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Sample records for bone healing model

  1. A MULTI-SITE SHEEP MODEL FOR CANCELLOUS BONE HEALING

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    Angad eMalhotra

    2014-09-01

    Full Text Available Appropriate, well characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14mm of fixed depth (25mm were compared in both skeletally immature (18 month old and aged sheep (5 year old. In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at four weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using µCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects, with woven bone normally forming near the periphery of the defect. Bone volume fraction (BV/TV significantly decreased with an increasing defect diameter. Actual bone volume (BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal, and encourages a reduction in animal numbers required for preclinical research.

  2. Growth hormone stimulates bone healing in a critical-sized bone defect model

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    Theyse, L. F. H.; Oosterlaken-Dijksterhuis, M. A.; van Doorn, J.; Dhert, W. J. A.; Hazewinkel, H. A. W.

    2006-01-01

    Growth hormone plays an important role in bone metabolism. Treating bone deficits is a major topic in orthopaedic surgery. Our hypothesis was that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Bone formation in the defects was qu

  3. Evaluation of the bone healing process in an experimental tibial bone defect model in ovariectomized rats.

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    Kido, Hueliton Wilian; Bossini, Paulo Sérgio; Tim, Carla Roberta; Parizotto, Nivaldo Antônio; da Cunha, Anderson Ferreira; Malavazi, Iran; Renno, Ana Claudia Muniz

    2014-10-01

    The aim of this study was to evaluate the influence of postmenopausal bone loss (induced by ovariectomy) in the process of bone healing in a tibial bone defect model in rats by means of histological evaluation of bone defects and the analysis of the expression of genes and proteins involved in bone consolidation. Twenty female Wistar rats (12 weeks old, weighing ±250 g) were randomly divided into two groups: control group (CG) and ovariectomized group (OG). Rats of OG were submitted to ovariectomy and after 8 weeks post-surgery, all animals were submitted to the tibial bone defect model. The main histological finding analysis revealed that ovariectomized animals showed a higher amount of granulation tissue and immature newly formed bone compared to CG. Furthermore, quantitative histological analysis showed that OG presented a significant decrease in the amount of newly formed bone (p = 0.0351). RT-PCR analysis showed no difference in Runx2, ALP, RANK, RANKL and Osterix gene expression 14-day post-surgery. Interestingly, immunohistochemical evaluation showed that Runx2 was down expressed (p = 0.0001) and RANKL was up expressed (p = 0.0022) in the OG. In conclusion, these data highlight that bone loss induced by ovariectomy causes an impairment in the capacity of bone to heal mainly probably because of alterations in the imbalance of osteoblasts and osteoclasts activities.

  4. Bone healing in 2016

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    Buza, John A.; Einhorn, Thomas

    2016-01-01

    Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

  5. Histomorphometric evaluation of bone healing in rabbit fibular osteotomy model without fixation

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    Paixão Fabio B

    2008-01-01

    Full Text Available Abstract Background Animal models of fracture consolidation are fundamental for the understanding of the biological process of bone repair in humans, but histological studies are rare and provide only qualitative results. The objective of this article is to present the histomorphometric study of the bone healing process using an experimental model of osteotomy in rabbit fibula without interference of synthesis material. Methods Fifteen rabbits were submitted to fibular osteotomy without any fixation device. Groups of five animals were submitted to pharmacological euthanasia during a period of one (group A, two (group B and four weeks (group C after osteotomy. Histomorphometric evaluation was performed in the histological sections. Results During week one there was intense cellularity (67/field, a large amount of woven bone (75.7% and a small amount of lamellar bone (7.65%. At two weeks there was a decrease in woven bone (41.59% and an increase in lamellar bone (15.16%. At four weeks there was a decrease of cellularity (19.17/field and lamellar bone (55.56% exceeded the quantity of woven bone (31.68%. Conclusion Histomorphometric (quantitative evaluation of the present study was shown to be compatible with bone healing achieved in qualitative experimental models that have been commended in the literature.

  6. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

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    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  7. Histopathological comparison of bone healing effects of endonasal and percutaneous lateral osteotomy methods in rabbit rhinoplasty model.

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    Öğreden, Şahin; Rüzgar, Sedat; Tansuker, Hasan Deniz; Taşkın, Ümit; Alimoğlu, Yalçın; Aydın, Salih; Oktay, Mehmet Faruk; İzol, Uğur

    2017-07-17

    Lateral osteotomy is mainly performed either endonasally or percutaneously in rhinoplasty which is a frequently performed operation for the correction of nasal deformities. Both techniques have both advantages and disadvantages relative to each other. The aim of this study was to compare the histopathological effects of endonasal and percutaneous osteotomy techniques performed in rhinoplasty on bone healing and nasal stability in an experimental animal model. Eight one year-old New Zealand white rabbits were included. Xylazine hydrocloride and intramuscular ketamine anesthesia were administered to the rabbits. Endonasal osteotomy (8 bones) was performed in Group 1 (n=4), and percutaneous osteotomy (8 bones) in Group 2 (n=4). One month later the rabbits were sacrificed. Bone healing of the rabbits was staged according to the bone healing score of Huddleston et al. In both groups, nasal bone integrity was assessed subjectively. In the percutaneous osteotomy group, Grade 1 bone healing was observed in two samples (25%), Grade 2 bone healing in two samples (25%), Grade 3 bone healing in four samples (50%). In the endonasal osteotomy group, Grade 1 bone healing was observed in 6 samples (75%) and Grade 2 bone healing was observed in 2 samples (25%). In the percutaneous group, fibrous tissue was observed in 2, predominantly fibrous tissue and a lesser amount of cartilage was observed in 2 and an equal amount of fibrous tissue and cartilage was observed in 4 samples. In the endonasal group, fibrous tissue was observed in 6 samples, and predominantly fibrous tissue with a lesser amount of cartilage was observed in 2 samples. In both groups, when manual force was applied to the nasal bones, subjectively the same resistance was observed. Percutaneous lateral osteotomy technique was found to result in less bone and periost trauma and better bone healing compared to the endonasal osteotomy technique. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia

  8. Octacalcium phosphate (OCP) collagen composites enhance bone healing in a dog tooth extraction socket model.

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    Iibuchi, S; Matsui, K; Kawai, T; Sasaki, K; Suzuki, O; Kamakura, S; Echigo, S

    2010-02-01

    The authors have reported that a scaffold constructed of synthetic octacalcium phosphate (OCP) and porcine atelocollagen sponge (OCP/Col) enhanced bone regeneration more than sintered beta-tricalcium phosphate collagen composite or sintered hydroxyapatite collagen composite with a rat calvarial defect model. To aim for clinical application, the present study investigated whether OCP/Col would enhance bone healing in a dog tooth extraction socket model. Six adult, male, beagle dogs were used. The tooth extraction socket model was made by extracting bilateral third maxillary incisors and the subsequent removal of buccal bone. Disks of OCP/Col were implanted into one side of the model and the other side was untreated. The specimens were fixed 1 or 3 months after implantation. In radiographic analysis, the OCP/Col-treated group showed a wider range of radiopacity than the untreated control. Histologically, the OCP/Col-treated group showed more abundant newly formed bone than untreated control, and the implanted OCP was gradually resorbed. In morphometrical analysis, enlargement of the buccal alveolus in the OCP/Col group was significantly greater than in the untreated control. This study showed that implanted OCP/Col would be replaced by newly formed bone and OCP/Col implantation would enhance bone healing in a tooth socket model.

  9. Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing.

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    Jäger, Marten; Ott, Claus-Eric; Grünhagen, Johannes; Hecht, Jochen; Schell, Hanna; Mundlos, Stefan; Duda, Georg N; Robinson, Peter N; Lienau, Jasmin

    2011-03-24

    The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences. Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite de novo transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled de novo from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO) analysis showed that the differentially expressed genes were enriched in terms including extracellular matrix, cartilage development, contractile fiber, and chemokine activity. Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which no sequence information was previously available. This

  10. Quantitative assessment of bone defect healing by multidetector CT in a pig model

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    Riegger, Carolin; Kroepil, Patric; Lanzman, Rotem S.; Miese, Falk R.; Antoch, Gerald; Scherer, Axel [University Duesseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Jungbluth, Pascal; Hakimi, Mohssen; Wild, Michael [University Duesseldorf, Medical Faculty, Department of Traumatology and Hand Surgery, Duesseldorf (Germany); Hakimi, Ahmad R. [Universtity Duesseldorf, Medical Faculty, Department of Oral Surgery, Duesseldorf (Germany)

    2012-05-15

    To evaluate multidetector CT volumetry in the assessment of bone defect healing in comparison to histopathological findings in an animal model. In 16 mini-pigs, a circumscribed tibial bone defect was created. Multidetector CT (MDCT) of the tibia was performed on a 64-row scanner 42 days after the operation. The extent of bone healing was estimated quantitatively by MDCT volumetry using a commercially available software programme (syngo Volume, Siemens, Germany).The volume of the entire defect (including all pixels from -100 to 3,000 HU), the nonconsolidated areas (-100 to 500 HU), and areas of osseous consolidation (500 to 3,000 HU) were assessed and the extent of consolidation was calculated. Histomorphometry served as the reference standard. The extent of osseous consolidation in MDCT volumetry ranged from 19 to 92% (mean 65.4 {+-} 18.5%). There was a significant correlation between histologically visible newly formed bone and the extent of osseous consolidation on MDCT volumetry (r = 0.82, P < 0.0001). A significant negative correlation was detected between osseous consolidation on MDCT and histological areas of persisting defect (r = -0.9, P < 0.0001). MDCT volumetry is a promising tool for noninvasive monitoring of bone healing, showing excellent correlation with histomorphometry. (orig.)

  11. In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2.

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    Frederico O Ribeiro

    Full Text Available The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2 has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies.

  12. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model

    NARCIS (Netherlands)

    Fisher, J.P.; Lalani, Z.; Bossano, C.M.; Brey, E.M.; Demian, N.; Johnston, C.M.; Dean, D.; Jansen, J.A.; Wong, M.E.; Mikos, A.G.

    2004-01-01

    In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion.

  13. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model

    NARCIS (Netherlands)

    Fisher, J.P.; Lalani, Z.; Bossano, C.M.; Brey, E.M.; Demian, N.; Johnston, C.M.; Dean, D.; Jansen, J.A.; Wong, M.E.; Mikos, A.G.

    2004-01-01

    In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion.

  14. Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing

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    Mundlos Stefan

    2011-03-01

    Full Text Available Abstract Background The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences. Results Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite de novo transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled de novo from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO analysis showed that the differentially expressed genes were enriched in terms including extracellular matrix, cartilage development, contractile fiber, and chemokine activity. Conclusions Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which

  15. Parathyroid hormone and bone healing

    DEFF Research Database (Denmark)

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-01-01

    , no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...... in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment...

  16. Modulation of fixation stiffness from flexible to stiff in a rat model of bone healing.

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    Bartnikowski, Nicole; Claes, Lutz E; Koval, Lidia; Glatt, Vaida; Bindl, Ronny; Steck, Roland; Ignatius, Anita; Schuetz, Michael A; Epari, Devakara R

    2016-11-14

    Background and purpose - Constant fixator stiffness for the duration of healing may not provide suitable mechanical conditions for all stages of bone repair. We therefore investigated the influence of stiffening fixation on callus stiffness and morphology in a rat diaphyseal osteotomy model to determine whether healing time was shortened and callus stiffness increased through modulation of fixation from flexible to stiff. Material and methods - An external unilateral fixator was applied to the osteotomized femur and stiffened by decreasing the offset of the inner fixator bar at 3, 7, 14, and 21 days after operation. After 5 weeks, the rats were killed and healing was evaluated with mechanical, histological, and microcomputed tomography methods. Constant fixation stiffness control groups with either stiff or flexible fixation were included for comparison. Results - The callus stiffness of the stiff group and all 4 experimental groups was greater than in the flexible group. The callus of the flexible group was larger but contained a higher proportion of unmineralized tissue and cartilage. The stiff and modulated groups (3, 7, 14, and 21 days) all showed bony bridging at 5 weeks, as well as signs of callus remodeling. Stiffening fixation at 7 and 14 days after osteotomy produced the highest degree of callus bridging. Bone mineral density in the fracture gap was highest in animals in which the fixation was stiffened after 14 days. Interpretation - The predicted benefit of a large robust callus formed through early flexible fixation could not be shown, but the benefits of stabilizing a flexible construct to achieve timely healing were demonstrated at all time points.

  17. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model.

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    Fisher, John P; Lalani, Zahid; Bossano, Carla M; Brey, Eric M; Demian, Nagi; Johnston, Carol M; Dean, David; Jansen, John A; Wong, Mark E K; Mikos, Antonios G

    2004-03-01

    In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion. To test this hypothesis, healing bone was investigated within a rabbit incisor extraction socket, a subcritical size bone defect that resists significant soft tissue invasion by virtue of its conformity. After removal of the incisor teeth, one tooth socket was left as an empty control, one was filled with crosslinked polymer networks formed from the hydrophobic polymer poly(propylene fumarate) (PPF), and one was filled with a hydrogel formed from the hydrophilic oligomer oligo(poly(ethylene glycol) fumarate) (OPF). At five different times (4 days as well as 1, 2, 4, and 8 weeks), jaw bone specimens containing the tooth sockets were removed. We analyzed bone healing by histomorphometrical analysis of hematoxylin and eosin stained sections as well as immunohistochemically stained sections. The proposed hypothesis, that a hydrophilic material would hinder bone healing, was supported by the histomorphometrical results. In addition, the immunohistochemical results reflect molecular signaling indicative of the early invasion of platelets, the vascularization of wound-healing tissue, the differentiation of migrating progenitor cells, and the formation and remodeling of bone tissue. Finally, the results emphasize the need to consider biomaterial properties and their differing effects upon endogenous growth factors, and thus bone healing, during the development of tissue engineering devices. Copyright 2003 Wiley Periodicals, Inc.

  18. The healing of fractured bones

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    Bacon, G.E. [Central Electricity Generating Board, Cheltenham (United Kingdom)

    1997-04-01

    A method utilising neutron beams of width 1 mm, used on D1B (2.4 A) and D20 (1.3 A) to study the healing of fractured bones is presented. It is found that the callus bone uniting the fractured tibia of a sheep, whose healing had been encouraged by daily mechanical vibration over a period of three months, showed no trace of the large preferential vertical orientation of the apatite crystals which is characteristic of the normal bone. Nevertheless the bone had regained about 60% of its mechanical strength and the callus bone, although not oriented, was well crystallized. It is considered that the new monochromator for D20, expected to give increased intensity at 2.5 A, will be of considerable advantage. (author). 2 refs.

  19. Effects of low-intensity pulsed ultrasound on new trabecular bone during bone-tendon junction healing in a rabbit model: a synchrotron radiation micro-CT study.

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    Hongbin Lu

    Full Text Available This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point. The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate

  20. Coating with a modular bone morphogenetic peptide promotes healing of a bone-implant gap in an ovine model.

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    Yan Lu

    Full Text Available Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation. We have developed a modular bone growth factor, herein termed "modular bone morphogenetic peptide (mBMP", which was designed to efficiently bind to the surface of orthopedic implants and also stimulate new bone formation. The purpose of this study was to coat a hydroxyapatite-titanium implant with mBMP and evaluate bone healing across a bone-implant gap in the sheep femoral condyle. The mBMP molecules efficiently bound to a hydroxyapatite-titanium implant and 64% of the initially bound mBMP molecules were released in a sustained manner over 28 days. The results demonstrated that the mBMP-coated implant group had significantly more mineralized bone filling in the implant-bone gap than the control group in C-arm computed tomography (DynaCT scanning (25% more, histological (35% more and microradiographic images (50% more. Push-out stiffness of the mBMP group was nearly 40% greater than that of control group whereas peak force did not show a significant difference. The results of this study demonstrated that mBMP coated on a hydroxyapatite-titanium implant stimulates new bone formation and may be useful to improve implant fixation in total joint arthroplasty applications.

  1. Rodent animal models of delayed bone healing and non-union formation: a comprehensive review

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    P Garcia

    2013-07-01

    Full Text Available Despite the growing knowledge on the mechanisms of fracture healing, delayed healing and non-union formation remain a major clinical challenge. Animal models are needed to study the complex process of normal and impaired fracture healing and to develop new therapeutic strategies. Whereas in the past mainly large animals have been used to study normal and impaired fracture healing, nowadays rodent models are of increasing interest. New osteosynthesis techniques for rat and mice have been developed during the last years, which allowed for the first time stable osteosynthesis in these animals comparable to the standards in large animals and humans. Based on these new implants, different models in rat and mice have been established to study delayed healing and non-union formation. Although in humans the terms delayed union and non-union are well defined, in rodents definitions are lacking. However, especially in scientific studies clear definitions are necessary to develop a uniform scientific language and allow comparison of the results between different studies. In this consensus report, we define the basic terms “union”, “delayed healing” and “non-union” in rodent animal models. Based on a review of the literature and our own experience, we further provide an overview on available models of delayed healing and non-union formation in rats and mice. We further summarise the value of different approaches to study normal and delayed fracture healing as well as non-union formation, and discuss different methods of data evaluation.

  2. Medicinal plants and bone healing.

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    Singh, Vibha

    2017-01-01

    Fracture is defined as complete or incomplete separation in the continuity of bone Fracture healing is a complex physiological process that involves the coordinated participation of hematopoietic and immune cells within bone marrow. It conjunction with vascular and skeletal cell precursors it also includes mesenchymal stem cells which are recruited from the circulation and the surrounding tissues. It is estimated that 80% of the population in developing countries still rely on the traditional herbal medicines. Healing is practiced by people from all levels of society, who live and work in intimate relation with their environment. They range from bone setting, treatment of snake bite and mental disorders. Knowledge of Medicinal plants and their identification should be gain with the help of cowherds, hermits, hunters, forest dwellers and those who gather plants of forest for food. Sushruta Samita Sutrasthanam 36 V.10. Herbs can effective in reducing swelling pain and soreness of the fracture and al so speedy recovery of function. In last few decades there has been growing In alternative forms of therapy globally. Herbal medicines are currently in demand and their popularity is increasing.

  3. The effect of traumatic brain injury on bone healing: an experimental study in a novel in vivo animal model.

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    Tsitsilonis, Serafeim; Seemann, Ricarda; Misch, Martin; Wichlas, Florian; Haas, Norbert P; Schmidt-Bleek, Katharina; Kleber, Christian; Schaser, Klaus-Dieter

    2015-04-01

    Among many factors determining the outcome of complex fractures in polytrauma patients, the role of traumatic brain injury (TBI) remains only partly understood. The aim of the present study was to examine the effect of traumatic brain injury on bone healing through the establishment of a novel standardised animal model that sequentially combines traumatic brain injury (TBI) with a long bone injury. Thirty-six female twelve-week old C57/BL6 mice were randomised in two groups (fracture (Fx)-group and combined-trauma (Fx/TBI) group). The methods of the Control Cortical Impact Injury for induction of TBI and of the femoral osteotomy, fixed with an external fixator for the simulation of the long bone fracture, were combined. No TBI was induced in the Fx-group. Bone healing was examined using in vivo micro-CT measurements over a period of three weeks. The severity of the TBI was sufficient to stimulate a significantly increased callus formation in the Fx/TBI-group with an acceptable mortality rate. The micro-CT analysis of fracture healing displayed a significantly increased callus volume in the Fx/TBI-group already from the second postoperative week. This difference remained significant throughout the entire study period. The successful and standardised combination of TBI and fracture in a mouse model allows systematic and quantitative in vivo analysis of underlying pathways that trigger the mutual interaction between musculoskeletal trauma and brain injury, as well as, corresponding differences in fracture healing using micro-CT methods. The present study offers three new aspects: a standardised model for combined injury of TBI and femoral osteotomy; direct and serial in vivo imaging and quantification of fracture healing response using micro-CT; testing of potentially beneficial therapeutic regimens for fracture treatment in presence of TBI. Thus this model provides a valuable basic approach for the study of the amplifying effect of TBI on callus formation seen in

  4. Ultrasound stimulation of maxillofacial bone healing

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    Schortinghuis, J; Stegenga, B; Raghoebar, GM; de Bont, LGM

    2003-01-01

    A substantial part of the maxillofacial surgery practice deals with maxillofacial bone healing. In the past decades, low-intensity ultrasound treatment has been shown to reduce the healing time of fresh fractures of the extremities up to 38%, and to heal delayed and non-unions up to 90% and 83%, res

  5. Dynamics of bone graft healing around implants

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    Narayan Venkataraman

    2015-01-01

    A few questions arise pertaining to the use of bone grafts along with implants are whether these are successful in approximation with implant. Do they accelerate bone regeneration? Are all defects ultimately regenerated with new viable bone? Is the bone graft completely resorbed or integrated in new bone? Does the implant surface characteristic positively affect osseointegration when used with a bone graft? What type of graft and implant surface can be used that will have a positive effect on the healing type and time? Finally, what are the dynamics of bone graft healing around an implant? This review discusses the cellular and molecular mechanisms of bone graft healing in general and in vicinity of another foreign, avascular body, namely the implant surface, and further, the role of bone grafts in osseointegration and/or clinical success of the implants.

  6. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice.

    Science.gov (United States)

    Colnot, C; Huang, S; Helms, J

    2006-11-24

    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.

  7. 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

    2017-02-01

    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.

  8. Effects of mouse genotype on bone wound healing and irradiation-induced delay of healing.

    Science.gov (United States)

    Glowacki, Julie; Mizuno, Shuichi; Kung, Jason; Goff, Julie; Epperly, Michael; Dixon, Tracy; Wang, Hong; Greenberger, Joel S

    2014-01-01

    We tested the effects of mouse genotype (C57BL/6NHsd, NOD/SCID, SAMR1, and SAMP6) and ionizing irradiation on bone wound healing. Unicortical wounds were made in the proximal tibiae, and the time course of spontaneous healing and effects of irradiation were monitored radiographically and histologically. There was reproducible healing beginning with intramedullary osteogenesis, subsequent bone resorption by osteoclasts, gradual bridging of the cortical wound, and re-population of medullary hematopoietic cells. The most rapid wound closure was noted in SAMR1 mice, followed by SAMP6, C57BL/6NHsd, and NOD/SCID. Ionizing irradiation (20 Gy) to the leg significantly delayed bone wound healing in mice of all four genotypes. Mice with genetically-determined predisposition to early osteopenia (SAMP6) or with immune deficiency (NOD/SCID) had impairments in bone wound healing. These mouse models should be valuable for determining the effects of irradiation on bone healing and also for the design and testing of novel bone growth-enhancing drugs and mitigators of ionizing irradiation.

  9. Muscle-bone Interactions During Fracture Healing

    Science.gov (United States)

    2015-03-01

    physical trauma31, orthopaedic surgery32, or due to disease like fibrodysplasia ossificans progressiva, which has been identified to be a result of a...responsible for bone healing may provide opportunities to develop therapies to augment normal physiologic mechanisms underlying bone regeneration. Current... osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab 2008; 26:159-64. 70. Hill M, Goldspink G. Expression and splicing of the in- sulin

  10. Coating with a modular bone morphogenetic peptide promotes healing of a bone-implant gap in an ovine model

    National Research Council Canada - National Science Library

    Lu, Yan; Lee, Jae Sung; Nemke, Brett; Graf, Ben K; Royalty, Kevin; Illgen, 3rd, Richard; Vanderby, Jr, Ray; Markel, Mark D; Murphy, William L

    2012-01-01

    Despite the potential for growth factor delivery strategies to promote orthopedic implant healing, there is a need for growth factor delivery methods that are controllable and amenable to clinical translation...

  11. The effect of vancomycin powder on bone healing in a rat spinal rhBMP-2 model.

    Science.gov (United States)

    Mendoza, Marco C; Sonn, Kevin A; Kannan, Abhishek S; Bellary, Sharath S; Mitchell, Sean M; Singh, Gurmit; Park, Christian; Yun, Chawon; Stock, Stuart R; Hsu, Erin L; Hsu, Wellington K

    2016-08-01

    OBJECTIVE This study aims to quantify the impact of vancomycin powder application on new bone formation and spine fusion rates in a rat posterolateral arthrodesis model. METHODS Thirty-six female Sprague-Dawley rats underwent a posterolateral lumbar spinal fusion (PLF) at the L-4 and L-5 vertebrae. Fusion was elicited via implantation of an absorbable collagen sponge containing 3 µg rhBMP-2. Rats were divided into 3 groups: no vancomycin (control), standard-dose vancomycin, and high-dose vancomycin, based on what was applied to the fusion bed. Clinical studies typically describe the application of 1 g vancomycin into the surgical wound. Presuming an average individual patient weight of 70 kg, a weight-based equivalent dose of vancomycin powder was applied subfascially in the PLF model constituting a "standard-dose" treatment group (14.3 mg/kg, n = 12). To determine whether there is a critical threshold beyond which vancomycin increases the risk of pseudarthrosis, a 10-fold higher dose was administered to a "high-dose" treatment group (143 mg/kg, n = 12). No vancomycin powder was applied to the surgical site in the control group (n = 12). Fusion was evaluated with plain radiographs at 4 and 8 weeks after surgery. The spines were harvested after the 8-week radiographs were obtained and evaluated using manual palpation, microCT analysis, and histological analysis. RESULTS Radiographs demonstrated equivalent bridging bone formation in all groups. No significant differences in fusion scores were seen in the standard-dose (mean 2.25) or high-dose (2.13) treatment groups relative to untreated control animals (1.78). Similarly, fusion rates did not differ significantly different between vancomycin-treated animals (100% for both groups) and control animals (92%). Quantification of new bone formation via microCT imaging revealed no significant between-groups differences in the volume of newly regenerated bone (control vs standard-dose vancomycin, p = 0.57; control vs high

  12. The effects of low-intensity pulsed ultrasound on tendon-bone healing in a transosseous-equivalent sheep rotator cuff model.

    Science.gov (United States)

    Lovric, Vedran; Ledger, Michael; Goldberg, Jerome; Harper, Wade; Bertollo, Nicky; Pelletier, Matthew H; Oliver, Rema A; Yu, Yan; Walsh, William R

    2013-02-01

    The purpose of this study was to examine the effects Low-intensity Pulsed Ultrasound has on initial tendon-bone healing in a clinically relevant extra-articular transosseous-equivalent ovine rotator cuff model. Eight skeletally mature wethers, randomly allocated to either control group (n = 4) or treatment group (n = 4), underwent rotator cuff surgery following injury to the infraspinatus tendon. All animals were killed 28 days post surgery to allow examination of early effects of Low-intensity Pulsed Ultrasound treatment. General improvement in histological appearance of tendon-bone integration was noted in the treatment group. Newly formed woven bone with increased osteoblast activity along the bone surface was evident. A continuum was observed between the tendon and bone in an interdigitated fashion with Sharpey's fibres noted in the treatment group. Low-intensity Pulsed Ultrasound treatment also increased bone mineral density at the tendon-bone interface (p tendon-bone healing process in patients who have undergone rotator cuff repair. This treatment may also be beneficial following other types of reconstructive surgeries involving the tendon-bone interface.

  13. Histomorphometric Study of Alveolar Bone Healing in Rats Fed a Boron-Deficient Diet

    Science.gov (United States)

    Bone healing after tooth extraction in rats is a suitable experimental model to study bone formation. Thus, we performed a study to determine the effects of boron (B) deficiency on bone healing by using this model. Weanling Wistar rats were divided into two groups: control (+B; 3 mg B/kg diet), and ...

  14. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

    Science.gov (United States)

    Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

    2015-03-13

    Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

  15. A novel coupled system of non-local integro-differential equations modelling Young's modulus evolution, nutrients' supply and consumption during bone fracture healing

    Science.gov (United States)

    Lu, Yanfei; Lekszycki, Tomasz

    2016-10-01

    During fracture healing, a series of complex coupled biological and mechanical phenomena occurs. They include: (i) growth and remodelling of bone, whose Young's modulus varies in space and time; (ii) nutrients' diffusion and consumption by living cells. In this paper, we newly propose to model these evolution phenomena. The considered features include: (i) a new constitutive equation for growth simulation involving the number of sensor cells; (ii) an improved equation for nutrient concentration accounting for the switch between Michaelis-Menten kinetics and linear consumption regime; (iii) a new constitutive equation for Young's modulus evolution accounting for its dependence on nutrient concentration and variable number of active cells. The effectiveness of the model and its predictive capability are qualitatively verified by numerical simulations (using COMSOL) describing the healing of bone in the presence of damaged tissue between fractured parts.

  16. Long-term morphology of a healing bone-tendon interface: a histological observation in the sheep model.

    Science.gov (United States)

    Newsham-West, R; Nicholson, H; Walton, M; Milburn, P

    2007-03-01

    The purpose of this study was to examine and describe the sequence of events involved in long-term biological reconstruction of a tendon-bone interface following surgical reattachment. Patellar tendon re-attachment in the adult sheep was used to investigate and describe the biological components involved in healing and repair of a tendon enthesis. Light microscopy was used to describe the healing morphology at time intervals of 8, 12, 26, 52 and 104 weeks. By 8 weeks a collagen continuum was observed between the tendon and bone. Over time this fibrous bridge became anchored into the original tissues (tendon and bone), with the resultant enthesis resembling more a fibrous rather than the original fibrocartilagenous enthesis. The associated collagen fibrils between the two tissues gradually changed in morphology over time to reflect the fibres seen in the original tendon tissue. The fibrous tissue of the forming enthesis remained hypercellular when compared with the controls. The resultant long-term morphology may be a reflection of functional adaptation rather than anatomical replication.

  17. Bioengineered periosteal progenitor cell sheets to enhance tendon-bone healing in a bone tunnel

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Chang

    2012-12-01

    Full Text Available Background: Tendon-bone tunnel healing is crucial for long term success in anterior cruciate liga­ment (ACL reconstruction. The periosteum contains osteochondral progenitor cells that can differenti­ate into osteoblasts and chondroblasts during tendon-bone healing. We developed a scaf­fold-free method using polymerized fibrin-coated dishes to make functional periosteal progenitor cell (PPC sheets. Bioengineered PPC sheets for enhancing tendon-bone healing were evaluated in an extra-articular bone tunnel model in rabbit. Methods: PPC derived from rabbit tibia periosteum, cultivated on polymerized fi­brin-coated dishes and harvested as PPC sheet. A confocal microscopy assay was used to evaluate the morphology of PPC sheets. PPC sheets as a periosteum to wrap around hamstring tendon grafts were pulled into a 3-mm diameter bone tunnel of tibia, and compared with a tendon graft without PPC sheets treatment. Rabbits were sacrificed at 4 and 8 weeks postoperatively for biochemical as­say and histological assay to demonstrate the enhancement of PPC sheets in tendon-bone healing. Results: PPC spread deposit on fibrin on the dish surface with continuous monolayer PPC was ob­served. Histological staining revealed that PPC sheets enhance collagen and glycosaminoglycans deposi­tion with fibrocartilage formation in the tendon-bone junction at 4 weeks. Collagen fiber with fibrocartilage formation at tendon-bone junction was also found at 8 weeks. Matured fibrocartilage and dense collagen fiber were formed at the tendon-bone interface at 8 weeks by Masson trichrome and Safranin-O staining Conclusions: Periosteal progenitor cell monolayer maintains the differentiated capacity and osteochon­dral potential in order to promote fibrocartilage formation in tendon-bone junction. Bioengi­neered PPC sheets can offer a new feasible therapeutic strategy of a novel approach to en­hance tendon-bone junction healing.

  18. Combined application of low-intensity pulsed ultrasound and functional electrical stimulation accelerates bone-tendon junction healing in a rabbit model.

    Science.gov (United States)

    Hu, Jianzhong; Qu, Jin; Xu, Daqi; Zhang, Tao; Qin, Ling; Lu, Hongbin

    2014-02-01

    The objective of this study was to elucidate the combined use of low-intensity pulsed ultrasound (LIPUS) and functional electrical stimulation (FES) on patella-patellar tendon (PPT) junction healing using a partial patellectomy model in rabbits. LIPUS was delivered continuously starting day 3 postoperative until week 6. FES was applied on quadriceps muscles to induce tensile force to the repaired PPT junction 5 days per week for 6 weeks since week 7 postoperatively. Forty rabbits with partial patellectomy were randomly divided into four groups: control, LIPUS alone, FES alone, and LIPUS + FES groups. At week 12, the PPT complexes were harvested for histology, radiographs, peripheral quantitative computed tomography, and biomechanical testing. There was better remodeling of newly formed bone and fibrocartilage zone in the three treatment groups compared with the control group. LIPUS and/or FES treatments significantly increased the area and bone mineral content of new bone. The failure load and ultimate strength of PPT complex were also highly improved in the three treatment groups. More new bone formed and higher tensile properties were showed in the LIPUS + FES group compared with the LIPUS or FES alone groups. Early LIPUS treatment and later FES treatment showed the additive effects of accelerating PPT junction healing.

  19. The effects of chronic unloading and gap formation on tendon-to-bone healing in a rat model of massive rotator cuff tears.

    Science.gov (United States)

    Killian, Megan L; Cavinatto, Leonardo; Shah, Shivam A; Sato, Eugene J; Ward, Samuel R; Havlioglu, Necat; Galatz, Leesa M; Thomopoulos, Stavros

    2014-03-01

    The objective of this study was to understand the effect of pre-repair rotator cuff chronicity on post-repair healing outcomes using a chronic and acute multi-tendon rat rotator cuff injury model. Full-thickness dual tendon injuries (supra- and infraspinatus) were created unilaterally in adult male Sprague Dawley rats, and left chronically detached for 8 or 16 weeks. After chronic detachment, tears were repaired and acute dual tendon injuries were created and immediately repaired on contralateral shoulders. Tissue level outcomes for bone, tendon, and muscle were assessed 4 or 8 weeks after repair using histology, microcomputed tomography, biomechanical testing, and biochemical assays. Substantial gap formation was seen in 35% of acute repairs and 44% of chronic repairs. Gap formation negatively correlated with mechanical and structural outcomes for both healing time points regardless of injury duration. Bone and histomorphometry, as well as biomechanics, were similar between acute and chronic injury and repair regardless of chronicity and duration of healing. This study was the first to implement a multi-tendon rotator cuff injury with surgical repair following both chronic and acute injuries. Massive tear in a rodent model resulted in gap formation regardless of injury duration which had detrimental effects on repair outcomes. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

    Science.gov (United States)

    Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

    2016-01-01

    The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

  1. A novel implantation model for evaluation of bone healing response to dental implants: the goat iliac crest.

    NARCIS (Netherlands)

    Schouten, C.; Meijer, G.J.; Beucken, J.J.J.P. van den; Spauwen, P.H.M.; Jansen, J.A.

    2010-01-01

    OBJECTIVES: Despite the availability of numerous animal models for testing the biological performance of dental and orthopedic implants, the selection of a suitable model is complex. This paper presents a new model for objective and standardized evaluation of bone responses to implants using the ili

  2. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    OpenAIRE

    Petrizzi, Lucio; Mariscoli, Massimo; Valbonetti, Luca; Varasano, Vincenzo; Langhoff, Jens D; von Rechenberg, Brigitte

    2007-01-01

    Background Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a p...

  3. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    OpenAIRE

    Petrizzi, Lucio; Mariscoli, Massimo; Valbonetti, Luca; Varasano, Vincenzo; Langhoff, Jens D; von Rechenberg, Brigitte

    2007-01-01

    BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a ...

  4. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    OpenAIRE

    Langhoff Jens D; Varasano Vincenzo; Valbonetti Luca; Mariscoli Massimo; Petrizzi Lucio; Von Rechenberg Brigitte

    2007-01-01

    Abstract Background Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxo...

  5. Bone healing after median sternotomy: a comparison of two hemostatic devices.

    Science.gov (United States)

    Vestergaard, Rikke F; Jensen, Henrik; Vind-Kezunovic, Stefan; Jakobsen, Thomas; Søballe, Kjeld; Hasenkam, John M

    2010-11-24

    Bone wax is traditionally used as part of surgical procedures to prevent bleeding from exposed spongy bone. It is an effective hemostatic device which creates a physical barrier. Unfortunately it interferes with subsequent bone healing and increases the risk of infection in experimental studies. Recently, a water-soluble, synthetic, hemostatic compound (Ostene®) was introduced to serve the same purpose as bone wax without hampering bone healing. This study aims to compare sternal healing after application of either bone wax or Ostene®. Twenty-four pigs were randomized into one of three treatment groups: Ostene®, bone wax or no hemostatic treatment (control). Each animal was subjected to midline sternotomy. Either Ostene® or bone wax was applied to the spongy bone surfaces until local hemostasis was ensured. The control group received no hemostatic treatment. The wound was left open for 60 min before closing to simulate conditions alike those of cardiac surgery. All sterni were harvested 6 weeks after intervention.Bone density and the area of the bone defect were determined with peripheral quantitative CT-scanning; bone healing was displayed with plain X-ray and chronic inflammation was histologically assessed. Both CT-scanning and plain X-ray disclosed that bone healing was significantly impaired in the bone wax group (p wax inhibits bone healing and induces chronic inflammation in a porcine model. Ostene® treated animals displayed bone healing characteristics and inflammatory reactions similar to those of the control group without application of a hemostatic agent.

  6. Evaluation of a Topical Herbal Agent for the Promotion of Bone Healing

    Directory of Open Access Journals (Sweden)

    Wing-Sum Siu

    2015-01-01

    Full Text Available A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing.

  7. Bone healing around nanocrystalline hydroxyapatite, deproteinized bovine bone mineral, biphasic calcium phosphate, and autogenous bone in mandibular bone defects

    DEFF Research Database (Denmark)

    Broggini, Nina; Bosshardt, Dieter D; Jensen, Simon S

    2015-01-01

    The individual healing profile of a given bone substitute with respect to osteogenic potential and substitution rate must be considered when selecting adjunctive grafting materials for bone regeneration procedures. In this study, standardized mandibular defects in minipigs were filled with nanocr......The individual healing profile of a given bone substitute with respect to osteogenic potential and substitution rate must be considered when selecting adjunctive grafting materials for bone regeneration procedures. In this study, standardized mandibular defects in minipigs were filled...

  8. Computational simulation of bone fracture healing under inverse dynamisation.

    Science.gov (United States)

    Wilson, Cameron J; Schütz, Michael A; Epari, Devakara R

    2017-02-01

    Adaptive finite element models have allowed researchers to test hypothetical relationships between the local mechanical environment and the healing of bone fractures. However, their predictive power has not yet been demonstrated by testing hypotheses ahead of experimental testing. In this study, an established mechano-biological scheme was used in an iterative finite element simulation of sheep tibial osteotomy healing under a hypothetical fixation regime, "inverse dynamisation". Tissue distributions, interfragmentary movement and stiffness across the fracture site were compared between stiff and flexible fixation conditions and scenarios in which fixation stiffness was increased at a discrete time-point. The modelling work was conducted blind to the experimental study to be published subsequently. The simulations predicted the fastest and most direct healing under constant stiff fixation, and the slowest healing under flexible fixation. Although low fixation stiffness promoted more callus formation prior to bridging, this conferred little additional stiffness to the fracture in the first 5 weeks. Thus, while switching to stiffer fixation facilitated rapid subsequent bridging of the fracture, no advantage of inverse dynamisation could be demonstrated. In vivo data remains necessary to conclusively test this treatment protocol and this will, in turn, provide an evaluation of the model's performance. The publication of both hypotheses and their computational simulation, prior to experimental testing, offers an appealing means to test the predictive power of mechano-biological models.

  9. A unified theory of bone healing and nonunion: BHN theory.

    Science.gov (United States)

    Elliott, D S; Newman, K J H; Forward, D P; Hahn, D M; Ollivere, B; Kojima, K; Handley, R; Rossiter, N D; Wixted, J J; Smith, R M; Moran, C G

    2016-07-01

    This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91.

  10. Healing pattern of reamed bone following bone harvesting by a RIA device

    Directory of Open Access Journals (Sweden)

    DM Devine

    2015-01-01

    Full Text Available Intramedullary nailing has been used for decades to treat fractures of the long bones. However, complications related to the increase in medullary pressure culminated in the development of the Reamer Irrigator Aspirator (RIA. Since its first clinical use, the RIA has moved from a reaming device to a cell and autologous bone-harvesting tool. This increase in use brings with it further clinical questions; namely, does the endosteal bone regenerate sufficiently to allow subsequent reaming procedures. In the current study, endosteal bone regeneration post reaming was assessed in an ovine model. The study included six animals that had one tibia reamed, while the contralateral tibia acted as an intact control. Animals were administered fluorochrome labels in vivo, and bone regeneration was assessed using radiographical analysis. The endpoint of the study was 12 weeks post-surgery, at which time ex vivo analysis consisted of computed tomography and histological assessments. In vivo radiographs indicated limited healing of the reamed bone. However, ex vivo computer tomographical analysis indicated no significant differences in terms of bone volume between the reamed bone and the intact bone. Histological assessment of these regions indicated new bone formation. Fluorescent labelling indicates strong bone formation from 9 weeks post-surgery and as such, the bone formed at 12 weeks was immature in nature and was actively undergoing remodelling. These results indicate that bone regeneration post-reaming was continuing at three months. Therefore, given more time it may have sufficiently healed to allow a surgeon to use the intramedullary canal for a re-reaming procedure.

  11. Quality of Bone Healing: Perspectives and Assessment Techniques

    Science.gov (United States)

    2014-01-01

    from nails and screws to dental prostheses and total joint replacements. Direct mechanical testing The true efficacy of bone regeneration can be...method of choice to image bone fluid flow and permeability in vivo61 which is a strong indicator of a successful bone healing response. MRI is also...Bone permeability Fluid transport within bone is not usually estimated in a clinical setting. Recent advances in MRI and positron emis- sion

  12. Smoking and Bone Healing - A Risky Surgical Combination

    Science.gov (United States)

    ... Risky Surgical Combination A A A | Print | Share Smoking and Bone Healing – A Risky Surgical Combination Imagine ... saying that they'd prefer patients to quit smoking. There hasn't been a great deal of ...

  13. Effects of Light-Emitting Diode Photobiomodulation Therapy and BioOss as Single and Combined Treatment in an Experimental Model of Bone Defect Healing in Rats.

    Science.gov (United States)

    Havlucu, Uğur; Bölükbaşı, Nilüfer; Yeniyol, Sinem; Çetin, Şule; Özdemir, Tayfun

    2015-08-01

    The present study assesses histopathologically and histomorphometrically the effects of light-emitting diode (LED) photobiomodulation therapy (LPT) on bone healing in BioOss-filled femoral defects of rats. It has been reported that LPT modulates cellular metabolic processes, leading to an enhanced regenerative potential for biological tissues. Thirty-six male Wistar rats with femoral bone defects were divided into 4 groups: defect group (empty bone defect, without application of LPT), graft group (bone defect filled with BioOss, without application of LPT), (defect+LPT) group (empty bone defect, with application of LPT), and (graft+LPT) group (bone defect filled with BioOss, with application of LPT). An OsseoPulse LED device (wavelength: 618 nm; output power: 20 mW/cm(2)) was initiated 24 hours postsurgery and performed every 24 hours for 7, 14, and 21 days. The LPT-applied and BioOss-filled defects presented a higher amount of new bone formation with trabeculae formation. These defects showed statistically significant lower values of inflammation severity, and fewer remnants of biomaterial were present. Within the limitations of this study, LPT has positive effects on bone healing histopathologically and histomorphometrically for the defects filled with BioOss 3 weeks after the rats' femora injury.

  14. Interactions between MSCs and Immune Cells: Implications for Bone Healing

    Directory of Open Access Journals (Sweden)

    Tracy K. Kovach

    2015-01-01

    Full Text Available It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on both in vitro and in vivo studies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs.

  15. Photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells improve tendon graft healing in a bone tunnel.

    Science.gov (United States)

    Chen, Chih-Hwa; Liu, Hsia-Wei; Tsai, Ching-Lin; Yu, Chung-Ming; Lin, I-Hsuan; Hsiue, Ging-Ho

    2008-03-01

    Tissue-engineered solutions for promoting the tendon graft incorporation within the bone tunnel appear to be promising. To determine the feasibility that conjugation of hyaluronic acid-tethered bone morphogenetic protein-2 can be used to stimulate periosteal progenitor cells direct fibrocartilagenous attachment and new bone formation in an extra-articular tendon-bone healing model. Controlled laboratory study. A total of 42 mature New Zealand White rabbits were used. The long digitorum extensor tendon was transplanted into a bone tunnel of the proximal tibia. The tendon was pulled through a drill hole in the proximal tibia and attached to the medial aspect of the tibia. Photopolymerizable hydrogel based on poly (ethylene glycol) diacrylate with hyaluronic acid-tethered bone morphogenetic protein-2 was injected and photogelated in a bone tunnel. Histological and biomechanical examination of the tendon-bone interface was evaluated at postoperative weeks 3 and 6. Histological analysis showed an interface fibrocartilage and new bone formed by photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells at 6 weeks. Biomechanical testing revealed higher maximum pullout strength and stiffness in experimental groups with a statistically significant difference at 3 and 6 weeks after tendon transplantation. The healing tendon-bone interface undergoes a gradual remodeling process; it appears that photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells possesses a powerful inductive ability between the tendon and the bone to incorporate the healing in a rabbit model. Novel technologies, such as those described in this study, including photopolymerization and tissue engineering, may provide minimally invasive therapeutic procedures via arthroscopy to enhance biological healing after reconstruction of the anterior cruciate ligament.

  16. Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

    Directory of Open Access Journals (Sweden)

    Langhoff Jens D

    2007-05-01

    Full Text Available Abstract Background Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated with naloxone. Naloxone restored the altered cellular and tissue physiology by removing β-endorphins from specific receptors. However, this is only possible if the circulating Ca concentration is adequate. The aim of the present study was to evaluate the efficacy of parenteral naloxone administration in inducing fast mineralization and callus remodelling in a group of sheep with a standardised bone lesion. Methods Twenty ewes were randomly assigned to 4 treatment groups. Group A acted as control, group B received a solution of calcium gluconate, group C a solution of naloxone, and group D a solution of calcium gluconate and naloxone. A transverse hole was drilled in the left metacarpus, including both cortices, then parenteral treatment was administered intramuscularly, daily for four weeks. Healing was evaluated by weekly radiographic examination for eight weeks. For quantitative evaluation, the ratio of the radiographic bone density between the drill area and the adjacent cortical bone was calculated. After eight weeks the sheep were slaughtered and a sample of bone was collected for histopathology Results Group D showed a higher radiographic ratio than the other groups. Sheep not treated with naloxone showed a persistently lower ratio in the lateral than the medial cortex (P Conclusion A low-dose parenteral regimen of naloxone enhances

  17. Novel bone substitute material in alveolar bone healing following tooth extraction: an experimental study in sheep.

    Science.gov (United States)

    Liu, Jinyi; Schmidlin, Patrick R; Philipp, Alexander; Hild, Nora; Tawse-Smith, Andrew; Duncan, Warwick

    2016-07-01

    Electrospun cotton wool-like nanocomposite (ECWN) is a novel synthetic bone substitute that incorporates amorphous calcium phosphate nanoparticles into a biodegradable synthetic copolymer poly(lactide-co-glycolide). The objectives of this study were to develop a tooth extraction socket model in sheep for bone graft research and to compare ECWN and bovine-derived xenograft (BX) in this model. Sixteen cross-bred female sheep were used. Bilateral mandibular premolars were extracted atraumatically. Second and third premolar sockets were filled (Latin-square allocation) with BX, ECWN or left unfilled. Resorbable collagen membranes were placed over BX and selected ECWN grafted sockets. Eight sheep per time period were sacrificed after 8 and 16 weeks. Resin-embedded undemineralised sections were analysed for descriptive histology and histomorphometric analyses. At 8 weeks, there were with no distinct differences in healing among the different sites. At 16 weeks, osseous healing followed a fine trabecular pattern in ECWN sites. Non-grafted sites showed thick trabeculae separated by large areas of fibrovascular connective tissue. In BX grafted sites, xenograft particles were surrounded by newly formed bone or fibrovascular connective tissue. There were no statistically significant differences in bone formation across the four groups. However, ECWN sites had significantly less residual graft material than BX sites at 16 weeks (P = 0.048). This first description of a tooth extraction socket model in sheep supports the utility of this model for bone graft research. The results of this study suggested that the novel material ECWN did not impede bone ingrowth into sockets and showed evidence of material resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Effects of low power laser irradiation on bone healing in animals: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Houghton Pamela

    2010-01-01

    Full Text Available Abstract Purpose The meta-analysis was performed to identify animal research defining the effects of low power laser irradiation on biomechanical indicators of bone regeneration and the impact of dosage. Methods We searched five electronic databases (MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane Database of Randomised Clinical Trials for studies in the area of laser and bone healing published from 1966 to October 2008. Included studies had to investigate fracture healing in any animal model, using any type of low power laser irradiation, and use at least one quantitative biomechanical measures of bone strength. There were 880 abstracts related to the laser irradiation and bone issues (healing, surgery and assessment. Five studies met our inclusion criteria and were critically appraised by two raters independently using a structured tool designed for rating the quality of animal research studies. After full text review, two articles were deemed ineligible for meta-analysis because of the type of injury method and biomechanical variables used, leaving three studies for meta-analysis. Maximum bone tolerance force before the point of fracture during the biomechanical test, 4 weeks after bone deficiency was our main biomechanical bone properties for the Meta analysis. Results Studies indicate that low power laser irradiation can enhance biomechanical properties of bone during fracture healing in animal models. Maximum bone tolerance was statistically improved following low level laser irradiation (average random effect size 0.726, 95% CI 0.08 - 1.37, p 0.028. While conclusions are limited by the low number of studies, there is concordance across limited evidence that laser improves the strength of bone tissue during the healing process in animal models.

  19. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  20. Reaming debris as a novel source of autologous bone to enhance healing of bone defects

    NARCIS (Netherlands)

    Bakker, Astrid D.; Kroeze, Robert Jan; Korstjens, Clara; de Kleine, Ruben H.; Frolke, Jan Paul M.; Klein-Nulend, Jenneke

    2011-01-01

    Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone defe

  1. Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing

    Institute of Scientific and Technical Information of China (English)

    Zhi-min YING; Tiao LIN; Shi-gui YAN

    2012-01-01

    Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem.Successful anterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel.Enhancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return to pre-injury activity levels.No convenient,effective or inexpensive procedures exist to enhance tendon-bone (T-B) healing after surgery.Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation,enhances differentiation and proliferation of osteoblasts,and motivates osteogenic differentiation of mesenchymal stem cells (MSCs),and therefore,appears to be a potential non-invasive tool for T-B healing in early stage of rehabilitation of ACL reconstruction.It is conceivable that LIPUS could be used to stimulate T-B tunnel healing in the home,with the aim of accelerating rehabilitation and an earlier return to normal activities in the near future.The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular and molecular levels,describe studies in animal models,and provide a future direction for research.

  2. Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing

    OpenAIRE

    Okuno, Yuji; Nakamura-Ishizu, Ayako; Kishi,Kazuo; Suda, Toshio; Kubota, Yoshiaki

    2011-01-01

    Bone marrow-derived cells (BMDCs) contribute to postnatal vascular growth by differentiating into endothelial cells or secreting angiogenic factors. However, the extent of their endothelial differentiation highly varies according to the angiogenic models used. Wound healing is an intricate process in which the skin repairs itself after injury. As a process also observed in cancer progression, neoangiogenesis into wound tissues is profoundly involved in this healing process, suggesting the con...

  3. The impact of nicotine on bone healing and osseointegration

    DEFF Research Database (Denmark)

    Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

    2005-01-01

    OBJECTIVES: To examine the short-term effect of nicotine on bone healing and osseointegration. MATERIAL AND METHODS: Sixteen female rabbits were divided into two groups. The test group was exposed to nicotine tartrate for 8 weeks and the control group was exposed to placebo. Nicotine or placebo...... was administered via a miniosmotic pump and plasma cotinine levels were measured weekly. The pump delivered 15 mg of nicotine/day for the animals in the test group. All rabbits had three tibial bone preparations. In the proximal and distal bone bed, implants were placed after 4 weeks (right tibia) and after 6...... and the control group. CONCLUSION: Nicotine exposure in a short period of time did not have a significant impact on bone healing or implant osseointegration in rabbits....

  4. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog.

    Science.gov (United States)

    Rodeo, S A; Arnoczky, S P; Torzilli, P A; Hidaka, C; Warren, R F

    1993-12-01

    Our study evaluated tendon-to-bone healing in a dog model. Twenty adult mongrel dogs had a transplantation of the long digital extensor tendon into a 4.8-millimeter drill-hole in the proximal tibial metaphysis. Four dogs were killed at each of five time-periods (two, four, eight, twelve, and twenty-six weeks after the transplantation), and the histological and biomechanical characteristics of the tendon-bone interface were evaluated. Serial histological analysis revealed progressive reestablishment of collagen-fiber continuity between the bone and the tendon. A layer of cellular, fibrous tissue was noted between the tendon and the bone, along the length of the bone tunnel; this layer progressively matured and reorganized during the healing process. The collagen fibers that attached the tendon to the bone resembled Sharpey fibers. High-resolution radiographs showed remodeling of the trabecular bone that surrounded the tendon. At the two, four, and eight-week time-periods, all specimens had failed by pull-out of the tendon from the bone tunnel. The strength of the interface was noted to have significantly and progressively increased between the second and the twelfth week after the transplantation. At the twelve and twenty-six-week time-periods, all specimens had failed by pull-out of the tendon from the clamp or by mid-substance rupture of the tendon. The progressive increase in strength was correlated with the degree of bone ingrowth, mineralization, and maturation of the healing tissue, noted histologically.

  5. Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization.

    Science.gov (United States)

    Vieira, Andreia Espindola; Repeke, Carlos Eduardo; Ferreira Junior, Samuel de Barros; Colavite, Priscila Maria; Biguetti, Claudia Cristina; Oliveira, Rodrigo Cardoso; Assis, Gerson Francisco; Taga, Rumio; Trombone, Ana Paula Favaro; Garlet, Gustavo Pompermaier

    2015-01-01

    Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray) characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0 h), the development of a provisional immature granulation tissue is evident (7 d), characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors (BMP-2-4-7,TGFβ1,VEGFa), cytokines (TNFα, IL-10), chemokines & receptors (CXCL12, CCL25, CCR5, CXCR4), matrix (Col1a1-2, ITGA4, VTN, MMP1a) and MSCs (CD105, CD106, OCT4, NANOG, CD34, CD146) markers expression. Granulation tissue is sequentially replaced by more mature connective tissue (14 d), characterized by inflammatory infiltrate reduction along the increased bone formation, marked expression of matrix remodeling enzymes (MMP-2-9), bone formation/maturation (RUNX2, ALP, DMP1, PHEX, SOST) markers, and chemokines & receptors associated with healing (CCL2, CCL17, CCR2). No evidences of cartilage cells or tissue were observed, strengthening the intramembranous nature of bone healing. Bone microarchitecture analysis supports the evolving healing, with total tissue and bone volumes as trabecular number and thickness showing a progressive increase over time. The extraction socket healing process is considered complete (21 d) when the dental socket is filled by trabeculae bone with well-defined medullary canals; it being the expression of mature bone markers prevalent at this period. Our data confirms the intramembranous bone healing nature of the model used, revealing parallels between the gene expression profile and the

  6. Ultrasound Won't Help Broken Bones Heal, Expert Panel Says

    Science.gov (United States)

    ... fullstory_163763.html Ultrasound Won't Help Broken Bones Heal, Expert Panel Says Detailed review suggests it's ... LIPUS) -- to help speed the healing of broken bones. But an international panel of experts now says ...

  7. Effect of Ankaferd Blood Stopper on Early Bone Tissue Healing in ...

    African Journals Online (AJOL)

    on bone healing; in fact, ABS increases inflammation in vivo. Keywords: Ankaferd blood stopper, Wound healing, Mineralized bone tissue, Inflammatory cell infiltration, Osteoid tissue, Tooth ... rodent diet ad libitum. All procedures were.

  8. Low dose erythropoietin stimulates bone healing in mice.

    Science.gov (United States)

    Garcia, P; Speidel, V; Scheuer, C; Laschke, M W; Holstein, J H; Histing, T; Pohlemann, T; Menger, M D

    2011-02-01

    Beyond its classical role in regulation of erythropoiesis, erythropoietin (EPO) has been shown to exert protective and regenerative actions in a variety of non-hematopoietic tissues. However, little is known about potential actions in bone regeneration. To analyze fracture healing in mice, a femoral 0.25 mm osteotomy gap was stabilized with a pin-clip technique. Animals were treated with 500 U EPO/kg bw per day or with vehicle only. After 2 and 5 weeks, fracture healing was analyzed biomechanically, radiologically and histologically. Expression of PCNA and NFκB was examined by Western blot analysis. Vascularization was analyzed by immunohistochemical staining of PECAM-1. Circulating endothelial progenitor cells were measured by flow-cytometry. Herein, we demonstrate that EPO-treatment significantly accelerates bone healing in mice. This is indicated by a significantly greater biomechanical stiffness and a higher radiological density of the periosteal callus at 2 and 5 weeks after fracture and stabilization. Histological analysis demonstrated significantly more bone and less cartilage and fibrous tissue in the periosteal callus. Endosteal vascularization was significantly increased in EPO-treated animals when compared to controls. The number of circulating endothelial progenitor cells was significantly greater in EPO-treated animals. The herein shown acceleration of healing by EPO may represent a promising novel treatment strategy for fractures with delayed healing and non-union formation.

  9. Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing.

    Science.gov (United States)

    Okuno, Yuji; Nakamura-Ishizu, Ayako; Kishi, Kazuo; Suda, Toshio; Kubota, Yoshiaki

    2011-05-12

    Bone marrow-derived cells (BMDCs) contribute to postnatal vascular growth by differentiating into endothelial cells or secreting angiogenic factors. However, the extent of their endothelial differentiation highly varies according to the angiogenic models used. Wound healing is an intricate process in which the skin repairs itself after injury. As a process also observed in cancer progression, neoangiogenesis into wound tissues is profoundly involved in this healing process, suggesting the contribution of BMDCs. However, the extent of the differentiation of BMDCs to endothelial cells in wound healing is unclear. In this study, using the green fluorescent protein-bone marrow chim-eric experiment and high resolution confocal microscopy at a single cell level, we observed no endothelial differentiation of BMDCs in 2 acute wound healing models (dorsal excisional wound and ear punch) and a chronic wound healing model (decubitus ulcer). Instead, a major proportion of BMDCs were macrophages. Indeed, colony-stimulating factor 1 (CSF-1) inhibition depleted approximately 80% of the BMDCs at the wound healing site. CSF-1-mutant (CSF-1(op/op)) mice showed significantly reduced neoangiogenesis into the wound site, supporting the substantial role of BMDCs as macrophages. Our data show that the proangiogenic effects of macrophages, but not the endothelial differentiation, are the major contribution of BMDCs in wound healing.

  10. Periosteal BMP2 activity drives bone graft healing.

    Science.gov (United States)

    Chappuis, Vivianne; Gamer, Laura; Cox, Karen; Lowery, Jonathan W; Bosshardt, Dieter D; Rosen, Vicki

    2012-10-01

    Bone graft incorporation depends on the orchestrated activation of numerous growth factors and cytokines in both the host and the graft. Prominent in this signaling cascade is BMP2. Although BMP2 is dispensable for bone formation, it is required for the initiation of bone repair; thus understanding the cellular mechanisms underlying bone regeneration driven by BMP2 is essential for improving bone graft therapies. In the present study, we assessed the role of Bmp2 in bone graft incorporation using mice in which Bmp2 has been removed from the limb prior to skeletal formation (Bmp2(cKO)). When autograft transplantations were performed in Bmp2cKO mice, callus formation and bone healing were absent. Transplantation of either a vital wild type (WT) bone graft into a Bmp2(cKO) host or a vital Bmp2(cKO) graft into a WT host also resulted in the inhibition of bone graft incorporation. Histological analyses of these transplants show that in the absence of BMP2, periosteal progenitors remain quiescent and healing is not initiated. When we analyzed the expression of Sox9, a marker of chondrogenesis, on the graft surface, we found it significantly reduced when BMP2 was absent in either the graft itself or the host, suggesting that local BMP2 levels drive periosteal cell condensation and subsequent callus cell differentiation. The lack of integrated healing in the absence of BMP2 was not due to the inability of periosteal cells to respond to BMP2. Healing was achieved when grafts were pre-soaked in rhBMP2 protein, indicating that periosteal progenitors remain responsive in the absence of BMP2. In contrast to the requirement for BMP2 in periosteal progenitor activation in vital bone grafts, we found that bone matrix-derived BMP2 does not significantly enhance bone graft incorporation. Taken together, our data show that BMP2 signaling is not essential for the maintenance of periosteal progenitors, but is required for the activation of these progenitors and their subsequent

  11. Analysis of fracture healing in osteopenic bone caused by disuse: experimental study.

    Science.gov (United States)

    Paiva, A G; Yanagihara, G R; Macedo, A P; Ramos, J; Issa, J P M; Shimano, A C

    2016-03-01

    Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2), suspended and immobilized for 2 weeks after osteotomy (OS2), unrestricted and immobilized for 6 weeks after osteotomy (OU6), and suspended and immobilized for 6 weeks after osteotomy (OS6). Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, Pbones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, Pbone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension.

  12. Ultrasound stimulation of mandibular bone defect healing

    NARCIS (Netherlands)

    Schortinghuis, Jurjen

    2004-01-01

    The conclusions of the experimental work presented in this thesis are: 1. Low intensity pulsed ultrasound is not effective in stimulating bone growth into a rat mandibular defect, either with or without the use of osteoconductive membranes. 2. Low intensity pulsed ultrasound does not seem to have an

  13. Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Kuang, G M; Yau, W P; Lu, W W; Chiu, K Y

    2013-07-01

    We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

  14. Fractal texture analysis of the healing process after bone loss.

    Science.gov (United States)

    Borowska, Marta; Szarmach, Janusz; Oczeretko, Edward

    2015-12-01

    Radiological assessment of treatment effectiveness of guided bone regeneration (GBR) method in postresectal and postcystal bone loss cases, observed for one year. Group of 25 patients (17 females and 8 males) who underwent root resection with cystectomy were evaluated. The following combination therapy of intraosseous deficits was used, consisting of bone augmentation with xenogenic material together with covering regenerative membranes and tight wound closure. The bone regeneration process was estimated, comparing the images taken on the day of the surgery and 12 months later, by means of Kodak RVG 6100 digital radiography set. The interpretation of the radiovisiographic image depends on the evaluation ability of the eye looking at it, which leaves a large margin of uncertainty. So, several texture analysis techniques were developed and used sequentially on the radiographic image. For each method, the results were the mean from the 25 images. These methods compute the fractal dimension (D), each one having its own theoretic basis. We used five techniques for calculating fractal dimension: power spectral density method, triangular prism surface area method, blanket method, intensity difference scaling method and variogram analysis. Our study showed a decrease of fractal dimension during the healing process after bone loss. We also found evidence that various methods of calculating fractal dimension give different results. During the healing process after bone loss, the surfaces of radiographic images became smooth. The result obtained show that our findings may be of great importance for diagnostic purpose.

  15. A first order system model of fracture healing

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-ping; ZHANG Xian-long; LI Zhu-guo; YU Xin-gang

    2005-01-01

    A first order system model is proposed for simulating the influence of stress stimulation on fracture strength during fracture healing. To validate the model, the diaphyses of bilateral tibiae in 70 New Zealand rabbits were osteotomized and fixed with rigid plates and stress-relaxation plates, respectively. Stress shielding rate and ultimate bending strength of the healing bone were measured at 2 to 48 weeks postoperatively. Ratios of stress stimulation and fracture strength of the healing bone to those of intact bone were taken as the system input and output. The assumed first order system model can approximate the experimental data on fracture strength from the input of stress stimulation over time, both for the rigid plate group and the stress-relaxation plate group, with different system parameters of time constant and gain. The fitting curve indicates that the effect of mechanical stimulus occurs mainly in late stages of healing. First order system can model the stress adaptation process of fracture healing. This approach presents a simple bio-mathematical model of the relationship between stress stimulation and fracture strength, and has the potential to optimize planning of functional exercises and conduct parametric studies.

  16. Stimulation of Bone Healing by Sustained Bone Morphogenetic Protein 2 (BMP-2 Delivery

    Directory of Open Access Journals (Sweden)

    Mirja Faßbender

    2014-05-01

    Full Text Available The aim of the study was to investigate the effect of a sustained release of bone morphogenetic protein2 (BMP-2 incorporated in a polymeric implant coating on bone healing. In vitro analysis revealed a sustained, but incomplete BMP-2 release until Day 42. For the in vivo study, the rat tibia osteotomy was stabilized either with control or BMP-2 coated wires, and the healing progress was followed by micro computed tomography (µCT, biomechanical testing and histology at Days 10, 28, 42 and 84. MicroCT showed an accelerated formation of mineralized callus, as well as remodeling and an increase of mineralized/total callus volume (p = 0.021 at Day 42 in the BMP-2 group compared to the control. Histology revealed an increased callus mineralization at Days 42 and 84 (p = 0.006 with reduced cartilage at Day 84 (p = 0.004 in the BMP-2 group. Biomechanical stiffness was significantly higher in the BMP-2 group (p = 0.045 at Day 42. In summary, bone healing was enhanced after sustained BMP-2 application compared to the control. Using the same drug delivery system, but a burst release of BMP-2, a previous published study showed a similar positive effect on bone healing. Distinct differences in the healing outcome might be explained due to the different BMP release kinetics and dosages. However, further studies are necessary to adapt the optimal release profiles to physiological mechanisms.

  17. A study of the bone healing kinetics of plateau versus screw root design titanium dental implants.

    LENUS (Irish Health Repository)

    Leonard, Gary

    2009-03-01

    This study was designed to compare the bone healing process around plateau root from (PRF) and screw root from (SRF) titanium dental implants over the immediate 12 week healing period post implant placement.

  18. Effects of trypsinization and mineralization on intrasynovial tendon allograft healing to bone.

    Science.gov (United States)

    Qu, Jin; van Alphen, Nick A; Thoreson, Andrew R; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C; Schmid, Thomas M; Zhao, Chunfeng

    2015-04-01

    The purpose of the current study was to develop a novel technology to enhance tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft-to-bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short-term in vivo study. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. CXC receptor knockout mice: characterization of skeletal features and membranous bone healing in the adult mouse.

    Science.gov (United States)

    Bischoff, David S; Sakamoto, Taylor; Ishida, Kenji; Makhijani, Nalini S; Gruber, Helen E; Yamaguchi, Dean T

    2011-02-01

    The potential role of CXC chemokines bearing the glu-leu-arg (ELR) motif in bone repair was studied using a cranial defect (CD) model in mice lacking the CXC receptor (mCXCR(-/-) knockout mice), which is homologous to knockout of the human CXC receptor 2 (CXCR2) gene. During the inflammatory stage of bone repair, ELR CXC chemokines are released by inflammatory cells and serve as chemotactic and angiogenic factors. mCXCR(-/-) mice were smaller in weight and length from base of tail to nose tip, compared to WT littermates. DEXA analysis indicated that bone mineral density (BMD), bone mineral content (BMC), total area (TA), bone area (BA), and total tissue mass (TTM) were decreased in the mCXCR(-/-) mice at 6, 12, and 18 weeks of age. Trabecular bone characteristics in mCXCR(-/-) (% bone, connectivity, number, and thickness) were reduced, and trabecular spacing was increased as evidenced by μCT. There was no difference in bone formation or resorption indices measured by bone histomorphometry. Trabecular BMD was not altered. Cortical bone volume, BMD, and thickness were reduced; whereas, bone marrow volume was increased in mCXCR(-/-). Decreased polar moment of inertia (J) in the tibias/femurs suggested that the mCXCR(-/-) long bones are weaker. This was confirmed by three-point bending testing of the femurs. CDs created in 6-week-old male mCXCR(-/-) and WT littermates were not completely healed at 12 weeks; WT animals, however, had significantly more bone in-growth than mCXCR(-/-). New bone sites were identified using polarized light and assessed for numbers of osteocyte (OCy) lacunae and blood vessels (BlV) around the original CD. In new bone, the number of BlV in WT was >2× that seen in mCXCR(-/-). Bone histomorphometry parameters in the cranial defect did not show any difference in bone formation or resorption markers. In summary, studies showed that mCXCR(-/-) mice have (1) reduced weight and size; (2) decreased BMD and BMC; (3) decreased amounts of trabecular

  20. No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study

    DEFF Research Database (Denmark)

    Petruskevicius, Juozas; Nielsen, Mette Strange; Kaalund, Søren;

    2002-01-01

    We studied the effects of a newly marketed bone substitute, Osteoset, on bone healing in a tibial defect in humans. 20 patients undergoing an ACL (anterior cruciate ligament) reconstruction with bone-patella tendon-bone graft were block-randomized into 2 groups of 10 each. In the treatment group...

  1. Human ex vivo wound healing model.

    Science.gov (United States)

    Stojadinovic, Olivera; Tomic-Canic, Marjana

    2013-01-01

    Wound healing is a spatially and temporally regulated process that progresses through sequential, yet overlapping phases and aims to restore barrier breach. To study this complex process scientists use various in vivo and in vitro models. Here we provide step-by-step instructions on how to perform and employ an ex vivo wound healing model to assess epithelization during wound healing in human skin.

  2. Early cellular responses in cortical bone healing around unloaded titanium implants: an animal study.

    Science.gov (United States)

    Slaets, Elke; Carmeliet, Geert; Naert, Ignace; Duyck, Joke

    2006-06-01

    A clear understanding of the early cellular events leading to osseointegration of implants is currently lacking. To gain better insight, titanium implants were inserted in a rabbit model and histologic and histomorphometric analyses were performed at early time points after insertion. Thirty-six cylindrical implants were inserted in the tibial diaphysis of six rabbits and left to heal for 1 to 42 days. Samples were processed into paraffin or methylmethacrylate sections, on which the surface of new bone, region of altered nuclear morphology, relative surface of basic multicellular units (BMUs) and blood vessels, and bone-to-implant contact were measured. After coagulum formation, osteoclasts and osteoblasts were observed at the bone surface 1 week after healing. In the preexisting bone, osteocytic lacunae appeared to be devoid of cells. This region of altered nuclear morphology continued to extend for 28 days (P osteocytes surrounding the implantation site, intensive bone remodeling, and the formation of new bone, eventually leading to the osseointegration of the implant.

  3. Effects of folk medicinal plant extract Ankaferd Blood Stopper® on early bone healing

    Directory of Open Access Journals (Sweden)

    Sabri Cemil İşler

    2010-08-01

    Full Text Available OBJECTIVE: Several haemostatic agents are available for clinical use. Ankaferd Blood Stopper® (ABS, a mixture of five medicinal plant extracts, has been used historically as a haemostatic agent. The aim of this in vivo study was to investigate the effects of ABS on early bone healing using a rat tibia defect model. MATERIAL AND METHODS: Sixteen male Wistar rats were randomized into two groups of 8 animals each. After deep anesthesia with ketamine, bone defects (3 mm diameter and 2 mm deep were created in the right and left tibiae of all animals and either treated with 1 cc of ABS (Group 1 or left untreated (Group 2; control. Surgical areas were closed primarily. The animals were sacrificed on the 7th postoperative day and bone samples were collected from the tibias. The samples were examined histopathologically for infection, necrosis, fibrosis, new bone formation and foreign body reaction. The histomorphometric results were analyzed statistically by the chi square test, with the level of significance set at p<0.05. RESULTS: Significant differences were found in both groups in terms of inflammation, necrosis and new bone formation (p=0.001, p=0.0001, p=0.001. No foreign body reaction was observed in the experimental group. ABS application decreased fibrosis in the experimental group, but there were no statistically significant differences from the control group. CONCLUSIONS: Histopathologically, it was observed that the application of ABS decreased the occurrence of inflammation and necrosis, while increasing new bone formation in early bone healing period. Further in vitro and in vivo studies are necessary for evaluating the benefits and possible adverse effects of the application of this herbal product on wound healing.

  4. Double-plating of ovine critical sized defects of the tibia: a low morbidity model enabling continuous in vivo monitoring of bone healing

    Directory of Open Access Journals (Sweden)

    Pearce Alexandra

    2011-09-01

    Full Text Available Abstract Background Recent studies using sheep critical sized defect models to test tissue engineered products report high morbidity and complications rates. This study evaluates a large bone defect model in the sheep tibia, stabilized with two, a novel Carbon fibre Poly-ether-ether-ketone (CF-PEEK and a locking compression plate (LCP which could sustain duration for up to 6 month with an acceptable low complication rate. Methods A large bone defect of 3 cm was performed in the mid diaphysis of the right tibia in 33 sheep. The defect was stabilised with the CF - PEEK plate and an LCP. All sheep were supported with slings for 8 weeks after surgery. The study was carried out for 3 months in 6 and for 6 months in 27 animals. Results The surgical procedure could easily be performed in all sheep and continuous in vivo radiographic evaluation of the defect was possible. This long bone critical sized defect model shows with 6.1% a low rate of complications compared with numbers mentioned in the literature. Conclusions This experimental animal model could serve as a standard model in comparative research. A well defined standard model would reduce the number of experimental animals needed in future studies and would therefore add to ethical considerations.

  5. Experimental fracture healing: evaluation using radionuclide bone imaging: concise communication. [/sup 99m/Tc-methylene diphosphonate; rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Gumerman, L.W.; Fogel, S.R.; Goodman, M.A.; Hanley, E.N. Jr.; Kappakas, G.S.; Rutkowski, R.; Levine, G.

    1978-12-01

    Radionuclide bone imaging was performed in a rabbit model to observe the course of fracture healing and to establish criteria for distinguishing nonunion and delayed healing from normal healing. Sequential gamma-camera images (with pinhole collimator) were collected and subjected to computer analysis. Five groups were established: (a) control--immobilization; (b) control--immobilization plus periosteal stripping; (c) simple fracture--osteotomy; (d) delayed union--osteotomy plus periosteal stripping; and (e) nonunion--osteotomy, periosteal stripping and polymethyl methacrylate interposed between fracture fragments. Histographic representation of absolute count rates along rabbit tibias followed a predictable pattern in the simple-fracture and delayed-union groups. They differed only in the time of appearance of phases. The non-union group demonstrated no recognizable sequential pattern. In this experimental model, serial bone scanning the quantitative data analysis has shown potential for indicating the course of healing in fractures and for serving as a guide to treatment.

  6. Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

    Science.gov (United States)

    Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

    2015-01-01

    Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

  7. The accuracy of the imaging reformation of cone beam computed tomography for the assessment of bone defect healing

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ho Duk; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan [Kyung Hee Univ., Seoul (Korea, Republic of)

    2007-06-15

    To evaluate the accuracy of the imaging reformation of cone beam computed tomography for the assessment of bone defect healing in rat model. Sprague-Dawely strain rats weighing about 350 gms were selected. Then critical size bone defects were done at parietal bone with implantation of collagen sponge. The rats were divided into seven groups of 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, and 8 weeks. The healing of surgical defect was assessed by multiplanar reconstruction (MPR) images and three-dimensional (3-D) images of cone beam computed tomography, compared with soft X-ray radiograph and histopathologic examination. MPR images and 3-D images showed similar reformation of the healing amount at 3 days, 1 week, 2 weeks, and 8 weeks, however, lower reformation at 3 weeks, 4 weeks, and 6 weeks. According to imaging-based methodologies, MPR images revealed similar reformation of the healing mount than 3-D images compare with soft X-ray image. Among the four threshold values for 3-D images, 400-500 HU revealed similar reformation of the healing amount. Histopathologic examination confirmed the newly formed trabeculation correspond with imaging-based mythologies. MPR images revealed higher accuracy of the imaging reformation of cone beam computed tomography and cone beam computed tomography is a clinically useful diagnostic tool for the assessment of bone defect healing.

  8. Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

    Energy Technology Data Exchange (ETDEWEB)

    Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR—Central Glass and Ceramic Research Institute, Kolkata (India); Basu, Debabrata [Bioceramics and Coating Division, CSIR—Central Glass and Ceramic Research Institute, Kolkata (India)

    2013-04-01

    Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 ± 2%) with wide distribution of macroporous (70–900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 ± 2 and 90 ± 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FTIR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples. - Highlights: ► Fabrication and characterization of porous chitosan with or without IGF-1 and BMP-2 ► Highly porous growth factor loaded chitosan studied in animal subjects for 3 months ► Parameters studied: histopathology, radiology and fluorochrome labeling ► IGF-1 loaded porous chitosan found to be very effective for bone defect healing.

  9. Immunohistochemical characterization of wound healing at two different bone graft substitutes.

    Science.gov (United States)

    Sager, M; Ferrari, D; Wieland, M; Dard, M; Becker, J; Schwarz, F

    2012-05-01

    The immunohistochemical characteristics of wound healing following application of a biphasic calcium phosphate or a collagen coated natural bone combined with a native collagen membrane in a dog model was assessed. Standardized buccal dehiscence-type defects were surgically created following implant bed preparation in 6 dogs. Following implant placement, defects were randomly filled with a collagen coated natural bone mineral (GBO), or a biphasic hydroxyapatite/beta tricalcium phosphate (SBC), and covered with a native collagen membrane. After 1, 4, and 9 weeks' submerged healing, dissected blocks were processed for immunohistochemical (collagen type I (CI), osteocalcin (OC), angiogenesis (TG)) analysis. At 1 week, GBO and SBC granules were homogeneously surrounded by a well vascularized, non-mineralized tissue (NMT). CI and OC antigen reactivity was commonly observed adjacent to both bone graft substitutes. At 4 and 9 weeks, SBC and GBO granules were completely integrated into a secondly formed network of spongiosa. At 9 weeks, dissolution of some granules was observed in the SBC group. Adjacent to these granules, NMT was significantly increased and revealed a pronounced CI, OC and TG antigen reactivity. The initial pattern of bone regeneration and graft integration was comparable in both groups; bone remodelling was more pronounced with SBC.

  10. The Effect of 58S Bioactive Glass Coating on Polyethylene Terephthalates in Graft-Bone Healing

    Institute of Scientific and Technical Information of China (English)

    Yang Wu; Shiyi Chen; Jia Jiang; Hong Li; Kai Gao; Pengyun Zhang

    2012-01-01

    In this study the effects of surface modification of Polyethylene Terephthalates (PET) fibers with 58S bioactive glasses on osteoblasts proliferation and osseointegration in the tibia-articular tendon-bone healing model were investigated.PET sheets were coated with 58S bioactive glass and uncoated PET sheets were used as a control.Scanning Electron Microscope (SEM) and X-ray photoelectron spectrometer were adopted to analyze the surface characteristics of the fibers.MT3T3-E 1 cells were cultured with the PET fibers and the MTT and ALP were tested at 1,3,5 days.Twenty-four skeletally mature male New Zealand white rabbits were randomly divided into two groups,the 58S-PET group and the PET group.Both groups underwent a surgical procedure to establish a tibia-articular tendon-bone healing model.Mechanical examinations and histological assays were taken to verify the coating effects in vivo.Results of both MTT and ALP tests show significant differences (P < 0.01) between the 58S-PET group and the PET group.At 6 weeks and 12 weeks,the max load-to-failure was significantly higher in the 58S-PET group.In the histological assays,distinct new bone formation was observed only in the 58S-PET group and stronger osseointegration was seen in the 58S-PET group than that in the control group.The 58S-coating on PET could enhance the proliferation and activity of the osteoblasts and therefore promote the new bone formation and tendon-bone healing.

  11. Increase in bone protein components with healing rat fractures: enhancement by zinc treatment.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    1999-12-01

    The alteration in bone components in the femoral-diaphyseal tissues with fracture healing was investigated. Rats were sacrificed 7 and 14 days after the femoral fracture. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that many protein molecules were induced in the diaphyseal tissues with fracture healing. Moreover, when the femoral-diaphyseal tissues with fracture healing were cultured for 24 and 48 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Also, the culture of the diaphyseal tissues with fracture healing caused a significant increase in bone alkaline phosphatase activity and deoxyribonucleic acid (DNA) content. Meanwhile, the presence of zinc acexamate (10-5 and 10-4 M), a stimulator of bone formation, in a culture medium induced a significant elevation of protein content and alkaline phosphatase activity in the diaphyseal tissues with fracture healing. Such an effect was completely abolished by the presence of cycloheximide (10-6 M), an inhibitor of protein synthesis. The present study suggests that fracture healing induces a newly synthesized bone protein component including stimulatory factor(s) for bone formation. Zinc supplementation may stimulate the healing of femoral fracture.

  12. In vivo study of microarc oxidation coated biodegradable magnesium plate to heal bone fracture defect of 3mm width.

    Science.gov (United States)

    Wu, Y F; Wang, Y M; Jing, Y B; Zhuang, J P; Yan, J L; Shao, Z K; Jin, M S; Wu, C J; Zhou, Y

    2017-06-23

    Microarc oxidation (MAO) coated magnesium (Mg) with improved corrosion resistance appeal increasing interests as a revolutionary biodegradable metal for fractured bone fixing implants application. However, the in vivo corrosion degradation of the implants and bone healing response are not well understood, which is highly required in clinic. In the present work, 10μm and 20μm thick biocompatible MAO coatings mainly composed of MgO, Mg2SiO4, CaSiO3 and Mg3(PO4)2 phases were fabricated on AZ31 magnesium alloy. The electrochemical tests indicated an improved corrosion resistance of magnesium by the MAO coatings. The 10μm and 20μm coated and uncoated magnesium plates were separately implanted into the radius bone fracture site of adult New Zealand white rabbits using a 3mm width bone fracture defect model to investigate the magnesium implants degradation and uninhibited bone healing. Taking advantage of the good biocompatibility of the MAO coatings, no adverse effects were detected through the blood test and histological examination. The implantation groups of coated and uncoated magnesium plates were both observed the promoting effect of bone fracture healing compared with the simple fracture group without implant. The releasing Mg(2+) by the degradation of implants into the fracture site improved the bone fracture healing, which is attributed to the magnesium promoting CGRP-mediated osteogenic differentiation. Mg degradation and bone fracture healing promoting must be tailored by microarc oxidation coating with different thickness for potential clinic application. Copyright © 2017. Published by Elsevier B.V.

  13. Crestal bone resorption in augmented bone using mineralized freeze-dried bone allograft or pristine bone during submerged implant healing: a prospective study in humans.

    Science.gov (United States)

    Huang, Hsiang-yun; Ogata, Yumi; Hanley, James; Finkelman, Matthew; Hur, Yong

    2016-02-01

    There is limited evidence on the crestal bone level changes around implants placed in bone augmented by guided bone regeneration (GBR) during submerged healing. The purpose of this study was to prospectively compare radiographic crestal bone changes around implants placed in augmented bone with changes around implants placed in pristine bone. Patients receiving dental implants in the augmented or pristine mandibular posterior edentulous ridge were included in the study. The digital standardized radiographs from the implant placement procedure were compared to the radiographs from the second-stage procedure to evaluate the peri-implant marginal bone level changes. The soft tissue thickness (ST), width of keratinized mucosa (wKM), and early cover screw exposure (eIE) were measured at the time of the second-stage procedure. A total of 29 implants in 26 patients, 11 in augmented bone (test group) and 18 in pristine bone (control group), were analyzed. The mean peri-implant bone loss (ΔBL) was 0.74 ± 0.74 mm (mean ± SD) in the test group and 0.25 ± 0.55 mm (mean ± SD) in the control group. The differences between the test and control groups in the mesial, distal, and mean peri-implant crestal bone level changes were statistically significant (P = 0.009, P = 0.004, and P = 0.001, respectively). The confounding factors (ST, wKM, and eIE) were adjusted. More peri-implant crestal bone loss during the submerged healing period was observed in augmented bone than in pristine bone. Augmented bone may not exhibit the same characteristics as pristine bone during the implant submerged healing period. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Enhancement of tendon–bone healing via the combination of biodegradable collagen-loaded nanofibrous membranes and a three-dimensional printed bone-anchoring bolt

    Science.gov (United States)

    Chou, Ying-Chao; Yeh, Wen-Lin; Chao, Chien-Lin; Hsu, Yung-Heng; Yu, Yi-Hsun; Chen, Jan-Kan; Liu, Shih-Jung

    2016-01-01

    A composite biodegradable polymeric model was developed to enhance tendon graft healing. This model included a biodegradable polylactide (PLA) bolt as the bone anchor and a poly(D,L-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with collagen as a biomimic patch to promote tendon–bone interface integration. Degradation rate and compressive strength of the PLA bolt were measured after immersion in a buffer solution for 3 months. In vitro biochemical characteristics and the nanofibrous matrix were assessed using a water contact angle analyzer, pH meter, and tetrazolium reduction assay. In vivo efficacies of PLGA/collagen nanofibers and PLA bolts for tendon–bone healing were investigated on a rabbit bone tunnel model with histological and tendon pullout tests. The PLGA/collagen-blended nanofibrous membrane was a hydrophilic, stable, and biocompatible scaffold. The PLA bolt was durable for tendon–bone anchoring. Histology showed adequate biocompatibility of the PLA bolt on a medial cortex with progressive bone ingrowth and without tissue overreaction. PLGA nanofibers within the bone tunnel also decreased the tunnel enlargement phenomenon and enhanced tendon–bone integration. Composite polymers of the PLA bolt and PLGA/collagen nanofibrous membrane can effectively promote outcomes of tendon reconstruction in a rabbit model. The composite biodegradable polymeric system may be useful in humans for tendon reconstruction. PMID:27601901

  15. Low intensity pulsed ultrasound increases the mechanical properties of the healing tissues at bone-tendon junction.

    Science.gov (United States)

    Lu, Min-Hua; Zheng, Yong-Ping; Huang, Qing-Hua; Lu, Hong-Bin; Qin, Ling

    2009-01-01

    The re-establishment of bone-tendon junction (BTJ) tissues is involved in many trauma and reconstructive surgeries. A direct BTJ repair requires a long period of immobilization which may be associated with a postoperative weak knee. In this study, we investigated if low-intensity pulsed ultrasound treatment increases the material properties of healing tissues at bone-tendon junction (BTJ) after partial patellectomy using rabbit models. Standard partial patellectomy was conducted on one knee of twenty four rabbits which were randomly divided into an ultrasound group and a control group. The bony changes of BTJ complexes around the BTJ healing interface were measured by anteroposterior x-ray radiographs; then the volumetric bone-mineral density (BMD) of the new bone was assessed using a peripheral computed tomography scanner (pQCT). The stiffness of patellar cartilage, fibrocartilage at the healing interface and the tendon were measured in situ using a novel noncontact ultrasound water jet indentation system. Not only significantly more newly formed bone at the BTJ healing interface but also increased stiffness of the junction tissues were found in the ultrasound group compared with the controls at week 18. In addition, the ultrasound group also showed significantly 44% higher BMD at week 6 than controls.

  16. Hyaluronic Acid Accelerates Tendon-to-Bone Healing After Rotator Cuff Repair.

    Science.gov (United States)

    Honda, Hirokazu; Gotoh, Masafumi; Kanazawa, Tomonoshin; Ohzono, Hiroki; Nakamura, Hidehiro; Ohta, Keisuke; Nakamura, Kei-Ichiro; Fukuda, Kanji; Teramura, Takeshi; Hashimoto, Takashi; Shichijo, Shigeki; Shiba, Naoto

    2017-09-01

    There is growing evidence that the subacromial injection of hyaluronic acid (HA) is effective for pain relief in rotator cuff tears; however, its effect on tendon-to-bone healing remains unknown. To examine the effect of HA on the chondrogenesis of mesenchymal stem cells (MSCs) in vitro and on tendon-to-bone healing in a rotator cuff repair model. Controlled laboratory study. Bilateral complete tears of the infraspinatus tendon were made in rabbits and subsequently repaired. Before closure, 1 mL HA was applied to the repaired site, and phosphate-buffered saline was used in the opposite side as a control. Biomechanical, histological, and immunohistochemical analyses were performed at 4, 8, and 12 weeks after surgery. After euthanizing each animal, the bone marrow was isolated from the femoral bone in the same rabbits. Then, MSCs were cultured in media for chondrogenic differentiation, and the chondral pellet production and cartilage-related gene expression levels in the cells were examined at various concentrations of HA. At 4 and 8 weeks after surgery, ultimate load-to-failure was significantly greater in the HA group than in the control group (45.61 ± 9.0 N vs 32.42 ± 9.4 N at 4 weeks, 90.7 ± 16.0 N vs 66.97 ± 10.0 N at 8 weeks; both P .05). Linear stiffness was not significant throughout the time point evaluation. The chondroid formation area at the tendon-bone interface stained by safranin O (control vs HA group) was 0.33% ± 0.7% versus 13.5% ± 12.3% at 4 weeks after surgery ( P .05), and 1.8% ± 4.0% versus 5.4% ± 4.2% at 12 weeks after surgery ( P > .05). Compared with the control group, HA significantly increased the volume of cartilaginous pellet produced by MSCs (0.0016 ± 0.0015 mm(3) at 0 mg/mL of HA, 0.0041 ± 0.0023 mm(3) at 1.0 mg/mL, and 0.0041 ± 0.0018 mm(3) at 4.0 mg/mL), with increased mRNA expression (relative ratio to control) of type 2 collagen (1.34 ± 0.38), SOX9 (1.58 ± 0.31), and aggrecan (1.30 ± 0.22) genes in the pellet ( P

  17. Healed or non-healed? computed tomography (CT) visualisation of morphology of bite trace ichnotaxa on a dinosaur bone

    DEFF Research Database (Denmark)

    Jacobsen, Aase Roland; Lauridsen, Henrik; Fiirgaard, Bente

    2015-01-01

    examined by correlating traditional naked-eye in spection with computed to mography (CT) imaging, used to visualise the internal morphology of the bite traces and in particular, to clarify the appearance of one possibly healed bite trace. A forensic pathologist visually examined the bone with the aid...

  18. Enhancement of tendon–bone healing via the combination of biodegradable collagen-loaded nanofibrous membranes and a three-dimensional printed bone-anchoring bolt

    Directory of Open Access Journals (Sweden)

    Chou YC

    2016-08-01

    Full Text Available Ying-Chao Chou,1,2 Wen-Lin Yeh,2 Chien-Lin Chao,1 Yung-Heng Hsu,1,2 Yi-Hsun Yu,1,2 Jan-Kan Chen,3 Shih-Jung Liu1,2 1Department of Mechanical Engineering, Chang Gung University, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 3Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, Taiwan Abstract: A composite biodegradable polymeric model was developed to enhance tendon graft healing. This model included a biodegradable polylactide (PLA bolt as the bone anchor and a poly(D,L-lactide-co-glycolide (PLGA nanofibrous membrane embedded with collagen as a biomimic patch to promote tendon–bone interface integration. Degradation rate and compressive strength of the PLA bolt were measured after immersion in a buffer solution for 3 months. In vitro biochemical characteristics and the nanofibrous matrix were assessed using a water contact angle analyzer, pH meter, and tetrazolium reduction assay. In vivo efficacies of PLGA/collagen nanofibers and PLA bolts for tendon–bone healing were investigated on a rabbit bone tunnel model with histological and tendon pullout tests. The PLGA/collagen-blended nanofibrous membrane was a hydrophilic, stable, and biocompatible scaffold. The PLA bolt was durable for tendon–bone anchoring. Histology showed adequate biocompatibility of the PLA bolt on a medial cortex with progressive bone ingrowth and without tissue overreaction. PLGA nanofibers within the bone tunnel also decreased the tunnel enlargement phenomenon and enhanced tendon–bone integration. Composite polymers of the PLA bolt and PLGA/collagen nanofibrous membrane can effectively promote outcomes of tendon reconstruction in a rabbit model. The composite biodegradable polymeric system may be useful in humans for tendon reconstruction. Keywords: polylactide–polyglycolide nanofibers, PLGA, collagen, 3D printing, polylactide, PLA, bone-anchoring bolts, tendon healing

  19. Expression of endogenous BMP-2 in periosteal progenitor cells is essential for bone healing.

    Science.gov (United States)

    Wang, Qun; Huang, Chunlan; Xue, Ming; Zhang, Xinping

    2011-03-01

    Bone morphogenic protein 2 (BMP-2) plays a key role in skeletal development, repair and regeneration. To gain a better understanding of the role of BMP-2 in periosteum-mediated bone repair, we deleted BMP-2 postnatally at the initiation stage of healing utilizing a Tamoxifen-inducible CreER mouse model. To mark the mutant cells, we further generated a BMP-2(f/f); CreER; RosaR mouse model that enabled the activation of a LacZ reporter gene upon treatment of Tamoxifen. We demonstrated that deletion of BMP-2 at the onset of healing abolished periosteum-mediated bone/cartilage callus formation. In a chimeric periosteal callus with cells derived from both wild type and the mutant, over 90% of the mutant mesenchymal progenitors remained undifferentiated. Within differentiated bone and cartilage tissues, only a few cells could be identified as mutants. Using a bone graft transplantation approach, we further showed that transplantation of a mutant bone graft into a wild type host failed to rescue the deficient differentiation of the mutant cells at day 10 post-grafting. These data strongly suggest that the endogenous expression of BMP-2 plays a critical role in osteogenic and chondrogenic differentiation of periosteal progenitors during repair. To determine whether BMP-2 deficient cells remained responsive to exogenous BMP-2, we isolated periosteal mesenchymal progenitors from BMP-2 deficient bone autografts. The isolated cells demonstrated a 90% reduction of endogenous BMP-2 expression, accompanied by significant decrease in cellular proliferation and a near blockade of osteogenic differentiation. The addition of exogenous BMP-2 partially rescued impaired proliferation and further enhanced osteogenic differentiation in a dose dependent manner. Taken together, our data show that the initiation of the cortical bone repair in vivo is controlled by endogenous BMP-2. Future studies are necessary to determine the mechanisms by which the BMP-2 pathway is activated in periosteal

  20. Influence of fracture gap size on the pattern of long bone healing: a computational study.

    Science.gov (United States)

    Gómez-Benito, M J; García-Aznar, J M; Kuiper, J H; Doblaré, M

    2005-07-07

    Following fractures, bones restore their original structural integrity through a complex process in which several cellular events are involved. Among other factors, this process is highly influenced by the mechanical environment of the fracture site. In this study, we present a mathematical model to simulate the effect of mechanical stimuli on most of the cellular processes that occur during fracture healing, namely proliferation, migration and differentiation. On the basis of these three processes, the model then simulates the evolution of geometry, distributions of cell types and elastic properties inside a healing fracture. The three processes were implemented in a Finite Element code as a combination of three coupled analysis stages: a biphasic, a diffusion and a thermoelastic step. We tested the mechano-biological regulatory model thus created by simulating the healing patterns of fractures with different gap sizes and different mechanical stimuli. The callus geometry, tissue differentiation patterns and fracture stiffness predicted by the model were similar to experimental observations for every analysed situation.

  1. Mimicking Bone Healing Process to Self Repair Concrete Structure Novel Approach Using Porous Network Concrete

    NARCIS (Netherlands)

    Sangadji, S.; Schlangen, H.E.J.G.

    2013-01-01

    To repair concrete cracks in difficult or dangerous conditions such as underground structures or hazardous liquid containers, self healing mechanism is a promising alternative method. This research aims to imitate the bone self healing process by putting porous concrete internally in the concrete

  2. Mimicking Bone Healing Process to Self Repair Concrete Structure Novel Approach Using Porous Network Concrete

    NARCIS (Netherlands)

    Sangadji, S.; Schlangen, H.E.J.G.

    2013-01-01

    To repair concrete cracks in difficult or dangerous conditions such as underground structures or hazardous liquid containers, self healing mechanism is a promising alternative method. This research aims to imitate the bone self healing process by putting porous concrete internally in the concrete st

  3. A wound healing model with sonographic monitoring.

    Science.gov (United States)

    Hoffmann, K; Winkler, K; el-Gammal, S; Altmeyer, P

    1993-05-01

    The methods used hitherto for quantification of skin repair processes only allow an examiner a two-dimensional assessment of superficial wound healing. With the recent advent of high frequency B-scan ultrasonography in dermatology it has become possible to follow the course of healing and evaluate the healing processes in deeper layers of the skin. In this investigation 80 patients received cryosurgery for treatment of basal cell carcinomas on the face or neck region. As the size of cryosurgical defects can be precisely controlled they are potentially useful as standardized wound healing models. The course of wound healing after cryosurgery using a digital ultrasound scanner (DUB 20, Taberna pro medicum, Lüneburg, Germany) was monitored. The usable depth of penetration of the echo signal is approximately 7 mm. The lateral resolution is approximately 200 microns, the axial resolution approximately 80 microns. The cryolesion and the repair processes were examined ultrasonographically and clinically over a period of at least 3 weeks or until the wound had completely healed. The depth of invasion and lateral extent of the basal cell carcinoma as well as the size of the induced cryolesion can be determined by ultrasound. The exudative phase after cryosurgery, with developing oedema and necrosis, can be quantified on the basis of the reduced reflectivity in the corium. The repair processes taking place in the region of necrosis can be visualized in the ultrasound scan. The ultrasonically monitored wound healing model which we have demonstrated is particularly suitable for investigating the efficacy of drugs which promote healing.

  4. A Concert between Biology and Biomechanics: The Influence of the Mechanical Environment on Bone Healing

    Science.gov (United States)

    Glatt, Vaida; Evans, Christopher H.; Tetsworth, Kevin

    2017-01-01

    In order to achieve consistent and predictable fracture healing, a broad spectrum of growth factors are required to interact with one another in a highly organized response. Critically important, the mechanical environment around the fracture site will significantly influence the way bone heals, or if it heals at all. The role of the various biological factors, the timing, and spatial relationship of their introduction, and how the mechanical environment orchestrates this activity, are all crucial aspects to consider. This review will synthesize decades of work and the acquired knowledge that has been used to develop new treatments and technologies for the regeneration and healing of bone. Moreover, it will discuss the current state of the art in experimental and clinical studies concerning the application of these mechano-biological principles to enhance bone healing, by controlling the mechanical environment under which bone regeneration takes place. This includes everything from the basic principles of fracture healing, to the influence of mechanical forces on bone regeneration, and how this knowledge has influenced current clinical practice. Finally, it will examine the efforts now being made for the integration of this research together with the findings of complementary studies in biology, tissue engineering, and regenerative medicine. By bringing together these diverse disciplines in a cohesive manner, the potential exists to enhance fracture healing and ultimately improve clinical outcomes. PMID:28174539

  5. Comparison of tendon-bone healing between autografts and allografts after anterior cruciate ligament reconstruction using magnetic resonance imaging.

    Science.gov (United States)

    Ge, Yunshen; Li, Hong; Tao, Hongyue; Hua, Yinghui; Chen, Jiwu; Chen, Shiyi

    2015-04-01

    The purpose of the study is to compare tendon-bone healing between autograft tendons and allograft tendons after anterior cruciate ligament (ACL) reconstruction using 3.0T magnetic resonance imaging. A total of 36 participants (18 with autograft and 18 with allograft reconstruction) underwent MRI scans at least 2 years after the ACL reconstruction operation. Oblique axial images were obtained on three-dimensional dual-echo steady-state images and imported into solid modelling software for three-dimensional model reconstruction of the bone tunnel. The graft signal intensity in the tunnel, tendon-bone interface, tunnel morphology, and tunnel area was analysed using the Siemens software packages to determine the tendon-bone healing between the groups. For the tunnel morphology, both groups exhibited bone tunnel enlargement either at the femoral or tibial tunnel aperture. For the tendon-bone interface, one patient in the autograft group and two patients in the allograft group exhibited a significant fibrous scar tissue bands at the tendon-bone interface. The graft signal/noise quotient values of the allograft group were higher than the autograft group. However, there was no significant difference in the tunnel area between the allograft group and the autograft group. Although the autograft tendons exhibited a better remodelling effect than did the allograft tendons in the bone tunnel, there was no significant difference in the tendon-bone healing between the autograft tendons and the allograft tendons postoperatively. These findings indicate that the biomechanical effect of graft motion may play a significant role in the tunnel aperture. III.

  6. Treatment with Carnitine Enhances Bone Fracture Healing under Osteoporotic and/or Inflammatory Conditions.

    Science.gov (United States)

    Aydin, Ali; Halici, Zekai; Albayrak, Abdulmecit; Polat, Beyzagul; Karakus, Emre; Yildirim, Omer Selim; Bayir, Yasin; Cadirci, Elif; Ayan, Arif Kursad; Aksakal, Ahmet Murat

    2015-09-01

    The aim of this study was to examine the effects of carnitine on bone healing in ovariectomy (OVX) and inflammation (INF)-induced osteoporotic rats. The rats were randomly divided into nine groups (n = 8 animals per group): sham-operated (Group 1: SHAM); sham + magnesium silicate (Mg-silicate) (Group 2: SHAM + INF); ovariectomy (Group 3: OVX); ovariectomy + femoral fracture (Group 4: OVX + FRC); ovariectomy + femoral fracture + Mg-silicate (Group 5: OVX + FRC + INF); ovariectomy + femoral fracture + carnitine 50 mg/kg (Group 6: OVX + FRC + CAR50); ovariectomy + femoral fracture + carnitine 100 mg/kg (Group 7: OVX + FRC + CAR100); ovariectomy + femoral fracture + Mg-silicate + carnitine 50 mg/kg (Group 8: OVX + FRC + INF + CAR50); and ovariectomy + femoral fracture + Mg-silicate + carnitine 100 mg/kg (Group 9: OVX + FRC + INF + CAR100). Eight weeks after OVX, which allowed for osteoporosis to develop, INF was induced with subcutaneous Mg-silicate. On day 80, all of the rats in groups 4-9 underwent fracture operation on the right femur. Bone mineral density (BMD) showed statistically significant improvements in the treatment groups. The serum markers of bone turnover (osteocalcin and osteopontin) and pro-inflammatory cytokines (tumour necrosis factor α, interleukin 1β and interleukin 6) were decreased in the treatment group. The X-ray images showed significantly increased callus formation and fracture healing in the groups treated with carnitine. The present results show that in a rat model with osteoporosis induced by ovariectomy and Mg-silicate, treatment with carnitine improves the healing of femur fractures.

  7. Vitamin E and the Healing of Bone Fracture: The Current State of Evidence

    Directory of Open Access Journals (Sweden)

    Boekhtiar Borhanuddin

    2012-01-01

    Full Text Available Background. The effect of vitamin E on health-related conditions has been extensively researched, with varied results. However, to date, there was no published review of the effect of vitamin E on bone fracture healing. Purpose. This paper systematically audited past studies of the effect of vitamin E on bone fracture healing. Methods. Related articles were identified from Medline, CINAHL, and Scopus databases. Screenings were performed based on the criteria that the study must be an original study that investigated the independent effect of vitamin E on bone fracture healing. Data were extracted using standardised forms, followed by evaluation of quality of reporting using ARRIVE Guidelines, plus recalculation procedure for the effect size and statistical power of the results. Results. Six animal studies fulfilled the selection criteria. The study methods were heterogeneous with mediocre reporting quality and focused on the antioxidant-related mechanism of vitamin E. The metasynthesis showed α-tocopherol may have a significant effect on bone formation during the normal bone remodeling phase of secondary bone healing. Conclusion. In general, the effect of vitamin E on bone fracture healing remained inconclusive due to the small number of heterogeneous and mediocre studies included in this paper.

  8. Leptin Influences Healing in the Sprague Dawley Rat Fracture Model

    Science.gov (United States)

    Liu, Pengcheng; Cai, Ming

    2017-01-01

    Background Leptin plays a crucial role in bone metabolism, and its level is related to bone callus formation in the fracture repair process. The objective of this study was to evaluate the effect of recombinant leptin on the healing process of femoral fractures in rats. Material/Methods Forty-eight male Sprague Dawley (SD) rats with an average body weight of 389 g (range: 376–398 g) and an average age of 10 weeks were included in this animal research, and all rats were randomly divided into two major groups. Then standardized femur fracture models were implemented in all SD rats. Rats in the control group were treated with only 0.5 mL of physiological saline, and rats in the experimental group were treated with recombinant leptin 5 μg/kg/d along with the same 0.5 mL of physiological saline for 42 days intraperitoneally. At the same time, each major group was evenly divided into three parallel subgroups for each parallel bone evaluation separately at the second, fourth, and sixth weeks. Each subgroup included eight rats. Results The total radiological evaluation results showed that the healing progress of femoral fracture in the experimental group was superior to that in the control group from the fourth week. At the sixth week, experimental group rats began to present significantly better femoral fracture healing progress than that of the control group rats. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of the experimental group rats was significantly increased compared with that of the control group rats from the fourth week. Conclusions Our results suggest that leptin may have a positive effect on SD rat femur fracture healing. PMID:28088810

  9. Effect of allogeneic bone marrow derived stromal cells on induced third-degree skin burn healing in mouse

    Directory of Open Access Journals (Sweden)

    Leyla Soleymani

    2014-10-01

    Conclusion: This experimental modulation of wound healing suggests that bone marrow-derived stromal cells can significantly enhance the rate of wound healing possibly through stimulation of granulation tissue, angiogenesis, fibroblast proliferation and collagen deposition.

  10. Influence of bioactive material coating of Ti dental implant surfaces on early healing and osseointegration of bone

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, In-Sung [Seoul National University, Seoul (Korea, Republic of); Min, Seung-Ki [Seoul National University Dental Hospital, Seoul (Korea, Republic of); An, Young-Bai [Osstem Implant Co., Ltd., Busan (Korea, Republic of)

    2010-12-15

    The dental implant surface type is one of many factors that determine the long-term clinical success of implant restoration. The implant surface consists of bioinert titanium oxide, but recently coatings with bioactive calcium phosphate ceramics have often been used on Ti implant surfaces. Bio-active surfaces are known to significantly improve the healing time of the human bone around the inserted dental implant. In this study, we characterized two types of coated implant surfaces by scanning electron microscopy, energy dispersive spectrometry, and surface roughness testing. The effect of surface modification on early bone healing was then tested by using the rabbit tibia model to measure bone-to-implant contact ratios and removal torque values. These modified surfaces showed different characteristics in terms of surface topography, chemical composition, and surface roughness. However, no significant differences were found in the bone-to-implant contact and the resistance to removal torque between these surfaces. Both the coated implants may induce similar favorable early bone responses in terms of the early functioning and healing of dental implants even though they differed in their surface characteristics.

  11. 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

    2013-01-01

    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.

  12. Evaluation of laser photobiomodulation on healing of bone defects grafted with bovine bone in diabetic rats

    Science.gov (United States)

    Paraguassú, Gardênia Matos; da Costa Lino, Maíra Doria Martinez; de Carvalho, Fabíola Bastos; Cangussu, Maria Cristina; Pinheiro, Antônio Luiz Barbosa; Ramalho, Luciana Maria Pedreira

    2012-09-01

    Previous studies have shown positive effects of Low Level Laser Therapy (LLLT) on the repair of bone defects, but there is a few that associates bone healing in the presence of a metabolic disorder such as Diabetes Mellitus, a systemic disorder associated to impair of the repair of different tissues. The aim of this study was to assess, histologically, the repair of surgical defects created in the femur of diabetic and non-diabetic rats treated or not with LLLT (λ780nm, 70mW, CW, o/˜0.4mm, 16J/cm2 per session) associated or not to the use of a biomaterial. Surgical tibial bone defects were created in 60 animals that were divided into 4 groups: Group B (non-diabetic + biomaterial); Group BL (non-diabetic + biomaterial + LLLT); Group BD (diabetic + biomaterial); Group BDL (diabetic + biomaterial + LLLT). The irradiated group received 16 J/cm2 per session divided into 4 points around the defect, being the first irradiation carried out immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The specimens underwent a semi-quantitative analysis. The results showed inflammation more intense in the BD and BDL groups than in the B and BL groups in the period of 15 days (p = 0.02), however the cortical repair in the BDL group was below 25% in more than half of the specimens, while in the BD group, the repair was more than to 25% in all specimens. At 30 days, both osteoblastic activity and collagen deposition were significantly higher in the B group when compared to the BD group (p=0.04). Bone deposition was significantly higher in the BL group (p=0.023) than in BDL group. It is concluded that LLLT has a positive biomodulative effect in the early stages of the healing process of bone defects grafted with biomaterial in diabetic and non-diabetic rats.

  13. A new zebrafish bone crush injury model

    Directory of Open Access Journals (Sweden)

    Sara Sousa

    2012-07-01

    While mammals have a limited capacity to repair bone fractures, zebrafish can completely regenerate amputated bony fin rays. Fin regeneration in teleosts has been studied after partial amputation of the caudal fin, which is not ideal to model human bone fractures because it involves substantial tissue removal, rather than local tissue injury. In this work, we have established a bone crush injury model in zebrafish adult caudal fin, which consists of the precise crush of bony rays with no tissue amputation. Comparing these two injury models, we show that the initial stages of injury response are the same regarding the activation of wound healing molecular markers. However, in the crush assay the expression of the blastema marker msxb appears later than during regeneration after amputation. Following the same trend, bone cells deposition and expression of genes involved in skeletogenesis are also delayed. We further show that bone and blood vessel patterning is also affected. Moreover, analysis of osteopontin and Tenascin-C reveals that they are expressed at later stages in crushed tissue, suggesting that in this case bone repair is prolonged for longer than in the case of regeneration after amputation. Due to the nature of the trauma inflicted, the crush injury model seems more similar to fracture bone repair in mammals than bony ray amputation. Therefore, the new model that we present here may help to identify the key processes that regulate bone fracture and contribute to improve bone repair in humans.

  14. Amorphous Silica: A New Antioxidant Role for Rapid Critical-Sized Bone Defect Healing.

    Science.gov (United States)

    Ilyas, Azhar; Odatsu, Tetsuro; Shah, Ami; Monte, Felipe; Kim, Harry K W; Kramer, Philip; Aswath, Pranesh B; Varanasi, Venu G

    2016-09-01

    Traumatic fractures cause structurally unstable sites due to severe bone loss. Such fractures generate a high yield of reactive oxygen species (ROS) that can lead to oxidative stress. Excessive and prolonged ROS activity impedes osteoblast differentiation and instigates long healing times. Stimulation of antioxidants such as superoxide dismutase (SOD1), are crucial to reduce ROS, stimulate osteogenesis, and strengthen collagen and mineral formation. Yet, no current fixative devices have shown an ability to enhance collagen matrix formation through antioxidant expression. This study reports plasma-enhanced chemical vapor deposition based amorphous silicon oxynitride (Si(ON)x) as a potential new fracture healing biomaterial that adheres well to the implant surface, releases Si(+4) to enhance osteogenesis, and forms a surface hydroxyapatite for collagen mineral attachment. These materials provide a sustained release of Si(+4) in physiological environment for extended times. The dissolution rate partially depends on the film chemistry and can be controlled by varying O/N ratio. The presence of Si(+4) enhances SOD1, which stimulates other osteogenic markers downstream and leads to rapid mineral formation. In vivo testing using a rat critical-sized calvarial defect model shows a more rapid bone-regeneration for these biomaterials as compared to control groups, that implies the clinical significance of the presented biomaterial.

  15. Effect of Alendronate on Bone Formation during Tooth Extraction Wound Healing.

    Science.gov (United States)

    Tanoue, R; Koi, K; Yamashita, J

    2015-09-01

    Alendronate (ALN) is an antiresorptive agent widely used for the treatment of osteoporosis. Its suppressive effect on osteoclasts has been extensively studied. However, the effect of ALN on bone formation is not as clear as its effect on resorption. The objective was to determine the effect of short-term ALN on bone formation and tooth extraction wound healing. Molar tooth extractions were performed in mice. ALN, parathyroid hormone (PTH), or saline (vehicle control) was administered. PTH was used as the bone anabolic control. Mice were euthanized at 3, 5, 7, 10, and 21 d after extractions. Hard tissue healing was determined histomorphometrically. Neutrophils and lymphatic and blood vessels were quantified to evaluate soft tissue healing. Gene expression in the wounds was assessed at the RNA level. Furthermore, the vossicle bone transplant system was used to verify findings from extraction wound analysis. Alkaline phosphatase (ALP) was visualized in the vossicles to assess osteoblast activity. ALN exhibited no negative effect on bone formation. In intact tibiae, ALN increased bone mass significantly more than PTH did. Consistently, significantly elevated osteoblast numbers were noted. In the extraction sockets, bone fill in the ALN-treated mice was equivalent to the control. Genes associated with bone morphogenetic protein signaling, such as bmp2, nog, and dlx5, were activated in the extraction wounds of the ALN-treated animals. Bone formation in vossicles was significantly enhanced in the ALN versus PTH group. In agreement with this, ALN upregulated ALP activity considerably in vossicles. Neutrophil aggregation and suppressed lymphangiogenesis were evident in the soft tissue at 21 d after extraction, although gross healing of extraction wounds was uneventful. Bone formation was not impeded by short-term ALN treatment. Rather, short-term ALN treatment enhanced bone formation. ALN did not alter bone fill in extraction sockets.

  16. Effect of Electromagnetic Wave on Bone Healing in Fixed and Unfixed Conditions.

    Science.gov (United States)

    Onger, Mehmet Emin; Göçer, Hasan; Çirakli, Alper; Büyükceran, Ismail; Kiliç, Mesut; Kaplan, Süleyman

    2016-09-01

    Mobile phones have come into daily life and are now one of the most frequently used devices for communication. The aim of this study was to evaluate possible effect of electromagnetic wave (EMW) with and without fixation material on bone healing.Forty male rats were exposed to fracture on tibia bone and were randomly divided into 4 groups as E(+)K(+), E(+)K(-), E(-)K(+), and E(-)K(-) where E(+) means EMW exposure and K(+) means Kirschner wire fixation. At the end of study tibia samples were taken from all the groups for the quantitative evaluation of regeneration.Significant difference was found between Group E(+)K(+) and E(-)K(+) in terms of both new bone and capillary volume.Electromagnetic wave may be harmful for bone healing with fixation whereas it has no same effect on bone regeneration without fixation.

  17. Effect of Cervus and Cucumis Peptides on Osteoblast Activity and Fracture Healing in Osteoporotic Bone

    Directory of Open Access Journals (Sweden)

    Ai-Yuan Wang

    2014-01-01

    Full Text Available Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP on bone fracture healing in ovariectomized (OVX osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2, bone morphogenetic protein 4 (BMP4, and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.

  18. Pulsed electromagnetic field treatment enhances healing callus biomechanical properties in an animal model of osteoporotic fracture.

    Science.gov (United States)

    Androjna, Caroline; Fort, Brian; Zborowski, Maciej; Midura, Ronald J

    2014-09-01

    Delayed bone healing has been noted in osteoporosis patients and in the ovariectomized (OVX) rat model of estrogen-depletion osteopenia. Pulsed electromagnetic field (PEMF) devices are clinically approved as an adjunct to cervical fusion surgery in patients at high risk for non-fusion and for the treatment of fracture non-unions. These bone growth stimulating devices also accelerate the healing of fresh fracture repair in skeletally mature normal rats but have not been tested for efficacy to accelerate and/or enhance the delayed bone repair process in OVX rats. The current study tested the hypothesis that daily PEMF treatments would improve the fracture healing response in skeletally mature OVX rats. By 6 weeks of healing, PEMF treatments resulted in improved hard callus elastic modulus across fibula fractures normalizing the healing process in OVX rats with respect to this mechanical property. Radiographic evidence showed an improved hard callus bridging across fibula fractures in OVX rats treated with PEMF as compared to sham treatments. These findings provide a scientific rationale for investigating whether PEMF might improve bone-healing responses in at-risk osteoporotic patients.

  19. Residual (ghost) sockets in bisphosphonate use--evidence of poor healing and slow bone turnover.

    Science.gov (United States)

    Shetty, Kishore; Bouquot, J

    2009-01-01

    Patients taking bisphosphonate drug therapy have demonstrated extremely poor alveolar bone healing after relatively minor oral surgical procedures. It would seem logical that extraction sockets could remain visible radiographically for an extended period after surgery, even in cases with soft tissue healing. This article chronicles the case of a patient who had been taking zoledronic acid chronically for metastatic cancer and who demonstrated numerous residual sockets (also known as ghost sockets), with lamina dura outlines that were visible radiographically.

  20. Stimulation of bone formation and fracture healing with pulsed electromagnetic fields: biologic responses and clinical implications.

    Science.gov (United States)

    Chalidis, B; Sachinis, N; Assiotis, A; Maccauro, G

    2011-01-01

    Pulsed electromagnetic fields (PEMF) have been used for several years to supplement bone healing. However, the mode of action of this non-invasive method is still debated and quantification of its effect on fracture healing is widely varied. At cellular and molecular level, PEMF has been advocated to promote the synthesis of extracellular matrix proteins and exert a direct effect on the production of proteins that regulate gene transcription. Electromagnetic fields may also affect several membrane receptors and stimulate osteoblasts to secrete several growth factors such as bone morphogenic proteins 2 and 4 and TGF-beta. They could also accelerate intramedullary angiogenesis and improve the load to failure and stiffness of the bone. Although healing rates have been reported in up to 87 % of delayed unions and non-unions, the efficacy of the method is significantly varied while patient or fracture related variables could not be clearly associated with a successful outcome.

  1. Increase in bone growth factors with healing rat fractures: the enhancing effect of zinc.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    2001-10-01

    The effect of zinc, a stimulator of bone formation, on bone protein components in the femoral-diaphyseal tissues with fracture healing was investigated. Rats were sacrificed between 1 and 7 days after the femoral fracture, and the diaphyseal tissues were cultured in a serum-free Dulbecco's modified Eagle's medium for 24 h. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. The amount of protein in the medium cultured with the diaphyseal tissues obtained from fracture healing rats was markedly elevated as compared with that of normal rats, indicating that bone protein components were secreted into culture medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel elecrophoresis (SDS-PAGE) showed that many protein molecules were secreted from the diaphyseal tissues with fracture healing. Especially, protein molecule of about 66 kDa was markedly secreted by fracture healing. The presence of zinc acexamate (10(-5) and 10(-4) M) in culture medium induced a significant elevation of medium protein content; the zinc effect was enhanced by culture with the diaphyseal tissues of fracture healing rats. Also, the culture of diaphyseal tissues with fracture healing caused a significant increase in insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) in culture medium. The production of IGF-I and TGF-beta1 from bone tissues with fracture healing was significantly enhanced in the presence of zinc acexamate (10(-6)-10(-4) M). Moreover, the addition of IGF-I (10(-8) M) or TGF-beta1 (10(-10) M) in a culture medium caused a significant elevation of protein content in the medium cultured with the femoral-diaphyseal tissues from normal and fracture healing rats. The effect of IGF-I or TGF-beta1 was significantly enhanced in the presence of zinc acexamate (10(-4) M). Also, deoxyribonucleic acid (DNA) content in the diaphyseal tissues from normal and fracture healing rats was significantly raised by the

  2. Novel Model of Tendon Regeneration Reveals Distinct Cell Mechanisms Underlying Regenerative and Fibrotic Tendon Healing

    Science.gov (United States)

    Howell, Kristen; Chien, Chun; Bell, Rebecca; Laudier, Damien; Tufa, Sara F.; Keene, Douglas R.; Andarawis-Puri, Nelly; Huang, Alice H.

    2017-01-01

    To date, the cell and molecular mechanisms regulating tendon healing are poorly understood. Here, we establish a novel model of tendon regeneration using neonatal mice and show that neonates heal via formation of a ‘neo-tendon’ that differentiates along the tendon specific lineage with functional restoration of gait and mechanical properties. In contrast, adults heal via fibrovascular scar, aberrant differentiation toward cartilage and bone, with persistently impaired function. Lineage tracing identified intrinsic recruitment of Scx-lineage cells as a key cellular mechanism of neonatal healing that is absent in adults. Instead, adult Scx-lineage tenocytes are not recruited into the defect but transdifferentiate into ectopic cartilage; in the absence of tenogenic cells, extrinsic αSMA-expressing cells persist to form a permanent scar. Collectively, these results establish an exciting model of tendon regeneration and uncover a novel cellular mechanism underlying regenerative vs non-regenerative tendon healing. PMID:28332620

  3. How prayer heals: a theoretical model.

    Science.gov (United States)

    Levin, J S

    1996-01-01

    This article presents a theoretical model that outlines various possible explanations for the healing effects of prayer. Four classes of mechanisms are defined on the basis of whether healing has naturalistic or supernatural origins and whether it operates locally or nonlocally. Through this framework, most of the currently proposed hypotheses for understanding absent healing and other related phenomena-hypotheses that invoke such concepts as subtle energy, psi, consciousness, morphic fields, and extended mind-are shown to be no less naturalistic than the Newtonian, mechanistic forces of allopathic biomedicine so often derided for their materialism. In proposing that prayer may heal through nonlocal means according to mechanisms and theories proposed by the new physics, Dossey is almost alone among medical scholars in suggesting the possible limitations and inadequacies of hypotheses based on energies, forces, and fields. Yet even such nonlocal effects can be conceived of as naturalistic; that is, they are explained by physical laws that may be unbelievable or unfamiliar to most physicians but that are nonetheless becoming recognized as operant laws of the natural universe. The concept of the supernatural, however, is something altogether different, and is, by definition, outside of or beyond nature. Herein may reside an either wholly or partly transcendent Creator-God who is believed by many to heal through means that transcend the laws of the created universe, both its local and nonlocal elements, and that are thus inherently inaccessible to and unknowable by science. Such an explanation for the effects of prayer merits consideration and, despite its unprovability by medical science, should not be dismissed out of hand.

  4. The effects of a novel-reinforced bone substitute and Colloss®E on bone defect healing in sheep

    DEFF Research Database (Denmark)

    Ding, Ming; Røjskjaer, Jesper; Cheng, Liming

    2012-01-01

    /β-TCP-PDLLA), Colloss®E, and combination of substitute with Colloss®E on bone formation in vivo were evaluated. Cylindrical critical size defects were created at distal femoral condyles bilaterally in sheep. Titanium implant with concentric gap filling with one of the four materials was inserted. After 9 weeks....... Significant new bone formation could be seen in vivo in all four groups and there were no significant differences between them. The PDLLA-reinforced substitute seems to be good alternative substitute material for bone healing in sheep. Further investigations should be performed to validate this novel...... substitute material....

  5. Does longstanding nicotine exposure impair bone healing and osseointegration? An experimental study in rabbits

    DEFF Research Database (Denmark)

    Gotfredsen, Klaus; Lindh, Christian H; Berglundh, Tord

    2009-01-01

    OBJECTIVES: The aim of this study was to analyze the effect of longstanding nicotine exposure on bone healing and osseointegration of titanium implants. MATERIALS AND METHODS: 20 female rabbits received either nicotine (n = 10) or saline (n = 10) administered subcutaneously via mini-osmotic pumps...... for 32 weeks. The pump delivered 6 microg/kg/min of nicotine for the animals in the test group. Blood samples were collected and plasma cotinine levels were measured monthly. Six months after the commencement of nicotine or saline administration three osteotomy preparations, one in right, femoral condyle...... increase in RMT between 2 and 4 weeks within each group. The histomorphometric analysis of bone-to-implant contact and bone density in the bone defects revealed no differences between the test and the control group after 2 or 4 weeks of healing. CONCLUSION: Longstanding (6 months) nicotine exposure did...

  6. Collagenases and gelatinases in bone healing. The focus on mandibular fractures

    Directory of Open Access Journals (Sweden)

    Kurzepa Jacek

    2014-06-01

    Full Text Available Due to high amount of collagen fibres in the structure of bone, the enzymes capable of collagen digestion play a key role in bone remodelling. Matrix metalloproteinases (MMPs, prevailing extracellular endopeptideses, can digest extracellularly located proteins, e.g. collagen, proteoglycans, elastin or fibronectin. Among MMPs, collagenases (MMP-1, MMP-8 and MMP-13 and gelatinases (MMP-2 and MMP-9 can cleave collagen particles to forms that are able to undergo further steps of catabolism intracellularly. In addition, activity of the gelatinases (as an activation of proinflammatory cytokines facilitates spreading inflammation that is necessary during the first stage of bone healing. Further studies related to the role of various MMPs in mandibular fractures should precisely explain their function in the bone healing and evaluate the influence of MMPs inhibitors on that process. This review provides the basic information about two groups among MMPs family, collagenases and gelatinases, and their role in repairing processes after mandibular fractures.

  7. Chronic Kidney Disease Impairs Bone Defect Healing in Rats.

    Science.gov (United States)

    Liu, Weiqing; Kang, Ning; Seriwatanachai, Dutmanee; Dong, Yuliang; Zhou, Liyan; Lin, Yunfeng; Ye, Ling; Liang, Xing; Yuan, Quan

    2016-03-09

    Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson's Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.

  8. Monitoring the Changes of Material Properties at Bone-Implant Interface during the Healing Process In Vivo: A Viscoelastic Investigation

    Science.gov (United States)

    Chen, Hsiang-Ho; Lai, Wei-Yi; Chee, Tze-Jian

    2017-01-01

    The aim of this study was to monitor the changes of viscoelastic properties at bone-implant interface via resonance frequency analysis (RFA) and the Periotest device during the healing process in an experimental rabbit model. Twenty-four dental implants were inserted into the femoral condyles of rabbits. The animals were sacrificed immediately after implant installation or on day 14, 28, or 56 after surgery. Viscoelastic properties at bone-implant interface were evaluated by measuring the implant stability quotient (ISQ) using RFA and by measuring the Periotest values (PTVs) using the Periotest device. The bone/implant specimens were evaluated histopathologically and histomorphometrically to determine the degree of osseointegration (BIC%). The BIC% values at different time points were then compared with the corresponding ISQ values and PTVs. The mean ISQ value increased gradually and reached 81 ± 1.7 on day 56, whereas the mean PTV decreased over time, finally reaching −0.7 ± 0.5 on day 56. Significant correlations were found between ISQ and BIC% (r = 0.701, p < 0.001), PTV and BIC% (r = −0.637, p < 0.05), and ISQ and PTV (r = −0.68, p < 0.05). These results show that there is a positive correlation between implant stability parameters and peri-implant-bone healing, indicating that the RFA and Periotest are useful for measuring changes of viscoelastic properties at bone-implant interface and are reliable for indirectly predicting the degree of osseointegration. PMID:28373978

  9. Enhancement of albumin expression in bone tissues with healing rat fractures.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Igarashi, Aki; Misawa, Hiroyuki; Tsurusaki, Yoshinori

    2003-05-15

    The characterization of 66 kDa protein molecule, a major protein component which is produced from femoral-diaphyseal tissues with fracture healing (Igarashi and Yamaguchi [2002] Int. J. Mol. Med. 9:503-508), was investigated. Weaning rats were killed at 7 and 14 days after femoral fracture. When the femoral-diaphyseal tissues with fracture healing were cultured for 48 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein molecule of approximately 66 kDa was markedly increased in culture medium from bone tissues with fracture healing. N-terminal sequencing of 66 kDa protein indicated that its N-terminus was identical to that of rat albumin. Western blot analysis of medium 66 kDa protein showed expression of albumin. This expression was significantly enhanced by fracture healing. The expression of albumin was seen in the diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues of rat femur. When the femoral-diaphyseal tissues obtained at 7 days after femoral fracture were cultured in a serum-free medium containing either vehicle, parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or zinc acexamate (10(-4) M), medium albumin was significantly increased in the presence of those bone-stimulating factors. The addition of albumin (0.5 or 1.0 mg/ml of medium) caused a significant increase in calcium and deoxyribonucleic acid contents in the femoral-diaphyseal and -metaphyseal tissues obtained from normal rats in vitro. The present study demonstrates that fracture healing induces a remarkable production of albumin which is a major protein component produced from femoral-diaphyseal tissues of rats, and that albumin has an anabolic effect on bone components.

  10. Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects.

    Science.gov (United States)

    Kitami, Megumi; Kaku, Masaru; Rocabado, Juan Marcelo Rosales; Ida, Takako; Akiba, Nami; Uoshima, Katsumi

    2016-09-01

    Considering the increased interest in cell-based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti-apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3-E1 osteoblastic cells from H2 O2 -induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27-overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4-week of transplantation, both control cell- and Hsp27 overexpressed cell-transplanted groups showed significantly higher new bone formation in comparison with cell-free gel-transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4-week but did not differentiate into bone-forming osteoblasts. In conclusion, cell-containing collagen gel accelerated calvarial bone defect healing in comparison with cell-free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation-based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974-1982, 2016. © 2016 Wiley Periodicals, Inc.

  11. The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

    Science.gov (United States)

    Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

    2011-03-01

    Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

  12. Histological and TEM examination of early stages of bone healing after Er:YAG laser irradiation.

    Science.gov (United States)

    Pourzarandian, Amir; Watanabe, Hisashi; Aoki, Akira; Ichinose, Shizuko; Sasaki, Katia M; Nitta, Hiroshi; Ishikawa, Isao

    2004-08-01

    The aim of this study was to analyze the early healing process of bone tissue irradiated by Er:YAG laser and compare it with that treated by mechanical drilling and CO(2) laser. Er:YAG laser has a great potential for cutting hard tissues as it is capable of ablation with less thermal damage. Twenty-four male Wistar rats were used for this study. The calvarial bone of rats was exposed and straight grooves were prepared by Er:YAG laser, mechanical bur and continuous wave CO(2) laser. Four rats each were sacrificed at six time points: 10 min, 6 and 24 h and 3, 7, and 14 days post-surgery. Sections were prepared for light and transmission electron microscopic (TEM) observations. Compared to mechanical bur and CO(2) groups, the inflammatory cell infiltration adjacent to the irradiated bone surface, fibroblastic reaction, and revascularization were more pronounced in the Er:YAG laser-irradiated tissues. A cell-rich granulation tissue with fibroblasts and osteoblasts was predominant in 7-day specimens of Er:YAG laser group. Histopathological analysis of 14-day specimens in the Er:YAG group also revealed significantly greater new bone formation, compared with the mechanical bur and CO(2) laser groups. Initial bone healing following Er:YAG laser irradiation occurred faster than that after mechanical bur and CO(2) laser. Er:YAG laser treatment may be advantageous for wound healing of bone tissue, presumably by providing a favorable surface for cell attachment.

  13. Longitudinal analysis of osteogenic and angiogenic signaling factors in healing models mimicking atrophic and hypertrophic non-unions in rats.

    Directory of Open Access Journals (Sweden)

    Susann Minkwitz

    Full Text Available Impaired bone healing can have devastating consequences for the patient. Clinically relevant animal models are necessary to understand the pathology of impaired bone healing. In this study, two impaired healing models, a hypertrophic and an atrophic non-union, were compared to physiological bone healing in rats. The aim was to provide detailed information about differences in gene expression, vascularization and histology during the healing process. The change from a closed fracture (healing control group to an open osteotomy (hypertrophy group led to prolonged healing with reduced mineralized bridging after 42 days. RT-PCR data revealed higher gene expression of most tested osteogenic and angiogenic factors in the hypertrophy group at day 14. After 42 days a significant reduction of gene expression was seen for Bmp4 and Bambi in this group. The inhibition of angiogenesis by Fumagillin (atrophy group decreased the formation of new blood vessels and led to a non-healing situation with diminished chondrogenesis. RT-PCR results showed an attempt towards overcoming the early perturbance by significant up regulation of the angiogenic regulators Vegfa, Angiopoietin 2 and Fgf1 at day 7 and a further continuous increase of Fgf1, -2 and Angiopoietin 2 over time. However µCT angiograms showed incomplete recovery after 42 days. Furthermore, lower expression values were detected for the Bmps at day 14 and 21. The Bmp antagonists Dan and Twsg1 tended to be higher expressed in the atrophy group at day 42. In conclusion, the investigated animal models are suitable models to mimic human fracture healing complications and can be used for longitudinal studies. Analyzing osteogenic and angiogenic signaling patterns, clear changes in expression were identified between these three healing models, revealing the importance of a coordinated interplay of different factors to allow successful bone healing.

  14. Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma

    NARCIS (Netherlands)

    Bastian, Okan W; Kuijer, Anne; Koenderman, Leo; Stellato, Rebecca K; van Solinge, WW; Leenen, Luke PH; Blokhuis, Taco J

    2016-01-01

    Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major

  15. When blood and bones cry out: journeys through the soundscape of healing and reconciliation

    National Research Council Canada - National Science Library

    Lederach, John Paul; Lederach, Angela Jill

    2011-01-01

    ... for ways not just to survive but to heal. In When Blood and Bones Cry Out, John Paul Lederach, a pioneer of peace-building, and his daughter, Angela Jill Lederach, show how communities can recover and reconnect through the power of making...

  16. CaMKK2 Inhibition in Enhancing Bone Fracture Healing

    Science.gov (United States)

    2016-05-01

    mm) retrograde through the distal condyle of the femur. Radiographic analyses were performed to confirm the location and quality of the fractures...costs, loss of productivity and most importantly, loss of patient quality of life. Prolonged healing time and non-union occur in 5-10% of these...male C57BL6 (50) were purchased from Harlan Laboratories (Indianapolis) and housed under a 12-hr light and dark cycle, with food and water provided ad

  17. Early cortical bone healing around loaded titanium implants: a histological study in the rabbit.

    Science.gov (United States)

    Slaets, Elke; Naert, Ignace; Carmeliet, Geert; Duyck, Joke

    2009-02-01

    To identify the role of immediate implant loading on the early phases of the bone healing responses. Implants were placed in rabbit tibial diaphyses and left to heal for 3, 7, 14, 28 or 42 days. Half of the animals received an immediate loading protocol of 2.2 N at 3 Hz for 1800 cycles and 5 days/week, whereas the others served as unloaded controls. Histological assessment was combined with histomorphometrical measurements. At early time-points, an endosteal and periosteal new bone formation was found, while the cortex itself contained damaged osteocytes. At later time-points, new bone formation was also found at the cortical level itself. Differences between groups were found mainly in this new bone formation process, with larger reactions for the endosteal and periosteal bone in the loaded group after 28 and 42 days, respectively. At the end-point of the experiment, bone formation at the cortical level was reduced in the loaded group compared with the control group. These results show that the immediate loading protocol caused no differences in the sequential events leading to osseointegration in cortical bone. However, the processes of new bone formation originating from the endosteum and the periosteum lasted longer compared with the unloaded controls.

  18. Histopathological and Histomorphometrical Effects of Atorvastatin on Experimental Femoral Cortical Bone Defect Healing in Rats

    Directory of Open Access Journals (Sweden)

    M Valilu

    2012-05-01

    Full Text Available Background: Bone remodeling has always been the goal of surgeons for a long time. Recently, it was shown that statins that are commonly prescribed for lowering cholesterol also have beneficial effects on bone healing. Therefore, the present study was undertaken to evaluate the probable effects of atorvastatin on osteogenesis in the rat femur. Methods: This experimental study was conducted on 30 male Sprague-Dawley (SD rats. The animals were divided randomly into one control and two experiment groups. After induction of anesthesia, a hole of 2 mm in diameter was made in femur width. The control group received physiological serum but the experiment groups one and two, respectively, received 10 and 20 mg/kg/PO of atorvastatin on daily basis. After euthanizing the rats, histopathological and histomorphometrical evaluations of the bones were performed 45 days after the intervention. Results: In the control group, the defects seemed to be filled with woven bone and bone marrow, depictive of a poor osteogenic activity. In the experiment groups, many osteoblast groupings and young bone trabeculae had been formed and bone trabeculae were more organized. Histomorphometric results, showed that atorvastatin had significantly promoted bone healing in the experiment groups compared with the controls (P<0.001. Moreover, the analysis showed that atorvastatin had more significant effects in group three receiving high doses of the medication in comparison with group two (P<0.001. Conclusion: The findings of this study showed that atorvastatin is capable of stimulating osteogenesis in rats.

  19. Effect of Microfracture on Meniscal Tear Healing in a Goat (Capra hircus) Model.

    Science.gov (United States)

    Howarth, William R; Brochard, Kevin; Campbell, Scot E; Grogan, Brian F

    2016-01-01

    Meniscal injuries are an extremely common cause of knee pain. Meniscal repairs performed with concomitant anterior cruciate ligament reconstruction appear to heal at a higher rate than meniscal repairs performed in isolation. This may be due in part to the release of marrow elements into the knee and the time of meniscal repair. In cases of isolated meniscal repair, some orthopedic surgeons use microfracture to release marrow elements into the joint as an adjunct to enhance meniscal healing. This study evaluated rates of meniscal tear healing with or without the performance of microfracture in a goat (Capra hircus) model. Forty castrated young adult male goats underwent either a horizontal or a longitudinal 1.0-cm meniscal tear with or without microfracture. All procedures were performed open, in a bloodless field. Meniscal tears were created in the peripheral half of the body of the medial meniscus. The goats were euthanized at 6 months, and meniscal tears were analyzed and classified as complete healing, partial healing, or no healing by direct visualization. A probe was used as an aid to evaluate and classify the meniscal tears. Twenty (87%) of 23 goat meniscal tears showed at least partial healing when performed with concomitant microfracture. Only 5 (29%) of 17 menisci showed any healing in goats that did not receive microfracture. This difference in healing rates was statistically significant (P<.001). Fifteen (65%) meniscal tears accomplished with microfracture were completely healed, whereas only 2 (12%) menisci showed complete healing without microfracture (P<.001). The results of this study suggest that the release of bone marrow elements into the knee by microfracture improves meniscal healing rates.

  20. BMP2-coprecipitated calcium phosphate granules enhance osteoinductivity of deproteinized bovine bone, and bone formation during critical-sized bone defect healing.

    Science.gov (United States)

    Liu, Tie; Zheng, Yuanna; Wu, Gang; Wismeijer, Daniel; Pathak, Janak L; Liu, Yuelian

    2017-01-31

    Most materials used clinically for filling critical-sized bone defects (CSBD), such as deproteinized bovine bone (DBB), lack osteoinductivity so that their therapeutic effects are far from satisfactory. The effect of bone morphogenic protein 2 (BMP2)-coprecipitated biomimetic calcium phosphate granules (BMP2-cop.BioCaP) on osteoinduction of DBB graft(s) during CSBD healing is still unknown. We investigated whether BMP2-cop.BioCaP affects the osteoinductivity of DBB, bone formation, and foreign body reaction during CSBD healing. DBB + BMP2-cop.BioCaP, DBB, DBB + BMP2, DBB + BioCaP, and autologous bone grafts were implanted in the CSBD of sheep. Bone formation, DBB/BioCaP degradability, foreign body reaction, and osteoinductivity of DBB were analyzed histologically and histomorphometrically at week 4 and 8. Combination of BMP2-cop.BioCaP and DBB healed CSBD as effectively as autologous bone grafts. About 95% of the BMP2-cop.BioCaP had been degraded and replaced by new bone at week 8 in the DBB + BMP2-cop.BioCaP-group. Foreign body reaction was reduced in the DBB + BMP2-cop.BioCaP-group compared to the other groups. The independent use of the BMP2-cop.BioCaP did not achieve a satisfactory bone repair. In conclusion, the BMP2-cop.BioCaP showed good degradability and biocompatibility, and enhanced osteoinductivity of DBB during CSBD healing in sheep, suggesting BMP2-cop.BioCaP as a potential osteoinducer to enhance the therapeutic effects of the graft materials in clinic.

  1. Ozone treatment of alveolar bone in the cape chacma baboon does not enhance healing following trauma.

    Science.gov (United States)

    Kotze, Marthinus; Bütow, Kürt-W; Olorunju, Steve A; Kotze, Harry F

    2014-06-01

    In the international literature, the role of Ozone (O3) in the advancement in alveolar bone healing in the absence of bone pathology was not tested before. The purpose of this study was to evaluate alveolar bone regeneration after a bone defect was created and treated with a single topical administration of O3. Alveolar bone defects were created on five healthy chacma baboons. One side of the maxilla and mandible was topically treated with a single treatment of an O3/O2 mixture (3,5-4 % O3), while the opposite sides were not treated and thus served as control. Regeneration was measured radiologically, using a standardized gray scale, as the increase in bone density in the treatment area at 3 and 6 weeks post-operative and was statistically analyzed using multivariate analysis of variance (MANOVA). There were no significant differences in densities observed between the O3/O2 mixture treatment and the control (p > 0.05). A single O3 treatment did not increase alveolar bone healing over a 3- and 6-week period in the mandible and the maxilla.

  2. Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects

    Science.gov (United States)

    2013-04-29

    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

  3. Dual-Purpose Bone Grafts Improve Healing and Reduce Infection

    Science.gov (United States)

    2011-08-01

    and PUR+BMP (High) (n = 14) groups. Two-thirds of the animals were used to assess bone formation, and the remainder was used to assess bacterial ...stabilized segmental defect in the rat femur. J Orthopaedic Res. 2005;23:816–823. 14. Anglen JO. Comparison of soap and antibiotic solutions for irrigation of

  4. Healing

    Science.gov (United States)

    Ventres, William B.

    2016-01-01

    My personal ethos of healing is an expression of the belief that I can and do act to heal patients while I attend to the traditional goals of medicine. The 7 supporting principles that inform my ethos are dignity, authenticity, integrity, transparency, solidarity, generosity, and resiliency. I invite others, including medical students, residents, and practicing physicians, to reflect and discover their own ethos of healing and the principles that guide their professional growth. A short digital documentary accompanies this essay for use as a reflective prompt to encourage personal and professional development. PMID:26755787

  5. Relationship among bone mineral density, collagen composition, and biomechanical properties of callus in the healing of osteoporotic fracture

    Institute of Scientific and Technical Information of China (English)

    SHEN Bin; MU Jian-xiong; PEI Fu-xing

    2007-01-01

    Objective: To study the change and relationship among bone mineral density (BMD), collagen composition and biomechanical properties of the callus in the healing process of osteoporotic fracture.Methods: The osteoporotic rat model and fracture model were established through bilateral ovariectomy(OVX) and osteotomy of the middle shaft of the right hind tibiae, respectively. Ninety female SD rats were randomly divided into OVX group and sham group. With the samples of blood and callus, roentgenoraphic and histological observation were performed for the assessment of the healing progress of the fracture, and the serum concentration of TRAP-5b, proportion of type Ⅰ collagen,BMD and biomechanical properties of the callus were measured.Results: The OVX group experienced a significant delay of fracture healing. The mean serum concentration of TRAP-5b of rats in the OVX group was much higher than that in the sham group after the operation (P < 0.05), but the difference at the same time point after fracture was smaller than that before fracture (P < 0.05 ). The BMD of the callus in both groups reached the peak value at the 6 th week after fracture while the proportion of the type Ⅰ collagen and the biomechanical strength reached the peak at the 8th week.Conclusions: The deficiency of estrogen after the ovariectomy could induce the up-regulation of the osteoclasts activities, whereas the potency of further activation after fracture was depressed. Although the synthesis of collagen together with its mineralization determines the biomechanical properties of new bone, the accumulation of collagen could be assessed as an index in the prediction of biomechanical strength of bones independent of the bone mineral deposition.

  6. Evolution of bone biomechanical properties at the micrometer scale around titanium implant as a function of healing time

    Science.gov (United States)

    Vayron, Romain; Matsukawa, Mami; Tsubota, Ryo; Mathieu, Vincent; Barthel, Etienne; Haiat, Guillaume

    2014-03-01

    The characterization of the biomechanical properties of newly formed bone tissue around implants is important to understand the osseointegration process. The objective of this study is to investigate the evolution of elastic properties of newly formed bone tissue as a function of healing time. To do so, nanoindentation and micro-Brillouin scattering techniques are coupled following a multimodality approach using histological analysis. Coin-shaped implants were placed in vivo at a distance of 200 µm from the cortical bone surface, leading to an initially empty cavity. Two rabbits were sacrificed after 7 and 13 weeks of healing time. The histological analyses allow us to distinguish mature and newly formed bone tissue. The bone mechanical properties were measured in mature and newly formed bone tissue. Analysis of variance and Tukey-Kramer tests reveals a significant effect of healing time on the indentation modulus and ultrasonic velocities of bone tissue. The results show that bone mass density increases by 12.2% (2.2% respectively) between newly formed bone at 7 weeks (13 weeks respectively) and mature bone. The dependence of bone properties on healing time may be explained by the evolution of bone microstructure and mineralization.

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

    Science.gov (United States)

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

    2015-06-01

    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.

  8. An experimental setup to evaluate innovative therapy options for the enhancement of bone healing using BMP as a benchmark – a pilot study

    Directory of Open Access Journals (Sweden)

    B Preininger

    2012-04-01

    Full Text Available Critical or delayed bone healing in rat osteotomy (OT models is mostly achieved through large defects or instability. We aimed to design a rat OT model for impaired bone healing based on age, gender and parity. The outcome should be controllable through variations of the haematoma in the OT including a bone morphogenetic protein (BMP 2 guided positive control.Using external fixation to stabilise femoral a 2 mm double OT in 12 month old, female Sprague Dawley rats after a minimum of 3 litters healing was characterised following in situ haematoma formation (ISH-group, transplantation of a BMP charged autologous blood clot (BMP-group and the artificial blood clot only (ABC-group into the OT-gap. In vivo micro-computer tomography (µCT scans were performed after 2, 4 and 6 weeks. After 6 weeks specimens underwent histological analyses.In µCT examinations and histological analyses no bony bridging was observed in all but one animal in the ISH-group. In the BMP group complete bridging was achieved in all animals. The ABC-group showed less mineralised tissue formation and smaller bridging scores during the course of healing than the ISH-group.In this pilot study we introduce a model for impaired bone healing taking the major biological risk factors into account. We could show that the in situ fracture haematoma is essential for bone regeneration. Using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.

  9. In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation.

    Science.gov (United States)

    Wittkowske, Claudia; Reilly, Gwendolen C; Lacroix, Damien; Perrault, Cecile M

    2016-01-01

    This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g., due to extended periods of bed rest or microgravity in space are associated with altered bone remodeling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. Particular attention is given to in vitro set-ups, which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibers, which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  10. In vitro bone cell models: Impact of fluid shear stress on bone formation

    Directory of Open Access Journals (Sweden)

    Claudia Wittkowske

    2016-11-01

    Full Text Available This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodelling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g. due to extended periods of bed rest or microgravity in space are associated with altered bone remodelling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signalling factors such as nitric oxide and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signalling, collagen deposition and matrix mineralization. Particular attention is given to in vitro set-ups which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibres which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  11. Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring.

    Science.gov (United States)

    Li, Zhonghua; Wang, Haiqin; Yang, Bo; Sun, Yukai; Huo, Ran

    2015-12-01

    The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing.

  12. Effects of cryosurgery on the healing pattern of rabbit mandibular bone. A triple fluorochrome labelling study.

    Science.gov (United States)

    Kuylenstierna, R; Nathanson, A; Lundquist, P G

    1981-01-01

    The reparative process of rabbit mandibular bone injured by cryosurgery was studied by a triple fluorochromic method. The regeneration started late, when compared with fracture healing, and reached its maximum some 4-8 weeks after cryosurgery. A normal distribution of fluorochromes was registered after l2 weeks. The regeneration occurred mainly through growth from the marrow cavity region where the cryogenic impact may have stimulated osteogenesis from surviving endosteum and bone marrow. The destroyed periosteum at the site of the probe-tip attachment did not regenerate, although new bone formation of periosteal origin was noticed at the border of the injured cortex. The general distribution of fluorochromes seemed to follow closely the autoradiographic image obtained using 99TcmMDP in a similar experiment, suggesting comparable ways of accumulation in bone tissue.

  13. Experimental study on healing process of rat mandibular bone fracture examined by radiological procedures

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Yukio; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1994-06-01

    The healing process of rat mandibular fractures was stereoscopically observed daily, using plain roentgenography in the lateral-oblique and tooth axis directions and bone scintigraphy using 99m-Tc-methylene diphosphoric acid (Tc-99m-MDP). The findings were compared with microradiograms of regional polished specimens. X-ray findings included the following. Up to 3 days after bone fracture, the fracture mesiodistally showed distinct radiolucency, with sharp and irregular fracture stump. Radiopacity of the fracture site gradually increased 7 days or later, and bone trabecular formation by callus and stump bridging started to occur at 14 days. Findings similar to those in the control group were observed 49 days or later. The inside was difficult to differentiate, irrespective of the observation time. Bone scans in the mesiodistal and buccolingual planes revealed tracer uptake in the areas of mandibular and soft tissue damage one day after bone fracture. Tracer uptake began to be seen in the fracture site 3 days later, and became marked at 14 days. Then Tc-99m DMP began to be localized and returned to the findings similar to those at 49 days. Bone scanning tended to show wider areas earlier than roentgenography. Microradiographic mesiodistal examination revealed distinct radiopacy of the fracture line for 3 days after bone fracture. Seven days later, bone resorption cavity occurred in the cortical bone around the fracture stump, along with neogenesis of callus. Neogenesis and calcification began to occur gradually, and 14 days later, the fracture osteoremodeling of the internal bone trabeculae was observed. Bone trabecular formation within the bone, however, occurred later. (N.K.).

  14. Adipose Stem Cells as Alternatives for Bone Marrow Mesenchymal Stem Cells in Oral Ulcer Healing

    Science.gov (United States)

    Aziz Aly, Lobna Abdel; Menoufy, Hala El-; Ragae, Alyaa; Rashed, Laila Ahmed; Sabry, Dina

    2012-01-01

    Background and Objectives Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. Methods and Results Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. Results: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. Conclusions MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing. PMID:24298363

  15. Repeatability and accuracy of a paralleling technique for radiographic evaluation of distal bone healing after impacted third molar surgery

    National Research Council Canada - National Science Library

    Inocêncio Faria, A; Gallas Torreira, M; López Ratón, M

    2013-01-01

    The purpose of this study was to investigate the repeatability and radiographic accuracy of an intraoral paralleling technique to evaluate periodontal bone healing on the distal surface of the second mandibular molar (2 Mm...

  16. Cola beverage consumption delays alveolar bone healing: a histometric study in rats

    Directory of Open Access Journals (Sweden)

    Juliana Mazzonetto Teófilo

    2010-06-01

    Full Text Available Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group or tap water (control group ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01. Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

  17. Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study

    Science.gov (United States)

    Ye, Chenyi; Zhang, Wei; Wang, Shengdong; Jiang, Shuai; Yu, Yuanbin; Chen, Erman; Xue, Deting; Chen, Jianzhong; He, Rongxin

    2016-01-01

    To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group (n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group (n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy. PMID:27792147

  18. Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study.

    Science.gov (United States)

    Ye, Chenyi; Zhang, Wei; Wang, Shengdong; Jiang, Shuai; Yu, Yuanbin; Chen, Erman; Xue, Deting; Chen, Jianzhong; He, Rongxin

    2016-10-25

    To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group (n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group (n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy.

  19. Ultrasound to stimulate mandibular bone defect healing : A placebo-controlled single-blind study in rats

    NARCIS (Netherlands)

    Schortinghuis, J; Ruben, JL; Raghoebar, GM; Stegenga, B

    2004-01-01

    Purpose: Because of the limitations of the body to heal large maxillofacial bone defects, an attempt was made to stimulate mandibular defect healing with low intensity pulsed ultrasound in rats. This ultrasound consists of a 1.5-MHz pressure wave administered in pulses of 200 musec, with an average

  20. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone.

    Science.gov (United States)

    Augat, Peter; Simon, Ulrich; Liedert, Astrid; Claes, Lutz

    2005-03-01

    Fracture repair, which aims at regaining the functional competence of a bone, is a complex and multifactorial process. For the success of fracture repair biology and mechanics are of immense importance. The biological and mechanical environments must be compatible with the processes of cell and tissue proliferation and differentiation. The biological environment is characterized by the vascular supply and by many biochemical components, the biochemical milieu. A good vascular supply is a prerequisite for the initiation of the fracture repair process. The biochemical milieu involves complex interactions among local and systemic regulatory factors such as growth factors or cytokines. The mechanical environment is determined by the local stress and strain within the fracture. However, the local stress and strain is not accessible, and the mechanical environment, therefore, is described by global mechanical factors, e.g., gap size or interfragmentary movement. The relationship between local stress and strain and the global mechanical factors can be obtained by numerical models (Finite Element Model). Moreover, there is considerable interaction between biological factors and mechanical factors, creating a biomechanical environment for the fracture healing process. The biomechanical environment is characterized by osteoblasts and osteocytes that sense the mechanical signal and express biological markers, which effect the repair process. This review will focus on the effects of biomechanical factors on fracture repair as well as the effects of age and osteoporosis.

  1. Healing of open fracture of shoulder bone in owl

    Directory of Open Access Journals (Sweden)

    Prokić Branislav

    2007-01-01

    Full Text Available Curing and treatment of accidental injuries in birds that have the nature of complex, old and contaminated wounds demand maximum caution from the surgeon. Birds, in particular wild fowl, are sensitive to manipulation during examinations and the diagnosis of the injuries. The estimate of the complexity of an injury and the general condition of the patient are of key importance for the correct choice of diagnostic procedures, anesthesia, and the operative procedure. The implementation of ketamine and diazepam for general injection anesthesia provides possibilities for the unhindered executing of the surgical procedure. The implementation of Kischner needles and pins is a good choice for the fixation of long bones in birds. The postoperative course in the patient requires constant medical and professional supervision which must be followed to the letter.

  2. [The influence of chemically-modified SLA on bone defect healing around implants in dogs].

    Science.gov (United States)

    Lv, Xiao-fei; Zhuang, Long-fei; Liu, Xin; Zhang, Zhi-yong; Lai, Hong-chang

    2010-06-01

    The study was designed to investigate the effect of surface chemical modification on the process of bone defect healing around implants in dogs. Six Beagle dogs were used in this study. The mandibular premolars and first molars were extracted bilaterally. Three months after tooth extraction the procedure of implant placement was performed. Four canals with a diameter of 2.8 mm and 10 mm in depth were prepared at the third premolar (P3) and the first molar (M1) sites of both sides of the mandible, of which the coronal 5 mm portion were further widened with the 5.3 mm diameter twist drill. In each side of the mandible one modSLA (chemically-modified SLA) implant and one SLA (sandblasted, large-grit, acid-etched) implant with a diameter of 3.3 mm and 10 mm in length were installed, respectively. Thus, the circumferential defect that was 5mm deep and 1mm wide created between the implant surface and the bony wall. Four implants placed in both sides of the mandible were allowed for non-submerged healing. Two dogs were sacrificed at the week 2, 4 and 8 following implant placement, respectively, and the specimens were prepared and stained with trinitrophenol- fuchsin for histological and histomorphometric analyses to acquire the bone-to-implant contact (BIC%), new bone fill (NBF%) and the distance between the most coronal level of bone-to-implant contact and the bottom of the surgically created bone defect(B-D). Statistical analysis was conducted with SPSS13.0 software package. No implant was loosen or lost during the study. The histomorphometric results demonstrated that new bone formation was observed in the defect region around both groups of implants at all time points and the newly formed bone occurred initially from the apical and lateral bony wall of the defect region, the bone defect almost was filled at week 8. At 2 and 4 weeks of healing, the BIC%, NBF% and B-D values were significantly higher for modSLA implants (P0.05). The SLA implants processed by means of

  3. Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhonghua [Department of Burn and Plastic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Department of Burn and Plastic Surgery, The Fourth People' s Hospital Of Jinan, Jinan 250031 (China); Wang, Haiqin [Department of Obstetrics and Gynecology, The Fifth People' s Hospital Of Jinan, Jinan 250022 (China); Yang, Bo; Sun, Yukai [Department of Burn and Plastic Surgery, The Fourth People' s Hospital Of Jinan, Jinan 250031 (China); Huo, Ran, E-mail: rhuo12@163.com [Department of Burn and Plastic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2015-12-01

    The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. - Highlights: • The GFs promoted the growth and proliferation of MSCs. • The GFs loaded with MSCs obviously facilitated wound closure in the animal model. • An anti-scarring effect was observed in the presence of 3D-GF scaffold and MSCs. • The GF scaffold loaded with MSCs has great effect on skin wound healing.

  4. The progress of early phase bone healing using porous granules produced from calcium phosphate cement

    Directory of Open Access Journals (Sweden)

    Jungbluth P

    2010-05-01

    Full Text Available Abstract Objective Bone grafting is a vital component in many surgical procedures to facilitate the repair of bone defects or fusions. Autologous bone has been the gold standard to date in spite of associated donor-site morbidity and the limited amount of available donor bone. The aim of this study was to investigate the progress of bone regeneration and material degradation of calcium phosphate granules (CPG produced from a calcium phosphate self-setting cement powder compared to the use of autologous bone grafting in the treatment of "critical size defects" on load-bearing long bones of minipigs. Methods A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft or with micro- and macroporous carbonated, apatic calcium phosphate granules (CPG produced from a calcium phosphate self-setting cement powder. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. The amount of new bone formation was analysed histomorphometrically. Results The semi-quantitative analysis of the radiological results showed a complete osseous bridging of the defect in three cases for the autograft group. In the same group five animals showed a beginning, but still incomplete bridging of the defect, whereas in the CPG group just two animals developed this. All other animals of the CPG group showed only a still discontinuous new bone formation. Altogether, radiologically a better osseous bridging was observed in the autograft group compared to the CPG group. Histomorphometrical analysis after six weeks of healing revealed that the area of new bone was significantly greater in the autograft group concerning the central area of the defect zone (p Conclusions Within the limits of the present study it could be demonstrated that autologous cancellous grafts lead to a significantly better bone regeneration compared to the application of calcium phosphate granules (CPG produced from a calcium

  5. The effects of physiologic dynamic compression on bone healing under external fixation

    Energy Technology Data Exchange (ETDEWEB)

    Aro, H.T.; Kelly, P.J.; Lewallen, D.G.; Chao, E.Y. (Mayo Clinic/Mayo Foundation, Rochester, MN (USA))

    1990-07-01

    The effects of early physiologic dynamic compression on fracture healing were studied in the dog. Transverse midtibial osteotomies were performed bilaterally and stabilized with a relatively rigid external fixation system in a neutralization mode (800 microns) to prevent compression of the osteotomy ends during weight bearing. On the 15th day, one osteotomy in each animal was subjected to dynamic compression through weight bearing by release of the fixator-telescoping mechanism (axial dynamization), while the other side remained unchanged as the control. Analysis of sequential roentgenograms showed that the callus distribution was more symmetric on the dynamic compression side. The two sides showed no significant differences in quantitative technetium-99 bone scans or in osteotomy-site blood flow. There were no statistical differences in new bone formation, bone porosity, or maximum torque between sides. The fixation had maintained the initially created osteotomy gap on the control side and tended to unite through a gap-healing mechanism. The dynamic compression side showed reduction in gap size and union by more of a contact-healing mechanism. There were no statistical differences in the rate of pin loosening, but its distribution according to pin location was significantly different between the two sides.

  6. Numerical Modelling of Self Healing Mechanisms

    Science.gov (United States)

    Remmers, Joris J. C.; de Borst, René

    A number of self healing mechanisms for composite materials have been presented in the previous chapters of this book. These methods vary from the classical concept of micro-encapsulating of healing agents in polymer systems to the autonomous healing of concrete. The key feature of these self healing mechanisms is the transport of material to the damaged zone in order to establish the healing process. Generally, this material is a fluid and its motion is driven by capillary action which enables transportation over relatively large distances requiring little or no work. In the microencapsulated polymers as developed by White et al. [1], this liquid material is a healing agent, which is enclosed in the material by micro-encapsulation. When the capsule is ruptured by a crack, the healing agent will flow into the crack, driven by capillary action. Polymerisation of this healing agent is triggered by contact with catalysts which are inserted in the material and whose position is fixed. The new polymerised material will rebond the crack surfaces.

  7. Soluble VEGFR1 reverses BMP2 inhibition of intramembranous ossification during healing of cortical bone defects.

    Science.gov (United States)

    Hu, Kai; Besschetnova, Tatiana Y; Olsen, Bjorn R

    2016-09-07

    BMP2 is widely used for promotion of bone repair and regeneration. However, bone formation induced by BMP2 is quite variable. Bone forming progenitor cells in different locations appear to respond to BMP2 in different ways, and repair outcomes can vary as a consequence of modulating effects by other factors. In this study, we have examined the effects of VEGF on BMP2-induced repair of a cortical bone defect, a 1 mm diameter drill hole, in the proximal tibia of mice. Treatment of the defect with either a bolus of PBS or soluble VEGFR1 (sVEGFR1), a decoy receptor for VEGF, had the same effects on bone formation via intramembranous ossification in the defect and cartilage formation and injured periosteum, during the healing process. In contrast, treatment with BMP2 inhibited intramembranous bone formation in the defect while it promoted cartilage and endochondral bone formation in the injured periosteum compared with mice treated with PBS or sVEGFR1. The inhibitory effect of BMP2 on bone formation was unlikely due to increased osteoclast activity and decreased invasion of blood vessels in the defect. Most importantly, co-delivery of BMP2 and sVEGFR1 reversed the inhibition of intramembranous bone formation by BMP2. Furthermore, the decreased accumulation of collagen and production of bone matrix proteins in the defect of groups with BMP2 treatment could also be prevented by co-delivery of BMP2 and sVEGFR1. Our data indicate that introducing a VEGF-binding protein, such as sVEGFR1, to reduce levels of extracellular VEGF, may enhance the effects of BMP2 on intramembranous bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  8. An Experimental Animal Model for Abdominal Fascia Healing after Surgery

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H-C; Klein, M

    2013-01-01

    Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...

  9. Effects of laser and ozone therapies on bone healing in the calvarial defects.

    Science.gov (United States)

    Kazancioglu, Hakki Oguz; Ezirganli, Seref; Aydin, Mehmet Serif

    2013-11-01

    This study aims to analyze the effect of the low-level laser therapy (LLLT) and ozone therapy on the bone healing of critical size defect (CSD) in rat calvaria. A total of 30 Wistar male rats were used. A 5-mm-diameter trephine bur was used to create CSD on the right side of the parietal bone of each rat calvarium. Once the bone was excised, a synthetic biphasic calcium phosphate graft material was implanted to all the bone defect sites. The animals were randomly divided into 3 groups as follows: the control group (n = 10), which received no LLLT or ozone therapy; the LLLT group (n = 10), which received only LLLT (120 seconds, 3 times a week for 2 weeks); and the ozone therapy group (n = 10) (120 seconds, 3 times a week for 2 weeks). After 1 month, all the rats were killed, and the sections were examined to evaluate the presence of inflammatory infiltrate, connective tissue, and new bone formation areas. Histomorphometric analyses showed that in the LLLT and ozone groups, the new bone areas were significantly higher than in the control group (P ozone group (P ozone and laser therapies had a positive effect on bone formation in rat calvarial defect, compared with the control group; however, ozone therapy was more effective than LLLT (808 nm; 0.1 W; 4 J/cm(2); 0.028 cm(2), continuous wave mode).

  10. The effect of L-PRF membranes on bone healing in rabbit tibiae bone defects: micro-CT and biomarker results.

    Science.gov (United States)

    Faot, Fernanda; Deprez, Sanne; Vandamme, Katleen; Camargos, Germana V; Pinto, Nelson; Wouters, Jasper; van den Oord, Joost; Quirynen, Marc; Duyck, Joke

    2017-04-12

    More insight into the biological fundamentals of leukocyte platelet-rich fibrin (L-PRF) guided healing is necessary to recommend its application, in particular in deficient bone sites that need to support implants. This study investigated the short-term bone healing effect of L-PRF treatment in cylindrical non-critical sized bone defects with 3 mm diameter and 6 mm depth in tibiae of 18 adult male New Zealand White rabbits. After a randomization process, 96 bone defects were prepared and half of them were filled with a L-PRF membrane, while untreated defects in the opposite tibia served as control group. The rabbits were euthanized after 7, 14 or 28 days of healing. The bone healing of the cortical and medullary areas was investigated by micro-CT, while the expression of molecular markers (RUNX2, VEGFA, COL1A2 and BMP2) was assessed by qRT-PCR. Treatment with L-PRF did not affect the micro-structural bone characteristics of the repaired bone tissue, except for a decrease in the trabecular connectivity at the cortical level after 14 days of healing. At this time, RUNX2 and VEGFA mRNA levels were significantly lower in the treated defects. L-PRF membranes thus had a temporary negative influence on the bone microarchitecture (Tb.Pf) and on the RUNX2 and VEGFA expression during early bone healing. Overall, L-PRF treatment did not enhance bone regeneration in these non-critical size defects after 28 days.

  11. Healing from Childhood Sexual Abuse: A Theoretical Model

    Science.gov (United States)

    Draucker, Claire Burke; Martsolf, Donna S.; Roller, Cynthia; Knapik, Gregory; Ross, Ratchneewan; Stidham, Andrea Warner

    2011-01-01

    Childhood sexual abuse is a prevalent social and health care problem. The processes by which individuals heal from childhood sexual abuse are not clearly understood. The purpose of this study was to develop a theoretical model to describe how adults heal from childhood sexual abuse. Community recruitment for an ongoing broader project on sexual…

  12. Healing from Childhood Sexual Abuse: A Theoretical Model

    Science.gov (United States)

    Draucker, Claire Burke; Martsolf, Donna S.; Roller, Cynthia; Knapik, Gregory; Ross, Ratchneewan; Stidham, Andrea Warner

    2011-01-01

    Childhood sexual abuse is a prevalent social and health care problem. The processes by which individuals heal from childhood sexual abuse are not clearly understood. The purpose of this study was to develop a theoretical model to describe how adults heal from childhood sexual abuse. Community recruitment for an ongoing broader project on sexual…

  13. Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study

    Directory of Open Access Journals (Sweden)

    Yaman F

    2016-06-01

    Full Text Available Ferhan Yaman,1 Izzet Acikan,1 Serkan Dundar,2 Sercan Simsek,3 Mehmet Gul,4 İbrahim Hanifi Ozercan,3 James Komorowski,5 Kazim Sahin6 1Department of Oral-Maxillofacial Surgery, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 2Department of Periodontology, Faculty of Dentistry, Firat University, Elazig, Turkey; 3Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey; 4Department of Periodontology, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 5Nutrition 21, LLC, Purchase, NY, USA; 6Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey Background: Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25% is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. Objective: The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. Methods: The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. Results: Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05. New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05. However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05. Conclusion: ASI supplementation significantly improved bone tissue

  14. Mathematical models of wound healing and closure: a comprehensive review.

    Science.gov (United States)

    Jorgensen, Stephanie N; Sanders, Jonathan R

    2016-09-01

    Wound healing is a complex process comprised of overlapping phases and events that work to construct a new, functioning tissue. Mathematical models describe these events and yield understanding about the overall process of wound healing. Generally, these models are focused on only one phase (or a few phases) to explain healing for a specific system. A review of the literature reveals insights as reported on herein regarding the variety of overlapping inputs and outputs for any given type of model. Specifically, these models have been characterized with respect to the phases of healing and their mathematical/physical basis in an effort to shed light on new opportunities for model development. Though all phases of wound healing have been modeled, previous work has focused mostly on the proliferation and related contraction phases of healing with fewer results presented regarding other phases. As an example, a gap in the literature has been identified regarding models to describe facilitated wound closure techniques (e.g., suturing and its effect on resultant scarring). Thus, an opportunity exists to create models that tie the transient processes of wound healing, such as cell migration, to resultant scarring when considering tension applied to skin with given suturing techniques.

  15. [Rotator cuff repair with decellularized tendon slices for enhancing tendon-bone healing in rabbits].

    Science.gov (United States)

    Pan, Juan; Liu, Guoming; Ning, Liangju; Luo, Jingcong; Huang, Fuguo; Qin, Tingwu

    2013-09-01

    To investigate the effect of canine decellularized tendon slices (DTSs) on tendon-bone healing in repairing rotator cuff injury of rabbit. Canine DTSs were prepared by repetitive freeze/thaw 5 times combined with nuclease processing for 12 hours from the adult Beagles Achilles tendons. Histological observation and cytocompatibility evaluation for the canine DTSs were performed in vitro. Twenty-four mature male New Zealand white rabbits, weighing 2.5-3.0 kg, were randomly selected. U-shaped defect of more than 50% of normal tendon in width and 8 mm in length was made in infraspinatus tendons of unilateral limb as the experimental group; the canine DTSs were used to repair defect, and the insertion of infraspinatus tendon on greater tuberosity of humerus was reconstructed in the experimental group. No treatment was done on the contralateral limb as the control group. At 4, 8, and 12 weeks after operation, the specimens were harvested for histological observation and biomechanical test. Histological examination showed that collagen fibers of canine DTSs were well preserved, without residual cells. The cytocompatibility examination showed that fibroblasts attached well to canine DTSs. Biomechanical test showed that the maximum load and stiffness increased significantly with time, and the maximum load and stiffness at 12 weeks were significantly higher than those at 4 and 8 weeks (P tendon-bone insertion. In the experimental group at 4 weeks, the tendon-bone interface was filled with granulation tissue, and a small amount of Sharpey's fibers-like connected the tendon to bone; granulation tissue disappeared, and fibroblasts, Sharpey's fiber, new cartilage, and chondrocytes significantly increased with time; tendon-bone interface became mature, but the tide line was not observed between the unmineralized fibrocartilage and mineralized fibrocartilage. Canine DTSs prepared by repetitive freeze/thaw 5 times combined with nuclease processing for 12 hours, can enhance the

  16. Effect of Simvastatin collagen graft on wound healing of defective bone

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jun Ho; Kim, Gyu Tae [Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of); Choi, Yong Suk; Lee, Hyeon Woo; Hwang, Eui Hwan [Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

    2008-09-15

    To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson's trichrome stain. Results : 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. Histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.

  17. The influence of root surface distance to alveolar bone and periodontal ligament on periodontal wound healing

    Science.gov (United States)

    2016-01-01

    Purpose The purpose of this animal study was to perform a 3-dimensional micro-computed tomography (micro-CT) analysis in order to investigate the influence of root surface distance to the alveolar bone and the periodontal ligament on periodontal wound healing after a guided tissue regeneration (GTR) procedure. Methods Three adult Sus scrofa domesticus specimens were used. The study sample included 6 teeth, corresponding to 2 third mandibular incisors from each animal. After coronectomy, a circumferential bone defect was created in each tooth by means of calibrated piezoelectric inserts. The experimental defects had depths of 3 mm, 5 mm, 7 mm, 9 mm, and 11 mm, with a constant width of 2 mm. One tooth with no defect was used as a control. The defects were covered with a bioresorbable membrane and protected with a flap. After 6 months, the animals were euthanised and tissue blocks were harvested and preserved for micro-CT analysis. Results New alveolar bone was consistently present in all experimental defects. Signs of root resorption were observed in all samples, with the extent of resorption directly correlated to the vertical extent of the defect; the medial third of the root was the most commonly affected area. Signs of ankylosis were recorded in the defects that were 3 mm and 7 mm in depth. Density and other indicators of bone quality decreased with increasing defect depth. Conclusions After a GTR procedure, the periodontal ligament and the alveolar bone appeared to compete in periodontal wound healing. Moreover, the observed decrease in bone quality indicators suggests that intrabony defects beyond a critical size cannot be regenerated. This finding may be relevant for the clinical application of periodontal regeneration, since it implies that GTR has a dimensional limit. PMID:27800213

  18. Inducible models of bone loss.

    Science.gov (United States)

    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions. Copyright © 2014 John Wiley & Sons, Inc.

  19. Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

    Science.gov (United States)

    Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

    2015-10-01

    To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

  20. The influence of local administration of simvastatin in calvarial bone healing in rats.

    Science.gov (United States)

    Calixto, Jimmy Cavalcanti; Lima, Carlos Eugênio Villaboim de Castro; Frederico, Lilian; Lima, Rafaela Pio dos Santos de Castro; Anbinder, Ana Lia

    2011-04-01

    Some authors have associated the use of statins, hypolipidemic drugs, and new bone formation. The aim of this work was to evaluate the effect of locally administered simvastatin on bone healing. Bone calvarial defects 5mm in diameter were made in 64 rats. The animals were divided into four groups according to the graft material: the control group, in which the defects were not treated, the SIM-1 group, which received a sponge of collagen soaked with simvastatin (2.2 mg/50 μl), the SIM-2 group, which received a sponge of collagen soaked with simvastatin (0.5 mg/50 μl), and the carrier (CAR) group, which received a sponge of collagen and water. The animals were sacrificed after 30 or 60 days. The skulls were removed, and radiographic densitometry and histometric analyses of the bone defect area were performed. Local crust formation was clinically verified in SIM-1 and SIM-2 animals. After statistical analysis (p<0.05) of bone area data, we observed no significant differences among the groups after 30 days. After 60 days, however, there was less bone formation in the CAR and SIM-2 groups. The SIM-2 group also presented with lower radiographic densities after 60 days. According to the methodology used, we conclude that locally administered simvastatin was detrimental to the repair of defects in the calvaria of rats.

  1. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug.

    Science.gov (United States)

    Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A; Schense, Jason C

    2009-03-01

    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.

  2. Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma

    Directory of Open Access Journals (Sweden)

    Bastian OW

    2016-05-01

    Full Text Available Okan W Bastian,1 Anne Kuijer,1 Leo Koenderman,2 Rebecca K Stellato,3 Wouter W van Solinge,4 Luke PH Leenen,1 Taco J Blokhuis1 1Department of Traumatology, 2Department of Respiratory Medicine, 3Department of Biostatistics and Research Support, Julius Center, 4Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands Abstract: Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major trauma affect leukocyte kinetics. We therefore retrospectively compared the cellular composition of peripheral blood during the first 2 weeks after injury between multitrauma patients with normal (n=48 and impaired (n=32 fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes differed significantly between patients with normal and impaired fracture healing during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and <0.0001, respectively. Mean myeloid cell counts were above reference values during the second week after injury. Our data indicate that leukocyte kinetics differ significantly between patients with normal and impaired fracture healing during the first 2 weeks after major injury. This finding suggests that the systemic immune response to major trauma can disturb tissue regeneration. Keywords: SIRS, inflammation, neutrophils, myelopoiesis, regeneration

  3. Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

    Directory of Open Access Journals (Sweden)

    Shota Ikegami

    2009-10-01

    Full Text Available Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men with femoral neck fracture and 21 patients (17 women and 4 men with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX, as well as urine levels of C-terminal telopeptide of type I collagen (CTX and deoxypyridinoline (DPD, were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX, five weeks (serum NTX and DPD, and 2-3 weeks (CTX after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

  4. Influence of PRF in the healing of bone and gingival tissues. Clinical and histological evaluations.

    Science.gov (United States)

    Marrelli, M; Tatullo, M

    2013-07-01

    The healing of bone tissues around dental implants is based primarily on a correct osseointegration. Typically, implants stability and peri-implant tissues health are anticipated to decrease during the early weeks of healing; this is followed by an increase in stability. The aim of the present study is to assess a predictable protocol in order to increase the peri-implant tissues maintenance around post-extractive dental implants, thanks to the use of Platelet-Rich Fibrin (PRF) membrane. This is a retrospective observational study of 127 tapered dental implants placed in the immediate post-extraction sites of maxillary bone of 59 patients. Atraumatic dental extraction and flapless implant surgery was performed in all reported cases. The cortical bone position relative to the implant reference point was evaluated at implant placement and 10 to 24 months following implantology. The gap between bone tissue and the implant surface was measured up to a maximum of 3 mm. After placing implants we have filled the surgical site with a PRF gel, so as to fill the gap between bone tissue and the implant surface, and then we have covered the surgical site with a PRF membrane, so as to coat the gap between the alveolar crest and the implant. In all cases, we observed the complete covering of the dental implants, with newly formed soft tissue of variable thickness between 1 and 3 mm. Cortical bone adaptation from the time of implant placement up to 30 months following prosthetic restoration ranged from 0.4 mm to 1.7 mm. Our study showed a series of successful rehabilitations, with post-extraction implantology technique, in 99.8 percent of cases, despite the success rates in the medium and long-term post-extraction implantology reported in the literature range between 92.7 percent and 98.0 percent. Long-term maintenance of crestal bone and the rapid healing of soft tissue dimension with maintenance of peri-implant papilla were observed as outcomes after post-extractive implants

  5. Evaluation of Bone Healing on Sandblasted and Acid Etched Implants Coated with Nanocrystalline Hydroxyapatite: An In Vivo Study in Rabbit Femur

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    Lory Melin Svanborg

    2014-01-01

    Full Text Available This study aimed at investigating if a coating of hydroxyapatite nanocrystals would enhance bone healing over time in trabecular bone. Sandblasted and acid etched titanium implants with and without a submicron thick coat of hydroxyapatite nanocrystals (nano-HA were implanted in rabbit femur with healing times of 2, 4, and 9 weeks. Removal torque analyses and histological evaluations were performed. The torque analysis did not show any significant differences between the implants at any healing time. The control implant showed a tendency of more newly formed bone after 4 weeks of healing and significantly higher bone area values after 9 weeks of healing. According to the results from this present study, both control and nano-HA surfaces were biocompatible and osteoconductive. A submicron thick coating of hydroxyapatite nanocrystals deposited onto blasted and acid etched screw shaped titanium implants did not enhance bone healing, as compared to blasted and etched control implants when placed in trabecular bone.

  6. Expression of chondro-osteogenic BMPs in ossified failed tendon healing model of tendinopathy.

    Science.gov (United States)

    Yee Lui, Pauline Po; Wong, Yin Mei; Rui, Yun Feng; Lee, Yuk Wa; Chan, Lai Shan; Chan, Kai Ming

    2011-06-01

    Chondrocytes phenotype/markers were expressed in clinical samples of tendinopathy and calcifying tendinopathy. This study examined the spatial-temporal expression of chondro-osteogenic Bone Morphogenetic Proteins (BMPs), which might contribute to ectopic chondro-osteogenesis and failed healing process in tendinopathy. Collagenase was injected into patellar tendon of rats to induce ossified failed tendon healing. At week 2, 4, 8, 12, and 16, the patella tendon was harvested for immunohistochemical staining and analysis of BMP-2/4/7. BMP-4/7 showed similar expression patterns, which was different from BMP-2. The expression of BMP-2 in the tendon matrix increased at week 2 and was reduced to nearly undetectable level afterwards except at the chondro-ossification sites. However, the expression of BMP-4/7 in the healing tendon fibroblast-like cells and matrix increased at week 2, reduced at week 4 and 8 and increased again at week 12 and 16, consistent with transient healing at week 8 in this animal model. There was increasing strong expression of BMP-4/7 in the chondrocyte-like cells in the un-ossified and ossified areas from week 8-16. BMP-4/7, besides BMP-2, might also contribute to ectopic chondro-osteogenesis and failed healing in tendon injuries. BMP-4/7, but not BMP-2, might be involved in regulating late events in ossified failed tendon healing.

  7. Therapeutic potential of bone marrow-derived mesenchymal stem cells in cutaneous wound healing

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    Jerry S Chen

    2012-07-01

    Full Text Available Despite advances in wound care, many wounds never heal and become chronic problems that result in significant morbidity and mortality to the patient. Cellular therapy for cutaneous wounds has recently come under investigation as a potential treatment modality for impaired wound healing. Bone marrow-derived mesenchymal stem cells (MSCs are a promising source of adult progenitor cells for cytotherapy as they are easy to isolate and expand and have been shown to differentiate into various cell lineages. Early studies have demonstrated that MSCs may enhance epithelialization, granulation tissue formation, and neovascularization resulting in accelerated wound closure. It is currently unclear if these effects are mediated through cellular differentiation or by secretion of cytokines and growth factors. This review discusses the proposed biological contributions of MSCs to cutaneous repair and their clinical potential in cell-based therapies.

  8. Diabetes mellitus impairs tendon-bone healing after rotator cuff repair

    Science.gov (United States)

    Bedi, Asheesh; Fox, Alice J.S.; Harris, Paul E.; Deng, Xiang-Hua; Ying, Liang; Warren, Russell F.; Rodeo, Scott A.

    2017-01-01

    Introduction Studies have demonstrated a significant decrease in skeletal mass, bone mineral density, and impaired fracture healing in the diabetic population. However, the effect of sustained hyperglycemia on tendon-to-bone healing is unknown. Materials and methods Forty-eight male, Lewis rats underwent unilateral detachment of the supraspinatus tendon followed by immediate anatomic repair with transosseous fixation. In the experimental group (n = 24), diabetes was induced preoperatively via intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and confirmed with both pre- and post-STZ injection intraperitoneal glucose tolerance tests (IPGTT). Animals were sacrificed at 1 and 2 weeks post-operatively for biomechanical, histomorphometric, and immunohistochemical analysis. Serum hemoglobin A1c (HbA1c) levels were measured at 2 weeks postoperatively. Statistical comparisons were performed using Student t tests with significance set at P diabetic compared to control animals (P diabetic and control groups, respectively (P Diabetic animals demonstrated significantly less fibrocartilage and organized collagen, and increased AGE deposition at the tendon-bone interface (P diabetic animals demonstrated a significantly reduced ultimate load-to-failure (4.79 ± 1.33N vs 1.60 ± 1.67N and 13.63 ± 2.33N vs 6.0 ± 3.24N for control versus diabetic animals at 1 and 2 weeks, respectively) and stiffness compared to control animals (P diabetic patients with poor glycemic control. Level of Evidence Basic Science Study. PMID:20303293

  9. Wound healing after irradiation of bone tissues by Er:YAG laser

    Science.gov (United States)

    Watanabe, Hisashi; Yoshino, Toshiaki; Aoki, Akira; Ishikawa, Isao

    1997-05-01

    Clinical applications of Er:YAG laser are now developing in periodontics and restorative dentistry. To date, there have been few studies indicating safety criteria for intraoral usage of the Er:YAG laser. The present study examined the effects of the Er:YAG laser on bone tissues, supposing mis- irradiation in the oral cavity during dental application, especially periodontal surgery. The experiments were performed using the newly-developed Er:YAG laser apparatus equipped with a contact probe. In experiment 1, 10 pulses of laser irradiation were administered to the parietal bone of a rat at 50, 150 and 300 mJ/pulse with and without water irrigation, changing the irradiation distance to 0, 5, 10 and 20 mm, respectively. As a control, electric knife was employed. Macroscopic and SEM observations of the wound surface were performed. In experiment 2, laser irradiation in a straight line was performed at 150 mJ/pulse, 1- pps and 0,5, 10 mm irradiation distance without water irrigation. Wound healing was observed histologically at 0, 3, 7, 14 and 28 days after laser irradiation and compared with that of the control. Non-contact irradiation by Er:YAG laser did not cause severe damage to the parietal bone tissue under water irrigation. Contact irradiation induced a limited wound, however, new bone formation was observed 28 days after laser irradiation, while osseous defect with thermal degenerative tissue remained at the control site. In conclusion, irradiation with an Er:YAG laser would not cause severe damage to surrounding bone tissues in the oral cavity when used within the usual power settings for dental treatment. Furthermore, this laser may be applicable for osseous surgery because of its high ablation efficiency and good wound healing after irradiation.

  10. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice.

    Science.gov (United States)

    Zhou, Xin; von der Mark, Klaus; Henry, Stephen; Norton, William; Adams, Henry; de Crombrugghe, Benoit

    2014-12-01

    One of the crucial steps in endochondral bone formation is the replacement of a cartilage matrix produced by chondrocytes with bone trabeculae made by osteoblasts. However, the precise sources of osteoblasts responsible for trabecular bone formation have not been fully defined. To investigate whether cells derived from hypertrophic chondrocytes contribute to the osteoblast pool in trabecular bones, we genetically labeled either hypertrophic chondrocytes by Col10a1-Cre or chondrocytes by tamoxifen-induced Agc1-CreERT2 using EGFP, LacZ or Tomato expression. Both Cre drivers were specifically active in chondrocytic cells and not in perichondrium, in periosteum or in any of the osteoblast lineage cells. These in vivo experiments allowed us to follow the fate of cells labeled in Col10a1-Cre or Agc1-CreERT2 -expressing chondrocytes. After the labeling of chondrocytes, both during prenatal development and after birth, abundant labeled non-chondrocytic cells were present in the primary spongiosa. These cells were distributed throughout trabeculae surfaces and later were present in the endosteum, and embedded within the bone matrix. Co-expression studies using osteoblast markers indicated that a proportion of the non-chondrocytic cells derived from chondrocytes labeled by Col10a1-Cre or by Agc1-CreERT2 were functional osteoblasts. Hence, our results show that both chondrocytes prior to initial ossification and growth plate chondrocytes before or after birth have the capacity to undergo transdifferentiation to become osteoblasts. The osteoblasts derived from Col10a1-expressing hypertrophic chondrocytes represent about sixty percent of all mature osteoblasts in endochondral bones of one month old mice. A similar process of chondrocyte to osteoblast transdifferentiation was involved during bone fracture healing in adult mice. Thus, in addition to cells in the periosteum chondrocytes represent a major source of osteoblasts contributing to endochondral bone formation in vivo.

  11. Non-Invasive Monitoring of Temporal and Spatial Blood Flow during Bone Graft Healing Using Diffuse Correlation Spectroscopy.

    Directory of Open Access Journals (Sweden)

    Songfeng Han

    Full Text Available Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10. Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF, a parameter defined to estimate graft-specific changes, was elevated at 1-2 weeks for the autograft group, and at 2-4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05. These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts.

  12. Decreased BMP2 signal in GIT1 knockout mice slows bone healing.

    Science.gov (United States)

    Sheu, T J; Zhou, Wei; Fan, Jin; Zhou, Hao; Zuscik, Michael J; Xie, Chao; Yin, Guoyong; Berk, Bradford C

    2014-12-01

    Endochondral ossification, an important stage of fracture healing, is regulated by a variety of signaling pathways. Transforming growth factor β (TGFβ) superfamily plays important roles and comprises TGFβs, bone morphogenetic proteins (BMPs), and growth differentiation factors. TGFβs primarily regulate cartilage formation and endochondral ossification. BMP2 shows diverse efficacy, from the formation of skeleton and extraskeletal organs to the osteogenesis and remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1 (GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by promoting bone formation and increasing the secretion of vascular endothelial growth factor. Our study examined whether GIT1 regulates fracture healing through the BMP2 signaling pathway and/or through the TGFβ signaling pathway. GIT1 knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8 (pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2 stimulus. We detected no significant change in the pSmad2/3 level after TGFβ1 stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on transcription via pSmad2/3 after TGFβ1 stimulus. Our results indicate that GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2 expression, thus affecting endochondral ossification at the fracture site.

  13. Novel perfused compression bioreactor system as an in vitro model to investigate fracture healing

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    Waldemar eHoffmann

    2015-02-01

    Full Text Available Secondary bone fracture healing is a physiological process that leads to functional tissue regeneration via endochondral bone formation. In vivo studies have demonstrated that early mobilization and the application of mechanical loads enhances the process of fracture healing. However, the influence of specific mechanical stimuli and particular effects during specific phases of fracture healing remain to be elucidated. In this work, we have developed and provided proof-of-concept of an in vitro human organotypic model of physiological loading of a cartilage callus, based on a novel perfused compression bioreactor system (PCB. We then used the fracture callus model to investigate the regulatory role of dynamic mechanical loading. Our findings provide a proof-of-principle that dynamic mechanical loading applied by the PCB can enhance the maturation process of mesenchymal stromal cells towards late hypertrophic chondrocytes and the mineralization of the deposited extracellular matrix. The PCB provides a promising tool to study fracture healing and for the in vitro assessment of alternative fracture treatments based on engineered tissue grafts or pharmaceutical compounds, allowing for the reduction of animal experiments.

  14. The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice.

    Science.gov (United States)

    de Mayo, Tomas; Conget, Paulette; Becerra-Bayona, Silvia; Sossa, Claudia L; Galvis, Virgilio; Arango-Rodríguez, Martha L

    2017-01-01

    Mesenchymal stromal cells (MSCs) have shown to be a promising tool in cell therapies to treat different conditions. Several pre-clinical and clinical studies have proved that the transplantation of MSCs improves wound healing. Here, we compare the beneficial effects of mouse bone marrow-derived allogeneic MSCs (allo-mBM-MSCs) and their acelullar derivatives (allo-acd-mMSCs) on skin wound healing in Non-Obese Diabetic (NOD) mice. One dose of allo-mBM-MSCs (1×106 cells) or one dose of allo-acd-mMSCs (1X) were intradermally injected around wounds in 8-10 week old female NOD mice. Wound healing was evaluated macroscopically (wound closure) every two days, and microscopically (reepithelialization, dermoepidermal junction, skin appendage regeneration, leukocyte infiltration, vascularization, granulation tissue formation, and density of collagen fibers in the dermis) after 16 days of MSC injection. In addition, we measured growth factors and specific proteins that were present in the allo-acd-mMSCs. Results showed significant differences in the wound healing kinetics of lesions that received allo-acd-mMSCs compared to lesions that received vehicle or allo-mBM-MSCs. In particular, mice treated with allo-acd-mMSCs reached significantly higher percentages of wound closure at day 4, 6 and 8, relative to the allo-mBM-MSCs and vehicle groups (p wound closure percentages could not be statistically distinguished between the allo-mBM-MSCs and vehicle groups. Also, allo-acd-mMSCs had a greater influence in the skin would healing process. Specifically, they caused a less pronounced inflammatory severe response (p wound healing such as IGF-1, KGF, HGF, VEGF, ANG-2, MMP-1, CoL-1 and PGE2. Compared to allo-acd-mMSCs, the administration of allo-mBM-MSCs is insufficient for wound healing in diabetic mice and delays the therapeutic effect, which maybe explained by the fact that trophic factors secreted by MSCs are critical for skin regeneration, and not the cells per se, suggesting that

  15. Effect of the attachment remnant preservation on tendon-bone healing in a rabbit model of anterior cruciate ligament reconstruction%保留残迹对前交叉韧带移植物腱骨愈合影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    赵宗峤; 吴波; 李士光; 孙磊

    2012-01-01

    目的 探讨保留残迹重建前交叉韧带对移植物腱骨愈合的影响.方法 32只新西兰兔一期行双侧前交叉韧带重建术,一侧保留残端纤维,对侧切除残端纤维.重建术后6、12、18及24周时,采用HE染色、甲苯胺蓝染色观测,分析移植物腱骨愈合变化情况.结果 重建术后各观察时间点上,保留残迹组移植物腱骨界面组织构建更接近正常,术后24周时保留残迹组腱骨界面软骨细胞含量明显高于切除残迹组[(56.5±2.4) vs (45.7±2.7),P<0.05].结论 保留残迹重建前交叉韧带有助于移植物腱骨愈合.%Objective To investigate the effect of attachment remnant preservation on the healing of tendon-bone interface in a rabbit model of anterior cruciate ligament (ACL) reconstruction. Methods 32 New Zealand rabbits were involved and both knees of each rabbit received transection of anterior cruciate ligament simultaneously. ACL of one knee was reconstructed with preservation of the residual portion of ligament, and the contralateral one was reconstructed with excision of the remnant. At6, 12, 18, and 24 weeks after reconstruction, the healing status and morphology of tendon-bone interface were observed in vitro by hemaetoxylin-eosin staining and Toluidine Blue staining. Results At each observation time point, the morphology and structure of tendon-bone interface in the remnant-preserved group were improved similar to normal, and the number of chondrocytes at the interface was significantly increased in the remnant-preserved group compared with that of control group [ (56. 5 ±2. 4) vs (45. 7 ±2. 7) , P <0. 05]. Conclusions The preservation of attachment remnant in anterior cruciate ligament reconstruction could enhance the healing of tendon-bone interface.

  16. Models of wound healing: an emphasis on clinical studies.

    Science.gov (United States)

    Wilhelm, K-P; Wilhelm, D; Bielfeldt, S

    2017-02-01

    The healing of wounds has always provided challenges for the medical community whether chronic or acute. Understanding the processes which enable wounds to heal is primarily carried out by the use of models, in vitro, animal and human. It is generally accepted that the use of human models offers the best opportunity to understand the factors that influence wound healing as well as to evaluate efficacy of treatments applied to wounds. The objective of this article is to provide an overview of the different methodologies that are currently used to experimentally induce wounds of various depths in human volunteers and examines the information that may be gained from them. There is a number of human volunteer healing models available varying in their invasiveness to reflect the different possible depth levels of wounds. Currently available wound healing models include sequential tape stripping, suction blister, abrasion, laser, dermatome, and biopsy techniques. The various techniques can be utilized to induce wounds of variable depth, from removing solely the stratum corneum barrier, the epidermis to even split-thickness or full thickness wounds. Depending on the study objective, a number of models exist to study wound healing in humans. These models provide efficient and reliable results to evaluate treatment modalities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Bone healing at implants with a fluoride-modified surface: an experimental study in dogs.

    Science.gov (United States)

    Berglundh, T; Abrahamsson, I; Albouy, J-P; Lindhe, J

    2007-04-01

    The aim of the present experiment was to study early stages of osseointegration to implants with a fluoride-modified surface. Six mongrel dogs, about 1-year old, were used. All mandibular premolars and the first mandibular molars were extracted. Three months later, mucoperiosteal flaps were elevated in one side of the mandible and six sites were identified for implant placement. The control implants (MicroThread) had a TiOblast surface, while the test implants (OsseoSpeed) had a fluoride-modified TiOblast surface. Both types of implants had a similar geometry, a diameter of 3.5 mm and were 8 mm long. Following installation, cover screws were placed and the flaps were adjusted and sutured to cover all implants. Four weeks after the first implant surgery, the installation procedure was repeated in the opposite side of the mandible. Two weeks later, biopsies were obtained and prepared for histological analysis. The void that occurred between the cut bone wall of the recipient site and the macro-threads of the implant immediately following implant installation was used to study early bone formation. It was demonstrated that the amount of new bone that formed in the voids within the first 2 weeks of healing was larger at fluoride-modified implants (test) than at TiOblast (control) implants. It was further observed that the amount of bone-to-implant contact that had been established after 2 weeks in the macro-threaded portion of the implant was significantly larger at the test implants than at the controls. It is suggested that the fluoride-modified implant surface promotes osseointegration in the early phase of healing following implant installation.

  18. Great increase in bone 66 kDa protein and osteocalcin at later stages with healing rat fractures: effect of zinc treatment.

    Science.gov (United States)

    Igarashi, Aki; Yamaguchi, Masayoshi

    2003-02-01

    Fracture healing has been demonstrated to increase production of bone growth factors, and this elevation has been shown to be enhanced by zinc treatment. Moreover, the effect of zinc treatment on production of bone osteocalcin, which is a kind of Ca2+-binding protein localized in bone matrix, at the later stages with bone fracture was investigated. Rats were sacrificed 7 (earlier stage) or 21 (later stage) days after fracture of femoral diaphysis. Femoral-diaphyseal tissues with fracture healing were cultured in a serum-free medium for 24 h. Many proteins in the bone tissues were released into the medium. Bone protein production was markedly elevated 21 days after bone fracture as compared with that of 7 days. A approximately 66 kDa protein molecule, a major protein component which was produced by the diaphyseal tissues during fracture healing, was predominantly increased at the later stages with fracture healing. Bone osteocalcin production was significantly increased during fracture healing. This increase was enhanced at the later stages with fracture healing. The presence of zinc acexamate (10(-4) M) in culture medium caused a significant increase in bone protein and osteocalcin production at 7 or 21 days after bone fracture. The effect of zinc acexamate in increasing bone total protein and osteocalcin production was remarkable at the later stages with fracture healing. Moreover, zinc treatment caused a significant increase in alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium content in the femoral-diaphyseal tissues of the later stages with fracture healing in vitro. The present study demonstrates that bone protein production is markedly increased at the later stages with fracture healing, and that zinc treatment can enhance production of bone protein components including osteocalcin in vitro. Zinc treatment may stimulate the healing of femoral fracture at earlier and later stages.

  19. [Bone fracture and the healing mechanisms. Fragility fracture and bone quality].

    Science.gov (United States)

    Mawatari, Taro; Iwamoto, Yukihide

    2009-05-01

    Fracture occurs in bone having less than normal elastic resistance without any violence. Numerous terms have been used to classify various types of fractures from low trauma events; "fragility fracture", "stress fracture", "insufficiency fracture", "fatigue fracture", "pathologic fracture", etc. The definitions of these terms and clinical characteristics of these fractures are discussed. Also state-of-the-art bone quality assessments; Finite element analysis of clinical CT scans, assessments of the Microdamage, and the Cross-links of Collagen are introduced in this review.

  20. Chondrocyte BMP2 signaling plays an essential role in bone fracture healing.

    Science.gov (United States)

    Mi, Meng; Jin, Hongting; Wang, Baoli; Yukata, Kiminori; Sheu, Tzong-Jen; Ke, Qiao Han; Tong, Peijian; Im, Hee-Jeong; Xiao, Guozhi; Chen, Di

    2013-01-10

    The specific role of endogenous Bmp2 gene in chondrocytes and in osteoblasts in fracture healing was investigated by generation and analysis of chondrocyte- and osteoblast-specific Bmp2 conditional knockout (cKO) mice. The unilateral open transverse tibial fractures were created in these Bmp2 cKO mice. Bone fracture callus samples were collected and analyzed by X-ray, micro-CT, histology analyses, biomechanical testing and gene expression assays. The results demonstrated that the lack of Bmp2 expression in chondrocytes leads to a prolonged cartilage callus formation and a delayed osteogenesis initiation and progression into mineralization phase with lower biomechanical properties. In contrast, when the Bmp2 gene was deleted in osteoblasts, the mice showed no significant difference in the fracture healing process compared to control mice. These findings suggest that endogenous BMP2 expression in chondrocytes may play an essential role in cartilage callus maturation at an early stage of fracture healing. Our studies may provide important information for clinical application of BMP2.

  1. Efficacy of healing process of bone defects after apicectomy: results after 6 and 12 months.

    Science.gov (United States)

    Dominiak, M; Lysiak-Drwal, K; Gedrange, T; Zietek, M; Gerber, H

    2009-12-01

    The aim of this study was to assess the efficacy of selected surgical treatment techniques of bone defects after apectomy. A total of 106 postresection bone defects, located in maxilla and mandible were included in the study: the defects were treated with resorbable collagen membrane (BG I- 26 defects), xenogenic bovine material (BOC II- 30 defects) and xenogenic bovine material with platelet rich plasma (BOC/PRP III- 20 defects). In the control group the defects were left to heal spontaneously. Clinical and radiological assessment was performed at 6 and 12 months after the procedures. The analysis among groups revealed higher efficiency of the method of treatment that uses guide bone regeneration in comparison to the group in both post-operative control periods. After 6 months, the differences were statistically significant for each group using the regeneration methods, but after 12 months only for the BOC/PRP group. Treatment using selected guided bone regeneration techniques proved superior to the control group in both observation periods, but after 6 as well 12 months the best results in the BOC/PRP group were observed.

  2. Inflammatory response and bone healing capacity of two porous calcium phosphate ceramics in critical size cortical bone defects.

    Science.gov (United States)

    Chatterjea, Anindita; van der Stok, Johan; Danoux, Charlène B; Yuan, Huipin; Habibovic, Pamela; van Blitterswijk, Clemens A; Weinans, Harrie; de Boer, Jan

    2014-05-01

    In the present study, two open porous calcium phosphate ceramics, β-tricalcium phosphate (β-TCP), and hydroxyapatite (HA) were compared in a critical-sized femoral defect in rats. Previous comparisons of these two ceramics showed significantly greater osteoinductive potential of β-TCP upon intramuscular implantation and a better performance in a spinal fusion model in dogs. Results of the current study also showed significantly more bone formation in defects grafted with β-TCP compared to HA; however, both the ceramics were not capable of increasing bone formation to such extend that it bridges the defect. Furthermore, a more pronounced degradation of β-TCP was observed as compared to HA. Progression of inflammation and initiation of new bone formation were assessed for both materials at multiple time points by histological and fluorochrome-based analyses. Until 12 days postimplantation, a strong inflammatory response in absence of new bone formation was observed in both ceramics, without obvious differences between the two materials. Four weeks postimplantation, signs of new bone formation were found in both β-TCP and HA. At 6 weeks, inflammation had subsided in both ceramics while bone deposition continued. In conclusion, the two ceramics differed in the amount of bone formed after 8 weeks of implantation, whereas no differences were found in the duration of the inflammatory phase after implantation or initiation of new bone formation.

  3. Evaluation of bone-tendon junction healing using water jet ultrasound indentation method.

    Science.gov (United States)

    Lu, Min-Hua; Zheng, Yong-Ping; Lu, Hong-Bin; Huang, Qing-Hua; Qin, Ling

    2009-11-01

    The re-establishment of bone-tendon junction (BTJ) tissues with the junction, characterized as a unique transitional fibrocartilage zone, is involved in many trauma and reconstructive surgeries. Experimental and clinical findings have shown that a direct BTJ repair requires a long period of immobilization, which may be associated with a postoperative weak knee. Therefore, it is necessary to evaluate the morphologic and mechanical properties of BTJ tissues in situ to better understand the healing process for the purpose of reducing the adverse effects of immobilization. We previously reported a noncontact ultrasound water jet indentation system for measuring and mapping tissue mechanical properties. The key idea was to utilize a water jet as an indenter as well as the coupling medium for high-frequency ultrasound. In this article, we used ultrasound water jet indentation to evaluate the BTJ healing process. The system's capability of measuring the material elastic modulus was first validated using tissue-mimicking phantoms. Then it was employed to assess the healing of the BTJ tissues after partial patellectomy over time on twelve 18-week-old female New Zealand White rabbits. It was found that in comparison with the normal control samples, the elastic modulus of the fibrocartilage of the postoperative samples was significantly smaller, while its thickness increased significantly. Among the postoperative sample groups, the elastic modulus of the fibrocartilage of the samples harvested at week 18 was significantly higher than those harvested at week 6 and week 12, which was even comparable with the value of the control samples at the same sacrifice time. The results suggested that the noncontact ultrasound water jet indentation system provided a nondestructive way to evaluate the material properties of small animal tissues in situ and thus had the ability to evaluate the healing process of BTJ.

  4. Effect of Combined Calcium Hydroxide and Accelerated Portland Cement on Bone Formation and Soft Tissue Healing in Dog Bone Lesions

    Directory of Open Access Journals (Sweden)

    Khorshidi H

    2015-09-01

    Full Text Available Statement of Problem: Recent literatures show that accelerated Portland cement (APC and calcium hydroxide Ca (OH2 may have the potential to promote the bone regeneration. However, certain clinical studies reveal consistency of Ca (OH2, as one of the practical drawbacks of the material when used alone. To overcome such inconvenience, the combination of the Ca (OH2 with a bone replacement material could offer a convenient solution. Objectives: To evaluate the soft tissue healing and bone regeneration in the periodontal intrabony osseous defects using accelerated Portland cement (APC in combination with calcium hydroxide Ca (OH2, as a filling material. Materials and Methods: Five healthy adult mongrel dogs aged 2-3 years old (approximately 20 kg in weight with intact dentition and healthy periodontium were selected for this study. Two one-wall defects in both mesial and distal aspects of the 3rd premolars of both sides of the mandible were created. Therefore, four defects were prepared in each dog. Three defects in each dog were randomly filled with one of the following materials: APC alone, APC mixed with Ca (OH2, and Ca (OH2 alone. The fourth defect was left empty (control. Upon clinical examination of the sutured sites, the amount of dehiscence from the adjacent tooth was measured after two and eight weeks, using a periodontal probe mesiodistally. For histometric analysis, the degree of new bone formation was estimated at the end of the eighth postoperative week, by a differential point-counting method. The percentage of the defect volume occupied by new osteoid or trabecular bone was recorded. Results: Measurement of wound dehiscence during the second week revealed that all five APCs had an exposure of 1-2 mm and at the end of the study all samples showed 3-4 mm exposure across the surface of the graft material, whereas the Ca (OH2, control, and APC + Ca (OH2 groups did not show any exposure at the end of the eighth week of the study. The most

  5. Mathematical Model of Bone Regeneration in a Porous Implant

    Science.gov (United States)

    Maslov, L. B.

    2017-07-01

    A mathematical model of the reparative regeneration of bone tissue governed by the law of cell differentiation and action of an external periodic mechanical loading is presented. The model allows one to study the recovery processes of injured human locomotor system elements under a dynamic loading and to theoretically substantiate the choice of an optimum periodic impact on the defective tissues for their fastest and steady healing.

  6. Below the Callus Surface: Applying Paleohistological Techniques to Understand the Biology of Bone Healing in Skeletonized Human Remains.

    Science.gov (United States)

    Assis, Sandra; Keenleyside, Anne

    2016-01-01

    Bone trauma is a common occurrence in human skeletal remains. Macroscopic and imaging scrutiny is the approach most currently used to analyze and describe trauma. Nevertheless, this line of inquiry may not be sufficient to accurately identify the type of traumatic lesion and the associated degree of bone healing. To test the usefulness of histology in the examination of bone healing biology, we used an integrative approach that combines gross inspection and microscopy. Six bone samples belonging to 5 adult individuals with signs of bone trauma were collected from the Human Identified Skeletal Collection from the Museu Bocage (Lisbon, Portugal). Previous to sampling, the lesions were described according to their location, morphology, and healing status. After sampling, the bone specimens were prepared for plane light and polarized light analysis. The histological analysis was pivotal: (1) to differentiate between types of traumatic lesions; (2) to ascertain the posttraumatic interval, and (3) to diagnose other associated pathological conditions. The outer surface of a bone lesion may not give a complete picture of the biology of the tissue's response. Accordingly, microscopic analysis is essential to differentiate, characterize, and classify trauma signs. © 2016 S. Karger AG, Basel.

  7. Augmentation of Bone Tunnel Healing in Anterior Cruciate Ligament Grafts: Application of Calcium Phosphates and Other Materials

    Directory of Open Access Journals (Sweden)

    F. R. Baxter

    2010-01-01

    Full Text Available Bone tunnel healing is an important consideration after anterior cruciate ligament (ACL replacement surgery. Recently, a variety of materials have been proposed for improving this healing process, including autologous bone tissue, cells, artificial proteins, and calcium salts. Amongst these materials are calcium phosphates (CaPs, which are known for their biocompatibility and are widely commercially available. As with the majority of the materials investigated, CaPs have been shown to advance the healing of bone tunnel tissue in animal studies. Mechanical testing shows fixation strengths to be improved, particularly by the application of CaP-based cement in the bone tunnel. Significantly, CaP-based cements have been shown to produce improvements comparable to those induced by potentially more complex treatments such as biologics (including fibronectin and chitin and cultured cells. Further investigation of CaP-based treatment in the bone tunnels during ACL replacement is therefore warranted in order to establish what improvements in healing and resulting clinical benefits may be achieved through its application.

  8. Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis.

    Science.gov (United States)

    Seebach, Elisabeth; Holschbach, Jeannine; Buchta, Nicole; Bitsch, Rudi Georg; Kleinschmidt, Kerstin; Richter, Wiltrud

    2015-07-01

    Large bone defects requiring long-term osteosynthetic stabilization or repeated surgeries show a considerable rate of infection. Mesenchymal stromal cells (MSCs) have been successfully used to enhance bone regeneration, but their powerful immunomodulatory effects may impose an enhanced risk for osteomyelitis development. In order to unravel whether implantation of MSCs aggravates a simultaneous bone infection, a hydrogel-supported osteomyelitis ostectomy model was developed in which rats received a femoral bone defect with rigid plate-fixation. After fibrin-assisted transfer of Staphylococcus aureus (SA), effects of MSC implantation on osteomyelitis development were quantified over 3-4 weeks. All SA-infected animals developed an acute local osteomyelitis with significantly increased blood neutrophil count, abscess formation and bone destruction. MSC-treatment of infected defects aggravated osteomyelitis according to a significantly elevated osteomyelitis score and enhanced distal bone loss with spongy alteration of cortical bone architecture. Increased attraction of macrophages, osteoclasts and regulation of pro- and anti-inflammatory mediators were potential MSC actions. Overall trophic actions of MSCs implanted into non-sterile bone defects may enhance an infection and/or exacerbate osteomyelitis. Studies on antibiotic carrier augmentation or antibiotic treatment are warranted to decide whether MSC implantation is a safe and promising therapy for orthopedic implant-stabilized bone defects at high risk for development of infection.

  9. Review of techniques for monitoring the healing fracture of bones for implementation in an internally fixated pelvis.

    Science.gov (United States)

    Wong, Lydia Chwang Yuh; Chiu, Wing Kong; Russ, Matthias; Liew, Susan

    2012-03-01

    Sacral fractures from high-impact trauma often cause instability in the pelvic ring structure. Treatment is by internal fixation which clamps the fractured edges together to promote healing. Healing could take up to 12 weeks whereby patients are bedridden to avoid hindrances to the fracture from movement or weight bearing activities. Immobility can lead to muscle degradation and longer periods of rehabilitation. The ability to determine the time at which the fracture is stable enough to allow partial weight-bearing is important to reduce hospitalisation time. This review looks into different techniques used for monitoring the fracture healing of bones which could lead to possible methods for in situ and non-invasive assessment of healing fracture in a fixated pelvis. Traditional techniques being used include radiology and CT scans but were found to be unreliable at times and very subjective in addition to being non in situ. Strain gauges have proven to be very effective for accurate assessment of fracture healing as well as stability for long bones with external fixators but may not be suitable for an internally fixated pelvis. Ultrasound provides in situ monitoring of stiffness recovery but only assesses local fracture sites close to the skin surface and has only been tested on long bones. Vibration analysis can detect non-uniform healing due to its assessment of the overall structure but may suffer from low signal-to-noise ratio due to damping. Impedance techniques have been used to assess properties of non-long bones but recent studies have only been conducted on non-biological materials and more research needs to be done before it can be applicable for monitoring healing in the fixated pelvis.

  10. Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Rajnikumar Sangani

    2014-03-01

    Full Text Available Bone marrow stromal cell (BMSC adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38 and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions.

  11. Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells.

    Science.gov (United States)

    Sangani, Rajnikumar; Pandya, Chirayu D; Bhattacharyya, Maryka H; Periyasamy-Thandavan, Sudharsan; Chutkan, Norman; Markand, Shanu; Hill, William D; Hamrick, Mark; Isales, Carlos; Fulzele, Sadanand

    2014-03-01

    Bone marrow stromal cell (BMSC) adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38) and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions.

  12. Vibration acceleration promotes bone formation in rodent models

    Science.gov (United States)

    Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

    2017-01-01

    All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the

  13. Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats

    OpenAIRE

    2010-01-01

    Prostaglandins control osteoblastic and osteoclastic function under physiological or pathological conditions and are important modulators of the bone healing process. The non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and consequently prostaglandins synthesis. Experimental and clinical evidence has indicated a risk for reparative bone formation related to the use of non-selective (COX-1 and COX-2) and COX-2 selective NSAIDs. Ketorolac is a non-selective N...

  14. In vivo tracking of segmental bone defect healing reveals that callus patterning is related to early mechanical stimuli

    Directory of Open Access Journals (Sweden)

    M Mehta

    2012-11-01

    Full Text Available This study addresses the hypothesis that callus formation, patterning, and mineralisation are impaired during the early phase of critical sized bone defect healing, and may relate to inter-fragmentary tissue strains within the bone defect area. Twenty four 12 week old Sprague Dawley rats were used for this study. They were divided into two groups defined by the femur bone defect size: (i 1 mm resulting in normal healing (NH, and (ii a large sized 5 mm defect resulting in critical healing (CH. Callus formation, patterning, and mineralisation kinetics in both groups were examined in the periosteal and osteotomy gap regions using a novel longitudinal study setup. Finite element analyses on µCT generated tomograms were used to determine inter-fragmentary tissue strain patterns and compared to callus formation and patterning over the course of time. Using a novel longitudinal study technique with µCT, in vivo tracking and computer simulation approaches, this study demonstrates that: (i periosteal bone formation and patterning are significantly influenced by bone defect size as early as 2 weeks; (ii osteotomy gap callus formation and patterning are influenced by bone defect size, and adapt towards a non-union in critical cases by deviating into a medullary formation route as early as 2 weeks after osteotomy; (iii the new bone formation in the osteotomy gap enclosing the medullary cavity in the CH group is highly mineralised; (iv inter-fragmentary strain patterns predicted during the very early soft callus tissue phase (less than 2 weeks are concurrent with callus formation and patterning at later stages. In conclusion, bone defect size influences early onset of critical healing patterns.

  15. 99mTC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice

    Institute of Scientific and Technical Information of China (English)

    Zhendong A Zhong; Anderson Peck; Shihong Li; Jeff VanOss; John Snider; Casey J Droscha; Tingtung A Chang; Bart O Williams

    2015-01-01

    99mTc-Methylene diphosphonate (99mTc-MDP) is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography (gamma scintigraphy or SPECT), ex vivo micro-computed tomography, and histology to monitor 99mTc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with 99mTc-MDP at different time points, and quantitated for 99mTc-MDP uptake with a gamma counter. We demonstrated that 99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The 99mTc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. 99mTc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that 99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for 99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.

  16. Effect of bone marrow and low power lasers on fracture healing with destruction of both periosteum and endosteum in rabbits

    Directory of Open Access Journals (Sweden)

    M. G. Thanoon

    2010-01-01

    Full Text Available Ten mature rabbits of local breed were used in this study; weighing between 1.5 to 1.75 kg and aged about 1–2 years. These animals were divided into two equal groups; in group A destruction of both periosteum and endosteum was done one centimeter from each side of mid-shaft femoral bone fracture, then sufficient amount of autogenously bone marrow was injected directly at the fracture site after immobilization by intramedullary pin. In group B a similar procedure was achieved as in group A, but in additional to that He-Ne infrared laser therapy was used for several sessions. The result of radiological findings indicated that, the fracture healing occurred within group B at fifteen weeks, whereas in group A the healing occurred at eighteen weeks after operation. The implantation of autologous bone marrow enhanced the fracture healing, whereas using of combinations of autologous bone marrow and He-Ne infrared laser therapy hastened the healing.

  17. Efficacy of Electrical Stimulators for Bone Healing: A Meta-Analysis of Randomized Sham-Controlled Trials.

    Science.gov (United States)

    Aleem, Ilyas S; Aleem, Idris; Evaniew, Nathan; Busse, Jason W; Yaszemski, Michael; Agarwal, Arnav; Einhorn, Thomas; Bhandari, Mohit

    2016-08-19

    Electrical stimulation is a common adjunct used to promote bone healing; its efficacy, however, remains uncertain. We conducted a meta-analysis of randomized sham-controlled trials to establish the efficacy of electrical stimulation for bone healing. We identified all trials randomizing patients to electrical or sham stimulation for bone healing. Outcomes were pain relief, functional improvement, and radiographic nonunion. Two reviewers assessed eligibility and risk of bias, performed data extraction, and rated the quality of the evidence. Fifteen trials met our inclusion criteria. Moderate quality evidence from 4 trials found that stimulation produced a significant improvement in pain (mean difference (MD) on 100-millimeter visual analogue scale = -7.7 mm; 95% CI -13.92 to -1.43; p = 0.02). Two trials found no difference in functional outcome (MD = -0.88; 95% CI -6.63 to 4.87; p = 0.76). Moderate quality evidence from 15 trials found that stimulation reduced radiographic nonunion rates by 35% (95% CI 19% to 47%; number needed to treat = 7; p < 0.01). Patients treated with electrical stimulation as an adjunct for bone healing have less pain and are at reduced risk for radiographic nonunion; functional outcome data are limited and requires increased focus in future trials.

  18. Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model.

    Science.gov (United States)

    Chen, Guobao; Yang, Li; Lv, Yonggang

    2016-04-01

    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. Healing of bone in the rat following surgery with the erbium-YAG laser

    Science.gov (United States)

    Dickinson, Mark R.; Devlin, Hugh; El Montaser, Monsour A.; Sloan, Philip

    1996-12-01

    Background and objectives: the aim of this study was to examine the pattern of healing in rat calvarial defects prepared with the erbium-YAG laser, using the 'guided tissue regeneration' technique. Materials and method: PTFE membranes were placed over lased skull defects, and the skin wounds sutured. Rats were killed humanely at intervals after surgery, and the skulls processed for paraffin wax histology. A further group of mature rats were also killed humanely and the calvariae removed. Slots were prepared using the erbium-YAG laser and immediately examined under the environmental scanning electron microscope (ESEM) in hydrated conditions, which avoided drying artifacts. Results: An amorphous, mineral-rich carbon layer surrounds the lased bone defect, which in the in vivo experiments was seen as a basophilic zone which was resistant to resorption.

  20. Effect of a Novel Nonviral Gene Delivery of BMP-2 on Bone Healing

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    P. Schwabe

    2012-01-01

    Full Text Available Background. Gene therapeutic drug delivery approaches have been introduced to improve the efficiency of growth factors at the site of interest. This study investigated the efficacy and safety of a new nonviral copolymer-protected gene vector (COPROG for the stimulation of bone healing. Methods. In vitro, rat osteoblasts were transfected with COPROG + luciferase plasmid or COPROG + hBMP-2 plasmid. In vivo, rat tibial fractures were intramedullary stabilized with uncoated versus COPROG+hBMP-2-plasmid-coated titanium K-wires. The tibiae were prepared for biomechanical and histological analyses at days 28 and 42 and for transfection/safety study at days 2, 4, 7, 28, and 42. Results. In vitro results showed luciferase expression until day 21, and hBMP-2-protein was measured from day 2 – day 10. In vivo, the local application of hBMP-2-plasmid showed a significantly higher maximum load after 42 days compared to that in the control. The histomorphometric analysis revealed a significantly less mineralized periosteal callus area in the BMP-2 group compared to the control at day 28. The rt-PCR showed no systemic biodistribution of luciferase RNA. Conclusion. A positive effect on fracture healing by nonviral BMP-2 plasmid application from COPROG-coated implants could be shown in this study; however, the effect of the vector may be improved with higher plasmid concentrations. Transfection showed no biodistribution to distant organs and was considered to be safe.

  1. Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-wei; LI Wei; XU Shao-wen; YANG Di-sheng; WANG Yun; LIN Min; ZHAO Guang-feng

    2005-01-01

    Objective: To evaluate the influence of osteoporosis on the middle and late periods of fracture healing process through observing the histomorphological changes, bone mineral density and biomechanical properties in ovariectomized rats. Methods: Eighty-four female SD rats of 4 months old were randomly divided into osteoporosis group and sham operation group, 42 in each. Rats in osteoporosis group were performed ovariectomy operation while those in sham operation group were given sham operation. A midshaft tibia fracture model was established 10 weeks after ovariectomy. Tibias were harvested 2, 4, 6, 12, 18 weeks after fracture for bone mineral density, histomorphological and biomechanical evaluation. Results: Compared with the sham operation group, callus bone mineral density was 12.8%, 18.0%, 17.0% lower in osteoporosis group 6, 12, 18 weeks after fracture, respectively (P<0.05); callus failure load was 24.3%, 31.5%, 26.6%, 28.8% lower in osteoporosis group, and callus failure stress was 23.9%, 33.6%, 19.1%, 24.9% lower in osteoporosis group 4, 6, 12, 18 weeks after fracture, respectively (P<0.05). In osteoporosis group, endochondral bone formation was delayed, more osteoclast cells could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. Conclusions: Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporotic model. The impairment is considered to be the result of combined effects of prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.

  2. Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

    Directory of Open Access Journals (Sweden)

    D Wulsten

    2011-02-01

    Full Text Available This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5 mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue.Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

  3. Effect of GBR in Combination with Deproteinized Bovine Bone Mineral on the Healing of Calvarial Defects in Rabbits

    OpenAIRE

    Khoshkhoonejad AA.; Miremadi, A.; Rokn AR.; B. Eslami; Dehghan, M.; H. Kalbassi

    2006-01-01

    Statement of problem: The guided bone regeneration (GBR) technique does not always produce consistent results. Bone filling within the space provided by the membrane can be incomplete.Purpose: The aim of this study was to evaluate the effect of a collagen membrane (Bio-Gide) in combination with or without deproteinezed bovine bone mineral (Bio-Oss) on the healing of calvarial defects in rabbits.Materials and Methods: Twelve New Zealand white rabbits were used in this randomized single-blind e...

  4. The rational use of animal models in the evaluation of novel bone regenerative therapies

    OpenAIRE

    Perić, Mihaela; DUMIĆ-ČULE, Ivo; Grčević, Danka; Matijašić, Mario; Verbanac, Donatella; Paul, Ruth; Grgurević, Lovorka; Trkulja, Vladimir; Bagi, Čedo M.; Vukičević, Slobodan

    2015-01-01

    Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poo...

  5. Abnormal joint and bone wound healing in hemophilia mice is improved by extending factor IX activity after hemarthrosis.

    Science.gov (United States)

    Sun, Junjiang; Hua, Baolai; Livingston, Eric W; Taves, Sarah; Johansen, Peter B; Hoffman, Maureane; Ezban, Mirella; Monroe, Dougald M; Bateman, Ted A; Monahan, Paul E

    2016-12-30

    Wound healing requires interactions between coagulation, inflammation, angiogenesis, cellular migration, and proliferation. Healing in dermal wounds of hemophilia B mice is delayed when compared to hemostatically normal wild type (WT) mice, with abnormal persistence of iron deposition, inflammation, and neovascularity. We observed healing following induced joint hemorrhage in WT and factor IX (FIX) knockout (FIX(-/-)) mice, examining also parameters previously studied in an excisional skin wound model. Hemostatically normal mice tolerated this joint bleeding challenge, cleared blood from the joint, and healed with minimal pathology, even if additional autologous blood was injected intra-articularly at the time of wounding. Following hemarthrosis, joint wound healing in hemophilia B mice was impaired and demonstrated similar abnormal histologic features as previously described in hemophilic dermal wounds. Therefore, studies of pathophysiology and therapy of hemophilic joint bleeding performed in hemostatically normal animals are not likely to accurately reflect the healing defect of hemophilia. We additionally explored the hypothesis that the use of a FIX replacement protein with extended circulating FIX activity could improve synovial and osteochondral wound healing in hemophilic mice, when compared to treatment with unmodified recombinant FIX (rFIX) in the established joint bleeding model. Significantly improved synovial wound healing and preservation of normal osteochondral architecture are achieved by extending FIX activity after hemarthrosis using glycoPEGylated FIX when compared to an equivalent dose of rFIX. These results suggest that treating joint bleeding only until hemostasis is achieved may not result in optimal joint healing, which is improved by extending factor activity.

  6. Wound healing and hyper-hydration: a counterintuitive model.

    Science.gov (United States)

    Rippon, M G; Ousey, K; Cutting, K F

    2016-02-01

    Winter's seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle, confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model 'hyper-hydration' of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration. Declaration of interest: K. Cutting is a Clinical Research Consultant to the medical device and biotechnology industry. M. Rippon is Visiting Clinical Research Fellow, University of Huddersfield and K. Ousey provides consultancy for a range of companies through the University of Huddersfield including consultancy services for Paul Hartmann Ltd on HydroTherapy products.

  7. [Healing of osseous defects by guided bone regeneration using ribose cross linked collagen membranes].

    Science.gov (United States)

    Tal, H

    2004-07-01

    The ultimate goal of periodontal therapy has long been the complete regeneration of the periodontal attachment apparatus. Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) are two regenerative procedures which converted this goal from a dream to reality. In search of a biocompatible resorbable tissue barrier, collagen, being a natural protein and a weak antigen, has attracted much interest and became the focus of much intention during the 80's and the 90's. The understanding that cross linking of collagen with aldehyde sugars, especially ribose, produces collagen which is highly resistant to resorption in vivo led to the development of a "natural" Crossed-Linked Collagen Barrier (CB-SX). Animal and Human studies have shown that the newly developed membrane is biocompatible, remains intact in the tissues 6 months and more, and results in impressive guided tissue/bone regeneration. Spontaneous early exposure of the membrane is common but the healing potential of the resulted tissue dehiscence is favorable with no tendency for bacterial infection. The commercial version of the CB-SX is especially suitable for GBR procedures; it is highly recommended that the gingival flaps involved will properly be released, will lack tension, and be thoroughly sutured.

  8. A rat uterine horn model of genital tract wound healing.

    Science.gov (United States)

    Schlaff, W D; Cooley, B C; Shen, W; Gittlesohn, A M; Rock, J A

    1987-11-01

    A rat uterine horn model of genital tract wound healing is described. Healing was reflected by acquisition of strength and elasticity, measured by burst strength (BS) and extensibility (EX), respectively. A tensiometer (Instron Corp., Canton, MA) was used to assess these characteristics in castrated and estrogen-supplemented or nonsupplemented animals. While the horn weights (HW), BS, and EX of contralateral horns were not significantly different, the intra-animal variation of HW was 7.2%, BS was 17.7% and EX was 38.2%. In a second experiment, one uterine horn was divided and anastomosed, and the animal given estrogen supplementation or a placebo pellet. Estrogen administration was found to increase BS and EX of anastomosed horns prior to 14 days, but had no beneficial effect at 21 or 42 days. The data suggest that estrogen may be required for optimal early healing of genital tract wounds.

  9. [Effect of combined therapeutic methods on healing of periodontal vertical bone defects in regenerative surgery].

    Science.gov (United States)

    Dori, Ferenc

    2009-03-15

    Several methods are available to enhance the healing and regeneration of periodontal tissues after surgical therapy of intrabony defects. The main indications for the use of combined regenerative procedures are the extent and morphology of the osseous lesions. The six studies of the present dissertation focused on the clinical effect of different barrier techniques, bone substitutes, enamel matrix derivatives and a growth factors containing adjuvant used in various combinations on the healing of severe periodontal intrabony impairments. Synthetic, xenogenetic and autologous materials were used in these randomized clinical studies. Mechanical barriers (polytetrafluoroethylene and collagen membranes) for GTR, biological barriers/enamel matrix proteins (EMD), synthetic (beta-TCP) and xenogeneic (NBM) bone grafts and autologous platelet-rich plasma (PRP) were combined in the test and control groups of the trials. The main clinical variable was the clinical attachment level (CAL) and the subsidiary one was the probing pocket depth (PPD), estimated at baseline and after one year. The summation of the results after the statistical analysis takes cognizance of the followings: a) Each of the eleven regenerative methods evaluated (ten combined procedures) leads to significant CAL gain and PPD decrease. b) Using beta-TCP or NBM with EMD or with PRP+GTR and GTR's, the difference between the parameters of the test and control groups were not statistically significant. c) It was confirmed in four studies that the addition of PRP to graft materials has not increased significantly the positive outcomes independent of the type of barrier or graft. d) Adding platelet-rich plasma to natural bone mineral, no benefit was observed from the point of view of the clinical variables. e) The polypeptide proteins of the platelet-rich plasma do not enhance the clinical regenerative effect of enamel matrix proteins. In conclusion, the option of the periodontal surgeons between these methods

  10. The Healing Web: A Transformative Model for Nursing.

    Science.gov (United States)

    Bunkers, Sandra Schmidt

    1992-01-01

    A Navajo legend describes a web woven by Spider Woman that saved the people during a great flood. This article uses the imagery of the web to help education and service think more clearly about nursing's future. The Healing Web project seeks to educate nurses in a futuristic differentiated model. (Author/JOW)

  11. Experimental evaluation of the effects of Ankaferd Blood Stopper and collagenated heterologous bone graft on bone healing in sinus floor augmentation.

    Science.gov (United States)

    Cakir, Merve; Karaca, İnci Rana; Firat, Ayşegül; Kaymaz, Figen; Bozkaya, Suleyman

    2015-01-01

    The aim of this study was to evaluate the effect of collagenated heterologous bone graft (CHBG) and Ankaferd Blood Stopper (ABS), a plant extract, on bone healing after sinus floor augmentation. Thirty-six New Zealand rabbits were used. Bilateral sinus augmentation was performed, and 72 bone defects were created. The maxillary sinuses were grafted with four different biomaterials: blood clot (control group), CHBG (Apatos Mix, OsteoBiol, Tecnoss) (graft group), ABS (ABS group), and ABS + CHBG (ABS+graft group). The rabbits were sacrificed at 1, 4, and 8 weeks after surgery. Histochemical and immunohistochemical examinations were performed on all samples. Staining with hematoxylin-eosin and Masson trichrome was performed, and bone marker activity was evaluated. Lymphocyte infiltration was high at the first week in all groups and decreased from 1 to 8 weeks. All materials were biocompatible. Osteoclast numbers increased in the control group from 1 to 8 weeks and decreased in the other groups. There was no new bone formation in week 1 in all groups. New bone formation increased in all groups from 1 to 8 weeks, and at the fourth week, new bone formation was greater in the ABS and ABS+graft groups than in the other groups. There were osteoclasts around the bone graft materials, but degeneration of the graft was seen only in the ABS+graft group at week 8. ABS accelerates bone healing in sinus augmentation procedures and can be used alone or with CHBG. CHBG has osteoconductive properties, and ABS can accelerate bone graft degeneration.

  12. Mathematical model for bone mineralization

    Directory of Open Access Journals (Sweden)

    Svetlana V Komarova

    2015-08-01

    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.

  13. Human amniotic membrane, best healing accelerator, and the choice of bone induction for vestibuloplasty technique (an animal study

    Directory of Open Access Journals (Sweden)

    Ahad Khoshzaban

    2010-12-01

    Full Text Available Mohammad H Samandari1, Shahriar Adibi2, Ahad Khoshzaban3, Sara Aghazadeh5, Parviz Dihimi4, Siamak S Torbaghan6, Saeed H Keshel5, Zohreh Shahabi71Department of Oral and Maxillofacial Surgery, Dentistry Faculty, 2Dental Research of Torabinejad Research Centre, 3Iranian Tissue Bank Research and Preparation Centre, Imam Khomeini Hospital Complex, 4Department of Oral and Maxillofacial Pathology, Dentistry Faculty, Isfahan University of Medical Sciences, Isfahan, Iran; 5Stem Cells Preparation Unit, Eye Research Center, Farabi Hospital, 6Department of Pathology, Imam Khomeini Medical Centre, 7BMT Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranObjective: To investigate the effects of amniotic membrane (AM in bone induction and wound healing after vestibuloplasty surgery on animal samples while receptacle proteins such as growth factors were considered as accelerators for wound healing and bone induction after these operations.Material and methods: Ten adult dogs (5 females, 5 males; race, Iranian mixed; weight, 44 pounds were included, which underwent surgery for transplantation on mandible and maxillary. AM was used for promoting bone induction and healing.Results: The tissue samples were obtained after 2, 8, and 12 weeks for histology survey. No significant differences were observed between male and female or left and right jaws. AM decreased fibrinoleukocytic exudates and inflammation in the experimental group, had significant effects on bone formation, considerably improves wound healing, and gives rise to bone induction (P < 0.0001.Conclusions: Our study findings indicate that the AM is a suitable cover for different injuries and acellular AM has the potential for rapid improvement and bone induction. The AM contains collagen, laminin, and fibronectin, which provide an appropriate substrate for bone induction. This substrate promoted bone induction and might contribute to induction of the progenitor cells and/or stem

  14. An Activin A/BMP2 chimera displays bone healing properties superior to those of BMP2

    Science.gov (United States)

    Yoon, Byung-Hak; Esquivies, Luis; Ahn, Chihoon; Gray, Peter C.; Ye, Sang-kyu; Kwiatkowski, Witek; Choe, Senyon

    2014-01-01

    Recombinant Bone Morphogenetic Protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10-fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 Å that reveals a distinct BMP2-like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100-fold greater than that of BMP2. The structure also led to our identification of a single Activin A-derived amino acid residue which when mutated to the corresponding BMP2 residue resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non-union bone fractures. PMID:24692083

  15. An activin A/BMP2 chimera, AB204, displays bone-healing properties superior to those of BMP2.

    Science.gov (United States)

    Yoon, Byung-Hak; Esquivies, Luis; Ahn, Chihoon; Gray, Peter C; Ye, Sang-Kyu; Kwiatkowski, Witek; Choe, Senyon

    2014-09-01

    Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10-fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 Å that reveals a distinct BMP2-like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100-fold greater than that of BMP2. The structure also led to our identification of a single Activin A-derived amino acid residue, which, when mutated to the corresponding BMP2 residue, resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non-union bone fractures.

  16. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available Growing evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs enhance wound repair via paracrine. Because the extent of environmental oxygenation affects the innate characteristics of BM-MSCs, including their stemness and migration capacity, the current study set out to elucidate and compare the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of BM-MSC-derived paracrine molecules (e.g., cytokines, growth factors and chemokines that hypothetically contribute to cutaneous wound healing in vivo. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA analyses of normoxic and hypoxic BM-MSCs and their conditioned medium fractions showed that the stem cells expressed and secreted significantly higher amounts of basic fibroblast growth factor (bFGF,vascular endothelial growth factor A (VEGF-A interleukin 6 (IL-6 and interleukin 8 (IL-8 under hypoxic conditions. Moreover, hypoxic BM-MSC-derived conditioned medium (hypoCM vs. normoxic BM-MSC-derived conditioned medium (norCM or vehicle control medium significantly enhanced the proliferation of keratinocytes, fibroblasts and endothelial cells, the migration of keratinocytes, fibroblasts, endothelial cells and monocytes, and the formation of tubular structures by endothelial cells cultured on Matrigel matrix. Consistent with these in vitro results, skin wound contraction was significantly accelerated in Balb/c nude mice treated with topical hypoCM relative to norCM or the vehicle control. Notably increased in vivo cell proliferation, neovascularization as well as recruitment of inflammatory macrophages and evidently decreased collagen I, and collagen III were also found in the hypoCM-treated group. These findings suggest that BM-MSCs promote murine skin wound healing via hypoxia-enhanced paracrine.

  17. Bone Healing Improvements Using Hyaluronic Acid and Hydroxyapatite/Beta-Tricalcium Phosphate in Combination: An Animal Study

    Science.gov (United States)

    Chang, Yen-Lan; Lo, Yi-June; Huang, Yu-Chih; Tsai, Hsin-Yuan; Lin, Che-Tong; Fan, Kan-Hsin

    2016-01-01

    The purpose of this study was to investigate whether the use of HLA as an aqueous binder of hydroxyapatite/beta-tricalcium phosphate (HA-βTCP) particles can reduce the amount of bone graft needed and increase ease of handling in clinical situations. In this study, HA/βTCP was loaded in commercially available crosslinking HLA to form a novel HLA/HA-βTCP composite. Six New Zealand White rabbits (3.0–3.6 kg) were used as test subjects. Four 6 mm defects were prepared in the parietal bone. The defects were filled with the HLA/HA-βTCP composite as well as HA-βTCP particle alone. New bone formation was analyzed by micro-CT and histomorphometry. Our results indicated that even when the HA-βTCP particle numbers were reduced, the regenerative effect on bone remained when the HLA existed. The bone volume density (BV/TV ratio) of HLA/HA-βTCP samples was 1.7 times larger than that of the control sample at week 2. The new bone increasing ratio (NBIR) of HLA/HA-βTCP samples was 1.78 times higher than the control group at week 2. In conclusion, HA-βTCP powder with HLA contributed to bone healing in rabbit calvarial bone defects. The addition of HLA to bone grafts not only promoted osteoconduction but also improved handling characteristics in clinical situations. PMID:28070520

  18. The efficacy of hydrothermally obtained carbonated hydroxyapatite in healing alveolar bone defects in rats with or without corticosteroid treatment

    Directory of Open Access Journals (Sweden)

    Marković Dejan

    2014-01-01

    Full Text Available Background/Aim. Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histopathologic methods. Methods. Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50-250 μm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. Results. The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material’s particles took place after 25 weeks. Conclusion. Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects. [Projekat Ministarstva nauke Republike Srbije, br. 172026

  19. Effect of platelet-rich plasma and fibrin glue on healing of critical-size calvarial bone defects.

    Science.gov (United States)

    Findikcioglu, Kemal; Findikcioglu, Fulya; Yavuzer, Reha; Elmas, Cigdem; Atabay, Kenan

    2009-01-01

    Despite the insufficient number of experimental studies, platelet-rich plasma (PRP) including high amounts of growth factors is introduced to clinical use rapidly. The aim of this study was to compare the effects of PRP and platelet-poor plasma (PPP) on healing of critical-size bone defects.Bilateral full-thickness, critical-size bone defects were created in the parietal bones of 32 rabbits, which had been studied in 4 groups. Saline, thrombin solution, PPP, and PRP were applied to the created defects before closure. Radiologic defect area measurement results at 0, 4, and 16 weeks were compared between the groups. In addition, densities of the newly formed bones at 16th week were studied. Histologic parameters (primary and secondary bone trabecula, neovascularization, and bone marrow and connective tissue formation) were compared between 4- and 16-week groups.More rapid decrease in defect size was observed in groups 3 and 4 than in groups 1 and 2, both in the 4th and 16th weeks. Newly formed bone densities were also found to be higher in these 2 groups. New bone formation was detected to be more rapid considering histologic parameters, in groups 3 and 4 at 4th and 16th weeks.Study demonstrates that PRP and PPP might have favorable effects on bone healing. Although we cannot reveal any statistical difference between these 2 substances considering osteoinductive potential, PRP group has demonstrated superior results compared with fibrin glue group. Higher platelet concentrations may expose beneficial effects of PRP.

  20. Oncologic doses of zoledronic acid induce site specific suppression of bone modelling in rice rats.

    Science.gov (United States)

    Exposto, C R; Oz, U; Callard, J S; Allen, M J; Khurana, H; Atri, A D'; Mo, X; Fernandez, S A; Tatakis, D N; Edmonds, K; Westgate, P M; Huja, S S

    2017-06-01

    To examine the effect of zoledronic acid (ZOL) on cortical bone modelling and healing of extraction sockets in the jaw bones of a rodent model. We hypothesized ZOL suppresses both the bone formation in the modelling mode in the jaw bones and alters the extraction site healing. Rice rats were administered saline solution and two dose regimens of ZOL: 0.1 mg/kg, twice a week, for 4 weeks (n=17, saline=8 & ZOL=9) and a higher dose of 0.4 mg/kg, weekly, for 9 weeks (n=30, saline=15 & ZOL=15). Two pairs of fluorochrome bone labels were administered. Extraction of maxillary teeth was performed in maxilla. Mineral apposition rate, mineralizing surface and bone formation rate (BFR) were quantified on periodontal (PDL), alveolar and basal bone surfaces, and in the trabecular bone of proximal tibia. Bone volume (BV) was evaluated at extraction sockets. Multivariate Gaussian models were used to account for repeated measurements, and analyzes were conducted in SAS V9.3. ZOL suppressed bone modelling (BFR/BS) at the PDL surfaces in the mandible (Pmodelling mode in the jaws demonstrates the site specific effects of ZOL in rice rats. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. [Present status of research in bone marrow-derived mesenchymal stem cells for promoting the healing of diabetic ulcer].

    Science.gov (United States)

    Zheng, Shu-Juan; Jia, Chi-Yu

    2012-08-01

    The delayed healing of diabetic ulcer has been haunting the surgeons and researchers for a long time. Although we have been researching and exploring the effective therapies for many years, the progress has been limited. Bone marrow-derived mesenchymal stem cells (BMSCs) have gradually won worldwide attention for their characteristics of differentiating into tissue repair cells and secreting multiple cytokines as well as growth factors. In recent years, the role of BMSCs in the treatment of diabetic ulcer has been drawing more and more attention. This article reviewed the advancement in the research of BMSCs in promoting the healing of diabetic ulcer. Through a discussion of the treatment of diabetic ulcer, the related research in BMSCs, as well as its role in diabetic ulcer treatment, the mechanism of BMSCs in promoting healing of diabetic ulcers is discussed. We expect through further research, unified criteria for the quality of BMSCs, application approach and dosage of BMSCs could be established.

  2. Calvarial bone wound healing: a comparison between carbide and diamond drills, Er:YAG and Femtosecond lasers with or without BMP-7.

    Science.gov (United States)

    Cloutier, Martin; Girard, Bruno; Peel, Sean A F; Wilson, David; Sándor, George K B; Clokie, Cameron M L; Miller, Dayne

    2010-12-01

    This study compared the healing of 2 laser ablation units, erbium YAG and femtosecond lasers versus conventional mechanical cutting with carbide and diamond drills to explore future applications for bone surgery. The effects of laser or mechanical ablation combined with rhBMP-7 were also investigated. Following defect standardization, a full-thickness circular defect was created on the parietal bones of 160 mice divided into 4 groups: carbide drill, diamond drill, erbium YAG laser, and femtosecond laser. Each of the 4 ablation groups was treated with and without BMP 7. Hard tissue healing was assessed using microcomputerized tomography at 3 and 12 weeks postsurgical time points. The femtosecond laser created wounds that showed slightly delayed bone healing during the observation period when compared with mechanical drilling, although the difference was not statistically significant. The Er:YAG laser showed a healing rate similar to that of the mechanically ablated groups. When BMP 7 was added to the surgical sites, bone wound closure occurred at a similar rate in all test groups. The femtosecond and Er:YAG lasers are 2 laser modalities suitable for bone ablation that are comparable to mechanical instrumentation in terms of bone healing. This study suggested that BMP-7 may be used to enhance bone healing with success regardless of the ablative modality used, whether laser or mechanical drilling. Copyright © 2010 Mosby, Inc. All rights reserved.

  3. Multiscale Modeling of Bone

    Science.gov (United States)

    2014-12-01

    stiffnesses are in GPa. Location Femm Tibia Femur Femur Method illtrasound Mechanical illtrasound illtrasound Preferential Model Testing 95%EFM...0.2654 Femoral Neck [103] 0.2067 0.172 Femoral Head [104] 0.27 0.2 Distal Femm [105] 0.27 0.19 Proximal Femur [105] 0.105 Greater Trochanter [103...stiffer in compression than tension for all models. Additionally, the distal and proximal femm is stiffer than both the femoral neck and head. This is

  4. Three-dimensional percolation modeling of self-healing composites.

    Science.gov (United States)

    Dementsov, Alexander; Privman, Vladimir

    2008-08-01

    We study the self-healing process of materials with embedded "glue"-carrying cells, in the regime of the onset of the initial fatigue. Three-dimensional numerical simulations within the percolation-model approach are reported. The main numerical challenge taken up in the present work has been to extend the calculation of the conductance to three-dimensional lattices. Our results confirm the general features of the process: The onset of material fatigue is delayed, by development of a plateaulike time dependence of the material quality. We demonstrate that, in this low-damage regime, the changes in the conductance and thus in similar transport and response properties of the material can be used as measures of the material quality degradation. A new feature found for three dimensions, where it is much more profound than in earlier-studied two-dimensional systems, is the competition between the healing cells. Even for low initial densities of the healing cells, they interfere with each other and reduce each other's effective healing efficiency.

  5. Comparison of the Effects of Low-Level Laser Therapy and Ozone Therapy on Bone Healing.

    Science.gov (United States)

    Alan, Hilal; Vardi, Nigar; Özgür, Cem; Acar, Ahmet Hüseyin; Hüseyin, Ahmet; Yolcu, Ümit; Doğan, Derya Ozdemir

    2015-07-01

    This study aims to compare the effect of low-level laser therapy (LLLT) and ozone therapy on the bone healing. Thirty-six adult male Wistar albino rats were used for this study. Monocortical defects were shaped in right femur of all rats. Defects were filled with nano-hydroxyapatite graft. The animals were divided into 3 groups and each group was than divided into 2 subgroups. Then, LLLT with a diode laser was applied to the first group (G1), ozone therapy was applied to the second group (G2), and no treatment was applied to the third group as a control group (G3). Animals were sacrificed after 4th and 8th weeks and the sections were examined to evaluate the density of the inflammation, the formation of connective tissue, the osteogenic potential, and osteocalcin activity. As a result, there were no significant differences among the groups of 4 weeks in terms of new bone formation. In the immunohistochemical assessment, the number of osteocalcin-positive cells was higher in the laser group compared to the other group of 4 weeks; this difference was statistically significant in the LLLT and ozone groups (P ozone groups; furthermore, there was a statistically significant difference in the LLLT in comparison with the control group at 8th week (P < 0.05). At the same time immunohistochemical assessment showed that osteocalcin-positive cells were considerably higher in G2 than G1 at 8th week (P < 0.05). The findings of this study may be the result of differences in the number of treatment sessions. Further studies are therefore needed to determine the optimal treatment modality.

  6. Power Doppler assessment of the neovascularization during uncomplicated fracture healing of long bones in dogs and cats.

    Science.gov (United States)

    Risselada, Marije; Kramer, Martin; Saunders, Jimmy H; Verleyen, Piet; Van Bree, Henri

    2006-01-01

    The aims of this prospective study were to test the feasibility of assessing neovascularization with power Doppler ultrasonography and to investigate its usefulness to follow fracture healing of long bones in dogs and cats. A total of 51 patients (44 dogs and seven cats) were followed. Fracture types differed from simple to comminuted. Therapy ranged from external coaptation to plate osteosynthesis. Patients were followed with radiography, B-mode real time and power Doppler ultrasonography every 2-4 weeks until the fracture was healed. All fractures healed uneventfully. A semi-quantitative numerical score based on signal intensity, vessel area, and number of Doppler signals was assigned and the mean value was used to compare patients and examinations. Time postoperatively was divided into periods of 10 days. No Doppler signal was present during the first 10 days. The mean of the scores was highest between 11 and 20 days postoperatively and the median of the scores peaked between 21 and 30 days. A gradual decrease was seen thereafter. The mean of the scores was zero at 71-80 days and the median at 51-0 days postoperatively for the grouped results. In all positive power Doppler examinations, signals were present in and close to the callus. In seven patients (five dogs and two cats) signals were also present in the peripheral soft tissues in one of the follow up examinations. The normal healing process of fractured bones can be visualized using power Doppler ultrasonography and follows a distinctive time-dependent pattern.

  7. Biomimetic design of a bacterial cellulose/hydroxyapatite nanocomposite for bone healing applications

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Kristen A., E-mail: kazimmer@vt.edu [Department of Materials Science and Engineering, Virginia Tech, Blacksburg, VA 24060 (United States); School of Biomedical Engineering Sciences, Virginia Tech, Blacksburg, VA 24060 (United States); LeBlanc, Jill M.; Sheets, Kevin T.; Fox, Robert W. [Department of Materials Science and Engineering, Virginia Tech, Blacksburg, VA 24060 (United States); Gatenholm, Paul [Department of Materials Science and Engineering, Virginia Tech, Blacksburg, VA 24060 (United States); School of Biomedical Engineering Sciences, Virginia Tech, Blacksburg, VA 24060 (United States)

    2011-01-01

    This study describes the design and synthesis of bacterial cellulose/hydroxyapatite nanocomposites for bone healing applications using a biomimetic approach. Bacterial cellulose (BC) with various surface morphologies (pellicles and tubes) was negatively charged by the adsorption of carboxymethyl cellulose (CMC) to initiate nucleation of calcium-deficient hydroxyapatite (cdHAp). The cdHAp was grown in vitro via dynamic simulated body fluid (SBF) treatments over a one week period. Characterization of the mineralized samples was done with X-ray Photoelectron Spectroscopy (XPS) and Field Emission Scanning Electron Microscopy (FESEM) with Energy Dispersive Spectroscopy (EDS). The amount of cdHAp observed varied among different samples. XPS demonstrated that the atomic presence of calcium and phosphorus ranged from 0.44 at.% to 7.71 at.% Ca and 0.27 at.% to 11.18 at.% P. The Ca/P overall ratio ranged from 1.22 to 1.92. FESEM images showed that the cdHAp crystal size increased with increasing nanocellulose fibril density. To determine the viability of the scaffolds in vitro, the morphology and differentiation of osteoprogenitor cells was analyzed using fluorescence microscopy and alkaline phosphatase gene expression. The presence of cdHAp crystals on BC surfaces resulted in increased cell attachment.

  8. Bone marrow-derived cells contribute to epithelial engraftment during wound healing.

    Science.gov (United States)

    Borue, Xenia; Lee, Sean; Grove, Joanna; Herzog, Erica L; Harris, Robert; Diflo, Thomas; Glusac, Earl; Hyman, Kevin; Theise, Neil D; Krause, Diane S

    2004-11-01

    Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratin 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.

  9. Monitoring of Postoperative Bone Healing Using Smart Trauma-Fixation Device With Integrated Self-Powered Piezo-Floating-Gate Sensors.

    Science.gov (United States)

    Borchani, Wassim; Aono, Kenji; Lajnef, Nizar; Chakrabartty, Shantanu

    2016-07-01

    Achieving better surgical outcomes in cases of traumatic bone fractures requires postoperative monitoring of changes in the growth and mechanical properties of the tissue and bones during the healing process. While current in-vivo imaging techniques can provide a snapshot of the extent of bone growth, it is unable to provide a history of the healing process, which is important if any corrective surgery is required. Monitoring the time evolution of in-vivo mechanical loads using existing technology is a challenge due to the need for continuous power while maintaining patient mobility and comfort. This paper investigates the feasibility of self-powered monitoring of the bone-healing process using our previously reported piezo-floating-gate (PFG) sensors. The sensors are directly integrated with a fixation device and operate by harvesting energy from microscale strain variations in the fixation structure. We show that the sensors can record and store the statistics of the strain evolution during the healing process for offline retrieval and analysis. Additionally, we present measurement results using a biomechanical phantom comprising of a femur fracture fixation plate; bone healing is emulated by inserting different materials, with gradually increasing elastic moduli, inside a fracture gap. The PFG sensor can effectively sense, compute, and record continuously evolving statistics of mechanical loading over a typical healing period of a bone, and the statistics could be used to differentiate between different bone-healing conditions. The proposed sensor presents a reliable objective technique to assess bone-healing progress and help decide on the removal time of the fixation device.

  10. 组织工程修复肩袖损伤促进腱骨愈合的研究进展%Progress in tissue-engineering for tendon-to-bone healing after rotator cuff repair

    Institute of Scientific and Technical Information of China (English)

    赵晨; 王蕾

    2015-01-01

    Rotator cuff injury, considered as a resource of pain, disability and dyssomnia to serious decline in the quality of life, is a common disorder of the shoulder joint. Basic principles of rotator cuff repair aim at achieving high initial ifxation strength, maintaining mechanical stability and restoring the anatomic healing of the cuff tendon. After the routine surgical procedure for rotator cuff repair, the biology and histology of the normal enthesis are not restored. Tendon-to-bone healing occurs with a ifbrovascular scar tissue interface that is mechanically inferior to the native insertion site, which may lead to high re-rupture rate. For these reasons, new approaches are required to improve structural healing. Tissue engineering strategies have been suggested to improve the biological environment around the bone-tendon interface and to promote regeneration of the native insertion site. Although experimental applications of growth factors and scaffolds on animal models demonstrate promising results, techniques which can be used in human rotator cuff repair are still very limited. Tissue engineering to improve tendon-to-bone healing has bright future and requires more research before its clinical applications. This review will outline therapies of growth factors, scaffolds and stem cells in tendon healing and rotator cuff repair.

  11. Bone compaction enhances implant fixation in a canine gap model

    DEFF Research Database (Denmark)

    Kold, Søren; Rahbek, Ole; Toft, Marianne;

    2005-01-01

    implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm......) were bilaterally inserted into cavities initially expanded to 8 mm diameters in the proximal humeri. Each dog served as its own control; thus, one humerus had the implant cavity prepared with compaction, the other with drilling. Eight dogs were euthanized after 2 weeks, and 7 dogs after 4 weeks. Humeri...... from additional 7 dogs represented time 0. At time 0 a spring-back effect of compacted bone was demonstrated as cavities, initially expanded to 8 mm by compaction, were reduced to a median cavity diameter of 6.6 mm. In contrast, cavities initially expanded to 8 mm by drilling, had a median cavity...

  12. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    Science.gov (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  13. The effects of pentoxifylline adminstration on fracture healing in a postmenopausal osteoporotic rat model

    Science.gov (United States)

    Vashghani Farahani, Mohammad Mahdi; Ahadi, Reza; Abdollahifar, Mohammadamin

    2017-01-01

    Previous studies report positive effects of pentoxifylline (PTX) alone or in combination with other drugs on some pathologic bone diseases as well as an ability to accelerate osteogensis and fracture healing in both animal models and human patients. The aim of this present study was to evaluate the effects of PTX administration on Hounsfield unit and bone strength at catabolic response (bone resorbing) of a fracture in an experimental rat model of ovariectomy induced osteoporosis (OVX-D). Thirty adult female rats were divided into groups as follows: 1 (OVX, control, no treatment); 2 (OVX, sham: daily distilled water); 3 (OVX, daily alendronate: 3 mg/kg); 4 (OVX, twice daily 100 mg/kg PTX) and 5 (OVX, PTX+alenderonate). OVX was induced by bilateral ovariectomy in all rats. A complete standardized osteotomy of the right femur was made after 3.5 months. PTX and alendronate treatments were performed for eight weeks. Then, rats were euthanized and had its right femur subjected to computerized tomography scanning for measuring Hounsfield unit; eventually, the samples were sent for a three point bending test for evaluation of the bone strength. Administration of PTX with 200 mg/kg and alendronate alone and in combination showed no significant alteration in Hounsfield unit and biomechanical properties of repairing callus of the complete osteotomy compared with the control group. Results showed increased bending stiffness and stress high load mean values of repairing complete osteotomy in PTX-treated rats compared to the control OVX-D.

  14. Analyzing the behavior of a porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite for healing of bone defects.

    Science.gov (United States)

    Xiong, Yan; Ren, Cheng; Zhang, Bin; Yang, Hongsheng; Lang, Yun; Min, Li; Zhang, Wenli; Pei, Fuxing; Yan, Yonggang; Li, Hong; Mo, Anchun; Tu, Chongqi; Duan, Hong

    2014-01-01

    The aim of this study was to analyze the behavior of the porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite grafted for bone defect repair through a series of biological safety experiments, animal experiments, and a more than 5-year long clinical follow-up. The biological safety experiments, carried out in accordance with the Chinese Guo Biao and Tolerancing (GB/T)16886 and GB/T16175, revealed that porous n-HA/PA66 composite had no cytotoxicity, no sensitization effect, no pyrogenic reaction, and that its hemolysis rate was 0.59% (less than 5%). Rabbit models of tibia defects with grafted porous n-HA/PA66 composite were established. After 2 weeks, the experiment showed that osteogenesis was detected in the porous n-HA/PA66 composite; the density of new bone formation was similar to the surrounding host bone at 12 weeks. After 26 weeks, the artificial bone rebuilt to lamellar bone completely. In the clinical study, a retrospective review was carried out for 21 patients who underwent serial radiographic assessment after treatment with porous n-HA/PA66 composite grafts following bone tumor resection. All wounds healed to grade A. No postoperative infections, delayed deep infection, nonspecific inflammation, rejection, or fractures were encountered. At a mean follow-up of 5.3 years, the mean Musculoskeletal Tumor Society's (MSTS) 93 score was 29.3 points (range: 28-30 points) and mean radiopaque density ratio was 0.77±0.10. The radiologic analysis showed that porous n-HA/PA66 composite had been completely incorporated with the host bone about 1.5 years later. In conclusion, this study indicated that the porous n-HA/PA66 composite had biological safety, and good biocompatibility, osteoinduction, and osseointegration. Thus, the porous n-HA/PA66 composite is an ideal artificial bone substitute and worthy of promotion in the field.

  15. Characterization of the increase in bone 66 kDa protein component with healing rat fractures: stimulatory effect of zinc.

    Science.gov (United States)

    Igarashi, A; Yamaguchi, M

    2002-05-01

    The characterization of protein components produced from bone tissues with fracture healing was investigated. Weanling rats were sacrificed between 1 and 7 days after the femoral fracture. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. Moreover, when the femoral-diaphyseal tissues with fracture healing were cultured for 24 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that many protein molecules were released from the diaphyseal tissues with fracture healing. Especially, a protein molecule of approximately 66 kDa was markedly increased by fracture healing. This protein molecule was significantly increased, when the diaphyseal tissues with fracture healing were cultured in the presence of zinc acexamate (10(-6)-10(-4) M). Zinc acexamate (10(-4) M)-induced increase in medium 66 kDa protein molecule was significantly inhibited in the presence of actinomycin D (10(-7) M) or cycloheximide (10(-6) M). The zinc effect was completely blocked in the presence of PD98059 (10(-5) M), an inhibitor of MAPK kinase, or staurosporine (10(-6) M), an inhibitor of protein kinase C. The medium 66 kDa protein molecule was significantly elevated in the presence of parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or transforming growth factor-beta (10(-11) M), while 17beta-estradiol (10(-9) M) did not have an effect. The effect of these bone-stimulating factors was equal to the zinc effect. Zinc did not significantly enhance the effect of insulin-like growth factor-I in increasing medium 66 kDa protein molecule. The present study demonstrates that fracture healing increases production of the approximately 66 kDa protein molecule which is a major component produced from femoral-diaphyseal tissues of weanling rats, and that this elevation is enhanced by zinc treatment.

  16. Is there evidence that barrier membranes prevent bone resorption in autologous bone grafts during the healing period? A systematic review

    NARCIS (Netherlands)

    Gielkens, Pepijn F. M.; Bos, Ruud R. M.; Raghoebar, Gerry M.; Stegenga, Boudewijn

    2007-01-01

    Introduction: Autologous bone is considered the "reference standard" for bone-grafting procedures. A barrier membrane covering an autologous bone graft (guided bone regeneration [GBR]) is expected to prevent graft resorption. Good clinical results have been reported for GBR, although potential compl

  17. An extended Cellular Potts Model analyzing a wound healing assay.

    Science.gov (United States)

    Scianna, Marco

    2015-07-01

    A suitable Cellular Potts Model is developed to reproduce and analyze an in vitro wound-healing assay. The proposed approach is able both to quantify the invasive capacity of the overall cell population and to evaluate selected determinants of single cell movement (velocity, directional movement, and final displacement). In this respect, the present CPM allows us to capture differences and correlations in the migratory behavior of cells initially located at different distances from the wound edge. In the case of an undifferentiated extracellular matrix, the model then predicts that a maximal healing can be obtained by a chemically induced increment of cell elasticity and not by a chemically induced downregulation of intercellular adhesive contacts. Moreover, in the case of two-component substrates (formed by a mesh of collagenous-like threads and by a homogeneous medium), CPM simulations show that both fiber number and cell-fiber adhesiveness influence cell speed and wound closure rate in a biphasic fashion. On the contrary, the topology of the fibrous network affects the healing process by mediating the productive directional cell movement. The paper, also equipped with comments on the computational cost of the CPM algorithm, ends with a throughout discussion of the pertinent experimental and theoretical literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells

    Science.gov (United States)

    2016-01-01

    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

  19. Parathyroid Hormone (1-34 Might Not Improve Early Bone Healing after Sinus Augmentation in Healthy Rabbits

    Directory of Open Access Journals (Sweden)

    Jisun Huh

    2017-01-01

    Full Text Available Purpose. This study evaluated the effect of administering intermittent parathyroid hormone [PTH (1-34, henceforth PTH] on the early-stage bone healing of maxillary sinus augmentation in healthy rabbits. Materials and Methods. Bovine bone mineral was grafted on the sinuses of 20 female New Zealand white rabbits. The animals were randomly divided into two groups, PTH (n=10 or saline (n=10, in which either PTH or saline was injected subcutaneously 5 days a week for 2 weeks. Half of the animals in each group were killed at 2 weeks postoperatively and the other half were killed at 4 weeks postoperatively. The dosage of PTH was 10 μg/kg/day. Radiographic and histomorphometric analyses were performed. Result. The new bone area (NBA did not differ significantly between the PTH and saline groups. The NBA in the PTH group in the total augmented area and in the demarcated window, center, and Schneiderian membrane regions increased significantly from 2 to 4 weeks. The number of osteoclasts decreased significantly from 2 to 4 weeks in both groups, with no difference between the two groups. Conclusion. Intermittent PTH might not stimulate new bone formation in healthy rabbits during the first 4 weeks of healing.

  20. Experimental study of bone tissue healing potential%骨组织愈合潜力的实验研究

    Institute of Scientific and Technical Information of China (English)

    辜向东; 郁雪松

    2013-01-01

    近年来,骨生物学研究领域发展迅速。与依靠染色的传统实验方法相比,本研究利用解剖显微镜,相差显微镜,扫描电子显微镜,射线能谱分析的技术手段,对比研究了小鼠颅骨损伤在Dulbecco改良Eagle培养基(DMEM ),成骨细胞培养基(OM ),和二者混合的DMEM /OM 中的愈合情况。结果显示:骨损伤在DMEM /OM中愈合程度最大,生成编织骨;在OM中只在缺损边缘部分愈合;在DMEM 中发生了纤维性愈合。%Research in the field of bone biology is booming in recent years .This study was to compare the healing of neonatal mouse cranial injuries in three different culture media groups :Dulbecco’s Modified Eagle Medium (DMEM) group ,osteogenic medium (OM) group ,and DMEM/OM group ,analyzed with dissecting -microscope ,phase -contrast -microscope ,scanning -electron-microscopy ,and energy -dispersive -X -ray ,compared to traditional Von Kossa stain .The results :injuries in the DMEM/OM group showed the highest degree of healing and formed woven bone .Injuries in the OM group revealed limited bone healing at the edge .Fibrous healing occurred in the DMEM group .

  1. Comparative wound healing--are the small animal veterinarian's clinical patients an improved translational model for human wound healing research?

    Science.gov (United States)

    Volk, Susan W; Bohling, Mark W

    2013-01-01

    Despite intensive research efforts into understanding the pathophysiology of both chronic wounds and scar formation, and the development of wound care strategies to target both healing extremes, problematic wounds in human health care remain a formidable challenge. Although valuable fundamental information regarding the pathophysiology of problematic wounds can be gained from in vitro investigations and in vivo studies performed in laboratory animal models, the lack of concordance with human pathophysiology has been cited as a major impediment to translational research in human wound care. Therefore, the identification of superior clinical models for both chronic wounds and scarring disorders should be a high priority for scientists who work in the field of human wound healing research. To be successful, translational wound healing research should function as an intellectual ecosystem in which information flows from basic science researchers using in vitro and in vivo models to clinicians and back again from the clinical investigators to the basic scientists. Integral to the efficiency of this process is the incorporation of models which can accurately predict clinical success. The aim of this review is to describe the potential advantages and limitations of using clinical companion animals (primarily dogs and cats) as translational models for cutaneous wound healing research by describing comparative aspects of wound healing in these species, common acute and chronic cutaneous wounds in clinical canine and feline patients, and the infrastructure that currently exists in veterinary medicine which may facilitate translational studies and simultaneously benefit both veterinary and human wound care patients.

  2. Acacia honey accelerates in vitro corneal ulcer wound healing model.

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    Abd Ghafar, Norzana; Ker-Woon, Choy; Hui, Chua Kien; Mohd Yusof, Yasmin Anum; Wan Ngah, Wan Zurinah

    2016-07-29

    The study aimed to evaluate the effects of Acacia honey (AH) on the migration, differentiation and healing properties of the cultured rabbit corneal fibroblasts. Stromal derived corneal fibroblasts from New Zealand White rabbit (n = 6) were isolated and cultured until passage 1. In vitro corneal ulcer was created using a 4 mm corneal trephine onto confluent cultures and treated with basal medium (FD), medium containing serum (FDS), with and without 0.025 % AH. Wound areas were recorded at day 0, 3 and 6 post wound creation. Genes and proteins associated with wound healing and differentiation such as aldehyde dehydrogenase (ALDH), vimentin, alpha-smooth muscle actin (α-SMA), collagen type I, lumican and matrix metalloproteinase 12 (MMP12) were evaluated using qRT-PCR and immunocytochemistry respectively. Cells cultured with AH-enriched FDS media achieved complete wound closure at day 6 post wound creation. The cells cultured in AH-enriched FDS media increased the expression of vimentin, collagen type I and lumican genes and decreased the ALDH, α-SMA and MMP12 gene expressions. Protein expression of ALDH, vimentin and α-SMA were in accordance with the gene expression analyses. These results demonstrated AH accelerate corneal fibroblasts migration and differentiation of the in vitro corneal ulcer model while increasing the genes and proteins associated with stromal wound healing.

  3. The effects of supplemental melatonin administration on the healing of bone defects in streptozotocin-induced diabetic rats

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    Senem YILDIRIMTURK

    Full Text Available ABSTRACT Diabetes mellitus (DM causes an increased production of free radicals that can impair bone healing. Melatonin is a hormone secreted mainly by the pineal gland, which participates in the neutralization process of free radicals. Objective The aim of this study was to investigate histologic and biochemical effects of supplemental melatonin administration on bone healing and antioxidant defense mechanism in diabetic rats. Material and Methods Eighty-six Sprague-Dawley male rats were used in this study. Diabetes mellitus was induced by intraperitoneal (i.p. administration of 65 mg/kg streptozotocin (STZ. Surgical bone defects were prepared in the tibia of each animal. Diabetic animals and those in control groups were treated either with daily melatonin (250 μg/animal/day/i.p. diluted in ethanol, only ethanol, or sterile saline solution. Rats were humanely killed at the 10th and 30th postoperative days. Plasma levels of Advanced Oxidation Protein Products (AOPP, Malondialdehyde (MDA, and Superoxide Dismutase (SOD were measured. The number of osteoblasts, blood vessels and the area of new mineralized tissue formation were calculated in histologic sections. Results At the 10th day, DM+MEL (rats receiving both STZ and melatonin group had significantly higher number of osteoblasts and blood vessels as well as larger new mineralized tissue surfaces (p<0.05 for each when compared with DM group. At the 30th day, DM group treated with melatonin had significantly lower levels of AOPP and MDA than those of DM group (p<0.05. Conclusion Melatonin administration in STZ induced diabetic rats reduced oxidative stress related biomarkers and showed beneficial effects on bone healing at short term.

  4. A study of radiological features of healing in long bone fractures among infants less than a year

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    Warner, Christopher; Miller, Angie; Weinman, Jason; Fadell, Michael [Children' s Hospital Colorado, Department of Radiology, Aurora, CO (United States); Maguire, Sabine; Trefan, Laszlo [Cardiff University, Institute of Primary Care and Child Health, Cardiff (United Kingdom)

    2017-03-15

    To create a timetable for dating long bone fractures in infants aged less than 1 year using previously defined radiographic signs of fracture healing. A retrospective cross-sectional time series of long bone fractures in infants aged less than 1 year was conducted from 2006 to 2013. After exclusion criteria were applied 59 digital image series were available for review from 40 infants. Utilizing published criteria for dating fractures, the presence or absence of four pre-defined features of healing was scored: periosteal reaction, callus, bridging, and remodeling. Three radiologists independently scored radiographs with a 3-point scale, marking each feature as present, absent, or equivocal. The times in days when features were first seen, peaked (feature agreed present in >40% of images), and last seen were noted. Statistical analysis using free marginal kappa was conducted. The level of agreement among the three radiologists was high (0.64-0.85). The sequence in which the features were seen was: periosteal reaction range 7-130 (present in the majority of cases between 9 and 49 days); callus range 9-130 (present in the majority of cases between days 9-26); bridging range 15-130 (seen in the majority of cases between 15 and 67 days); remodeling range 51-247 days. This study provides a timetable of radiological features of long bone healing among young infants for the first time. Dating of incomplete long bone fractures is challenging, beyond the presence of periosteal reaction, but a consistent sequence of changes is present in complete fractures. (orig.)

  5. 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

    2016-01-01

    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.

  6. Comparison of crestal bone loss around dental implants placed in healed sites using flapped and flapless techniques: a systematic review.

    Science.gov (United States)

    Vohra, Fahim; Al-Kheraif, Abdulaziz A; Almas, Khalid; Javed, Fawad

    2015-02-01

    The aim of the present systematic review is to compare the crestal bone loss (CBL) around dental implants placed in healed sites using flapped and flapless surgical techniques. The focused question was, "Does flapped and flapless surgical technique influence CBL around dental implants placed in healed sites?" Databases were searched from 1975 up to and including May 2014 using different combinations of the following keywords: "crestal bone loss"; "dental implant"; "surgery"; "flap"; and "flapless." Unpublished data, experimental studies, letters to the editor, review articles, case reports, commentaries, and articles published in languages other than English were excluded. In all studies, the test group comprised implants placed using flapless surgery, and the control group, implants placed after reflection of a full-thickness mucoperiosteal flap. Ten clinical studies were included. In five studies, CBL around implants was comparable between the test and control groups. In four studies, implants in the test group showed significantly less CBL compared with the control group. In one study, CBL was significantly higher in the test group than the control group. CBL around dental implants placed in healed sites using flapped and flapless techniques is comparable.

  7. An Innovative Approach for Enhancing Bone Defect Healing Using PLGA Scaffolds Seeded with Extracorporeal-shock-wave-treated Bone Marrow Mesenchymal Stem Cells (BMSCs)

    Science.gov (United States)

    Chen, Youbin; Xu, Jiankun; Huang, Zhonglian; Yu, Menglei; Zhang, Yuantao; Chen, Hongjiang; Ma, Zebin; Liao, Haojie; Hu, Jun

    2017-01-01

    Although great efforts are being made using growth factors and gene therapy, the repair of bone defects remains a major challenge in modern medicine that has resulted in an increased burden on both healthcare and the economy. Emerging tissue engineering techniques that use of combination of biodegradable poly-lactic-co-glycolic acid (PLGA) and mesenchymal stem cells have shed light on improving bone defect healing; however, additional growth factors are also required with these methods. Therefore, the development of novel and cost-effective approaches is of great importance. Our in vitro results demonstrated that ESW treatment (10 kV, 500 pulses) has a stimulatory effect on the proliferation and osteogenic differentiation of bone marrow-derived MSCs (BMSCs). Histological and micro-CT results showed that PLGA scaffolds seeded with ESW-treated BMSCs produced more bone-like tissue with commitment to the osteogenic lineage when subcutaneously implanted in vivo, as compared to control group. Significantly greater bone formation with a faster mineral apposition rate inside the defect site was observed in the ESW group compared to control group. Biomechanical parameters, including ultimate load and stress at failure, improved over time and were superior to those of the control group. Taken together, this innovative approach shows significant potential in bone tissue regeneration. PMID:28272494

  8. Replacement, refinement, and reduction: necessity of standardization and computational models for long bone fracture repair in animals.

    Science.gov (United States)

    Reifenrath, Janin; Angrisani, Nina; Lalk, Mareike; Besdo, Silke

    2014-08-01

    In the field of fracture healing it is essential to know the impacts of new materials. Fracture healing of long bones is studied in various animal models and extrapolated for use in humans, although there are differences between the micro- and macrostructure of human versus animal bone. Unfortunately, recommended standardized models for fracture repair studies do not exist. Many different study designs with various animal models are used. Concerning the general principles of replacement, refinement and reduction in animal experiments (three "Rs"), a standardization would be desirable to facilitate better comparisons between different studies. In addition, standardized methods allow better prediction of bone healing properties and implant requirements with computational models. In this review, the principles of bone fracture healing and differences between osteotomy and artificial fracture models as well as influences of fixation devices are summarized. Fundamental considerations regarding animal model choice are discussed, as it is very important to know the limitations of the chosen model. In addition, a compendium of common animal models is assembled with special focus on rats, rabbits, and sheep as most common fracture models. Fracture healing simulation is a basic tool in reducing the number of experimental animals, so its progress is also presented here. In particular, simulation of different animal models is presented. In conclusion, a standardized fracture model is of utmost importance for the best adaption of simulation to experimental setups and comparison between different studies. One of the basic goals should be to reach a consensus for standardized fracture models.

  9. Effects of Anadara granosa shell combined with Sardinella longiceps oil on oesteoblast proliferation in bone defect healing process

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    Rima Parwati Sari

    2016-12-01

    Full Text Available Background: Alveolar bone damage is the most common case in dentistry. One way to fix the bone damage is by using bone graft. Anadara granosa shell is a potential bone substitute since it is rich in calcium which can be processed into hydroxyapatite. The addition of Sardinella longiceps oil rich in omega-3 can modulate inflammation, thus accelerating the healing process. Purpose: This study aimed to determine effects of application of Anadara granosa shell combined with Sardinella longiceps oil on osteoblast proliferation in the healing process of bone defects. Method: The subjects were 32 male rats type Wistar divided into 4 groups (n = 8. Making defect was performed on the right bone of the femurs with a half of the diameter of round Mcisinger® Germany bur sized 18. The first group (K is a negative control group that was not given anything. The second group (AG was given Anadara granosa pasta. The third group (AM10 was given Anadara granosa pasta combined with 10% Sardinella longiceps oil. And, the fourth group (AM30 was given Anadara granosa pasta combined with 30% Sardinella longiceps oil. Next, preparations and animal euthanasia were performed on the 7th day after the treatment. The number of osteoblasts then was measured after making preparations for HPA with Hematoxylin eosin staining (HE. Afterward, tabulation of data followed by statistical analysis of Anova and HSD Tukey was carried out. Result: The average number of osteoblasts in Groups K, AG, AM10, and AM30 was 19.00, 34.63, 33.50, and 38.50. The results of Anova test showed a significant difference (p<0.05. Similarly, the results of Tukey-HSD test also showed significant differences (p<0.05 between Group K and all other groups (AG, AM10, and AM30. Nevertheless, there were no significant differences between Group AG and Groups AM10 and AM30, as well as between Group AM10 and Group AM30. Conclusion: The application of the combination of Anadara granosa shell and Sardinella longiceps

  10. SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells contributes to bone fracture healing.

    Science.gov (United States)

    Kawakami, Yohei; Ii, Masaaki; Matsumoto, Tomoyuki; Kuroda, Ryosuke; Kuroda, Tomoya; Kwon, Sang-Mo; Kawamoto, Atsuhiko; Akimaru, Hiroshi; Mifune, Yutaka; Shoji, Taro; Fukui, Tomoaki; Kurosaka, Masahiro; Asahara, Takayuki

    2015-01-01

    CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived-factor 1 (SDF-1). SDF-1/CXCR4 interaction is reported to play an important role in vascular development. On the other hand, the therapeutic potential of endothelial progenitor cells (EPCs) in fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement at sites of fracture. The purpose of this study was to investigate the influence of the SDF-1/CXCR4 pathway in Tie2-lineage cells (including EPCs) in bone formation. We created CXCR4 gene conditional knockout mice using the Cre/loxP system and set two groups of mice: Tie2-Cre(ER) CXCR4 knockout mice (CXCR4(-/-) ) and wild-type mice (WT). We report here that in vitro, EPCs derived from of CXCR4(-/-) mouse bone marrow demonstrated severe reduction of migration activity and EPC colony-forming activity when compared with those derived from WT mouse bone marrow. In vivo, radiological and morphological examinations showed fracture healing delayed in the CXCR4(-/-) group and the relative callus area at weeks 2 and 3 was significantly smaller in CXCR4(-/-) group mice. Quantitative analysis of capillary density at perifracture sites also showed a significant decrease in the CXCR4(-/-) group. Especially, CXCR4(-/-) group mice demonstrated significant early reduction of blood flow recovery at fracture sites compared with the WT group in laser Doppler perfusion imaging analysis. Real-time RT-PCR analysis showed that the gene expressions of angiogenic markers (CD31, VE-cadherin, vascular endothelial growth factor [VEGF]) and osteogenic markers (osteocalcin, collagen 1A1, bone morphogenetic protein 2 [BMP2]) were lower in the CXCR4(-/-) group. In the gain-of-function study, the fracture in the SDF-1 intraperitoneally injected WT group healed significantly faster with enough callus formation compared with the SDF-1 injected CXCR4(-/-) group. We demonstrated that an EPC SDF-1/CXCR4 axis plays an

  11. Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

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    Shiyi Chen

    2012-10-01

    Full Text Available At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2 on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control, and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2 were used to reconstruct the anterior cruciate ligament (ACL in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N (P = 0.041 and P = 0.001, respectively. In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3 was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4 or control groups (12.4 ± 6.0 (p = 0.036 and 0.001, respectively. Based on the

  12. Spirit-body healing II: a nursing intervention model for spiritual/creative healing.

    Science.gov (United States)

    Lane, Mary Rockwood

    2008-01-01

    This article describes an advanced intervention for spiritual healing that evolved from spirit-body healing, a hermeneutic phenomenological research study. The research study examined the lived experience of art and healing with cancer patients in the Arts in Medicine program at Shands Hospital, University of Florida. Max Van Manen's method of researching the lived experience was used in 63 patients over a 4-year period. Healing themes that emerged from the research were (1) go into darkness, (2) go elsewhere, (3) art becomes the turning point, (4) slip through the veil, (5) know the truth and trust the process, (6) embody your spirit, (7) feel the healing energy of love and compassion, and (8) experience transcendence. The intervention we offer allows nurses to apply creativity and guided imagery as advanced therapeutics and to continue to provide the leadership needed for integrating spiritual healing into patient care. It is one that personifies the nursing mission formalized by many hospitals: a commitment to treat the bodies, minds, and spirits of patients to the best of our ability as part of our routine care.

  13. Histomorphometric evaluation of the effect of systemic and topical ozone on alveolar bone healing following tooth extraction in rats.

    Science.gov (United States)

    Erdemci, F; Gunaydin, Y; Sencimen, M; Bassorgun, I; Ozler, M; Oter, S; Gulses, A; Gunal, A; Sezgin, S; Bayar, G R; Dogan, N; Gider, I K

    2014-06-01

    The aim of this study was to investigate the effects of systemic and topical ozone applications on alveolar bone healing following tooth extraction. One hundred and twelve male Wistar rats were divided into eight groups of 14 rats each; seven groups were experimental (A-G) and one formed the control group (K). The experimental groups were further divided into two sub-groups, with seven rats in each - sacrificed on days 14 and 28 (subgroups 1 and 2). The maxillary right central incisors were extracted under general anaesthesia following the administration of local anaesthesia. After sacrifice, semi-serial histological sections were prepared, and mineralized and trabecular bone and osteoid and osteoblast surfaces were measured. Measurements of the trabecular bone showed statistically higher values in the groups treated with systemic ozone (D(2): 50.01 ± 2.12; E(2): 49.03 ± 3.03; F(2): 48.76 ± 2.61; G(2): 50.24 ± 3.37) than in the groups that underwent topical ozone administration (A(2): 46.01 ± 3.07; B(2): 46.79 ± 3.09; C(2): 47.07 ± 2.12; P = 0.030 (G(2)-A(2), G(2)-B(2), G(2)-C(2))). Within the limitations of the current study, it may be concluded that postoperative long-term systemic ozone application can accelerate alveolar bone healing following extraction. However, additional studies are required to clarify the effects of the different ozone applications on new bone formation.

  14. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  15. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  16. The effects of photobiomodulation and low-amplitude high-frequency vibration on bone healing process: a comparative study.

    Science.gov (United States)

    Rajaei Jafarabadi, M; Rouhi, G; Kaka, G; Sadraie, S H; Arum, J

    2016-12-01

    This study aimed at investigating the effects of photobiomodulation (PBM) and low-amplitude high-frequency (LAHF) whole body mechanical vibration on bone fracture healing process when metallic plates are implanted in rats' femurs. Forty male rats weighing between 250 and 350 g, 12 weeks old, were employed in this study. A transverse critical size defect (CSD) was made in their right femurs that were fixed by stainless steel plates. After the surgery, the rats were divided equally into four groups: low-level laser therapy group (GaAlAs laser, 830 nm, 40 mW, 4 J/cm(2), 0.35 cm beam diameter, LLLT), whole body vibration group (60 Hz, 0.1 mm amplitude, 1.5 g, WBV), a combination of laser and vibration group (LV), and the control group (C). Each group was divided into two subgroups based on sacrifice dates. The rats were sacrificed at intervals of 3 and 6 weeks after the surgery to extract their right femurs for radiography and biomechanical and histological analyses, and the results were analyzed using standard statistical methods. Radiographic analyses showed greater callus formation in the LLLT and WBV groups than in control group at both 3 (P low-amplitude high-frequency WBV both had a positive impact on bone healing process, for critical size defects in the presence of a stainless steel implant. But their combination, i.e., low-level laser therapy and low-amplitude high-frequency whole body vibration (LV), interestingly did not accelerate the fractured bone healing process.

  17. Notch pathway modulation on bone marrow-derived vascular precursor cells regulates their angiogenic and wound healing potential.

    Science.gov (United States)

    Caiado, Francisco; Real, Carla; Carvalho, Tânia; Dias, Sérgio

    2008-01-01

    Bone marrow (BM) derived vascular precursor cells (BM-PC, endothelial progenitors) are involved in normal and malignant angiogenesis, in ischemia and in wound healing. However, the mechanisms by which BM-PC stimulate the pre-existing endothelial cells at sites of vascular remodelling/recovery, and their contribution towards the formation of new blood vessels are still undisclosed. In the present report, we exploited the possibility that members of the Notch signalling pathway, expressed by BM-PC during endothelial differentiation, might regulate their pro-angiogenic or pro-wound healing properties. We demonstrate that Notch pathway modulates the adhesion of BM-PC to extracellular matrix (ECM) in vitro via regulation of integrin alpha3beta1; and that Notch pathway inhibition on BM-PC impairs their capacity to stimulate endothelial cell tube formation on matrigel and to promote endothelial monolayer recovery following wounding in vitro. Moreover, we show that activation of Notch pathway on BM-PC improved wound healing in vivo through angiogenesis induction. Conversely, inoculation of BM-PC pre-treated with a gamma secretase inhibitor (GSI) into wounded mice failed to induce angiogenesis at the wound site and did not promote wound healing, presumably due to a lower frequency of BM-PC at the wound area. Our data suggests that Notch pathway regulates BM-PC adhesion to ECM at sites of vascular repair and that it also regulates the capacity of BM-PC to stimulate angiogenesis and to promote wound healing. Drug targeting of the Notch pathway on BM-PC may thus represent a novel strategy to modulate neo-angiogenesis and vessel repair.

  18. Notch pathway modulation on bone marrow-derived vascular precursor cells regulates their angiogenic and wound healing potential.

    Directory of Open Access Journals (Sweden)

    Francisco Caiado

    Full Text Available Bone marrow (BM derived vascular precursor cells (BM-PC, endothelial progenitors are involved in normal and malignant angiogenesis, in ischemia and in wound healing. However, the mechanisms by which BM-PC stimulate the pre-existing endothelial cells at sites of vascular remodelling/recovery, and their contribution towards the formation of new blood vessels are still undisclosed. In the present report, we exploited the possibility that members of the Notch signalling pathway, expressed by BM-PC during endothelial differentiation, might regulate their pro-angiogenic or pro-wound healing properties. We demonstrate that Notch pathway modulates the adhesion of BM-PC to extracellular matrix (ECM in vitro via regulation of integrin alpha3beta1; and that Notch pathway inhibition on BM-PC impairs their capacity to stimulate endothelial cell tube formation on matrigel and to promote endothelial monolayer recovery following wounding in vitro. Moreover, we show that activation of Notch pathway on BM-PC improved wound healing in vivo through angiogenesis induction. Conversely, inoculation of BM-PC pre-treated with a gamma secretase inhibitor (GSI into wounded mice failed to induce angiogenesis at the wound site and did not promote wound healing, presumably due to a lower frequency of BM-PC at the wound area. Our data suggests that Notch pathway regulates BM-PC adhesion to ECM at sites of vascular repair and that it also regulates the capacity of BM-PC to stimulate angiogenesis and to promote wound healing. Drug targeting of the Notch pathway on BM-PC may thus represent a novel strategy to modulate neo-angiogenesis and vessel repair.

  19. Do Different Cyclooxygenase Inhibitors Impair Rotator Cuff Healing in a Rabbit Model?

    Institute of Scientific and Technical Information of China (English)

    Yi Lu; Yue Li; Feng-Long Li; Xu Li; Hong-Wu Zhuo; Chun-Yan Jiang

    2015-01-01

    Background:The effect of selective and non-selective cyclooxygenase (COX) inhibitors on tendon healing was variable.The purpose of the study was to evaluate the influence of non-selective COX inhibitor,ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor,celecoxib on the tendon healing process in a rabbit model.Methods:Ninety-six New Zealand rabbits were used as rotator cuff repair models.After surgery,they were divided randomly into four groups:Ibuprofen (10 mg·kg-1·d-1),celecoxib (8 mg·kg 1·d 1),flurbiprofen axetil (2 mg·kg 1·d-1),and control group (blank group).All drugs were provided for 7 days.Rabbits in each group were sacrificed at 3,6,and 12 weeks after tendon repair.Tendon biomechanical load failure tests were performed.The percentage of type Ⅰ collagen on the bone tendon insertion was calculated by Picric acid Sirius red staining and image analysis.All data were compared among the four groups at the same time point.All data in each group were also compared across the different time points.Qualitative histological evaluation of the bone tendon insertion was also performed among groups.Results:The load to failure increased significantly with time in each group.There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks (0.533 vs.0.700,P =0.002),6 weeks (0.607 vs.0.763,P =0.01),and 12 weeks (0.660 vs.0.803,P =0.002),and significantly lower percentage of type Ⅰ collagen at 3 weeks (l 1.5% vs.27.6%,P =0.001),6 weeks (40.5% vs.66.3%,P =0.005),and 12 weeks (59.5% vs.86.3%,P =0.001).Flurbiprofen axetil showed significant differences at 3 weeks (failure load:0.600 vs.0.700,P =0.024;percentage of type Ⅰ collagen:15.6% vs.27.6%,P =0.001),but no significant differences at 6 and 12 weeks comparing with control group,whereas the ibuprofen groups did not show any significant difference at each time point.Conclusions:Nonsteroidal anti-inflammatory drugs can delay tendon healing in the

  20. High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

    Science.gov (United States)

    Kang, Kyung Lhi; Kim, Eun-Cheol; Park, Joon Bong; Heo, Jung Sun; Choi, Yumi

    2016-02-01

    Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats.

  1. A review of mouse critical size defect models in weight bearing bones.

    Science.gov (United States)

    Harris, Jonathan S; Bemenderfer, Thomas B; Wessel, Alexander R; Kacena, Melissa A

    2013-07-01

    Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing. Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection - and it is here that many are aiming to find effective solutions. To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies. Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing. Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed. An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research--develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.

  2. Wound healing activity of the leaves of Artocarpus heterophyllus Lam. (Moraceae on ex-vivo porcine skin wound healing model

    Directory of Open Access Journals (Sweden)

    K Periyanayagam

    2013-05-01

    Full Text Available ABSTRACT Objective: To prescreen the ex- vivo wound healing activity of flavonoid rich fraction of ethyl acetate extract of the leaves of Artocarpus heterophyllus Lam. Family Moraceae using porcine skin wound healing model (PSWHM along with  phytochemical, XRF, HPTLC analysis. The aim of this present study is to provide pharmacological validation to the traditional claim for wound healing activity of Artocarpus heterophyllus leaves. Method: Total phenolic content by UV spectral methods and ursolic acid content by HPTLC, trace elements by X-ray fluorescence were determined.  The wound healing effect of the ethyl acetate extract of the leaves of A.heterophyllus (EAAH was evaluated using ex- vivo porcine skin wound healing model - a novel organ culture model system for evaluation of drugs in cell-cell junction in the wound healing process. Results: Total phenolic content by UV method, HPTLC determination of ursolic acid content of EAAH was found to be 376.5mg/g GAE, 134mg/g respectively. XRF study showed the presence of calcium (39.4%, potassium (29.6%, magnesium (2.06%, Iron (0.99%, sulphur (1.83%, zinc (0.083%, strontium (0.23%, manganese (0.13% and aluminium (0.005%.   Histopathological evaluation showed all treated wounds were sound with no signs of apoptosis, necrosis or bacterial contamination and no toxicity of the tested concentrations of EAAH of the leaves. Morphology of the wound margins, epidermis and dermis layer were found to be normal. Epidermal migration or keratinocyte migration distances from the edges of each wound were measured, normalized with the PBS control group and expressed as mean%. The result clearly showed EAAH (1.5% promoted statistically significant wound healing effect is comparable to the standard drug Mupirocin. Conclusion: This study indicates that the ethyl acetate extract of the leaves of A.heterophyllus possesses potential wound healing activity on ex-vivo porcine skin wound healing model. Wound healing

  3. Effect of membranes and porous hydroxyapatite on healing in bone defects around titanium dental implants. An experimental study in monkeys

    DEFF Research Database (Denmark)

    Gotfredsen, K; Warrer, K; Hjørting-Hansen

    1991-01-01

    The purpose of the present study was to examine the effect of treating bony craters around titanium dental implant with polytetrafluoroethylene membranes (PTFE), with and without grafting of hydroxyapatite (HA), and with HA alone. 4 standardized bone defects were prepared in the alveolar ridge...... of edentulous areas in each of 7 monkeys. A titanium implant was then placed centrally in each defect, and in each monkey, the defects were treated with 1 of the following 4 treatment modalities: (1) coverage with PTFE membrane; (2) grafting of HA and covering with a PTFE membrane; (3) HA grafting; (4......) no treatment. Following a healing period of 12 weeks, all animals were sacrificed and mesio-distal ground sections of the treated areas were prepared. The histological analysis showed that all bone defects around the implants treated with PTFE membranes and 5 of the defects treated with HA and PTFE membranes...

  4. Pattern of healing of calvarial bone in the rat following application of the erbium-YAG laser.

    Science.gov (United States)

    el Montaser, M A; Devlin, H; Sloan, P; Dickinson, M R

    1997-01-01

    The aim of this study was to examine the pattern of healing in rat calvarial defects prepared with the erbium-YAG laser, using the "guided tissue regeneration" technique [Dahlin et al., Scand J Plast Reconstr Hand Surg 1990;24: 13-19]. PTFE membranes were placed over the lased skull defects and the skin wounds sutured. Rats were killed humanely at intervals after surgery and the skulls processed for paraffin wax histology. A further group of mature rats was killed humanely and the calvariae removed. Slots were prepared using the erbium-YAG laser and immediately examined under the environmental scanning electron microscope (ESEM) in hydrated conditions, which avoided drying artefact. An amorphous, mineral-rich carbon layer surrounds the lased bone defect, which in the in vivo experiments was seen as a basophilic zone that was resistant to resorption. Bone infilling of the lased defect was retarded by delayed resorption of the amorphous, mineral-rich carbon layer.

  5. Bone healing in rabbits after compression osteosynthesis, studied by Tc-99m(Sn)polyphosphate scintimetry and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Greiff, J.

    1981-08-01

    The purpose of the present study was to determine the scintimetric time course (STC) for Tc-99m(Sn) polyphosphate in rabbit tibias after various osteosynthetic procedures, and to correlate the findings with those from serial radiographs and with autoradiographic and histologic evaluation of the bone. The STC was similar for all treatment groups, with a peak value within the second week after surgery. Significantly different levels of the STC were found after subperiosteal exploration, plate insertion, osteotomy and compression plating, or osteotomy and medullary nailing. The radiological, autoradiographic, and histological findings revealed that Tc-99m scintimetry monitors callus formation. The STC thus appears to be a valuable tool for the quantitative study of bone healing.

  6. [Advancement in methods of evaluation on bone fracture healing and its application in forensic medicine].

    Science.gov (United States)

    Li, Yu-fei

    2011-02-01

    It is frequently encountered to identify the time of bone fracture in forensic medicine. Hence it is important to develop the methods for evaluating the time of bone fracture. This article reviews the applications and values of the methods such as ultrasonic evaluation, impulse measurement, digital imaging technology and bone mineral density testing technology, etc. It is proposed that to use these methods jointly may provide more scientific evidence in determine the time of bone fracture.

  7. Changes in the fractal dimension, feret diameter, and lacunarity of mandibular alveolar bone during initial healing of dental implants.

    Science.gov (United States)

    Önem, Erinç; Baksı, B Güniz; Sogur, Elif

    2012-01-01

    To evaluate the combination of fractal dimension (FD), lacunarity, and Feret diameter (FeD) to quantitatively characterize structural changes of mandibular alveolar bone around dental implants during initial healing. Three standard-sized regions of interest (ROIs) (mesial and distal crest and apical area) around implants and three ROIs of the same size in the alveolar bone on the contralateral side were analyzed on digital panoramic images. FD was calculated using the box-counting method, and lacunarity was calculated using the FracLac plugin of Image J software. FeD was measured in the same ROIs. Comparisons of the groups were done with the Dunnett test. Forty-two implants in the posterior mandibles of 21 patients were used for FD measurements. A total of 189 ROIs was segmented into binary images. Mean FD values for mesial, distal, and apical ROIs around implants were 1.26, 1.36, and 1.4, respectively. The mean FD of alveolar bone around premolars/molars was 1.39 for all ROIs. The mean FeD for mesial, distal, and apical ROIs around implants was 7.63, 7.86, and 8.02, respectively, whereas it ranged between 7.88 and 8.13 for premolar teeth. Mean lacunarity values for mesial, distal, and apical ROIs around implants were 0.53, 0.51, and 0.48, respectively. Lacunarity values for ROIs around premolars ranged between 0.45 and 0.50. No significant differences were observed in FD, FeD, or lacunarity measurements between ROIs around implants and around teeth. The satisfactory healing of bone following implant placement may be monitored by calculating FD, lacunarity, and FeD using digital panoramic images. Although preliminary, these values may alert the practitioner to any implants with loss of stability.

  8. Full-thickness splinted skin wound healing models in db/db and heterozygous mice: implications for wound healing impairment.

    Science.gov (United States)

    Park, Shin Ae; Teixeira, Leandro B C; Raghunathan, Vijay Krishna; Covert, Jill; Dubielzig, Richard R; Isseroff, Roslyn Rivkah; Schurr, Michael; Abbott, Nicholas L; McAnulty, Jonathan; Murphy, Christopher J

    2014-01-01

    The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.

  9. Statistical shape and appearance models of bones.

    Science.gov (United States)

    Sarkalkan, Nazli; Weinans, Harrie; Zadpoor, Amir A

    2014-03-01

    When applied to bones, statistical shape models (SSM) and statistical appearance models (SAM) respectively describe the mean shape and mean density distribution of bones within a certain population as well as the main modes of variations of shape and density distribution from their mean values. The availability of this quantitative information regarding the detailed anatomy of bones provides new opportunities for diagnosis, evaluation, and treatment of skeletal diseases. The potential of SSM and SAM has been recently recognized within the bone research community. For example, these models have been applied for studying the effects of bone shape on the etiology of osteoarthritis, improving the accuracy of clinical osteoporotic fracture prediction techniques, design of orthopedic implants, and surgery planning. This paper reviews the main concepts, methods, and applications of SSM and SAM as applied to bone.

  10. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes.

    Science.gov (United States)

    Ansurudeen, Ishrath; Sunkari, Vivekananda Gupta; Grünler, Jacob; Peters, Verena; Schmitt, Claus Peter; Catrina, Sergiu-Bogdan; Brismar, Kerstin; Forsberg, Elisabete Alcantara

    2012-07-01

    Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing.

  11. Interaction of age and mechanical stability on bone defect healing: an early transcriptional analysis of fracture hematoma in rat.

    Directory of Open Access Journals (Sweden)

    Andrea Ode

    Full Text Available Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging and external fixator stiffness (mechanically challenging. From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability in combination rather than alone.

  12. [HEALING MODEL RESEARCH OF ROTATOR CUFF INJURY IN CANINE].

    Science.gov (United States)

    Ye, Wei; Bao, Nirong; Zhaq, Jianning

    2016-04-01

    To compare the difference of rotator cuff healing between different types of injury andbetween different repair methods, and to explore the animal model to accurately simulate the restorative process afterrepair of rotator cuff injury. Twelve adult male beagle dogs (weighing, 10-15 kg) were divided into 3 groups (n = 4) according to different processing methods: acute rotator cuff injury+Mason-Allen suture repair (group A), huge rotator cuff injury+Mason-Allen suture repair (group B), and huge rotator cuff injury+Mason-Allen combined with autogenous semitendinosus expansion suture repair (group C). The external fixation was used for immobilization after repair. After operation, the general situation of the animals was observed, and the infraspinatus tendon was harvested for gross observation at 6 weeks after operation. The biomechanical test of limit load and histological observation of tendon fibers were carried out. All the animals survived to the end of the experiment. All incisions healed well and no infection occurred. Gross observation showed more scar tissues at the end of infraspinatus muscle tendon than normal tendon in group A; no obvious tendon tissue was observed at the end of infraspinatus muscle tendon in group B; the infraspinatus muscle tendon was covered with some white scar tissue, but the tendon and the general direction could be observed in group C. The limit load of groups A, B, and C were (223.75 ± 24.28), (159.25 ± 34.87), and (233.25 ± 14.24) N respectively, group B was significantly lower than groups A and C (P 0.05). Histological observation showed normal arrangement of tendon fibers in group A; tendon fibers arranged disorderly in group B and tendon cells were significantly less than those of group A; tendon fibers arranged in neat in group C and tendon cells were more than those of group B. Canine autologous semitendinosus expansion repair of massive rotator cuff injury immobilization model can better simulate the clinical rotator

  13. The Synergistic Effect of Leukocyte Platelet-Rich Fibrin and Micrometer/Nanometer Surface Texturing on Bone Healing around Immediately Placed Implants: An Experimental Study in Dogs

    Science.gov (United States)

    Neiva, Rodrigo F.; Gil, Luiz Fernando; Tovar, Nick; Janal, Malvin N.; Marao, Heloisa Fonseca; Pinto, Nelson; Coelho, Paulo G.

    2016-01-01

    Aims. This study evaluated the effects of L-PRF presence and implant surface texture on bone healing around immediately placed implants. Methods. The first mandibular molars of 8 beagle dogs were bilaterally extracted, and implants (Blossom™, Intra-Lock International, Boca Raton, FL) were placed in the mesial or distal extraction sockets in an interpolated fashion per animal. Two implant surfaces were distributed per sockets: (1) dual acid-etched (DAE, micrometer scale textured) and (2) micrometer/nanometer scale textured (Ossean™ surface). L-PRF (Intraspin system, Intra-Lock International) was placed in a split-mouth design to fill the macrogap between implant and socket walls on one side of the mandible. The contralateral side received implants without L-PRF. A mixed-model ANOVA (at α = 0.05) evaluated the effect of implant surface, presence of L-PRF, and socket position (mesial or distal), individually or in combination on bone area fraction occupancy (BAFO). Results. BAFO values were significantly higher for the Ossean relative to the DAE surface on the larger mesial socket. The presence of L-PRF resulted in higher BAFO. The Ossean surface and L-PRF presence resulted in significantly higher BAFO. Conclusion. L-PRF and the micro-/nanometer scale textured surface resulted in increased bone formation around immediately placed implants. PMID:28042577

  14. The effect of a composite of polyorthoester and demineralized bone on the healing of large segmental defects of the radius in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Andersen, R

    1992-01-01

    The effect of a composite of demineralized bone mixed with polyorthoester on the healing of large segmental defects in the rat radius was studied. Sixty male Wistar rats were divided into four groups, A through D, and an osteoperiosteal diaphyseal defect of 50 per cent of the length of the bone...... was made in the right radius of each rat. In Group A, the defect was filled with polyorthoester and demineralized bone; in Group B, demineralized bone; and in Group C, polyorthoester. No material was implanted in the defects in the Group-D rats. The rats were killed fifty days postoperatively...

  15. Assessment of bone healing in rabbit calvaria grafted with three different biomaterials.

    Science.gov (United States)

    Takauti, Carlos Alberto Yoshihiro; Futema, Fabio; Brito Junior, Rui Barbosa de; Abrahão, Aline Corrêa; Costa, Claudio; Queiroz, Celso Silva

    2014-01-01

    This study evaluated the bone regeneration process in rabbit calvaria induced by three types of biomaterials: two xenogenous, consisting of deproteinized bovine bone, while the other was alloplastic, based on biphasic calcium phosphate. Five New Zealand white rabbits weighing between 2,900 and 3,500 g were submitted to four standard 8 mm-diameter perforations at the parietal bone. Three perforations were filled with three grafts and biomaterials, two of them received bovine Bio-Oss® and Endobon® Xenograft Granules, and the other consisted of fully alloplastic Straumann® Bone Ceramic. The fourth remaining cavity was used as control with coagulum. After eight weeks, the animals were sacrificed, and the samples were prepared for morphometric and qualitative analysis. The cavities filled with alloplastic biomaterials showed higher percentages of newly formed bone (pbiomaterials showed higher amount of residual graft (pbiomaterial for bone induction process.

  16. The spa as a model of an optimal healing environment.

    Science.gov (United States)

    Frost, Gary J

    2004-01-01

    "Spa" is an acronym for salus per aqua, or health through water. There currently are approximately 10,000 spas of all types in the United States. Most now focus on eating and weight programs with subcategories of sports activities and nutrition most prominent. The main reasons stated by clients for their use are stress reduction, specific medical or other health issues, eating and weight loss, rest and relaxation, fitness and exercise, and pampering and beauty. A detailed description of the Canyon Ranch, a spa facility in Tucson, AZ, is presented as a case study in this paper. It appears that the three most critical factors in creating an optimal healing environment in a spa venue are (1) a dedicated caring staff at all levels, (2) a mission driven organization that will not compromise, and (3) a sound business model and leadership that will ensure permanency.

  17. In Vivo Study of Ligament-Bone Healing after Anterior Cruciate Ligament Reconstruction Using Autologous Tendons with Mesenchymal Stem Cells Affinity Peptide Conjugated Electrospun Nanofibrous Scaffold

    Directory of Open Access Journals (Sweden)

    Jingxian Zhu

    2013-01-01

    Full Text Available Electrospinning nanofibrous scaffold was commonly used in tissue regeneration recently. Nanofibers with specific topological characteristics were reported to be able to induce osteogenic differentiation of MSCs. In this in vivo study, autologous tendon grafts with lattice-like nanofibrous scaffold wrapping at two ends of autologous tendon were used to promote early stage of ligament-bone healing after rabbit ACL reconstruction. To utilize native MSCs from bone marrow, an MSCs specific affinity peptide E7 was conjugated to nanofibrous meshes. After 3 months, H-E assessment and specific staining of collagen type I, II, and III showed direct ligament-bone insertion with typical four zones (bone, calcified fibrocartilage, fibrocartilage, and ligament in bioactive scaffold reconstruction group. Diameters of bone tunnel were smaller in nanofibrous scaffold conjugated E7 peptide group than those in control group. The failure load of substitution complex also indicated a stronger ligament-bone insertion healing using bioactive scaffold. In conclusion, lattice-like nanofibrous scaffold with specific MSCs affinity peptide has great potential in promoting early stage of ligament-bone healing after ACL reconstruction.

  18. Observations concerning different patterns of bone healing using the Point Contact Fixator (PC-Fix) as a new technique for fracture fixation.

    Science.gov (United States)

    Hofer, H P; Wildburger, R; Szyszkowitz, R

    2001-09-01

    The recent trend in all surgical disciplines has been the development of techniques in minimally invasive surgery and the optimal maintenance of the blood supply to the bone fragments during osteosynthesis. Currently, the Point Contact Fixator (PC-Fix) has been introduced as a new implant for the stabilization of forearm bones. This plate-like splint and screw fixation system, which actually acts as an internal fixator, is characterized by minimized isolated contacts to the bone and proven angular stability of the monocortically locked screws. By using the PC-Fix, a further reduction of damage to the blood supply to the bone is achieved. Since 1994, 38 patients have been treated with this new device; we have reviewed the radiographs of 52 consolidated forearm fractures/osteotomies in accordance with the patterns of bone healing associated with the different methods of implant application according to the fracture type. In the groups in which traditionally precise reduction, interfragmentary compression and stable fixation was achieved (N=31), we found in 71% an absence of periosteal callus (direct bone healing). In the groups in which compression and adaptation were combined, or even main fragments adapted without compression, with wedges remaining unreduced in soft tissue connection (N=21), we found a visible external callus in 81% (indirect healing) (P = 0.002). Indirect healing after internal fixation is no longer regarded as a disturbance to healing, but is a goal in itself. The appearance of callus is a welcome sign indicating a prompt and positive reaction in the course of bone union which will lead to progressive fracture immobilization. When using the PC-Fix in a "biological way", callus formation and solid union take place earlier than in conventional plating. The new internal fixator offers substantial technical and mechanical advantages in fracture treatment. Therefore, it is an ideal implant to satisfy the requirements of modern biological

  19. Broken Bones (For Parents)

    Science.gov (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. Mathematical Imaging and Modeling of Cortical Spreading Depression and Wound Healing

    Science.gov (United States)

    2015-02-05

    phase diagram that maps out when a retinal detachment is unstable, or is stable and will likely heal . We have begun to generalize this problem in two...Spreading Depression and W mmd Healing Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 611102 6. AUTHORS Sd. PROJECT NUMBER Tom Chou Se. TASK NUMBER...Spreading Depression and Wound Healing ." The research conducted under this grant represents advances made in image analysis, front tracking, modeling

  1. Means of enhancing bone fracture healing : Optimal cell source, isolation methods and acoustic stimulation

    NARCIS (Netherlands)

    Ghebes, Corina Adriana; Braham, Maaike Vera Jasmijn; Zeegers, Adelgunde Veronica Clemens Maria; Renard, Auke Jan Sijbe; Fernandes, Hugo; Saris, Daniel B F

    2016-01-01

    Background: The human body has an extensive capacity to regenerate bone tissue after trauma. However large defects such as long bone fractures of the lower limbs cannot be restored without intervention and often lead to nonunion. Therefore, the aim of the present study was to assess the pool and

  2. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  3. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  4. Tikkun Olam: A Model for Healing the World.

    Science.gov (United States)

    Berman, Dene S.; Davis-Berman, Jennifer

    1999-01-01

    Discusses Tikkun Olam--the Jewish tenet of healing the world through individual good deeds--and its applicability to the practice of adventure therapy. Focuses on the therapeutic relationship, as it develops in group settings, and the role of adventure leaders and therapists in nourishing such relationships to provide a vehicle for healing or…

  5. Bereavement healing ministry amongst Abaluyia: Towards a ‘circle for pastoral concern’ as a healing model

    Directory of Open Access Journals (Sweden)

    Benjamin Shikwati

    2013-10-01

    Full Text Available This article formulates a new integrated pastoral care approach to bereavement healing ministry in Africa, termed a circle for pastoral concern. In pursuit of this, the article highlights the pastoral challenge brought about by the occurrence of death and bereavement within the cultural and Christian intermix. Using the example of the Abaluyia of western Kenya, traditional cultural bereavement healing approaches are assessed against the backdrop of Christian influence on the understanding and response to death and bereavement healing and the resultant tension. The article juxtaposes the Abaluyia cultural concept of okhukura[to encircle with loving care] with the biblical koinōnia[fellowship, communion] as springboard for building culturally sensitive and biblically sound Christian caring communities. It is hoped that the juxtaposition helps to establish and promote meaningful engagement between therapeutic traditional beliefs and practices, and the gospel. The gospel-culture engagement within a local church setting provides the context in which bereavement healing and individual growth after the death of a significant other takes place. The juxtaposition is necessitated by the rampant practice in African pluralistic societies where Christians consciously, or otherwise, lurch back to cultural approaches in their effort to provide or find healing when faced with death and bereavement. The ‘circle for pastoral concern’ model encourages inclusiveness by enlisting the means and talents of the community of believers, both ordained and lay. The principle of inclusion ensures that the load of pastoral care is shared and assumes a deeper response due to diversity of gifts and talents within the caring community.

  6. A Crucial Role of Bone Morphogenetic Protein Signaling in the Wound Healing Response in Acute Liver Injury Induced by Carbon Tetrachloride

    Directory of Open Access Journals (Sweden)

    Nao Oumi

    2012-01-01

    Full Text Available Background. Acute liver injury induced by administration of carbon tetrachloride (CCl4 has used a model of wound repair in the rat liver. Previously, we reported transient expression of bone morphogenetic protein (Bmp 2 or Bmp4 at 6–24 h after CCl4 treatment, suggesting a role of BMP signaling in the wound healing response in the injured liver. In the present study, we investigated the biological meaning of the transient Bmp expression in liver injury. Methods. Using conditional knockout mice carrying a floxed exon in the BMP receptor 1A gene, we determined the hepatic gene expressions and proliferative activity following CCl4-treated liver. Results. We observed retardation of the healing response in the knockout mice treated with CCl4, including aggravated histological feature and reduced expressions of the albumin and Tdo2 genes, and a particular decrease in the proliferative activity shown by Ki-67 immunohistochemistry. Conclusion. Our findings suggest a crucial role of BMP signaling in the amelioration of acute liver injury.

  7. 膝关节持续被动活动对兔重建前交叉韧带腱骨愈合的影响%The effects of continuous passive motion on tendon-bone healing of the tendon autograft used for anterior cruciate ligament reconstruction in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    黄红拾; 敖英芳; 王永健; 李雪

    2008-01-01

    Objective To study the effects of continuous passive motion on the tendon-bone healing of the semitendinous tendon autograft used for anterior cruciate ligament (ACL) reconstruction in rabbits.Methods In 12 healthy 8-month-old male rabbits, an ACL reconstruction was performed by using double semitendinous tendon autograft. Postoperatively these animals were treated by either continuous passive motion(CPM) or cage activity. Specimens of the grafts were collected at 6, 12, 24 weeks postoperatively.Histological change in the tendon-bone healing was studied by haematoxylin-eosin and toluidine blue.Results There was more new fiber tissue in the anterior half of the interface. Osteoclasts were most numerous at the tunnel aperture and in the anterior half of the interface. Cartilage in the tendon-bone interface was localized to the posterior aspect of tunnels, the area where compressive stress would be predicted. CPM group developed a denser connective tissue with less vascularity and cellularity. The bone tunnel had more areas with ingrowing denser connective tissue compared with cage activity specimens. With the growth of Sharpery's fibers and fibrocartilage into the interface, a direct ligament insertion was found. In the CPM specimens, the interface tissue was more mature and the direct insertion was broader and more structured. Conclusions Compressive stress promotes chondroid formation, and the tension promotes fiber formation. Tendon-bone healing may be optimized by CPM after tendon transplantation into a bone tunnel.%目的 通过兔半腱肌腱腱后固定方法重建前交叉韧带(ACL)实验动物模型,研究持续被动活动(CPM)对移植物隧道内腱骨界面的组织学转归影响.方法 对12只雄性新西兰大白兔右侧后肢膝关节行自体双股半腱肌腱移植重建ACL.术后随机分为两组:CPM组(n=6)术后第2天开始早期CPM康复6周;自由活动组(n=6)笼养.分别于术后第6、12、24周取材,采用HE和甲苯胺蓝染色

  8. Wound Healing Activity of Rubus sanctus Schreber (Rosaceae): Preclinical Study in Animal Models.

    Science.gov (United States)

    Süntar, Ipek; Koca, Ufuk; Keleş, Hikmet; Akkol, Esra Küpeli

    2011-01-01

    Young shoots of Rubus species have been used for healing of wounds, infected insect bites and pimples in folk medicine for ages. In order to evaluate the wound healing activity of Rubus sanctus, four different extracts were prepared from the whole aerial parts of the plant by using n-hexane, chloroform, ethyl acetate and methanol, respectively. Incision wound healing model by using tensiometer on rats and excision model on mice were employed to assess the activity. Remarkable wound healing activity was observed with the ointment formulation of the methanol extract at 1% concentration on the mentioned models. The results of histopathological examination also supported the outcome of both incision and excision wound models. The wound healing effect was comparatively evaluated with a reference ointment Madecassol. The experimental data confirmed the ethnobotanical usage of R. sanctus.

  9. Wound Healing Activity of Rubus sanctus Schreber (Rosaceae: Preclinical Study in Animal Models

    Directory of Open Access Journals (Sweden)

    Ipek Süntar

    2011-01-01

    Full Text Available Young shoots of Rubus species have been used for healing of wounds, infected insect bites and pimples in folk medicine for ages. In order to evaluate the wound healing activity of Rubus sanctus, four different extracts were prepared from the whole aerial parts of the plant by using n-hexane, chloroform, ethyl acetate and methanol, respectively. Incision wound healing model by using tensiometer on rats and excision model on mice were employed to assess the activity. Remarkable wound healing activity was observed with the ointment formulation of the methanol extract at 1% concentration on the mentioned models. The results of histopathological examination also supported the outcome of both incision and excision wound models. The wound healing effect was comparatively evaluated with a reference ointment Madecassol. The experimental data confirmed the ethnobotanical usage of R. sanctus.

  10. Healing response to anorganic bone implantation in periodontal intrabony defects in dogs. Part I. Bone regeneration. A microradiographic study.

    Science.gov (United States)

    Clergeau, L P; Danan, M; Clergeau-Guérithault, S; Brion, M

    1996-02-01

    The purpose of the present study was to explore the regenerative potential of anorganic bone plus collagen (AB-C) in experimental intrabony defects. Eight healthy female beagle dogs, 3 to 4 years old and weighing 15 to 16 kilos, were used. After extraction of the mandibular third premolars (P3), surgical defects were created and inflammation induced by placement of cotton and steel braids. Eight weeks later, the braids were removed. The experimental lesions thus obtained were either treated by plain flap curettage (group 1: control) or were, in addition, implanted with AB-C (group 2: experimental). Blocks of AB-C alone were observed by scanning electron microscopy (SEM). The results show that the surface of the particles have the characteristics of a bone tissue. These particles are gathered together with a fibrillar network. Six, 18, and 36 weeks postoperative (PO), non-decalcified specimens from both groups were examined histologically by contact microradiography. In group 1, no significant bone regeneration was observed at 6, 18, or 36 weeks PO. In group 2, trabeculae undergoing mineralization and circumscribing dense particles above the reference notch were seen at 6 weeks PO; 18 and 36 week specimens showed significant bone regeneration with more or less dense remaining particles. The periodontal ligament space was always clear and the only signs of ankylosis noticed were deep in the notch on one 18 week group 2 specimen and on one 36 week group 1 specimen.

  11. Effect of Chenopodium ambrosioides on the healing process of the in vivo bone tissue.

    Science.gov (United States)

    Penha, Elizandra Silva da; Lacerda-Santos, Rogério; Carvalho, Maria Goretti Freire de; Oliveira, Patrícia Teixeira de

    2017-07-25

    The focus of this double-blind randomized study was on evaluating the effect of an aqueous extract of Mastruz (Chenopodium ambrosioides L.) on the bone repair process in vivo. In total, 36 male Wistar rats were randomly selected for this study, and divided into 3 groups (n = 12): Group HS (Hemostatic Sponge), Group SM (Hemostatic Sponge with Mastruz) and Group BC (Blood Clot). In each animal, bone defects measuring 2 mm in diameter were performed in both tibias for placement of the substances. After 3 and 10 days, the animals were sacrificed, and the tissues were analyzed under an optical microscope relative to the following events: inflammatory infiltrate; necrosis; young fibroblasts; osteoclastic and osteoblastic activity; endosteal and periosteal bone formation; and bone repair. The results were assessed by using Kruskal-Wallis and Mann-Whitney tests (p < .05). Inflammatory infiltrate demonstrated difference between Groups SM and BC in the time interval of 3 days (p = .004); an event related to the presence of the fibrin sponge and liquid of the extract, which induced a foreign body initial reaction. The presence of young fibroblasts (p = .003), osteoclastic (p = .003), and osteoblastic (p = .020) activity was statistically significant between Groups HS and BC in the time interval of 10 days; performance was related to the presence of the sponge within bone. As regards injured bone tissue repair, Group SM demonstrated a higher level of regenerative capacity (p = 0.004), due to a larger quantities of endosteal and periosteal bone formation, demonstrated in Group SM. The aqueous extract of mastruz stimulated bone neoformation, presenting wound closure with bone tissue at the end of 10 days. © 2017 Wiley Periodicals, Inc.

  12. Spatio-temporal Models of Lymphangiogenesis in Wound Healing.

    Science.gov (United States)

    Bianchi, Arianna; Painter, Kevin J; Sherratt, Jonathan A

    2016-09-01

    Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: (1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case and (2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here, we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.

  13. The effect of tendon surface treatment on cell attachment for potential enhancement of tendon graft healing: an ex vivo model.

    Science.gov (United States)

    Hashimoto, Takahiro; Sun, Yu-Long; An, Kai-Nan; Amadio, Peter C; Zhao, Chunfeng

    2012-12-01

    For both tendon allografts and autografts, the surface, initially optimized for gliding, may not be ideal to facilitate tissue integration for graft healing to host tendon or bone. As a prelude to studying tendon-bone integration, we investigated the effect of surface treatments with trypsin or mechanical abrasion on cell attachment to the tendon surface in a canine ex vivo intrasynovial tendon tissue culture model. Intrasynovial tendon allograft surfaces were seeded with cells after the following treatments: (1) no treatment, (2) mechanical abrasion, (3) trypsin, and (4) abrasion and trypsin. The area covered by cells was determined using confocal laser microscopy at one and two weeks. Results were compared to untreated extrasynovial tendon. Additional tendons were characterized with scanning electron microscopy. Tendons with trypsin treatment had significantly more surface coverage with cells than the other groups, after both one and two weeks of culture. In terms of the cellular shape and size, cells on tendons with trypsin treatment spread more and were more polygonal in shape, whereas tendons with mechanical abrasion with/without trypsin treatment contained smaller, more spindle-like cells. Surface roughening can affect cell behavior with topographical stimulation. Trypsin surface digestion exposes a mesh-like structure on the tendon surface, which could enhance cell adherence and, possibly, tendon/bone healing.

  14. Time course of 25(OHD3 vitamin D3 as well as PTH (parathyroid hormone during fracture healing of patients with normal and low bone mineral density (BMD

    Directory of Open Access Journals (Sweden)

    Wöfl Christoph

    2013-01-01

    Full Text Available Abstract Background Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OHD3 (Vitamin D as well as PTH (Parathyroid Hormone the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. Methods In the presented study, we analyse the time course of 25(OHD3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OHD3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. Results Serum levels of 25(OHD3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. Conclusions The time course of 25(OHD3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for

  15. Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

    Science.gov (United States)

    2012-03-29

    in children between the ages of 2 and 10 is particularly challenging as they have lost the ability to spontaneously heal, and split calvarial grafts...6] are not adequate due to the underdeveloped diploic space [7, 8]. On the battlefield, craniomaxillofacial injuries caused by explosive devices are...Lewis G 2007 Percutaneous vertebroplasty and kyphoplasty for the stand-alone augmentation of osteoporosis -induced vertebral compression fractures

  16. Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone.

    Science.gov (United States)

    Khedgikar, V; Kushwaha, P; Gautam, J; Verma, A; Changkija, B; Kumar, A; Sharma, S; Nagar, G K; Singh, D; Trivedi, P K; Sangwan, N S; Mishra, P R; Trivedi, R

    2013-01-01

    Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation. WFA increased expression of osteoblast-specific transcription factor and mineralizing genes, promoted osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA treatment decreased osteoclast number directly by decreasing expression of tartarate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our data show that in vitro treatment of WFA to calvarial osteoblast cells decreased expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2), preventing degradation of Runt-related transcription factor 2 (RunX2) and relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2. Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor α (TNFα) to primary osteoblast cells was decreased by WFA treatment. This was corroborated by using small interfering RNA against Smurf2. Further, WFA also blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data show that in vitro proteasome inhibition by WFA simultaneously promoted osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased expression of osteogenic genes. WFA

  17. Adult stem cells in small animal wound healing models.

    Science.gov (United States)

    Nauta, Allison C; Gurtner, Geoffrey C; Longaker, Michael T

    2013-01-01

    This chapter broadly reviews the use of stem cells as a means to accelerate wound healing, focusing first on the properties of stem cells that make them attractive agents to influence repair, both alone and as vehicles for growth factor delivery. Major stem cell reservoirs are described, including adult, embryonic, and induced pluripotent cell sources, outlining the advantages and limitations of each source as wound healing agents, as well as the possible mechanisms responsible for wound healing acceleration. Finally, the chapter includes a materials and methods section that provides an in-depth description of adult tissue harvest techniques.

  18. Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

    Science.gov (United States)

    Rubessa, Marcello; Polkoff, Kathryn; Bionaz, Massimo; Monaco, Elisa; Milner, Derek J; Holllister, Scott J; Goldwasser, Michael S; Wheeler, Matthew B

    2017-03-07

    Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

  19. Comparative study of the effect of ultrasound and electrostimulation on bone healing in rats.

    Science.gov (United States)

    Zorlu, U; Tercan, M; Ozyazgan, I; Taşkan, I; Kardaş, Y; Balkar, F; Oztürk, F

    1998-01-01

    This study was performed to compare the effects of direct current with ultrasound on fracture healing. Thirty-two rats were subjected to the experiment. Each rat's right legs were used as the experimental sample, and their left legs were used as the control. Four groups were formed, each consisting of 16 ultrasound, 16 electrostimulation, 16 ultrasound control, and 16 electrostimulation control animals. Fibular osteotome was applied to the rats under anesthesia. In the electrostimulation and electrostimulation control groups, a stainless steel cathode electrode was installed in the fractured side. In the electrostimulation group, 10 microA of direct current for 30 min, using a semi-invasive method, was given one day after fracture, for 15 days. On the control side, the aforementioned protocol was followed but sham treated. The ultrasound group was treated with 0.1 W/cm2 ultrasound for 2 min every second day for 6 days after fracture (4 times). Rats were killed on the 7th and 14th days to investigate the macroscopic, radiologic, and histopathologic parameters of fracture healing. There was a difference (P electrostimulation and the electrostimulation control groups on the 7th day. There was a difference (P electrostimulation groups, the fracture healing had been accelerated more so than in the control groups. There was no observed statistical difference between ultrasound and electrostimulation effects.

  20. Design and Use of Chimeric Proteins Containing a Collagen-Binding Domain for Wound Healing and Bone Regeneration.

    Science.gov (United States)

    Addi, Cyril; Murschel, Frederic; De Crescenzo, Gregory

    2016-12-12

    Collagen-based biomaterials are widely used in the field of tissue engineering; they can be loaded with biomolecules such as growth factors (GFs) to modulate the biological response of the host and thus improve its potential for regeneration. Recombinant chimeric GFs fused to a collagen-binding domain (CBD) have been reported to improve their bioavailability and the host response, especially when combined with an appropriate collagen-based biomaterial. This review first provides an extensive description of the various CBDs that have been fused to proteins, with a focus on the need for accurate characterization of their interaction with collagen. The second part of the review highlights the benefits of various CBD/GF fusion proteins that have been designed for wound healing and bone regeneration.

  1. Development of a cyclosporin-A-induced immune tolerant rat model to test marrow allograft cell type effects on bone repair.

    Science.gov (United States)

    Espitalier, Florent; Durand, Nicolas; Rémy, Séverine; Corre, Pierre; Sourice, Sophie; Pilet, Paul; Weiss, Pierre; Guicheux, Jérôme; Malard, Olivier

    2015-05-01

    Bone repair is an important concept in tissue engineering, and the ability to repair bone in hypotrophic conditions such as that of irradiated bone, represents a challenge for this field. Previous studies have shown that a combination of bone marrow and (BCP) was effective to repair irradiated bone. However, the origin and role played by each cell type in bone healing still remains unclear. In order to track the grafted cells, the development of an animal model that is immunotolerant to an allograft of bone marrow would be useful. Furthermore, because the immune system interacts with bone turnover, it is of critical importance to demonstrate that immunosuppressive drugs do not interfere with bone repair. After a preliminary study of immunotolerance, cyclosporin-A was chosen to be used in immunosuppressive therapy. Ten rats were included to observe qualitative and quantitative bone repair 8 days and 6 weeks after the creation of bone defects. The defects were filled with an allograft of bone marrow alone or in association with BCP under immunosuppressive treatment (cyclosporin-A). The results showed that there was no significant interaction of cyclosporin-A with osseous regeneration. The use of this new immunotolerant rat model of bone marrow allograft in future studies will provide insight on how the cells within the bone marrow graft contribute to bone healing, especially in irradiated conditions.

  2. Fetal wound healing using a genetically modified murine model: the contribution of P-selectin

    Science.gov (United States)

    During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wo...

  3. A simplified model for growth factor induced healing of circular wounds

    NARCIS (Netherlands)

    Vermolen, F.J.; E. van Baaren, E.; Adam, J.A.

    2005-01-01

    A mathematical model is developed for the rate of healing of a circular wound in a spherical skull. In this paper the regeneration, decay and transport of a generic "growth factor, which induces the healing of the wound, is taken into account. Further, an equation of motion is derived for the actual

  4. A simplified model for growth factor induced healing of circular wounds

    NARCIS (Netherlands)

    Vermolen, F.J.; E. van Baaren, E.; Adam, J.A.

    2005-01-01

    A mathematical model is developed for the rate of healing of a circular wound in a spherical skull. In this paper the regeneration, decay and transport of a generic "growth factor, which induces the healing of the wound, is taken into account. Further, an equation of motion is derived for the actual

  5. 自体浓缩骨髓移植促进腱骨愈合★%Condensed autologous bone marrow transplantation facilitates the tendon-bone healing

    Institute of Scientific and Technical Information of China (English)

    张义龙; 李宁; 宋有鑫; 方亚群; 张弘; 张金燕

    2013-01-01

    BACKGROUND:There are a lot of applications of hamstring tendons autografts in the reconstruction of anterior cruciate ligament, which needs a long term for the tendon-bone healing and restricts the early functional activities of patients. OBJECTIVE:To evaluate the effect of condensed autologous bone marrow transplantation on the tendon-bone interface in the reconstruction of anterior cruciate ligament. METHODS:One knee joint was chosen as the experimental group and the other side as the control group in 32 New Zealand rabbits experiencing the reconstruction of anterior cruciate liagment. The tibial tendon-bone interface was injected with condensed autologous bone marrow in the experimental side and the other side was not injected as the control. RESULTS AND CONCLUSION:The histological anatomy showed the tendon-bone interface was fil ed with granulation tissues that were loose, and there were some activities of bone formation in the control group at 2 weeks after operation;the tendon-bone interface was fil ed with granulation tissues that were not compact, but there were active activities of bone formation in the experimental group at 2 weeks after operations. The bound between the tendon and bone was becoming obscure, and there were col agen fiber-fibrocartilage-calcified fibrocartilage-bone transitional zones at the interface in the control group at 12 weeks after operation. In the experimental group, there were conspicuous col agen fiber-fibrocartilage-calcified fibrocartilage-bone transitional zones and clear tidal line at the interface. The maximal pul-out loads in the experimental group were higher than those in the control group at 4, 8 and 12 weeks after operation (P<0.05). These findings indicate that condensed autologous bone marrow transplantation can enhance the tensile strength of tendon-bone interface, and can do good to tendon-bone healing in a bone tunnel.%  背景:前交叉韧带断裂后应用自体腘绳肌腱移植进行重建应用较多

  6. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Hematoma quality (especially the fibrin matrix plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β on fibrin clot formation from platelet-poor plasma (PPP.Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG, blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM, confocal microscopy (CM, turbidity, and clot lysis assays.The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β compared to the control group without IL-1β (543.8 ± 205.8. Maximal turbidity was observed in the control group. IL-1β (500 pg/mL treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05. The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers.IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

  7. Effects of ionizing radiation on bone cell differentiation in an experimental murine bone cell model

    Science.gov (United States)

    Baumstark-Khan, Christa; Lau, Patrick; Hellweg, Christine; Reitz, Guenther

    During long-term space travel astronauts are exposed to a complex mixture of different radiation types under conditions of dramatically reduced weight-bearing activity. It has been validated that astronauts loose a considerable amount of bone mass at a rate up to one to two percent each month in space. Therapeutic doses of ionizing radiation cause bone damage and increase fracture risks after treatment for head-and-neck cancer and in pelvic irradiation. For low radiation doses, the possibility of a disturbed healing potential of bone was described. Radiation induced damage has been discussed to inflict mainly on immature and healing bone. Little is known about radiation effects on bone remodelling and even less on the combined action of microgravity and radiation. Bone remodelling is a life-long process performed by balanced action of cells from the osteoblast and osteoclast lineages. While osteoblasts differentiate either into bone-lining cells or into osteocytes and play a crucial role in bone matrix synthesis, osteoclasts are responsible for bone resorption. We hypothesize that the balance between bone matrix assembly by osteocytes and bone degradation by osteoclasts is modulated by microgravity as well as by ionizing radiation. To address this, a cell model consisting of murine cell lines with the potential to differentiate into bone-forming osteoblasts (OCT-1, MC3T3-E1 S24, and MC3T3-E1 S4) was used for studying radiation response after exposure to simulated components of cosmic radiation. Cells were exposed to graded doses of 150 kV X-rays, α particles (0.525 MeV/u, 160 keV/µm; PTB, Braunschweig, Germany) and accelerated heavy ions (75 MeV/u carbon, 29 keV/µm; 95 MeV/u argon, 230 keV/µm; GANIL, Caen, France). Cell survival was measured as colony forming ability; cell cycle progression was analyzed via fluorescence-activated cell scanning (FACS) by measurement of the content of propidium iodide-stained DNA, DNA damage was visualized by γH2AX

  8. Effects of ionizing radiation on wound healing of alveolar bone socket after extraction of rat maxillary molars

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, Hiroshi; Yosue, Takashi [Nippon Dental Univ., Tokyo (Japan). School of Dentistry; Nasu, Masanori

    2001-05-01

    The purpose of this study was to examine the effects of radiation on the healing process of tooth extraction wounds. X-ray doses of 10 Gy or 20 Gy were delivered, once, to the maxillofacial area of Wistar-strain rats. Then, 24 hours after irradiation, the maxillary first molars were extracted bilaterally. The animals were sacrificed 3, 7, 10, 14, 21, 42, and 84 days after tooth extraction, and the maxilla were sliced, to make thin sections. These specimens were then double stained with alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP). The ratio of bone area to socket area (bone formation ratio), the ratio of bone length to ALP positive area length (ALP positive ratio), and the number of TRAP-positive cells, were evaluated. The results showed: The bone formation ratios at days 3 and 7 after tooth extraction were significantly low in both irradiation groups, compared with those for the non-irradiation group. The ALP positive reaction ratio peaked 7 days after in the non-irradiation group. In both irradiation groups, the ratios that were worked out at 3 days and 7 days after were significantly lower than those in the non-irradiation group. There was no significant difference in the number of TRAP-positive cells between the non-irradiation group and the 10 Gy irradiation group. In the 20 Gy irradiation group, the TRAP-positive cell count plummeted to a significantly low level at 3 days after tooth extraction, compared with that in the non-irradiation group. (author)

  9. Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model.

    Science.gov (United States)

    Zhao, Ge; Usui, Marcia L; Underwood, Robert A; Singh, Pradeep K; James, Garth A; Stewart, Philip S; Fleckman, Philip; Olerud, John E

    2012-01-01

    Bacterial biofilm has been shown to play a role in delaying wound healing of chronic wounds, a major medical problem that results in significant health care burden. A reproducible animal model could be very valuable for studying the mechanism and management of chronic wounds. Our previous work showed that Pseudomonas aeruginosa (PAO1) biofilm challenge on wounds in diabetic (db/db) mice significantly delayed wound healing. In this wound time course study, we further characterize the bacterial burden, delayed wound healing, and certain aspects of the host inflammatory response in the PAO1 biofilm-challenged db/db mouse model. PAO1 biofilms were transferred onto 2-day-old wounds created on the dorsal surface of db/db mice. Control wounds without biofilm challenge healed by 4 weeks, consistent with previous studies; none of the biofilm-challenged wounds healed by 4 weeks. Of the biofilm-challenged wounds, 64% healed by 6 weeks, and all of the biofilm-challenged wounds healed by 8 weeks. During the wound-healing process, P. aeruginosa was gradually cleared from the wounds while the presence of Staphylococcus aureus (part of the normal mouse skin flora) increased. Scabs from all unhealed wounds contained 10(7) P. aeruginosa, which was 100-fold higher than the counts isolated from wound beds (i.e., 99% of the P. aeruginosa was in the scab). Histology and genetic analysis showed proliferative epidermis, deficient vascularization, and increased inflammatory cytokines. Hypoxia inducible factor expression increased threefold in 4-week wounds. In summary, our study shows that biofilm-challenged wounds typically heal in approximately 6 weeks, at least 2 weeks longer than nonbiofilm-challenged normal wounds. These data suggest that this delayed wound healing model enables the in vivo study of bacterial biofilm responses to host defenses and the effects of biofilms on host wound healing pathways. It may also be used to test antibiofilm strategies for treating chronic wounds.

  10. Evaluation of bone marrow derived mesenchymal stem cells for full-thickness wound healing in comparison to tissue engineered chitosan scaffold in rabbit.

    Science.gov (United States)

    Rajabian, Mohammad Hossein; Ghorabi, Gholam Hossein; Geramizadeh, Bita; Sameni, Safoura; Ayatollahi, Maryam

    2017-02-01

    Chronic wounds present a major challenge in modern medicine. Even under optimal conditions, the healing process may lead to scarring and fibrosis. The ability of mesenchymal stem cells (MSCs) to differentiate into other cell types makes these cells an attractive therapeutic tool for cell transplantation. Both tissue-engineered construct and MSC therapy are among the current wound healing procedures and potential care. Chitosan has been widely applied in tissue engineering because of its biocompatibility and biodegradability. The aim of the current work was to compare the efficiency of MSCs and chitosan dressing, alone or in combination treatment on wound healing. This study was conducted on 15 rabbits, which were randomly divided in 3 groups based on the type of treatment with MSCs, chitosan dressing and combination of both. A full-thickness skin defect was excised from the right and left side of the back of each animals. Defects on right sides were filled with treatments and left side defects were left as control. Evaluation of the therapeutic effectiveness was performed through a variety of clinical and microscopical evaluations and measurements of the process of wound healing on days 7, 14, 21, and 28. Histological evaluation of wound healing was classified by different scoring systems. The data indicated that wounds treated with bone marrow derived MSC had enhanced cellularity and better epidermal regeneration. During the early stages of wound healing, the closure rate of bone marrow derived MSC-treated wounds were significantly higher than other treatments (Pchitosan treatment was slower than the control group. This study revealed advanced granulation tissue formation and epithelialization in wounds treated with MSCs, and may suggests this treatment as an effective applicant in wound healing process. Chitosan scaffold dressings, whether alone or in combination with MSCs, have worsened the wound healing as compared to the control group. Copyright © 2016

  11. The Digital Astronaut Project Bone Remodeling Model

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem; Lewandowski, Beth E.; Thompson, William K.; Sibonga, Jean D.

    2014-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

  12. Effects of Silk Sericin on Incision Wound Healing in a Dorsal Skin Flap Wound Healing Rat Model

    Science.gov (United States)

    Ersel, Murat; Uyanikgil, Yigit; Akarca, Funda Karbek; Ozcete, Enver; Altunci, Yusuf Ali; Karabey, Fatih; Cavusoglu, Turker; Meral, Ayfer; Yigitturk, Gurkan; Cetin, Emel Oyku

    2016-01-01

    Background The wound healing process is complex and still poorly understood. Sericin is a silk protein synthesized by silk worms (Bombyx mori). The objective of this study was to evaluate in vivo wound healing effects of a sericin-containing gel formulation in an incision wound model in rats. Material/Methods Twenty-eight Wistar-Albino rats were divided into 4 groups (n=7). No intervention or treatment was applied to the Intact control group. For other groups, a dorsal skin flap (9×3 cm) was drawn and pulled up with sharp dissection. The Sham operated group received no treatment. The Placebo group received placebo gel without sericin applied to the incision area once a day from day 0 to day 9. The Sericin Group 3 received 1% sericin gel applied to the incision area once a day from day 0 to day 9. Hematoxylin and eosin stain was applied for histological analysis and Mallory-Azan staining was applied for histoimmunochemical analysis of antibodies and iNOS (inducible nitric oxide synthase), and desmin was applied to paraffin sections of skin wound specimens. Parameters of oxidative stress were measured in the wound area. Results Epidermal thickness and vascularization were increased, and hair root degeneration, edema, cellular infiltration, collagen discoloration, and necrosis were decreased in Sericin group in comparison to the Placebo group and the Sham operated group. Malonyldialdehyde (MDA) levels were decreased, but superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were increased in the sericin group. Conclusions We found that sericin had significant positive effects on wound healing and antioxidant activity. Sericin-based formulations can improve healing of incision wounds. PMID:27032876

  13. Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model.

    Directory of Open Access Journals (Sweden)

    Peter Michael Prodinger

    Full Text Available Low molecular weight heparin (LMWH is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus volume was enhanced (sign. for Rivaroxaban and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban. Trabecular thickness was reduced (sign. for Rivaroxaban. Furthermore, both drugs showed significant enlarged bone (callus surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits.

  14. Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model

    Science.gov (United States)

    Prodinger, Peter Michael; Burgkart, Rainer; Kreutzer, Kilian; Liska, Franz; Pilge, Hakan; Schmitt, Andreas; Knödler, Martina; Holzapfel, Boris Michael; Hapfelmeier, Alexander; Tischer, Thomas; Bissinger, Oliver

    2016-01-01

    Low molecular weight heparin (LMWH) is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto) is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus) volume was enhanced (sign. for Rivaroxaban) and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban). Trabecular thickness was reduced (sign. for Rivaroxaban). Furthermore, both drugs showed significant enlarged bone (callus) surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits. PMID:27455072

  15. Novel solutions for a model of wound healing angiogenesis

    Science.gov (United States)

    Harley, K.; van Heijster, P.; Marangell, R.; Pettet, G. J.; Wechselberger, M.

    2014-12-01

    We prove the existence of novel, shock-fronted travelling wave solutions to a model of wound healing angiogenesis studied in Pettet et al (2000 IMA J. Math. App. Med. 17 395-413) assuming two conjectures hold. In the previous work, the authors showed that for certain parameter values, a heteroclinic orbit in the phase plane representing a smooth travelling wave solution exists. However, upon varying one of the parameters, the heteroclinic orbit was destroyed, or rather cut-off, by a wall of singularities in the phase plane. As a result, they concluded that under this parameter regime no travelling wave solutions existed. Using techniques from geometric singular perturbation theory and canard theory, we show that a travelling wave solution actually still exists for this parameter regime. We construct a heteroclinic orbit passing through the wall of singularities via a folded saddle canard point onto a repelling slow manifold. The orbit leaves this manifold via the fast dynamics and lands on the attracting slow manifold, finally connecting to its end state. This new travelling wave is no longer smooth but exhibits a sharp front or shock. Finally, we identify regions in parameter space where we expect that similar solutions exist. Moreover, we discuss the possibility of more exotic solutions.

  16. Modeling the effects of systemic mediators on the inflammatory phase of wound healing.

    Science.gov (United States)

    Cooper, Racheal L; Segal, Rebecca A; Diegelmann, Robert F; Reynolds, Angela M

    2015-02-21

    The normal wound healing response is characterized by a progression from clot formation, to an inflammatory phase, to a repair phase, and finally, to remodeling. In many chronic wounds there is an extended inflammatory phase that stops this progression. In order to understand the inflammatory phase in more detail, we developed an ordinary differential equation model that accounts for two systemic mediators that are known to modulate this phase, estrogen (a protective hormone during wound healing) and cortisol (a hormone elevated after trauma that slows healing). This model describes the interactions in the wound between wound debris, pathogens, neutrophils and macrophages and the modulation of these interactions by estrogen and cortisol. A collection of parameter sets, which qualitatively match published data on the dynamics of wound healing, was chosen using Latin Hypercube Sampling. This collection of parameter sets represents normal healing in the population as a whole better than one single parameter set. Including the effects of estrogen and cortisol is a necessary step to creating a patient specific model that accounts for gender and trauma. Utilization of math modeling techniques to better understand the wound healing inflammatory phase could lead to new therapeutic strategies for the treatment of chronic wounds. This inflammatory phase model will later become the inflammatory subsystem of our full wound healing model, which includes fibroblast activity, collagen accumulation and remodeling.

  17. Radiologic assessment of bone healing after orthognathic surgery using fractal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kwang Soo; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul; Park, Tae Won [College of Dentistry, Seoul National University, Seoul (Korea, Republic of); Jeon, In Seong [Department of Dentistry, Inje University Sanggyepaik Hospital, Seoul (Korea, Republic of); Kim, Jong Dae [Division of Information and Communication Engineering, Hallym university, Chuncheon (Korea, Republic of)

    2002-12-15

    To evaluate the radiographic change of operation sites after orthognathic surgery using the digital image processing and fractal analysis. A series of panoramic radiographs of thirty-five randomly selected patients who had undergone mandibular orthognathic surgery (bilateral sagittal split ramus osteotomy) without clinical complication for osseous healing, were taken. The panoramic radiographs of each selected patient were taken at pre-operation (stage 0), 1 or 2 days after operation (stage 1), 1 month after operation (stage 2), 6 months after operation (stage 3), and 12 months after operation (stage 4). The radiographs were digitized at 600 dpi, 8 bit, and 256 gray levels. The region of interest, centered on the bony gap area of the operation site, was selected and the fractal dimension was calculated by using the tile-counting method. The mean values and standard deviations of fractal dimension for each stage were calculated and the differences among stage 0, 1, 2, 3, and 4 were evaluated through repeated measures of the ANOVA and paired t-test. The mean values and standard deviations of the fractal dimensions obtained from stage 0, 1, 2, 3, and 4 were 1.658 {+-} 0.048, 1.580 {+-} 0.050, 1.607 {+-} 0.046, 1.624 {+-} 0.049, and 1.641 {+-} 0.061, respectively. The fractal dimensions from stage 1 to stage 4 were shown to have a tendency to increase (p<0.05). The tendency of the fractal dimesion to increase relative to healing time may be a useful means of evaluating post-operative bony healing of the osteotomy site.

  18. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket.

    Science.gov (United States)

    Nishida, Erika; Miyaji, Hirofumi; Kato, Akihito; Takita, Hiroko; Iwanaga, Toshihiko; Momose, Takehito; Ogawa, Kosuke; Murakami, Shusuke; Sugaya, Tsutomu; Kawanami, Masamitsu

    2016-01-01

    Graphene oxide (GO) consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1 µg/mL GO scaffold were, respectively, approximately 2.5-fold and 1.4-fold greater than those of the control. Particularly, the infiltration of ED2-positive (M2) macrophages and blood vessels were prominent in the GO scaffold. Dog bone-formation tests showed that 1 µg/mL GO scaffold implantation enhanced bone formation. New bone formation following GO scaffold implantation was enhanced fivefold compared to that in control subjects. These results suggest that GO was biocompatible and had high bone-formation capability for the scaffold

  19. Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model.

    Science.gov (United States)

    Mohanty, Chandana; Das, Manasi; Sahoo, Sanjeeb K

    2012-10-01

    Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in impaired wound healing. Curcumin has been reported to improve wound healing in different animal models. In order to increase the efficacy of curcumin in the healing arena a curcumin loaded oleic acid based polymeric (COP) bandage was formulated. The in vivo wound healing potency was compared with void bandage and control (cotton gauze treatment) in a rat model. Biochemical parameters and histological analysis revealed increased wound reduction and enhanced cell proliferation in COP bandage treated groups due to its efficient free radical scavenging properties. Comparative acceleration in wound healing was due to early implementation of fibroblasts and its differentiation (increased level of α-smooth muscle actin). Western blotting and semiquantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals leading to reduced antioxidative enzyme activity. Further evidence at mRNA and protein level indicates that our system is potent enough to reduce the inflammatory response mediated by the NFκB pathway during wound healing. With this background, we anticipate that such a versatile approach may seed new arena for topical wound healing in the near future.

  20. From Pain to Healing:Cure for Trauma in Bone by Fae Myenne Ng

    Institute of Scientific and Technical Information of China (English)

    YAO Wei

    2015-01-01

    Fae Myenne Ng, one of dominant writers in American literary circle currently, had been making her efforts in Bone for ten years. In Bone, Ng depicts the trauma Chinese-Americans suffered profoundly while trying to offer therapy to the trauma⁃tized. The narrator, Leila and her stepfather Leon come to terms with trauma by their own ways. What ’s more, Ng records her own life experience in a way to work through trauma and remains her own understanding about the solution to trauma.

  1. Histological evaluation of healing after transalveolar maxillary sinus augmentation with bioglass and autogenous bone

    DEFF Research Database (Denmark)

    Stavropoulos, Andreas; Sima, Catalin; Sima, Andrea

    2012-01-01

    the transalveolar osteotomy by means of a trephine bur and non-decalcified sections through the long axis of the cylinder were produced. After a strict selection process, taking into account the presurgical residual bone height and biopsy length, 8 and 15 biopsies representing the new tissues formed inside...

  2. Type 2 diabetes mellitus impairs bone healing of dental implants in GK rats.

    Science.gov (United States)

    Wang, Feng; Song, Ying-liang; Li, De-hua; Li, Cui-xia; Wang, Yao; Zhang, Ning; Wang, Bao-gang

    2010-04-01

    Type 2 diabetes is an increasingly prevalent disease with oral health manifestations. In this study, titanium implants were placed in the femora of 10 type 2 diabetic and 10 age-matched normal rats. We compared the results of bone histomorphometry around the dental implants at 4 and 8 weeks postsurgery.

  3. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket

    Directory of Open Access Journals (Sweden)

    Nishida E

    2016-05-01

    Full Text Available Erika Nishida,1 Hirofumi Miyaji,1 Akihito Kato,1 Hiroko Takita,2 Toshihiko Iwanaga,3 Takehito Momose,1 Kosuke Ogawa,1 Shusuke Murakami,1 Tsutomu Sugaya,1 Masamitsu Kawanami11Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan; 2Support Section for Education and Research, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan; 3Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, JapanAbstract: Graphene oxide (GO consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM, physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1

  4. EXPERIMENTAL ANALYSIS OF THE HEALING PROCESS IN THE AREA OF TIBIAL BONE FRACTURE

    Directory of Open Access Journals (Sweden)

    I. F. Аkhtyamov

    2016-01-01

    Full Text Available Purpose. To quantify the density of the cortical bone of the tibia in the area of reparative regeneration and the state of the vascular bed (hemodynamics of the operated limb under intramedullary osteosynthesis using pins coated with titanium and hafnium nitrides. Materials and methods. In the experiment, changes in the bone density and the characteristics of the local blood supply were studied on 40 outbred rabbits which underwent intramedullary osteosynthesis by the use of pins with a nanocoating based on superhard compounds which consist of titanium and hafnium nitrides and pins without a coating. Using color Doppler mode helped to evaluate the condition of the vascular bed proximally to the fracture site. Results. It is noted that the use of pins with the described coating above did not violate the osteoregeneration staging. The density of the cortical bone in the test group exceeded that of the comparison group by an average of 30%. Bone remodeling processes in the test group completed at an earlier date, as determined by the higher rates of its density. In the study of the vascular bed of the operated limb, it was found that on the 10th day of the experiment, an increase in the maximal velocity of the blood flow was recorded (TAMAX. In animals of the test group this index approached preoperative values on the 30th day, while in animals of the comparison group this index approached the initial values only by the 60th day. Conclusion. The use of implants coated with titanium and hafnium nitrides which are characterized by high strength, thermal and chemical stability is accompanied by the formation of a cortical bone in the area of osteotomy with higher density characteristics. The changes which are typical of the vasodilatation in the area of injury in the early postoperative period can be regarded as a positive factor in the formation of primary bone union. In the group where implants coated with titanium and hafnium nitrides were used

  5. Healing of Stress Fracture in an Animal Model

    Science.gov (United States)

    2005-09-01

    performed on cross sections of the midshaft ulna. Periosteal woven bone formation on the periosteal surface resulted from fatigue loading. There was no...panel B (loaded I day microcracks, woven bone (W) on the periosteal surface and resorption spaces before imaging). (R) in the cortex were found 14 days...al.(3") showed that and, subsequently, the number of loading cycles to which a tibial aBMD increased by 5.2% in military recruits during a bone is

  6. Modeling Self-Healing of Concrete Using Hybrid Genetic Algorithm–Artificial Neural Network

    National Research Council Canada - National Science Library

    Ramadan Suleiman, Ahmed; Nehdi, Moncef

    2017-01-01

    .... The model inputs include the cement content, water-to-cement ratio (w/c), type and dosage of supplementary cementitious materials, bio-healing materials, and both expansive and crystalline additives...

  7. Modeling and experimentation of bone drilling forces.

    Science.gov (United States)

    Lee, JuEun; Gozen, B Arda; Ozdoganlar, O Burak

    2012-04-05

    Prediction and control of bone drilling forces are critical to the success of many orthopaedic operations. Uncontrolled and large forces can cause drill-bit breakage, drill breakthrough, excessive heat generation, and mechanical damage to the bone. This paper presents a mechanistic model for prediction of thrust forces and torques experienced during bone drilling. The model incorporates the radially varying drill-bit geometry and cutting conditions analytically, while capturing the material and friction properties empirically through a specific energy formulation. The forces from the chisel edge are modeled by considering the indentation process that occurs in the vicinity of the drill-bit axis. A procedure is outlined to calibrate the specific energies, where only a small number of calibration experiments are required for a wide range of drilling conditions and drill-bit geometry. The calibration parameters for the cortical portions of bovine tibia are identified through drilling tests. Subsequently, a series of validation tests are conducted under different feed rates and spindle speeds. The thrust forces and torques were observed to vary considerably between bones from different animals. The forces from the model were seen to match well with those from the experimentation within the inherent variations from the bone characteristics. The model can be used to select favorable drilling conditions, to assist in robotic surgeries, and to design optimal orthopaedic drill bits. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Bone Marrow-Derived Cells Contribute to Epithelial Engraftment during Wound Healing

    OpenAIRE

    Borue, Xenia; Lee, Sean; Grove, Joanna; Herzog, Erica L.; Harris, Robert; Diflo, Thomas; Glusac, Earl; Hyman, Kevin; Theise, Neil D.; Krause, Diane S.

    2004-01-01

    Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (≤ 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mic...

  9. Histopathological evaluation of potential impact of β-tricalcium phosphate (HA+ β-TCP) granules on healing of segmental femur bone defect.

    Science.gov (United States)

    Eftekhari, H; Farahpour, M R; Rabiee, S M

    2015-01-01

    Histopathological evaluation of β-tricalcium phosphate (HA+ β-TCP) granules demonstrated that it has properties to heal segmental femur bone defect in rat. In this study, 27 male white rats were examined. Rats were divided into tree groups. Surgical procedures were done after IP administration of ketamine 5 % and xylazine HCL 2 %. Then an approximately 5-mm long, 3-mm deep and 2-mm wide bone defect was created in the femur of one of the hind limbs using a No. 0.14 round bur. After inducing the surgical wound, all rats were colored and randomly divided into three experimental groups of nine animals each: Group 1 received medical pure β-tricalcium phosphate granules, group 2 received hydroxyapatite and third group was a control group with no treatment. Histopathological evaluation was performed on days 15, 30 and 45 after surgery. On day 45 after surgery, the quantity of newly formed lamellar bone in the healing site in β-TCP group was better than onward compared to HA and control groups. In conclusion, β-tri calcium phosphate (β-TCP) granules exhibited a reproducible bone-healing potential (Fig. 10, Ref. 28).

  10. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  11. Characterization of an ovine bilateral critical sized bone defect iliac wing model to examine treatment modalities based on bone tissue engineering.

    Science.gov (United States)

    Lansdowne, Jennifer L; Devine, Declan; Eberli, Ursula; Emans, Pieter; Welting, Tim J M; Odekerken, Jim C E; Schiuma, Damiano; Thalhauser, Martin; Bouré, Ludovic; Zeiter, Stephan

    2014-01-01

    Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

  12. Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Jennifer L. Lansdowne

    2014-01-01

    Full Text Available Critical sized bone defect (CSBD animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control or filled with autologous corticocancellous bone graft (clinical gold standard, positive control was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

  13. [THE BONE DEFECT HEALING UNDER THE INFLUENCE OF RADIAL EXTRACORPOREAL SHOCK-WAVE THERAPY IN EXPERIMENT].

    Science.gov (United States)

    Gertsen, G I; Se-Fey; Ostapchuk, R M; Lesovoy, A V; Zherebchuk, V V

    2016-03-01

    In experiment on 24 rabbits the processes of reparative osteogenesis in perforated defect of proximal tibial metaphysis under the influence of extracorporeal shock-wave therapy were studied. In accordance to data of clinical, roentgenological and morphological investiagations, conducted in terms 5, 15, 30 and 45 days of observation, there was established, that under the influence of extracorporeal shock-wave therapy in the bone marrow in the traumatic region a vasodilatation, as well as the blood cells exit from capillaries and sinusoid vessels with creation of massive regions of osseous endostal regenerate, guaranteeing the tibial integrity restoration, occurs.

  14. Bone stimulation for fracture healing: What′s all the fuss?

    Directory of Open Access Journals (Sweden)

    Victoria Galkowski

    2009-01-01

    Full Text Available Approximately 10% of the 7.9 million annual fracture patients in the United States experience nonunion and/or delayed unions, which have a substantial economic and quality of life impact. A variety of devices are being marketed under the name of "bone growth stimulators." This article provides an overview of electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock waves. More research is needed for knowledge of appropriate device configurations, advancement in the field, and encouragement in the initiation of new trials, particularly large multicenter trials and randomized control trials that have standardized device and protocol methods.

  15. The Healing Effect of Bone Marrow-Derived Stem Cells in Knee Osteoarthritis: A Case Report

    Science.gov (United States)

    Mehrabani, Davood; Mojtahed Jaberi, Fereidoon; Zakerinia, Maryam; Hadianfard, Mohammad Javad; Jalli, Reza; Tanideh, Nader; Zare, Shahrokh

    2016-01-01

    Osteoarthritis (OA) is a prevalent chronic disease impacting on quality of life and has societal and economical burden increasing with age. Yet, no confirmed pharmacological, biological or surgical therapy could prevent the progressive destruction of OA joint. Mesenchymal stem cells (MSCs) with immunosuppressive activities emerged a potential therapy. We describe a magnetic resonance images (MRI) approved 47 years old nomad female suffering from a severe right knee OA. After intra-articular injection of 36×106 passage 2 of bone marrow-derived stem cells (BMSCs), the patient’s functional status of the knee, the number of stairs she could climb, the pain on visual analog scale (VAS) and walking distance improved after two months post-transplantation. MRI revealed an extension of the repaired tissue over subchondral bone. So as MSC transplantation is a simple technique, resulted into pain relief, minimized donor-site morbidity, provided a better quality of life, significantly improved cartilage quality with no need to hospitalization or surgery, cell transplantation can be considered as a reliable alternative treatment for chronic knee OA. Therefore these findings can be added to the literature on using BMSCs for treatment of OA. PMID:27579273

  16. Inhibition of Midkine Augments Osteoporotic Fracture Healing.

    Directory of Open Access Journals (Sweden)

    Melanie Haffner-Luntzer

    Full Text Available The heparin-binding growth and differentiation factor midkine (Mdk is proposed to negatively regulate osteoblast activity and bone formation in the adult skeleton. As Mdk-deficient mice were protected from ovariectomy (OVX-induced bone loss, this factor may also play a role in the pathogenesis of postmenopausal osteoporosis. We have previously demonstrated that Mdk negatively influences bone regeneration during fracture healing. Here, we investigated whether the inhibition of Mdk using an Mdk-antibody (Mdk-Ab improves compromised bone healing in osteoporotic OVX-mice. Using a standardized femur osteotomy model, we demonstrated that Mdk serum levels were significantly enhanced after fracture in both non-OVX and OVX-mice, however, the increase was considerably greater in osteoporotic mice. Systemic treatment with the Mdk-Ab significantly improved bone healing in osteoporotic mice by increasing bone formation in the fracture callus. On the molecular level, we demonstrated that the OVX-induced reduction of the osteoanabolic beta-catenin signaling in the bony callus was abolished by Mdk-Ab treatment. Furthermore, the injection of the Mdk-Ab increased trabecular bone mass in the skeleton of the osteoporotic mice. These results implicate that antagonizing Mdk may be useful for the therapy of osteoporosis and osteoporotic fracture-healing complications.

  17. Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats.

    Science.gov (United States)

    Gopal, Anu; Kant, Vinay; Gopalakrishnan, Anu; Tandan, Surendra K; Kumar, Dinesh

    2014-05-15

    Copper possesses efficacy in wound healing which is a complex phenomenon involving various cells, cytokines and growth factors. Copper nanoparticles modulate cells, cytokines and growth factors involved in wound healing in a better way than copper ions. Chitosan has been shown to be beneficial in healing because of its antibacterial, antifungal, biocompatible and biodegradable polymeric nature. In the present study, chitosan-based copper nanocomposite (CCNC) was prepared by mixing chitosan and copper nanoparticles. CCNC was applied topically to evaluate its wound healing potential and to study its effects on some important components of healing process in open excision wound model in adult Wistar rats. Significant increase in wound contraction was observed in the CCNC-treated rats. The up-regulation of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1(TGF-β1) by CCNC-treatment revealed its role in facilitating angiogenesis, fibroblast proliferation and collagen deposition. The tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were significantly decreased and increased, respectively, in CCNC-treated rats. Histological evaluation showed more fibroblast proliferation, collagen deposition and intact re-epithelialization in CCNC-treated rats. Immunohistochemistry of CD31 revealed marked increase in angiogenesis. Thus, we concluded that chitosan-based copper nanocomposite efficiently enhanced cutaneous wound healing by modulation of various cells, cytokines and growth factors during different phases of healing process.

  18. The Effect of Platelet-rich Fibrin Matrix on Rotator Cuff Healing in a Rat Model.

    Science.gov (United States)

    Hasan, S; Weinberg, M; Khatib, O; Jazrawi, L; Strauss, E J

    2016-01-01

    The purpose of the current study was to determine if the application of platelet-rich fibrin matrix could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model. 25 Lewis syngeneic rats underwent bilateral tenotomy and repair of the supraspinatus tendon. 10 separate rats were used for PRFM harvest. All left (control) shoulders underwent transosseous rotator cuff repair, while all right (treatment) shoulders were repaired similarly with PRFM augmentation. 9 rats were sacrificed at 2-weeks and ten at 4-weeks for biomechanical testing. 3 separate rats were sacrificed at 2-weeks and 4-weeks each for histologic analysis of the insertion site. At 2 weeks, the experimental group repairs were significantly stronger in ultimate load to failure (P=0.01), stress (P=0.03), and stiffness (P=0.03). Differences in biomechanical testing were not found between the groups at 4 weeks. Histological analysis revealed less collagen organization and cartilage formation at the insertion site in the experimental group. Semiquantitative histologic analysis confirmed our qualitative assessment of the specimens. PRFM does not recapitulate the native enthesis, but rather induces an exuberant and disordered healing response that is characterized by fibrovascular scar tissue.

  19. Modeling of the buccal and lingual bone walls of fresh extraction sites following implant installation.

    Science.gov (United States)

    Araújo, Mauricio G; Wennström, Jan L; Lindhe, Jan

    2006-12-01

    To determine whether the reduction of the alveolar ridge that occurs following tooth extraction and implant placement is influenced by the size of the hard tissue walls of the socket. Six beagle dogs were used. The third premolar and first molar in both quadrants of the mandible were used. Mucoperiostal flaps were elevated and the distal roots were removed. Implants were installed in the fresh extraction socket in one side of the mandible. The flaps were replaced to allow a semi-submerged healing. The procedure was repeated in the contra later side of the mandible after 2 months. The animals were sacrificed 1 month after the final implant installation. The mandibles were dissected, and each implant site was removed and processed for ground sectioning. Marked hard tissue alterations occurred during healing following tooth extraction and implant installation in the socket. The marginal gap that was present between the implant and the walls of the socket at implantation disappeared as a result of bone fill and resorption of the bone crest. The modeling in the marginal defect region was accompanied by marked attenuation of the dimensions of both the delicate buccal and the wider lingual bone wall. Bone loss at molar sites was more pronounced than at the premolar locations. Implant placement failed to preserve the hard tissue dimension of the ridge following tooth extraction. The buccal as well as the lingual bone walls were resorbed. At the buccal aspect, this resulted in some marginal loss of osseointegration.

  20. Suplementação de vitamina C não acelera o processo de consolidação de fratura da tíbia em ratos Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model

    Directory of Open Access Journals (Sweden)

    Vincenzo Giordano

    2012-01-01

    Full Text Available OBJETIVO: Investigar a função da suplementação de ácido ascórbico na consolidação de fraturas da tíbia de ratos. MÉTODOS: Trinta ratos Wistar machos foram aleatoriamente divididos nos grupos Vitamina C (Grupo A e sham (Grupo B, com 15 ratos em cada grupo. Ao grupo A foram administrados 200mg/kg de ácido ascórbico por dia intraperitonialmente e ao grupo B,5ml/kg de soro fisiológico intraperitonialmente uma vez ao dia. Os animais foram separados em duplas e colocados em gaiolas, com água e ração padrão ad libitum. As fraturas foram produzidas manualmente, não foram estabilizadas nem foi usado qualquer tipo de imobilização. Duas, quatro e seis semanas após a fratura, cinco ratos de cada grupo foram anestesiados e sacrificados por deslocamento cervical. O calo foi dissecado, preparado e analisado histologicamente. A análise histomorfológica foi realizada seis semanas após a fratura e o estágio de consolidação determinado a partir de escala de cinco pontos. RESULTADOS: Não houve diferenças histológicas e histomorfológicas entre os animais nos três diferentes estágios usados no experimento. Seis semanas após a fratura, os cinco animais de cada grupo apresentaram completa consolidação óssea. CONCLUSÃO: Nas condições estudadas, a suplementação de Vitamina C não acelerou o processo de consolidação de fraturas da tíbia de ratos. Nível de evidência II, estudo individual com delineamento experimental.OBJECTIVE: To investigate the role of ascorbic acid supplementation on bone healing after rat tibia fracture. METHODS: Thirty male Wistar rats were randomly divided into Vitamin C (Group A and sham (Group B groups (15 rats each. Group A received 200 mg intraperitoneally per kg per day of ascorbic acid and Group B was given saline 5 ml per kg per day intraperitoneally once a day. The animals were caged in pairs and allowed free access to tap water and a standard rodent chow ad libitum. Fractures were produced

  1. The effect of platelet releasate on wound healing in animal models.

    Science.gov (United States)

    Ksander, G A; Sawamura, S J; Ogawa, Y; Sundsmo, J; McPherson, J M

    1990-05-01

    The alpha granules of platelets contain growth factors that are important in wound healing. We found that a major effect of thrombin-induced human platelet releasates in animal models of wound healing is to enhance the development of granulation tissue and new connective tissue matrix. These studies provide further evidence that platelet-derived protein factors may be useful in treating full-thickness dermal wounds by increasing the rate of granulation tissue formation.

  2. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats

    OpenAIRE

    Mehanna, Radwa A.; Iman Nabil; Noha Attia; Bary, Amany A.; Razek, Khalid A.; Ahmed, Tamer A. E.; Fatma Elsayed

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (...

  3. Expression of bone morphogenetic protein-2 after using chitosan gel with different molecular weight on wound healing process of dental extraction

    Directory of Open Access Journals (Sweden)

    Sularsih Sularsih

    2015-06-01

    Full Text Available Background: Bone morphogenetic protein-2 (BMP-2 is bone stimulator which capable of inducing differentiation of mesenchymal cells into osteoblast, stimulating bone formation in wound healing process of dental extraction. Chitosan is polymer composed N-acetylD-glucosamine unit that has been used in various applications in wound healing process and bone tissue engineering. Purpose: The objective of this research was to analyzed expressions of BMP-2 for 7,14 and 21 days after using chitosan gel with different molecular weight on wound healing process of dental extraction. Method: The research was an experimental laboratory study. Rattus nornegicus strain wistar male, aged 8-16 weeks, divided into 3 treatment groups namely group 1 and II which given chitosan gel 1 % with high and low molecular weight and group III as control which were not given chitosan gel. Chitosan gel were applied into the socket of dental extraction. Rat was decaputated 7,14 and 21 days after chitosan gel application and the jaw in the treated regions and control group were cut for immunohistochemical examination to observe BMP-2. Data were analyzed using ANOVA test. Result: The result of this research showed significant differences on BMP-2 for 7,14 and 21 days observation (p<0,05. The increasing of BMP-2 were found in the group which given chitosan gel with high molecular weight. Conclusion: It may be concluded that chitosan gel with high molecular weight can enhance the expresion of BMP-2 on wound healing process ofdental extraction.

  4. Low-intensity pulsed ultrasound increases bone volume, osteoid thickness and mineral apposition rate in the area of fracture healing in patients with a delayed union of the osteotomized fibula

    NARCIS (Netherlands)

    Rutten, S.; Nolte, P.A.; Korstjens, C.M.; van Duin, M.A.; Klein-Nulend, J.

    2008-01-01

    Introduction Low-intensity pulsed ultrasound (LIPUS) accelerates impaired fracture healing, but the exact mechanism is unknown. The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed union of the osteotomized fibula, by using histology

  5. Dynamical effect of fractures combined with brain injury on the bone healing and bone metabolism%骨折合并脑损伤对骨愈合和骨代谢的影响

    Institute of Scientific and Technical Information of China (English)

    周青; 刘进炼; 刘超群; 周耀东; 陈豪

    2015-01-01

    BACKGROUND:Peri-fracture nerve injury can inhibit osteoclast activity and promote early fracture healing. OBJECTIVE:To investigate dynamical y the effects of traumatic brain injury on the bone mineral density, microstructure, biomechanics property and bone metabolism in rat models of fractures. METHODS:Sixty-three male rats were randomly divided into three groups:sham group, simple fracture group and fracture combined with brain injury group. After 3, 6, and 3 months, the animals were sacrificed in batches under anesthesia, and then, the bones and serum specimens were used to detect the bone mineral density, microstructure, biomechanics property, serum cross-linked N-telopeptide of col agen type I and osteocalcin levels. RESULTS AND CONCLUSION:Compared with the simple fracture group, the fracture combined brain injury group had significantly increased bone mineral density of the proximal tibia, bone volume fraction of the cancel ous bone, trabecular thickness, cross-sectional area of tibial cortical bone and total area of the bone marrow, ultimate load and stress of the tibia, serum cross-linked N-telopeptide of col agen type I and osteocalcin levels at 3 and 6 weeks after modeling (P  目的:观察了大鼠肢体骨折合并脑损伤对骨密度、骨微结构、骨生物力学特征和骨代谢影响。  方法:63只大鼠随机分为假手术组、单纯骨折组和脑损伤合并骨折组。在术后3周、6周和3个月分批麻醉处死动物保存骨骼和血清标本,检测骨密度、骨微结构和生物力学性能以及血清Ⅰ型胶原氨基末端肽和骨钙素水平的变化。  结果与结论:与单纯骨折组相比,在造模3周和6周后,脑损伤合并骨折组胫骨近端的骨密度、松质骨微结构骨体积分数、骨小梁厚度、胫骨皮质骨截面总面积和骨髓腔面积、胫骨极限载荷和极限应力、血清原氨基末端肽和骨钙素水平均显著增高(P<0.05),造模后3个月,3组间

  6. Ricinus communis-based biopolymer and epidermal growth factor regulations on bone defect repair: A rat tibia model

    Science.gov (United States)

    Mendoza-Barrera, C.; Meléndez-Lira, M.; Altuzar, V.; Tomás, S. A.

    2003-01-01

    We report the effect of the addition of an epidermal growth factor to a Ricinus communis-based biopolymer in the healing of a rat tibia model. Bone repair and osteointegration after a period of three weeks were evaluated employing photoacoustic spectroscopy and x-ray diffraction. A parallel study was performed at 1, 2, 3, 4, 5, 6, 7, and 8 weeks with energy dispersive x-ray spectroscopy. We conclude that the use of an epidermal growth factor (group EGF) in vivo accelerates the process of bony repair in comparison with other groups, and that the employment of the Ricinus communis-based biopolymer as a bone substitute decreases bone production.

  7. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  8. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  9. Evaluation of wound healing effects between Salvadora persica ointment and Solcoseryl jelly in animal model.

    Science.gov (United States)

    Imran, Hina; Ahmad, Mansoor; Rahman, Atiqur; Yaqeen, Zahra; Sohail, Tehmina; Fatima, Nudrat; Iqbal, Wasif; Yaqeen, Syed Shafay

    2015-09-01

    In this research study very first time a herbal ointment contain 10% Salvadora persica extract was compared with Solcosseryl jelly 10% and blank Vaseline to evaluate wound healing effects using excision wound healing model in animals. Three groups of rats (n-6) were experimentally wounded on the back of their neck. Group I was dressed with Vaseline containing 10% test drug, Group II was treated with thin layer of Solcoseryl jelly 10% as reference drug while Group III was dressed with thin layer of blank Vaseline as control group. The effect of vehicle on rate of wound healing were assessed and in all cases there were progressive decreased in wound area with time but wound dress with Vaseline containing S. persica extract and wound treated with Solcosseryl jelly significantly healed earlier than those treated with Vaseline. It is concluded that S. persica extract significantly enhance the acceleration rate of wound enclosure in rats.

  10. Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

    Science.gov (United States)

    Shen, Yu-I; Song, Hyun-Ho G; Papa, Arianne E; Burke, Jacqueline A; Volk, Susan W; Gerecht, Sharon

    2015-10-01

    Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients.

  11. A computational model for the flow of resin in self-healing composites

    Science.gov (United States)

    Hall, J.; Qamar, I. P. S.; Rendall, T. C. S.; Trask, R. S.

    2015-03-01

    To explore the flow characteristics of healing agent leaving a vascular network and infusing a damage site within a fibre reinforced polymer composite, a numerical model of healing agent flow from an orifice has been developed using smoothed particle hydrodynamics. As an initial validation the discharge coefficient for low Reynolds number flow from a cylindrical tank is calculated numerically, using two different viscosity formulations, and compared to existing experimental data. Results of this comparison are very favourable; the model is able to reproduce experimental results for the discharge coefficient in the high Reynolds number limit, together with the power-law behaviour for low Reynolds numbers. Results are also presented for a representative delamination geometry showing healing fluid behaviour and fraction filled inside the delamination for a variety of fluid viscosities. This work provides the foundations for the vascular self-healing community in calculating not only the flow rate through the network, but also, by simulating a representative damage site, the final location of the healing fluid within the damage site in order to assess the improvement in local and global mechanical properties and thus healing efficiency.

  12. Studies on focal alveolar bone healing with technetium (Tc)-99m labeled methylene diphosphonate and gold-collimated cadmium telluride probe

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchimochi, M.; Hosain, F.; Engelke, W.; Zeichner, S.J.; Ruttimann, U.E.; Webber, R.L. (National Institute of Dental Research, Bethesda, MD (USA))

    1991-01-01

    The benefit of using a collimator for a miniaturized cadmium telluride probe was evaluated by monitoring the bone-healing processes for 13 weeks after the induction of small iatrogenic alveolar bone lesions in one side of the mandible in beagles. Technetium (Tc)-99m labeled methylene diphosphonate (200 to 300 MBq, 5.1 to 8.1 mCi, in a solution of 0.5 to 1 ml, intravenously) was used as a bone-seeking radiopharmaceutical. The radioactivity over the bone lesion (L) and the contralateral normal site (C) in the mandible were measured between 1.5 and 2 hours after injection of the tracer, and the activity ratio L/C served as an index of relative bone uptake. A study of six dogs revealed that the healing response to a hemispheric bone defect of 2 mm diameter in the cortical bone could not be detected by an uncollimated probe, and in a repeated study in two dogs the use of a gold collimator (5 mm in diameter, 5 mm in length) did not increase the L/C ratio significantly. A second study in six dogs with 5 mm lesions showed that although systematic trends in the time courses of the L/C ratio obtained both with and without the collimator could be demonstrated, the L/C ratio of collimated versus uncollimated measurements was significantly (p less than 0.005) increased. In three of the latter six dogs, abscesses developed after 9 weeks, leading to a second increase (p less than 0.05) of the L/C ratio with collimation compared with the noninflammation group; without collimation no significant (p greater than 0.15) difference between the two groups could be demonstrated.

  13. The rational use of animal models in the evaluation of novel bone regenerative therapies.

    Science.gov (United States)

    Peric, Mihaela; Dumic-Cule, Ivo; Grcevic, Danka; Matijasic, Mario; Verbanac, Donatella; Paul, Ruth; Grgurevic, Lovorka; Trkulja, Vladimir; Bagi, Cedo M; Vukicevic, Slobodan

    2015-01-01

    Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poorly designed animal studies with inappropriate endpoints and inaccurate conclusions are being conducted. In this review, we discuss animal models, procedures, methods and technologies used in bone repair studies with the aim to assist investigators in planning and performing scientifically sound experiments that respect the wellbeing of animals. In the process of designing an animal study for bone repair investigators should consider: skeletal characteristics of the selected animal species; a suitable animal model that mimics the intended clinical indication; an appropriate assessment plan with validated methods, markers, timing, endpoints and scoring systems; relevant dosing and statistically pre-justified sample sizes and evaluation methods; synchronization of the study with regulatory requirements and additional evaluations specific to cell-based approaches. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Early Healing Events around Titanium Implant Devices with Different Surface Microtopography: A Pilot Study in an In Vivo Rabbit Model

    Directory of Open Access Journals (Sweden)

    Ester Orsini

    2012-01-01

    Full Text Available In the present pilot study, the authors morphologically investigated sandblasted, acid-etched surfaces (SLA at very early experimental times. The tested devices were titanium plate-like implants with flattened wide lateral sides and jagged narrow sides. Because of these implant shape and placement site, the device gained a firm mechanical stability but the largest portion of the implant surface lacked direct contact with host bone and faced a wide peri-implant space rich in marrow tissue, intentionally created in order to study the interfacial interaction between metal surface and biological microenvironment. The insertion of titanium devices into the proximal tibia elicited a sequence of healing events. Newly formed bone proceeded through an early distance osteogenesis, common to both surfaces, and a delayed contact osteogenesis which seemed to follow different patterns at the two surfaces. In fact, SLA devices showed a more osteoconductive behavior retaining a less dense blood clot, which might be earlier and more easily replaced, and leading to a surface-conditioning layer which promotes osteogenic cell differentiation and appositional new bone deposition at the titanium surface. This model system is expected to provide a starting point for further investigations which clarify the early cellular and biomolecular events occurring at the metal surface.

  15. Multiple verification in computational modeling of bone pathologies

    CERN Document Server

    Liò, Pietro; Paoletti, Nicola; 10.4204/EPTCS.67.8

    2011-01-01

    We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the...

  16. Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

    Science.gov (United States)

    Hambli, Ridha

    2014-01-01

    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

  17. The use of {sup 18}F-fluoride and {sup 18}F-FDG PET scans to assess fracture healing in a rat femur model

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, W.K.; Feeley, B.T.; Krenek, L.; Stout, D.B.; Chatziioannou, A.F. [David Geffen School of Medicine at UCLA, Center for Health Sciences, Department of Orthopaedic Surgery, Los Angeles, CA (United States); Lieberman, J.R. [University of Connecticut Health Center, The Musculoskeletal Institute, Department of Orthopaedic Surgery, Farmington, CT (United States)

    2007-08-15

    Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with {sup 18}F-fluoride ion, which localizes in regions of high osteoblastic activity, and {sup 18}F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, {sup 18}F-fluoride, and {sup 18}F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. {sup 18}F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using {sup 18}F-FDG PET imaging at any time point. This study suggests that {sup 18}F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time

  18. Mammalian cell models to advance our understanding of wound healing: a review.

    Science.gov (United States)

    Vidmar, Jerneja; Chingwaru, Constance; Chingwaru, Walter

    2017-04-01

    Rapid and efficient healing of damaged tissue is critical for the restoration of tissue function and avoidance of tissue defects. Many in vitro cell models have been described for wound healing studies; however, the mechanisms that underlie the process, especially in chronic or complicated wounds, are not fully understood. The identification of cell culture systems that closely simulate the physiology of damaged tissue in vivo is necessary. We describe the cell culture models that have enhanced our understanding, this far, of the wound healing process or have been used in drug discovery. Cell cultures derived from the epithelium, including corneal, renal, intestinal (IEC-8 cells and IEC-6), skin epithelial cells (keratinocytes, fibroblasts, and multipotent mesenchymal stem cells), and the endothelium (human umbilical vein endothelial cells, primary mouse endothelial cells, endodermal stem cells, human mesenchymal stem cells, and corneal endothelial cells) have played a pivotal role toward our understanding of the mechanisms of wound healing. More studies are necessary to develop co-culture cell models which closely simulate the environment of a wound in vivo. Cell culture models are invaluable tools to promote our understanding of the mechanisms that regulate the wound healing process and provide a platform for drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Modeling Self-Healing of Concrete Using Hybrid Genetic Algorithm-Artificial Neural Network.

    Science.gov (United States)

    Ramadan Suleiman, Ahmed; Nehdi, Moncef L

    2017-02-07

    This paper presents an approach to predicting the intrinsic self-healing in concrete using a hybrid genetic algorithm-artificial neural network (GA-ANN). A genetic algorithm was implemented in the network as a stochastic optimizing tool for the initial optimal weights and biases. This approach can assist the network in achieving a global optimum and avoid the possibility of the network getting trapped at local optima. The proposed model was trained and validated using an especially built database using various experimental studies retrieved from the open literature. The model inputs include the cement content, water-to-cement ratio (w/c), type and dosage of supplementary cementitious materials, bio-healing materials, and both expansive and crystalline additives. Self-healing indicated by means of crack width is the model output. The results showed that the proposed GA-ANN model is capable of capturing the complex effects of various self-healing agents (e.g., biochemical material, silica-based additive, expansive and crystalline components) on the self-healing performance in cement-based materials.

  20. Modeling Self-Healing of Concrete Using Hybrid Genetic Algorithm–Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Ahmed Ramadan Suleiman

    2017-02-01

    Full Text Available This paper presents an approach to predicting the intrinsic self-healing in concrete using a hybrid genetic algorithm–artificial neural network (GA–ANN. A genetic algorithm was implemented in the network as a stochastic optimizing tool for the initial optimal weights and biases. This approach can assist the network in achieving a global optimum and avoid the possibility of the network getting trapped at local optima. The proposed model was trained and validated using an especially built database using various experimental studies retrieved from the open literature. The model inputs include the cement content, water-to-cement ratio (w/c, type and dosage of supplementary cementitious materials, bio-healing materials, and both expansive and crystalline additives. Self-healing indicated by means of crack width is the model output. The results showed that the proposed GA–ANN model is capable of capturing the complex effects of various self-healing agents (e.g., biochemical material, silica-based additive, expansive and crystalline components on the self-healing performance in cement-based materials.

  1. Modeling Self-Healing of Concrete Using Hybrid Genetic Algorithm–Artificial Neural Network

    Science.gov (United States)

    Ramadan Suleiman, Ahmed; Nehdi, Moncef L.

    2017-01-01

    This paper presents an approach to predicting the intrinsic self-healing in concrete using a hybrid genetic algorithm–artificial neural network (GA–ANN). A genetic algorithm was implemented in the network as a stochastic optimizing tool for the initial optimal weights and biases. This approach can assist the network in achieving a global optimum and avoid the possibility of the network getting trapped at local optima. The proposed model was trained and validated using an especially built database using various experimental studies retrieved from the open literature. The model inputs include the cement content, water-to-cement ratio (w/c), type and dosage of supplementary cementitious materials, bio-healing materials, and both expansive and crystalline additives. Self-healing indicated by means of crack width is the model output. The results showed that the proposed GA–ANN model is capable of capturing the complex effects of various self-healing agents (e.g., biochemical material, silica-based additive, expansive and crystalline components) on the self-healing performance in cement-based materials. PMID:28772495

  2. Modeling keratinocyte wound healing dynamics: Cell-cell adhesion promotes sustained collective migration.

    Science.gov (United States)

    Nardini, John T; Chapnick, Douglas A; Liu, Xuedong; Bortz, David M

    2016-07-07

    The in vitro migration of keratinocyte cell sheets displays behavioral and biochemical similarities to the in vivo wound healing response of keratinocytes in animal model systems. In both cases, ligand-dependent Epidermal Growth Factor Receptor (EGFR) activation is sufficient to elicit collective cell migration into the wound. Previous mathematical modeling studies of in vitro wound healing assays assume that physical connections between cells have a hindering effect on cell migration, but biological literature suggests a more complicated story. By combining mathematical modeling and experimental observations of collectively migrating sheets of keratinocytes, we investigate the role of cell-cell adhesion during in vitro keratinocyte wound healing assays. We develop and compare two nonlinear diffusion models of the wound healing process in which cell-cell adhesion either hinders or promotes migration. Both models can accurately fit the leading edge propagation of cell sheets during wound healing when using a time-dependent rate of cell-cell adhesion strength. The model that assumes a positive role of cell-cell adhesion on migration, however, is robust to changes in the leading edge definition and yields a qualitatively accurate density profile. Using RNAi for the critical adherens junction protein, α-catenin, we demonstrate that cell sheets with wild type cell-cell adhesion expression maintain migration into the wound longer than cell sheets with decreased cell-cell adhesion expression, which fails to exhibit collective migration. Our modeling and experimental data thus suggest that cell-cell adhesion promotes sustained migration as cells pull neighboring cells into the wound during wound healing.

  3. Mathematical Model for the Mineralization of Bone

    Science.gov (United States)

    Martin, Bruce

    1994-01-01

    A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification 'halos,' in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. ne model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature.

  4. A predictive bone drilling force model for haptic rendering with experimental validation using fresh cadaveric bone.

    Science.gov (United States)

    Lin, Yanping; Chen, Huajiang; Yu, Dedong; Zhang, Ying; Yuan, Wen

    2017-01-01

    Bone drilling simulators with virtual and haptic feedback provide a safe, cost-effective and repeatable alternative to traditional surgical training methods. To develop such a simulator, accurate haptic rendering based on a force model is required to feedback bone drilling forces based on user input. Current predictive bone drilling force models based on bovine bones with various drilling conditions and parameters are not representative of the bone drilling process in bone surgery. The objective of this study was to provide a bone drilling force model for haptic rendering based on calibration and validation experiments in fresh cadaveric bones with different bone densities. Using a commonly used drill bit geometry (2 mm diameter), feed rates (20-60 mm/min) and spindle speeds (4000-6000 rpm) in orthognathic surgeries, the bone drilling forces of specimens from two groups were measured and the calibration coefficients of the specific normal and frictional pressures were determined. The comparison of the predicted forces and the measured forces from validation experiments with a large range of feed rates and spindle speeds demonstrates that the proposed bone drilling forces can predict the trends and average forces well. The presented bone drilling force model can be used for haptic rendering in surgical simulators.

  5. Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

    Science.gov (United States)

    Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M.; Longatto-Filho, Adhemar; Castro, António G.; Pedrosa, Jorge; Fraga, Alexandra G.

    2015-01-01

    Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

  6. Excisional wound healing is delayed in a murine model of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Akhil K Seth

    Full Text Available BACKGROUND: Approximately 15% of the United States population suffers from chronic kidney disease (CKD, often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment. METHODS: CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR. RESULTS: CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU and angiogenesis (CD31, with a concurrent increase in inflammation (CD45 as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS on qPCR. CONCLUSIONS: These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.

  7. 3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair.

    Science.gov (United States)

    Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong

    2014-09-10

    The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

  8. Impaired Fracture Healing after Hemorrhagic Shock

    Directory of Open Access Journals (Sweden)

    Philipp Lichte

    2015-01-01

    Full Text Available Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP of 35 mmHg for 90 minutes. Serum cytokines (IL-6, KC, MCP-1, and TNF-α were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. μCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.

  9. A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure

    NARCIS (Netherlands)

    Vermolen, F.J.; Javierre, E.

    2011-01-01

    A simplified finite-element model for wound healing is proposed. The model takes into account the sequential steps of dermal regeneration, wound contraction, angiogenesis and wound closure. An innovation in the present study is the combination of the aforementioned partially overlapping processes,

  10. A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure

    NARCIS (Netherlands)

    Vermolen, F.J.; Javierre, E.

    2011-01-01

    A simplified finite-element model for wound healing is proposed. The model takes into account the sequential steps of dermal regeneration, wound contraction, angiogenesis and wound closure. An innovation in the present study is the combination of the aforementioned partially overlapping processes, w

  11. Models for explaining the homeopathic healing process: a historical and critical account of principles central to homeopathy.

    Science.gov (United States)

    Guajardo, G; Wilson, J

    2005-01-01

    The success of Homeopathy in curing many diseases has been a serious challenge to science. Nineteenth century explanations for the healing process of Homeopathy cannot withstand the scrutiny of modern science and need to be abandoned or modified. The surviving propositions are discussed. A biocybernetic model with multilevels of electromagnetic feedback loops offers a hope of explaining the healing process. This model, its explanation of the healing process and experimental support are elaborated.

  12. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats

    Science.gov (United States)

    Mehanna, Radwa A.; Nabil, Iman; Attia, Noha; Bary, Amany A.; Razek, Khalid A.; Ahmed, Tamer A. E.; Elsayed, Fatma

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740

  13. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats

    Directory of Open Access Journals (Sweden)

    Radwa A. Mehanna

    2015-01-01

    Full Text Available Bone marrow-derived mesenchymal stem cells (BM-MSCs represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG, fibrin only group (FG, fibrin + MSCs group (FG + SCs, and fibrin + CM group (FG + CM. Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1 structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson’s trichrome-stained skin biopsies and (2 functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure.

  14. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats.

    Science.gov (United States)

    Mehanna, Radwa A; Nabil, Iman; Attia, Noha; Bary, Amany A; Razek, Khalid A; Ahmed, Tamer A E; Elsayed, Fatma

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although--later--none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM-via fibrin vehicle--could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure.

  15. An in vivo comparison of the modified Mason-Allen suture technique versus an inclined horizontal mattress suture technique with regard to tendon-to-bone healing: a biomechanical and histologic study in sheep.

    Science.gov (United States)

    Schlegel, Theodore F; Hawkins, Richard J; Lewis, Chad W; Turner, A Simon

    2007-01-01

    The purpose of this study is to examine long-term tendon-to-bone healing, by use of a sheep animal model, after rotator cuff repairs performed with 2 different suture techniques: an inclined horizontal mattress suture pattern placed with special arthroscopic instrumentation (HMS) and the modified Mason-Allen pattern (MMA). After a pre hoc power analysis, 18 skeletally mature sheep were randomly assigned to either the HMS or MMA repair technique, with contralateral limbs used for the control group. At 26 weeks, the animals were euthanized. Six sheep from each group underwent biomechanical testing. Load-to-failure and stiffness results indicated no statistically significant difference between the 2 groups. Avulsion of the tuberosity was the primary mode of failure for both groups. In the remaining 6 sheep, histologic evaluation demonstrated that, regardless of treatment, the tendon appeared completely healed in the bony trough. Because the long-term biomechanical and histologic properties of healed tendons repaired with an HMA technique are equal to those obtained with an MMA technique, the inclined horizontal mattress suture may be appropriate for arthroscopic rotator cuff repair. Short-term studies are necessary to determine whether these findings are true early after tendon repair, when failure may be most common.

  16. A finite deformation viscoelastic-viscoplastic constitutive model for self-healing materials

    Science.gov (United States)

    Shahsavari, H.; Naghdabadi, R.; Baghani, M.; Sohrabpour, S.

    2016-12-01

    In this paper, employing the Hencky strain, viscoelastic-viscoplastic response of self-healing materials is investigated. Considering the irreversible thermodynamics and using the effective configuration in the Continuum Damage-Healing Mechanics (CDHM), a phenomenological finite strain viscoelastic-viscoplastic constitutive model is presented. Considering finite viscoelastic and viscoplastic deformations, total deformation gradient is multiplicatively decomposed into viscoelastic and viscoplastic parts. Due to mathematical advantages and physical meaning of Hencky strain, this measure of strain is employed in the constitutive model development. In this regard, defining the damage and healing variables and employing the strain equivalence hypothesis, the strain tensor is determined in the effective configuration. Satisfying the Clausius-Duhem inequality, the evolution equations are introduced for the viscoelastic and viscoplastic strains. The damage and healing variables also evolve according to two different prescribed functions. To employ the proposed model in different loading conditions, the model is discretized in the semi-implicit form. Material parameters of the model are identified employing experimental tests on asphalt mixes available in the literature. Finally, capability of the model is demonstrated comparing the model predictions in the creep-recovery and repeated creep-recovery with the experimental results available in the literature and a good agreement between predicted and test results is revealed.

  17. The Effect of GSM Mobile Phone Electromagnetic Field on Femur Fracture Healing in a Rat Model

    Directory of Open Access Journals (Sweden)

    Ali Kalender

    2012-10-01

    Full Text Available Aim: Biological effects of electromagnetic field (EMF and their consequences on human health have been the subject of much interest and research in recent years. The aim of this study was to investigate the effects of 900 MHz EMF on femur fracture healing in a rat model. Material and Method: After sixty male Sprague-Dawley rats were exposed to a closed right femur fracture under anesthesia, the reduction and fixation were done with a 21 g needle. Then, 900 MHz radiation (2 W peak output power and 1.04 mW/cm2 power density was applied to EM group for one hour/day for seven days. The healing was assessed using radiological (Lane and Sandhu classification, histological (Huo scale for callus evaluation, and biomechanical (3-point bending measures at 2nd, 4th and 6th weeks after fracture. Results: Fracture healing, as assessed radiologically and histopathologically, in Group EM and control animals was similar at 2nd, 4th and 6th weeks. Fracture healing, as assessed biomechanically, was significantly better in Group EM compared to controls in those sacrificed at 2nd week post-procedure (p<0.05. Biomechanical strength was not different between the groups at 4th and 6th weeks. Discussion: 900 MHz EMF from a mobile phone in this rat femur fracture model resulted in no significant difference in healing from controls not exposed to EM radiation.

  18. Turing Systems, Entropy, and Kinetic Models for Self-Healing Surfaces

    Directory of Open Access Journals (Sweden)

    Eugene Kagan

    2010-03-01

    Full Text Available The paper addresses the methods of description of friction-induced self-healing at the interface between two solid bodies. A macroscopic description of self-healing is based on a Turing system for the transfer of matter that leads to self-organization at the interface in the case of an unstable state. A microscopic description deals with a kinetic model of the process and entropy production during self-organization. The paper provides a brief overview of the Turing system approach and statistical kinetic models. The relation between these methods and the description of the self-healing surfaces is discussed, as well as results of their application. The analytical considerations are illustrated by numerical simulations.

  19. The Healing of Bone Marrow-Derived Stem Cells on Motor Functions in Acute Spinal Cord Injury of Mice

    Directory of Open Access Journals (Sweden)

    N Gashmardi

    2016-10-01

    Full Text Available Background & aim: Spinal cord injury is a devastating damage that can cause motor and sensory deficits reducing quality of life and life expectancy of patients. Stem cell transplantation can be one of the promising therapeutic strategies. Bone marrow is a rich source of stem cells that is able to differentiate into various cell types. In this study, bone marrow stem cells were transplanted into mice spinal cord injury model to evaluate the motor function test. Methods: Bone marrow stem cells were isolated from 3 mice. Thirty six mice were randomly divided into 3 groups: the control, sham and experimental. In sham group, mice were subjected to spinal cord compression. In experimental group, one day after lesion, isolated stem cells (200,000 were injected intravenously. Assessment of locomotor function was done by Toyama Mouse Score (TMS after 1, 2, 3, 4, 5 week post-injury. The data were analyzed using one-way Analysis of Variance and Tukey tests and statistical software Graph Pad and SPSS.P > 0/05 was considered as significant difference.  Results: The score of TMS after cell transplantation was higher in cell transplantation group (experimental, while it was significantly higher after fifth week when compared to other groups. Conclusion: The increase in TMS score in cell transplantation group showed that injection of stem cells in acute spinal cord injury can have a therapeutic effect and promote locomotor function.

  20. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Directory of Open Access Journals (Sweden)

    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  1. Effect of platelet-rich plasma on the healing of mandibular defects treated with fresh frozen bone allograft: a radiographic study in dogs.

    Science.gov (United States)

    Messora, Michel R; Nagata, Maria J H; Fucini, Stephen E; Pola, Natália M; Campos, Natália; de Oliveira, Guillermo C V; Bosco, Alvaro F; Garcia, Valdir G; Furlaneto, Flávia A C

    2014-10-01

    The purpose of this study was to radiographically analyze the effect of autologous platelet rich plasma (PRP) on the healing of fresh frozen bone allograft (FFBA) placed in surgically created resection defects in mandibles of dogs. Bilateral resection defects measuring 1.5 cm × 1 cm were surgically created on the inferior border of the mandible in 10 adult male dogs. The defects were randomly divided into three groups: C, FFBA, and FFBA/PRP. In Group C, the defect was filled by blood clot only. In Group FFBA, the defect was filled with particulate fresh frozen bone allograft. In Group FFBA/PRP, it was filled with particulate fresh frozen bone allograft combined with PRP. At 90 days postoperative, standardized radiographs of the mandibles were obtained and results were quantitatively evaluated. Analysis of digitized radiographs indicated that non-PRP grafts were significantly less dense than the PRP grafts. Group FFBA/PRP also presented a statistically greater mineralized tissue area than Groups C and FFBA. Within the limits of this study, it can be concluded that PRP enhanced the healing of FFBA in resection defects in mandibles of dogs.

  2. Excellent healing rates and patient satisfaction after arthroscopic repair of medium to large rotator cuff tears with a single-row technique augmented with bone marrow vents.

    Science.gov (United States)

    Dierckman, Brian D; Ni, Jake J; Karzel, Ronald P; Getelman, Mark H

    2017-06-24

    This study evaluated the repair integrity and patient clinical outcomes following arthroscopic rotator cuff repair of medium to large rotator cuff tears using a single-row technique consisting of medially based, triple-loaded anchors augmented with bone marrow vents in the rotator cuff footprint lateral to the repair. This is a retrospective study of 52 patients (53 shoulders) comprising 36 males and 16 females with a median age of 62 (range 44-82) with more than 24-month follow-up, tears between 2 and 4 cm in the anterior-posterior dimension and utilizing triple-loaded anchors. Mann-Whitney test compared Western Ontario Rotator Cuff (WORC) outcome scores between patients with healed and re-torn cuff repairs. Multivariate logistic regression analysed association of variables with healing status and WORC score. Cuff integrity was assessed on MRI, read by a musculoskeletal fellowship-trained radiologist. Magnetic resonance imaging (MRI) demonstrated an intact repair in 48 of 53 shoulders (91%). The overall median WORC score was 95.7 (range 27.6-100.0). A significant difference in WORC scores were seen between patients with healed repairs 96.7 (range 56.7-100.0) compared with a re-tear 64.6 (27.6-73.8), p rotator cuff tears using a triple-loaded single-row repair augmented with bone marrow vents resulted in a 91% healing rate by MRI and excellent patient reported clinical outcomes comparable to similar reported results in the literature. IV.

  3. Effect of calcium citrate on bone integration in a rabbit femur defect model

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Peng-Fei Nie; Xiu-Cui Li; Ferdinand An Rompis; Hang Huang; Hua Zhang; Zhong-Lin Mu; Lei Peng; Wei Wang; Qing-Yu Chen; Zhong-Qin Lin; Shao-Wen Cheng; Dong-Quan Kou; Xiao-Zhou Ying; Yue Shen; Xiao-Jie Cheng

    2012-01-01

    ABSTRACT Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (GroupA, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus6.0 software after animal was sacrificed at 4th(GroupA), 6th(GroupB) and8th(GroupC) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative4th and6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to2.0 mm. No statistical difference was observed when these defects were larger than2.0 mm at all healing periods except at the4th week.Conclusions: Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects.

  4. Computational modeling of chemo-bio-mechanical coupling: a systems-biology approach toward wound healing.

    Science.gov (United States)

    Buganza Tepole, A; Kuhl, E

    2016-01-01

    Wound healing is a synchronized cascade of chemical, biological, and mechanical phenomena, which act in concert to restore the damaged tissue. An imbalance between these events can induce painful scarring. Despite intense efforts to decipher the mechanisms of wound healing, the role of mechanics remains poorly understood. Here, we establish a computational systems biology model to identify the chemical, biological, and mechanical mechanisms of scar formation. First, we introduce the generic problem of coupled chemo-bio-mechanics. Then, we introduce the model problem of wound healing in terms of a particular chemical signal, inflammation, a particular biological cell type, fibroblasts, and a particular mechanical model, isotropic hyperelasticity. We explore the cross-talk between chemical, biological, and mechanical signals and show that all three fields have a significant impact on scar formation. Our model is the first step toward rigorous multiscale, multifield modeling in wound healing. Our formulation has the potential to improve effective wound management and optimize treatment on an individualized patient-specific basis.

  5. An adaptation model for trabecular bone at different mechanical levels

    Directory of Open Access Journals (Sweden)

    Lv Linwei

    2010-07-01

    Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

  6. Local blockage of EMMPRIN impedes pressure ulcers healing in a rat model.

    Science.gov (United States)

    Zhao, Xi-Lan; Luo, Xiao; Wang, Ze-Xin; Yang, Guo-Li; Liu, Ji-Zhong; Liu, Ya-Qiong; Li, Ming; Chen, Min; Xia, Yong-Mei; Liu, Jun-Jie; Qiu, Shu-Ping; Gong, Xiao-Qing

    2015-01-01

    Excessive extracellular matrix degradation caused by the hyperfunction of matrix metalloproteinases (MMPs) has been implicated in the failure of pressure ulcers healing. EMMPRIN, as a widely expressed protein, has emerged as an important regulator of MMP activity. We hypothesize that EMMPRIN affects the process of pressure ulcer healing by modulating MMP activity. In the rat pressure ulcer model, the expression of EMMPRIN in ulcers detected by Western blot was elevated compared with that observed in normal tissue. To investigate the role of EMMPRIN in regulating ulcer healing, specific antibodies against EMMPRIN were used via direct administration on the pressure ulcer. Local blockage of EMMPRIN resulted in a poor ulcer healing process compared with control ulcers, which was the opposite of our expectation. Furthermore, inhibiting EMMPRIN minimally impacted MMP activity. However, the collagen content in the pressure ulcer was reduced in the EMMPRIN treated group. Angiogenesis and the expression of angiogenic factors in pressure ulcers were also reduced by EMMPRIN local blockage. The results in the present study indicate a novel effect of EMMPRIN in the regulation of pressure ulcer healing by controlling the collagen contents and angiogenesis rather than MMPs activity.

  7. Histology surrounding cystotomy healing in a Sprague-Dawley rat model.

    Science.gov (United States)

    Bilbao, Michelle; Spaniol, Alison; Bearss, Jeremy; Schellhase, Chris; Shippey, Stuart; Aungst, Matthew

    2014-01-01

    The purpose of this study was to histologically chronicle wound healing following cystotomy repair using a small animal model. Thirty female Sprague-Dawley rats were included in this study. Twenty-eight rats underwent a vertical cystotomy in the bladder dome, which was repaired in a single continuous fashion. Two rats served as histological controls. Following cystotomy repair, groups of three to four rats were studied at single day intervals for 4 days, then at 2-day intervals until 10 days post-repair. The animal bladders were harvested and examined for inflammation, scar formation, and bladder healing. Thirty rat bladders were histologically examined. An inflammatory wound phase was observed during the first 4 days after wounding. Transition from acute to chronic inflammation was observed at day 2 with chronic inflammation persisting through day 10. Inflammation severity peaked 4 days post-wounding without regression through day 10. Evidence of proliferative phase wound healing was first observed 4 days post-wounding. Early increases in wound healing are due to inflammatory events such as fibrin plugging of the wound. Later developments after day 4 are due to wound proliferation, collagen deposition, and re-epithelialization. Additionally, wound healing in the rat bladder is observed on a continuum and not necessarily in discrete stages observed on precisely the same postoperative day in each animal.

  8. In vivo toxicity of enoxaparin encapsulated in mucoadhesive nanoparticles: Topical application in a wound healing model

    Science.gov (United States)

    Huber, S. C.; Marcato, P. D.; Barbosa, R. M.; Duran, N.; Annichino-Bizzacchi, J. M.

    2013-04-01

    Wound healing comprises four distinct phases and involves many cell events and biologic markers. The use of nanoparticles for topical application has gaining attention due to its deeper penetration in the skin and the retention capacity of the drug in the site of application. In this study the effect and toxicity of mucoadhesive polymeric nanoparticles loaded with enoxaparin was evaluated in in vivo model of skin ulcer. Our results showed an interesting formulation based on mucoadhesive nanoparticles with enoxaparin that improved wound healing without cytotoxicity in vitro in all endpoint evaluated. Then, this semi-solid formulation is a promising option for skin ulcer treatment.

  9. Healing of Stoma After Magnetic Biliary-Enteric Anastomosis in Canine Peritonitis Models

    Institute of Scientific and Technical Information of China (English)

    Jian-hui Li; Long Guo; Wei-jie Yao; Zhi-yong Zhang; Shan-pei Wang; Shi-qi Liu; Zhi-min Geng; Xiao-ping Song; Yi Lv

    2014-01-01

    Objective To assese the healing of stoma after magnetic anastomosis for the reconstruction of biliary-enteric continuity under severe inflammation. Methods Acute bile duct injury was constructed as a bile peritonitis model in mongrel dogs (n=32). Magnetic anastomosis (group A, n=16) and traditional suture anastomosis (group B, n=16) were performed to reconstruct the biliary-enteric continuity in one stage. Half of the dogs in each group were euthanized on the 30th postoperative day, and the other half on the 90th postoperative day to harvest the stoma region. The healing conditions of the stoma after the 2 anastomotic approaches were observed with naked eyes, under light microscope and scanning electron microscope. Results The stoma leakage rate (50%versus 0%on the 30th postoperative day, 37.5%versus 12.5%on the 90th postoperative day, both P Conclusions Magnetic anastomosis stent ensures better healing of the stoma even under the circumstance of severe inflammation.

  10. Computational model generation and RVE design o self-healing concrete

    Institute of Scientific and Technical Information of China (English)

    Md. Shahriar QUAYUM[1; Xiaoying ZHUANG[1,2; Timon RABCZUK[1

    2015-01-01

    Computational homogenization is a versatile tool that can extract effective properties of heterogeneous or composite material through averaging technique. Self-healing concrete (SHC) is a heterogeneous material which has different constituents as cement matrix, sand and healing agent carrying capsules. Computational homogenization tool is applied in this paper to evaluate the effective properties of self-healing concrete. With this technique, macro and micro scales are bridged together which forms the basis for multi-scale modeling. Representative volume element (RVE) is a small (microscopic) cell which contains all the microphases of the microstructure. This paper presents a technique for RVE design of SHC and shows the influence of volume fractions of different constituents, RVE size and mesh uniformity on the homogenization results.

  11. Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model.

    Science.gov (United States)

    Lee, Jeong-Hyun; Kim, Hye-Lee; Lee, Mi Hee; You, Kyung Eun; Kwon, Byeong-Ju; Seo, Hyok Jin; Park, Jong-Chul

    2012-10-15

    Wound healing proceeds through a complex collaborative process involving many types of cells. Keratinocytes and fibroblasts of epidermal and dermal layers of the skin play prominent roles in this process. Asiaticoside, an active component of Centella asiatica, is known for beneficial effects on keloid and hypertrophic scar. However, the effects of this compound on normal human skin cells are not well known. Using in vitro systems, we observed the effects of asiaticoside on normal human skin cell behaviors related to healing. In a wound closure seeding model, asiaticoside increased migration rates of skin cells. By observing the numbers of cells attached and the area occupied by the cells, we concluded that asiaticoside also enhanced the initial skin cell adhesion. In cell proliferation assays, asiaticoside induced an increase in the number of normal human dermal fibroblasts. In conclusion, asiaticoside promotes skin cell behaviors involved in wound healing; and as a bioactive component of an artificial skin, may have therapeutic value.

  12. Modeling of Self-Healing Polymer Composites Reinforced with Nanoporous Glass Fibers

    OpenAIRE

    Privman, Vladimir; Dementsov, Alexander; Sokolov, Igor

    2006-01-01

    We report on our progress towards continuum rate equation modeling, as well as numerical simulations, of self-healing of fatigue in composites reinforced with glue carrying nanoporous fibers. We conclude that with the proper choice of the material parameters, effects of fatigue can be partially overcome and degradation of mechanical properties can be delayed.

  13. Effects of hydrogen peroxide in a keratinocyte-fibroblast co-culture model of wound healing.

    Science.gov (United States)

    Loo, Alvin Eng Kiat; Halliwell, Barry

    2012-06-29

    Recently, there has been renewed interest in the role of reactive oxygen species (ROS), especially H(2)O(2), in wound healing. We previously showed that H(2)O(2) stimulates healing in a keratinocyte scratch wound model. In this paper, we used a more complex and physiologically relevant model that involves co-culturing primary keratinocytes and fibroblasts. We found that the two main cell types within the skin have different sensitivities to H(2)O(2) and to the widely used "antioxidant"N-acetyl-l-cysteine (NAC). Keratinocytes were very resistant to the toxicity of H(2)O(2) (250 and 500 μM) or NAC (5 mM). However, the viability of fibroblasts was decreased by both compounds. Using the co-culture model, we also found that H(2)O(2) increases re-epithelialization while NAC retards it. Our data further illustrate the possible role of ROS in wound healing and the co-culture model should be useful for screening agents that may influence the wound healing process. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Simulation of the nutrient supply in fracture healing.

    Science.gov (United States)

    Chen, G; Niemeyer, F; Wehner, T; Simon, U; Schuetz, M A; Pearcy, M J; Claes, L E

    2009-11-13

    The healing process for bone fractures is sensitive to mechanical stability and blood supply at the fracture site. Most currently available mechanobiological algorithms of bone healing are based solely on mechanical stimuli, while the explicit analysis of revascularization and its influences on the healing process have not been thoroughly investigated in the literature. In this paper, revascularization was described by two separate processes: angiogenesis and nutrition supply. The mathematical models for angiogenesis and nutrition supply have been proposed and integrated into an existing fuzzy algorithm of fracture healing. The computational algorithm of fracture healing, consisting of stress analysis, analyses of angiogenesis and nutrient supply, and tissue differentiation, has been tested on and compared with animal experimental results published previously. The simulation results showed that, for a small and medium-sized fracture gap, the nutrient supply is sufficient for bone healing, for a large fracture gap, non-union may be induced either by deficient nutrient supply or inadequate mechanical conditions. The comparisons with experimental results demonstrated that the improved computational algorithm is able to simulate a broad spectrum of fracture healing cases and to predict and explain delayed unions and non-union induced by large gap sizes and different mechanical conditions. The new algorithm will allow the simulation of more realistic clinical fracture healing cases with various fracture gaps and geometries and may be helpful to optimise implants and methods for fracture fixation.

  15. Systemic Treatment with Strontium Ranelate Accelerates the Filling of a Bone Defect and Improves the Material Level Properties of the Healing Bone

    Directory of Open Access Journals (Sweden)

    Giovanna Zacchetti

    2014-01-01

    Full Text Available Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days or vehicle for 4, 8, or 12 weeks (10 rats per group per time point from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively.

  16. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    Science.gov (United States)

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover.

  17. A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Pengfei Lei

    Full Text Available Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2 deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones.Bones were deproteinized in H2O2 or pepsin for 8 hours. The morphologies were compared by HE staining. The content of protein and collagen I were measured by the Kjeldahl method and HPLC-MS, respectively. The physical properties were evaluated by SEM and mechanical tests. For in vivo study, X-ray, micro-CT and HE staining were employed to monitor the healing processes of radius defects in rabbit models transplanted with different graft materials.Compared with H2O2 deproteinized bones, no distinct morphological and physical changes were observed. However, pepsin deproteinized bones showed a lower protein content, and a higher collagen content were preserved. In vivo studies showed that pepsin deproteinized bones exhibited better osteogenic performance than H2O2 deproteinized bones, moreover, the quantity and quality of the newly formed bones were improved as indicated by micro-CT analysis. From the results of histological examination, the newly formed bones in the pepsin group were mature bones.Pepsin deproteinized xenograft bones show advantages over conventional H2O2 deproteinized bones with respect to osteogenic capacity; this new method may hold potential clinical value in the development of new biomaterials for bone grafting.

  18. Modeling and simulation of physical performance of a external unilateral mechatronic orthopaedic fixator - bone system.

    Science.gov (United States)

    Lesniewska, A; Choromanski, W; Deszczynski, J; Dobrzynski, G

    2006-01-01

    Restricted element study of the fracture healing by external fixation device was investigated. The analyses were performed under an axial and variable loaded boundary conditions. The effect of different fracture size and different distance between bone and the external fixator device on the stress distribution was investigated. The results show that stresses in the external fixator device are highest at the beginning of the fracture healing process, and are gradually decreasing with the time of the treatment. The analyses were carried out using the commercial package CATIA P3 V5R11. This allowed to build a three-dimensional model more similar to the geometrical architecture of the long bone as well as of the external fixator. Three-dimensional restricted element model also allowed a collection of more realistic results. However, the accuracy of the results depends not only on the quality of the model geometry but also on the material properties assigned to the model components. It also depends on the accuracy in the simulation of the finite element model and the optimized mesh generation.

  19. Pharmacological Evaluation of Chrozophora tinctoria as Wound Healing Potential in Diabetic Rat’s Model

    Directory of Open Access Journals (Sweden)

    Harikesh Maurya

    2016-01-01

    Full Text Available Objective. The study was designed to evaluate pharmacological potential of hydroalcoholic leaves extract of Chrozophora tinctoria intended for wound healing in diabetic rats’ model. Methods. The method used to evaluate the pharmacological potential of hydroalcoholic leave extract was physical incision rat model. In this model, cutting of the skin and/or other tissues with a sharp blade has been made and the rapid disruption of tissue integrity with minimal collateral damage was observed shortly. Animals used in the study were divided into four groups that consist of six animals in each group. Group I serves as normal control, Group II serves as disease control, Group III was used as standard treatment (Povidone iodine 50 mg/kg b.w., and Group IV was used for test drug (C. tinctoria 50 mg/kg b.w.. Result. The hydroalcoholic leave extract of Chrozophora tinctoria has been significantly observed to heal the wound (98% in diabetic rats within 21 days, while standard drug (Povidone iodine healed the wound about 95% in the same condition. The oral dose (50 mg/kg b.w. of Chrozophora tinctoria was also found to improve the elevated blood glucose level in comparison to disease control group, which increased after the oral administration of Streptozotocin. Conclusion. The Chrozophora tinctoria has significant wound healing potential in the animal having physically damaged tissue in diabetic condition.

  20. First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

    Directory of Open Access Journals (Sweden)

    Jorge Cubo

    Full Text Available Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

  1. First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

    Science.gov (United States)

    Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R

    2015-01-01

    Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

  2. First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs

    Science.gov (United States)

    Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R.

    2015-01-01

    Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older. PMID:26153689

  3. Attributes of Bio-Oss(®) and Moa-Bone(®) graft materials in a pilot study using the sheep maxillary sinus model.

    Science.gov (United States)

    Smith, M M; Duncan, W J; Coates, D E

    2017-09-04

    The aim of this pilot study was to characterize surface morphology and to evaluate resorption and osseous healing of two deproteinated bovine bone graft materials after sinus grafting in a large animal model. Surfaces of a novel particulate bovine bone graft, Moa-Bone(®) were compared with Bio-Oss(®) using scanning electron microscopy. Six sheep then had maxillary sinus grafting bilaterally, covered with BioGide(®) . Grafted maxillae were harvested after 4, 6 and 12 weeks. Healing was described for half of each site using resin-embedded ground sections. For the other half, paraffin-embedded sections were examined using tartrate resistant acid phosphatase staining for osteoclast activity, runt-related transcription factor2 immunohistochemistry for pre-osteoblasts and osteoblasts and proliferating cell nuclear antigen for proliferative cells. Moa-Bone(®) had a smoother, more porous fibrous structure with minimal globular particles compared with Bio-Oss(®) . After 4 weeks, woven bone formed on both grafts and the Moa-Bone(®) particles also showed signs of resorption. After 12 weeks, Moa-Bone(®) continued to be resorbed, however Bio-Oss(®) did not; both grafts were surrounded by maturing lamellar bone. Moa-Bone(®) was associated with earlier evidence of runt-related transcription factor 2-positive cells. Moa-Bone(®) but not Bio-Oss(®) was associated with strong tartrate resistant acid phosphatase-positive osteoclasts on the graft surface within resorption lacunae at both 4 and 6 weeks post-grafting. Both materials supported osseous healing and maturation without inflammation. Moa-Bone(®) showed marked osteoclast activity after 4 and 6 weeks and demonstrated positive attributes for grafting, if complete remodeling of the graft within the site is desired. Further optimization of Moa-Bone(®) for maxillofacial applications is warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Warmington, Kelly S; Morony, Sean; Gong, Jianhua; Cao, Jin; Gao, Yongming; Shalhoub, Victoria; Tipton, Barbara; Haldankar, Raj; Chen, Qing; Winters, Aaron; Boone, Tom; Geng, Zhaopo; Niu, Qing-Tian; Ke, Hua Zhu; Kostenuik, Paul J; Simonet, W Scott; Lacey, David L; Paszty, Chris

    2009-04-01

    The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

  5. Evaluation of Osteoconductive and Osteogenic Potential of a Dentin-Based Bone Substitute Using a Calvarial Defect Model

    Directory of Open Access Journals (Sweden)

    Ibrahim Hussain

    2012-01-01

    Full Text Available The aim of this study was to assess the osteoconductive and osteogenic properties of processed bovine dentin using a robust rabbit calvarial defect model. In total, 16 New Zealand White rabbits were operated to create three circular defects in the calvaria. One defect was left unfilled, one filled with collected autogenous bone, and the third defect was filled with the dentin-based bone substitute. Following surgery and after a healing period of either 1 or 6 weeks, a CT scan was obtained. Following sacrificing, the tissues were processed for histological examination. The CT data showed the density in the area grafted with the dentin-based material was higher than the surrounding bone and the areas grafted with autologous bone after 1 week and 6 weeks of healing. The area left unfilled remained an empty defect after 1 week and 6 weeks. Histological examination of the defects filled with the dentin product after 6 weeks showed soft tissue encapsulation around the dentin particles. It can be concluded that the rabbit calvarial model used in this study is a robust model for the assessment of bone materials. Bovine dentin is a biostable material; however, it may not be suitable for repairing large 4-wall defects.

  6. An intramembranous ossification model for the in silico analysis of bone tissue formation in tooth extraction sites.

    Science.gov (United States)

    Corredor-Gómez, Jennifer Paola; Rueda-Ramírez, Andrés Mauricio; Gamboa-Márquez, Miguel Alejandro; Torres-Rodríguez, Carolina; Cortés-Rodríguez, Carlos Julio

    2016-07-21

    The accurate modeling of biological processes allows us to predict the spatiotemporal behavior of living tissues by computer-aided (in silico) testing, a useful tool for the development of medical strategies, avoiding the expenses and potential ethical implications of in vivo experimentation. A model for bone healing in mouth would be useful for selecting proper surgical techniques in dental procedures. In this paper, the formulation and implementation of a model for Intramembranous Ossification is presented aiming to describe the complex process of bone tissue formation in tooth extraction sites. The model consists in a mathematical description of the mechanisms in which different types of cells interact, synthesize and degrade extracellular matrices under the influence of biochemical factors. Special attention is given to angiogenesis, oxygen-dependent effects and growth factor-induced apoptosis of fibroblasts. Furthermore, considering the depth-dependent vascularization of mandibular bone and its influence on bone healing, a functional description of the cell distribution on the severed periodontal ligament (PDL) is proposed. The developed model was implemented using the finite element method (FEM) and successfully validated by simulating an animal in vivo experiment on dogs reported in the literature. A good fit between model outcome and experimental data was obtained with a mean absolute error of 3.04%. The mathematical framework presented here may represent an important tool for the design of future in vitro and in vivo tests, as well as a precedent for future in silico studies on osseointegration and mechanobiology.

  7. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    Science.gov (United States)

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  8. Material model of pelvic bone based on modal analysis: a study on the composite bone.

    Science.gov (United States)

    Henyš, Petr; Čapek, Lukáš

    2017-02-01

    Digital models based on finite element (FE) analysis are widely used in orthopaedics to predict the stress or strain in the bone due to bone-implant interaction. The usability of the model depends strongly on the bone material description. The material model that is most commonly used is based on a constant Young's modulus or on the apparent density of bone obtained from computer tomography (CT) data. The Young's modulus of bone is described in many experimental works with large variations in the results. The concept of measuring and validating the material model of the pelvic bone based on modal analysis is introduced in this pilot study. The modal frequencies, damping, and shapes of the composite bone were measured precisely by an impact hammer at 239 points. An FE model was built using the data pertaining to the geometry and apparent density obtained from the CT of the composite bone. The isotropic homogeneous Young's modulus and Poisson's ratio of the cortical and trabecular bone were estimated from the optimisation procedure including Gaussian statistical properties. The performance of the updated model was investigated through the sensitivity analysis of the natural frequencies with respect to the material parameters. The maximal error between the numerical and experimental natural frequencies of the bone reached 1.74 % in the first modal shape. Finally, the optimised parameters were matched with the data sheets of the composite bone. The maximal difference between the calibrated material properties and that obtained from the data sheet was 34 %. The optimisation scheme of the FE model based on the modal analysis data provides extremely useful calibration of the FE models with the uncertainty bounds and without the influence of the boundary conditions.

  9. Pearl extract enhances the migratory ability of fibroblasts in a wound healing model.

    Science.gov (United States)

    Li, Yi-Chen; Chen, Chi-Ruei; Young, Tai-Horng

    2013-03-01

    For 2000 years, traditional Chinese medicine has been used as a remedy for general health improvement, including the fight against aging. Pearl powder has recently been used as a health food that has antioxidant, antiaging, antiradioactive, and tonic activities for cells; it is also applied to cure aphthous ulcer, gastric ulcer, and duodenal ulcer on clinical therapy. In addition, the mother of pearl, nacre, could enhance the cell adhesion and tissue regeneration of skin fibroblasts. Fibroblast is regarded as indispensable in the processes of wound healing. Therefore, the effect of pearl extract (PL) on fibroblasts is investigated in this study. PL is produced by a room temperature super extraction system (Taiwan patent no. I271 220). DMEM medium containing PL (300 μg/mL) was used to examine the effect of migration-promoting potential on human fibroblast cell line or human primary fibroblast cells in a wound healing model in vitro. Medium containing PL (300 μg/mL) demonstrated that the migratory cell numbers of fibroblasts were three times more than that without PL, and mRNA expression of collagen type III was higher than in collagen type I in fibroblasts. It revealed a migration-promoting potential of human fibroblasts in a wound healing model in vitro. The present study found that the migration-promoting effect in PL, which could be a supplement in cell culture. These data suggest PL could be useful for enhancing the wound healing of fibroblasts.

  10. The JCR:LA-cp rat: a novel model for impaired wound healing.

    Science.gov (United States)

    Bauer, Barbara S; Ghahary, Aziz; Scott, Paul G; Iwashina, Takashi; Demare, Jack; Russell, James C; Tredget, Edward E

    2004-01-01

    JCR:LA-cp/cp obese rats and their lean controls were evaluated as a type 2 diabetic wound healing model and the healing quality was characterized. This model of insulin resistance has been used extensively to study atherosclerosis but has not previously been used to study wound healing. Six circular excisional wounds were made on the dorsum of each rat and followed to day 21. Tracings of the wounds were made and used to assess the rate of wound closure. Planimetry showed a significantly diminished contraction of wounds in obese rats, but no significant difference in reepithelialization was observed. Collagen content was determined from the hydroxyproline content in wounded and unwounded skin. There were significantly lower levels of hydroxyproline in the wounds of obese compared to lean animals at day 21. Histology showed adipose tissue in place of dermal tissue in the JCR:LA-cp/cp rat in both unwounded tissue and in the wound at day 21. Active transforming growth factor-beta 1 (TGF-beta 1) was measured in the serum using the plasminogen activator inhibitor-1/luciferase assay and serum total TGF-beta was measured using an enzyme-linked immunosorbent assay. Active TGF-beta was significantly higher in the serum of obese animals compared with lean animals, while total TGF-beta 1 was not significantly different between the groups. Both active and total TGF-beta was measured in tissue sections using the plasminogen activator inhibitor-1/luciferase assay. There was no significant difference in active TGF-beta between genotypes, while obese rats had significantly higher levels of total TGF-beta at day 21. These results indicate a deficiency in wound healing in obese animals characterized by decreased wound contraction, decreased collagen production, and changes in histology. The JCR:LA-cp rat develops insulin resistance, atherosclerosis and early type 2 diabetes and may be a good model for impairment of wound healing in humans with metabolic syndrome.

  11. Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells

    Directory of Open Access Journals (Sweden)

    Johanna Bolander

    2017-03-01

    Full Text Available Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2. Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation. Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect.

  12. Simulation of Healing Threshold in Strain-Induced Inflammation through a Discrete Informatics Model.

    Science.gov (United States)

    Ibrahim, Israr; Oruganti, Sanjay Venkata; Pidaparti, Ramana

    2017-02-15

    Respiratory diseases such as asthma and acute respiratory distress syndrome as well as acute lung injury involve inflammation at the cellular level. The inflammation process is very complex and is characterized by the emergence of cytokines along with other changes in cellular processes. Due to the complexity of the various constituents that makes up the inflammation dynamics, it is necessary to develop models that can complement experiments to fully understand inflammatory diseases. In this study, we developed a discrete informatics model based on cellular automata (CA) approach to investigate the influence of elastic field (stretch/strain) on the dynamics of inflammation and account for probabilistic adaptation based on statistical interpretation of existing experimental data. Our simulation model investigated the effects of low, medium and high strain conditions on inflammation dynamics. Results suggest that the model is able to indicate the threshold of innate healing of tissue as a response to strain experienced by the tissue. When strain is under the threshold, the tissue is still capable of adapting its structure to heal the damaged part. However, there exists a strain threshold where healing capability breaks down. The results obtained demonstrate that the developed discrete informatics based CA model is capable of modeling and giving insights into inflammation dynamics parameters under various mechanical strain/stretch environments.

  13. Plasminogen activator inhibitor-1 controls bone marrow-derived cells therapeutic effect through MMP9 signaling: role in physiological and pathological wound healing.

    Science.gov (United States)

    Ebrahimian, Teni G; Squiban, Claire; Roque, Telma; Lugo-Martinez, Haydee; Hneino, Mohamad; Buard, Valerie; Gourmelon, Patrick; Benderitter, Marc; Milliat, Fabien; Tamarat, Radia

    2012-07-01

    We assessed the role of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase 9 (MMP9) in wound healing process and in the bone marrow mononuclear cells (BMMNC)-related effects on physiological and pathological wound healing. A full thickness excision wound was created by removal of the skin on the midback of irradiated and nonirradiated animals. Angiogenesis and re-epithelialization were markedly increased in PAI-1-/- mice compared to wild-type (WT) animals. We revealed high MMP activity in tissue of PAI-1-/- animals. Of interest, the wound healing process was reduced in PAI-1-/-:MMP9-/- animals compared to PAI-1-/- mice, suggesting a key role of MMP9 in beneficial effect of PAI-1 deficiency on wound closure. To unravel the role of PAI-1 in BMMNC relative effects, mice were treated with or without local injection of BMMNC isolated from WT, PAI-1-/-, and PAI-1-/-: MMP9-/- animals for 14 days (10(6) cells, n = 6 per group). In WT nonirradiated mice, transplantation of BMMNC isolated from PAI-1-/- animals enhanced wound formation when compared with WT BMMNC. BMMNC differentiation into cells with endothelial phenotype was enhanced by PAI-1 deficiency. These effects were abrogated in PAI-1-/-:MMP9-/- and MMP9-/- BMMNC. In addition, using chimeric mice, we demonstrated that PAI-1 deficiency environment increased the BMMNC-GFP recruitment to the wound site, whereas this effect was abrogated when using PAI-1-/-:MMP9-/- BMMNC. PAI-1 deficiency, at least through MMP9 upregulation, enhanced wound healing and BMMNC therapeutic potential in irradiated and nonirradiated animals.

  14. The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

    Science.gov (United States)

    Pennline, James; Mulugeta, Lealem

    2013-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of

  15. Second harmonic generation imaging of skin wound healing and scarring in a rabbit ear model

    Science.gov (United States)

    Tang, Yiyan; Zhu, Xiaoqin; Xiong, Shuyuan; Chen, Jianxin

    2012-12-01

    Skin wound healing and scarring in rabbit ears was examined by second harmonic generation (SHG) microscopy. Rabbit ear wound model was created by punching from the ventral surface with removal of epidermis, dermis and perichondrium. The samples were collected weekly, and cut into 100 μm thickness sections for SHG imaging. SHG imaging system was operated at 810 nm, producing SHG signals at half the excitation wavelength 405 nm. A Plan-Neofluar objective (x40 and NA=0.75) was employed for focusing the excitation beam into tissue samples and was also used to collect the backscattered intrinsic SHG signals. Our results showed apparent difference in collagen content and microstructure at various wound healing and scarring time points. It suggested that SHG signals from collagen can serve as a good indicator for characterization of wound status. With the advancement on miniaturization, microscopy based on SHG will become a valuable tool for monitoring the wound healing and scarring in vivo, and help to guide the improvement of scar appearance with appropriate and subtle modulation during wound healing based on better understanding of scarring response mechanism.

  16. Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

    Directory of Open Access Journals (Sweden)

    S. Murthy

    2013-01-01

    Full Text Available Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME was studied on wound models in rats. BME (25 mg/kg was administered orally, once daily for 10 days (incision and dead space wound models or for 21 days or more (excision wound model in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model, rate of contraction, period of epithelization, histology of skin (excision model, granulation tissue free radicals (nitric oxide and lipid peroxidation, antioxidants (catalase, superoxide dismutase, and reduced glutathione, acute inflammatory marker (myeloperoxidase, connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid, and deep connective tissue histology (dead space wound. BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity.

  17. Effect of a carbonated HAP/β-glucan composite bone substitute on healing of drilled bone voids in the proximal tibial metaphysis of rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Borkowski, Leszek, E-mail: leszek.borkowski@umlub.pl [Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodźki 1, 20-093 Lublin (Poland); Pawłowska, Marta; Radzki, Radosław P.; Bieńko, Marek [Department of Animal Physiology, University of Life Sciences in Lublin, Akademicka 12, 20-033 Lublin (Poland); Polkowska, Izabela [Department and Clinic of Animal Surgery, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin (Poland); Belcarz, Anna [Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodźki 1, 20-093 Lublin (Poland); Karpiński, Mirosław [Department of Companion and Wildlife Animals, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin (Poland); Słowik, Tymoteusz [Independent Radiology Unit at Lublin Small Animals Medical Centre, Stefczyka 11, 20-151 Lublin (Poland); Matuszewski, Łukasz [Children' s Orthopaedic Clinic and Rehabilitation Department, Medical University of Lublin, Chodzki 2, 20-093 Lublin (Poland); Ślósarczyk, Anna [Faculty of Materials Science and Ceramics, AGH-University of Science and Technology, Mickiewicza 30, 30-059 Krakow (Poland); Ginalska, Grażyna [Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodźki 1, 20-093 Lublin (Poland)

    2015-08-01

    A novel elastic hydroxyapatite-based composite of high surgical handiness has been developed. Its potential application in orthopedics as a filler of bone defects has been studied. The biomaterial was composed of carbonated hydroxyapatite (CHAP) granules and polysaccharide polymer (β-1,3-glucan). Cylinders of 4 mm in diameter and 6 mm in length were implanted into bone cavities created in the proximal metaphysis of tibiae of 24 New Zealand white rabbits. 18 sham-operated animals were used as controls. After 1, 3 or 6 months, the rabbits were euthanized, the bones were harvested and subjected to analysis. Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. Peripheral quantitative computed tomography (pQCT) indicated the stimulating effect of the biomaterial on bone formation and mineralization. Densitometry (DXA) analysis suggested that biomineralization of bones was preceded by bioresorption and gradual disappearance of porous ceramic granules. The findings suggest that the CHAP–glucan composite material enables regeneration of bone tissue and could serve as a bone defect filler. - Highlights: • Highly porous carbonate HAP granules and β-1,3-glucan were used to fill bone voids. • Critical size defects of rabbit tibiae were filled with the composite scaffolds. • Biocompatibility, mineralization and osseointegration of implants were examined. • Histological analysis indicated a high biocompatibility of composite grafts. • We report penetration of bony tissue into implants and advanced osseointegration.

  18. Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration in a rodent model: a description of the bone repair by light microscopy

    Science.gov (United States)

    Pinheiro, Antonio Luiz B.; Aciole, Gilberth T. S.; Soares, Luiz G. P.; Correia, Neandder A.; N. dos Santos, Jean

    2011-03-01

    We carried out a histological analysis on surgical bone defects grafted or not with MTA, treated or not with LED, BMPs and GBR. We have used several models to assess the effects of laser on bone. Benefits of the isolated or combined use them on bone healing has been suggested. There is no previous report on their association with LED light. 90 rats were divided into 10 groups. On Groups II and I the defect were filled with the clot. On Group II, were further irradiated. On groups III-VI, defect was filled with MTA + Collagen gel (III); animals of group IV were further irradiated. On groups V and VI, the defects filled with the MTA were covered with a membrane. Animals of Group VI were further irradiated. On Groups VII and VIII a pool of BMPs was added to the MTA and was further irradiated. On groups IX and X, the MTA + BMP graft was covered with a membrane. On group X, the defect was further irradiated. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 54s, 0.3W/cm2, 16 J/cm2) was applied at 48 h intervals during 15 days. Specimens were taken, processed, cut and stained with H&E and Sirius red and underwent histological analysis. The results showed that MTA seemed not being affected by LED light. However, its use positively affected healing around the graft. It is concluded that MTA is not affected by the LED light due to it characteristics, but beneficial results with LED usage was found.

  19. A feasibility investigation for modeling and optimization of temperature in bone drilling using fuzzy logic and Taguchi optimization methodology.

    Science.gov (United States)

    Pandey, Rupesh Kumar; Panda, Sudhansu Sekhar

    2014-11-01

    Drilling of bone is a common procedure in orthopedic surgery to produce hole for screw insertion to fixate the fracture devices and implants. The increase in temperature during such a procedure increases the chances of thermal invasion of bone which can cause thermal osteonecrosis resulting in the increase of healing time or reduction in the stability and strength of the fixation. Therefore, drilling of bone with minimum temperature is a major challenge for orthopedic fracture treatment. This investigation discusses the use of fuzzy logic and Taguchi methodology for predicting and minimizing the temperature produced during bone drilling. The drilling experiments have been conducted on bovine bone using Taguchi's L25 experimental design. A fuzzy model is developed for predicting the temperature during orthopedic drilling as a function of the drilling process parameters (point angle, helix angle, feed rate and cutting speed). Optimum bone drilling process parameters for minimizing the temperature are determined using Taguchi method. The effect of individual cutting parameters on the temperature produced is evaluated using analysis of variance. The fuzzy model using triangular and trapezoidal membership predicts the temperature within a maximum error of ±7%. Taguchi analysis of the obtained results determined the optimal drilling conditions for minimizing the temperature as A3B5C1.The developed system will simplify the tedious task of modeling and determination of the optimal process parameters to minimize the bone drilling temperature. It will reduce the risk of thermal osteonecrosis and can be very effective for the online condition monitoring of the process.

  20. Biomechanics Significance of Femoral Head and Neck of Grafting-bone Group After Femoral Neck Fracture-healing%股骨颈骨折愈合后钉道植骨的生物力学意义

    Institute of Scientific and Technical Information of China (English)

    唐洪涛; 仝允辉; 杨茹萍; 朱太永; 张美超; 赵卫东

    2011-01-01

    Objective To study biomechanical performance of fracture-healing femoral head and neck after the hollow compressionb screws are taken out in ungrafting-bone group, grafting-bone group, normal group, and provide theoretical basis for the treatment of necrosis of the femoral head by bone grafting in the channel of screws. Methods Nine femurs fixed and preserved by formalin were used in this test. They were randomly divided into three groups: normal group, ungrafting-bone group, grafting-bone group. According to inversed-triangle, at the range of physiological load, it tested the defixed bias-value of three group femoral head at different load. The data were collected and analyzed. The three-dimension finite element model of the femoral head and neck was calculated. Nodal solution of stress value and max-offset was calculated at area of femoral head and neck, then the data were compared and analyzed.Results Compared with the mean of load-offset about the femoral head and neck, biomechanical capability of ungrafting-bone group was lowest with regard to other two groups , the influence was very hard, P <0.05. But there was no singnificant difference between normal group and graflng-bone group, P >0.05. Analysis of the three-dimension finite element model showed that the massive stress was concentrated at weight loading region of ungrafting-bone group's femoral head, it was an dangerous chance to lead to femoral head collapse. Conclusion For the treatment of femur neck fractures with cannulated compression screws, bone grafting in the channel of screw should be used to improve biomechanical integrity after fracture healed and cannulated compression screws are taken out. This is of benefit to loading in early stage and to preventing the collapse of femoral head, etc.%目的 探讨股骨颈骨折愈合后取出空心加压螺钉遗留钉道不植骨、植骨及正常的股骨头颈部的生物力学特性,为临床提供实验依据.方法 收集9付股骨标本测量

  1. Evaluation of wound healing property of Terminalia catappa on excision wound models in Wistar rats.

    Science.gov (United States)

    Khan, A A; Kumar, V; Singh, B K; Singh, R

    2014-05-01

    Wound is defined as the loss of breaking cellular and functional continuity of the living tissues. Management of wounds is frequently encountered with different problems. Drug resistance and toxicity hindered the development of synthetic antimicrobial agents with wound healing activity. Many plants with potent pharmacological activities may offer better treatment options viz. Terminalia chebula, Terminalia bellirica and Phyllanthus emblica formulations have shown healing activities on wounds.The present study was planned to investigate the wound healing activity of Terminalia catappa on excision wound model in rats. Ointment was prepared by using bark extract of Terminalia catappa in soft paraffin and preservative. Wistar albino rats (200-250 gm) of either sex were used in the present study. A circular wound of 2 cm in diameter was made on the depilated dorsal thoracic region of the rats under ether anesthesia in aseptic conditions. The ointment was applied for 18 days and percent wound closure observed along with the parameters viz. Epithelization, granuloma weight and scar formation. Animals were observed on 3rd, 6th, 9th, 12th, 15th and 18th post-wounding day.Wound healing activity was compared with that of control and Betadine ointment as standard drug. Animals treated with Terminalia catappa ointment exhibited 97% reduction in wound area as compared to the control animals (81%). Ointment treated wounds