cells. However, isolation of the CD34+ cell fraction for clinical application has many disadvantages such as cost and invasiveness related to cell mobilization with cytokine. To investigate whether a purification step is in fact necessary for bone regeneration, we separated BMMNCs, CD34+, and CD34 - cells from the same initial volume of rabbit bone marrow aspirates. We then transplanted them back into a femoral bone defect of the same rabbit together with atelocollagen gel and basic fibroblast growth factor (bFGF) and evaluated neovascularization and bone regeneration up to 8 weeks after transplantation. The greatest potential for neovascularization and bone regeneration medicated by cells from the same volume of bone marrow aspirate was found in the BMMNC group. Although purified CD34+ cells might be an ideal cell source, BMMNCs could be a practical and feasible cell source for bone regeneration in present clinical settings with limited cost, availability of materials, and technical issues for transplantation. [source]

    Aplasia cutis congenita of the scalp: How much therapy is necessary in large defects?

    ACTA PAEDIATRICA, Issue 6 2005
    B Bernbeck
    Abstract Aim: To show that local antibiotic management and a regular inspection of aplasia cutis congenita of the skull can give an excellent result. Method: This case reports a girl born with aplasia cutis congenita of the skull presenting with a large aplasia of the epidermis, dermis, subcutaneous tissue and galea, including a bone defect without any additional risk factor, e.g. early eschar formation, cerebrospinal fluid leakage or uncommon dural blood vessels. Results: A primarily conservative treatment with local wet and antibiotic dressings together with a systemic antibiotic treatment for the first 2 wk led to an excellent result and thus prevented untimely operative and peri-operative procedures. Conclusions: Here we have shown that conservative treatment might be an option, even if the wound diameter is greater than 1 cm2, to prevent infants from any untimely operative procedure with an elevated operative risk if any additional risk factors are excluded. [source]

    Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model

    Tania Mary Cestari
    Abstract Objective: To histomorphometrically investigate the repair of critical size defects (CSDs) and bone augmentation in cranial walls using block of sintered bovine-derived anorganic bone (sBDAB) graft. Material and methods: Forty guinea-pigs were divided into test (n=20) and CSD control (n=20) groups. In each animal, a full-thickness bone defect with 9.5 mm diameter was made in the frontal bone. The defects were filled with an sBDAB block soaked in blood in the test group and with blood clot in the CSD control group. The skulls were collected at 0 h (n=2) and 30, 90 and 180 days (n=6/group and period) postoperatively. The volume density and total volume of newly formed bone, sBDAB, blood vessels and connective tissue, vertical thickness of removed bone plug, sBDAB block and graft area were evaluated. Results: The vertical thickness of the adapted sBDAB block was 3.8 times higher than that of the removed bone plug and did not show significant difference between periods, filling in average 29.8% of the total graft region. The sBDAB block exhibited complete osseointegration with the borders of the defect at 90 days. At 90 and 180 days, the vertical thickness of the graft was 279% in the average, and the total volume of bone augmentation was, respectively, 78.8% and 148.5% higher compared with the removed bone plug. The defects of the CDS control group showed limited osteogenesis and filling by connective tissue plus tegument. Conclusion: The sBDAB block can be used to promote repair of CSDs and bone augmentation in the craniomaxillofacial region, due to its good osteoconductive and slow resorptive properties. [source]

    Morphometric evaluation of the repair of critical-size defects using demineralized bovine bone and autogenous bone grafts in rat calvaria

    Rodrigo Cardoso de Oliveira
    Abstract Objective: To evaluate the repair of critical-size bone defects in rats treated with demineralized bovine bone (DBB) compared with autogenous bone (AB). Material and method: A bone defect of 8 mm in diameter was created in the calvaria of 50 Rattus norvegicus, treated either with DBB or AB. Sub-groups of five rats of each group were killed at 7, 14, 21, 30 and 90 days post-operatively, and the skulls were removed and processed histologically. Histological sections were stained with hematoxylin and eosin. Result: Histological analysis showed complete closure of the defects with new bone at 90 days in group AB, and substitution of the biomaterial by fibrotic connective tissue in the DBB group at 21 days. Morphometric analysis showed that DBB was rapidly absorbed at 14 days, with its volume density decreasing from 47%±0.8% at 7 days to 1.2%±0.41% at 14 days. Subsequently, volume densities of the connective tissue and neoformed bone increased from 51.1%±11.17% to 86.8%±7.92% and from 1.9%±1.13% to 12%±8.02%, respectively, for the same time interval. The volume density of AB particles did not change throughout the experimental periods, but the amount of new bone increased markedly between 7 and 90 days, from 4.5%±1.57% to 53.5%±6.42% (P<0.05). Conclusion: DBB did not provide complete repair of the defects, with significantly less new bone formation than in the AB group. [source]

    Studies on dentin grafts to bone defects in rabbit tibia and mandible; development of an experimental model

    Lars Andersson
    This property may possibly be used as an alternative or supplement to bone grafting to defective areas after trauma prior to treatment with osseointegrated implants. Hence, the objective of this study was to investigate if dentin can be used as a graft in bone defects in an experimental rabbit model. Materials and Methods:, Eight New Zealand White Rabbits were used to prepare bone cavities either in the angle of the mandible or tibia. Six of the eight tibial and six of the eight mandibular bone defects were filled with dentin blocks from human premolars which were extracted for orthodontic treatment. Two mandibular and two tibial bone cavities were used as controls and all the rabbits were sacrificed after 3 months. Radiographic and histological examinations were performed. Results:, There was a difference in healing pattern between the mandibular and tibial defects. In the mandible, the dentin blocks were resorbed to a larger extent and more often surrounded by fibrous tissue, probably due to the fact that the dentin blocks were mobile because of the thin mandibles and muscular activity in that area. Only some dentin blocks were ankylosed with the mandibular bone. In the tibia however, all dentin blocks were fused to bone over a large area. Osseous replacement resorption was seen. In control cavities, bone formation was seen but was never complete. No signs of inflammatory changes were seen in any fused grafts. Conclusions:, Dentin grafts have a potential to be incorporated in bone without inflammation and can be used as bone inducer and later replaced by bone. Thus, rabbit tibia served as a better model for further studies of this phenomenon when compared to the mandible. [source]

    Stimulation of intramembranous bone repair in rats by ghrelin

    Feilong Deng
    Researchers in our laboratory have previously shown that ghrelin, a gastric peptide hormone, may regulate mesenchymal cell differentiation into adipocytes and myocytes. Here we show that ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defects in rats. Rats with a 9 mm full-thickness calvarial bone defect received either Bio-Oss® (control group) or Bio-Oss® mixed with 20 ,g ghrelin (treatment group), followed by local administration of saline or ghrelin (10 ,g), respectively, on days 5, 10 and 15. After 6 and 12 weeks, new bone formation was assessed. Animals treated with ghrelin showed a significant increase in new bone formation as demonstrated by an increment in bone mineral density and fluorescence labelling of tetracycline relative to the control group. At 6 weeks, bone mineral density increased from 54 ± 7 (control group) to 78 ± 9 mg cm,2 in the treatment group, while the tetracycline fluorescence labelling increased by 61 ± 15%. A similar increment was observed at 12 weeks. Quantitative reverse transcriptase-polymerase chain reaction showed that expression of alkaline phosphatase (ALP), osteocalcin and collagen type I was elevated. Relative to the control animals, mRNAs for ALP, osteocalcin and collagen type I increased 2.4 ± 0.4-, 4.7 ± 1.9- and 4.0 ± 1.7-fold, respectively, in animals treated with ghrelin for 6 weeks (P < 0.05). At 12 weeks, mRNA levels of ALP, osteocalcin and collagen type I showed a decline relative to levels at 6 weeks but still remained significantly higher than in the control group, with fold changes of 2.4 ± 0.8, 2.4 ± 1.2 and 2.1 ± 0.7, respectively (P < 0.05). This study demonstrated that ghrelin stimulates intramembranous osteogenesis. [source]

    Simultaneous Immobilization of Bioactives During 3D Powder Printing of Bioceramic Drug-Release Matrices

    Elke Vorndran
    Abstract The combination of a degradable bioceramic scaffold and a drug-delivery system in a single low temperature fabrication step is attractive for the reconstruction of bone defects. The production of calcium phosphate scaffolds by a multijet 3D printing system enables localized deposition of biologically active drugs and proteins with a spatial resolution of approximately 300,µm. In addition, homogeneous or localized polymer incorporation during printing with HPMC or chitosan hydrochloride allows the drug release kinetics to be retarded from first to zero order over a period of 3,4 days with release rates in the range 0.68%,0.96%,h,1. The reduction in biological activity of vancomycin, heparin, and rhBMP-2 following spraying through the ink jet nozzles is between 1% and 18%. For vancomycin, a further loss of biological activity following incorporation into a cement and subsequent in vitro release is 11%. While previously acknowledged as theoretically feasible, is its shown for the first time that bone grafts with simultaneous geometry, localized organic bioactive loading, and localized diffusion control are a physical reality. This breakthrough offers a new future for patients by providing the required material function to match patient bone health status, site of repair, and age. [source]

    Primary oromandibular reconstruction using free flaps and thorp plates in cancer patients: A 5-year experience,

    Tito Poli MD
    Abstract Background. Low-profile second-generation THORP titanium plates combined with soft tissues free flaps (forearm or TRAM) can be used for oromandibular reconstruction in patients with SCC in advanced stage (stage III,IV). Methods. To evaluate long-term stability and possible complications of this reconstructive technique, we recorded, retrospectively, data of 25 patients with posterolateral oromandibular defects after tumor resection collected during a 5-year period. Results. All free flaps were successfully transferred, although eight patients were initially seen with delayed hardware-related reconstructive complications: plate exposure in four patients and plate fracture in four patients. Conclusions. Nowadays, the state-of-the-art treatment for mandibular defects is primary bone reconstruction with bone free flaps, but in selected cases (elderly patients, poor performance status, posterolateral oromandibular defects, soft tissue defects much more important than bone defects) the association with THORP plate-soft tissue free flaps represents a good reconstructive choice. © 2002 Wiley Periodicals, Inc. Head Neck 24: 000,000, 2002 [source]

    Lyophilization to improve drug delivery for chitosan-calcium phosphate bone scaffold construct: A preliminary investigation

    Benjamin T. Reves
    Abstract Lyophilization was evaluated in chitosan-calcium phosphate microspheres and scaffolds to improve drug delivery of growth factors and antibiotics for orthopedic applications. The dual delivery of an antibiotic and a growth factor from a composite scaffold would be beneficial for treatment of complex fracture sites, such as comminuted fractures and segmental bone defects. The aim of this investigation was to increase the loading capacity of the composite by taking advantage of the increased porosity, due to lyophilization, and to produce an extended elution profile using a secondary chitosan-bead coating. The physiochemical properties of the composite were investigated, and loading and elution studies were performed with alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and amikacin. Lyophilization was found to increase the surface area of scaffolds by over 400% and the porosity of scaffolds by 50%. Using ALP as a model protein, the loading capacity was increased by lyophilization from 4.3 ± 2.5 to 24.6 ± 3.6 ,g ALP/mg microspheres, and the elution profile was extended by a supplemental chitosan coating. The loading capacity of BMP-2 for composite microspheres was increased from 74.4 ± 3.7 to 102.1 ± 8.0 ,g BMP-2/g microspheres with lyophilization compared with nonlyophilized microspheres. The elution profiles of BMP-2 and the antibiotic amikacin were not extended with the supplemental coating. Additional investigations are planned to improve these elution characteristics for growth factors and antibiotics. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source]