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Sample records for bone regeneration gbr

  1. Guided bone regeneration (GBR) using cortical bone pins in combination with leukocyte- and platelet-rich fibrin (L-PRF).

    PubMed

    Toffler, Michael

    2014-03-01

    Two of the fundamental requisites for guided bone regeneration (GBR) are space maintenance and primary soft-tissue closure. Allogeneic cortical bone pins measuring 2 mm in diameter in customized lengths can protect surrounding graft materials, support bioresorbable membrane barriers, and resist wound compression from the overlying soft tissues. In addition, a second-generation platelet concentrate, leukocyte- and platelet-rich fibrin (L-PRF), may be incorporated into the augmentation procedure to provide multiple growth factors, accelerate wound healing, and aid in the maintenance of primary closure over the grafted materials. Highlighting two case reports, this article features a GBR technique that uses bone pins in combination with L-PRF membranes to provide both horizontal and vertical ridge augmentation at severely compromised implant sites.

  2. Guided bone regeneration (GBR) using membranes and calcium sulphate after apicectomy: a comparative histomorphometrical study.

    PubMed

    Yoshikawa, G; Murashima, Y; Wadachi, R; Sawada, N; Suda, H

    2002-03-01

    The purpose of the present study was to evaluate the effects of resorbable and non-resorbable membranes, and calcium sulphate on bone regeneration in osseous defects in conjunction with apicectomy. The mandibular third and fourth premolars of 12 beagle dogs were root treated, and apicectomies were performed. The osseous defects were divided randomly into five groups. In groups A, B and C the osseous defects were covered with e-PTFE membranes, PLGA membranes, and collagen membranes, respectively. In group D, defects were filled with calcium sulphate. Nothing was used in group E, which served as controls. The dogs were sacrificed 4, 8, and 16 weeks after the surgery. Undemineralized sections were obtained and evaluated histomorphometrically. Newly formed cortical bone had closed the defect in the cortical plate in all groups at 16 weeks. The degree of concavity of the new cortical bone at 16 weeks in groups A and D was significantly less than in group B (P < 0.01). The percentage of regenerated bone in group A was significantly greater than in groups B (P < 0.01), C (P < 0.05) and E (P < 0.05). In group D, it was significantly greater than in groups B (P < 0.01) and E (P < 0.05). The data suggests that e-PTFE membrane is more effective compared to resorbable membranes and controls for bone regeneration after apicectomy, and that calcium sulphate could be substituted for e-PTFE membrane.

  3. Comparison of the performance of natural latex membranes prepared with different procedures and PTFE membrane in guided bone regeneration (GBR) in rabbits.

    PubMed

    Moura, Jonas M L; Ferreira, Juliana F; Marques, Leonardo; Holgado, Leandro; Graeff, Carlos F O; Kinoshita, Angela

    2014-09-01

    This work assessed the performance of membranes made of natural latex extracted from Hevea brasiliensis prepared with three different methods: polymerized immediately after collection without the use of ammonia (L1); polymerized after preservation in ammonia solution (L2); and polymerized after storage in ammonia, followed by Soxhlet technique for the extraction of substances (L3). Polytetrafluoroethylene (PTFE) membrane was used as control. Two 10-mm diameter bone defects were surgically made in the calvaria of thirty adult male New Zealand rabbits. Defects (total n = 60) were treated with guided bone regeneration (GBR) using L1, L2, L3 or PTFE membranes (n = 15 for each membrane). Ten animals were euthanized after 7, 20 and 60 days postoperatively so that five samples (n = 5) of each treatment were collected at each time, and bone regeneration was assessed microscopically. The microscopic analysis revealed defects filled with blood clot and new bone formation at the margins of the defect in all 7-day samples, while 20-day defects were mainly filled with fibrous connective tissue. After 60 days defects covered with L1 membranes showed a significantly larger bone formation area in comparison to the other groups (P < 0.05, ANOVA, Tukey). Additionally, bone tissue hypersensitization for L1 and PTFE membranes was also investigated in six additional rabbits. The animals were subjected to the same surgical procedure for the confection of one 10-mm diameter bone defect that was treated with L1 (n = 3) or PTFE (n = 3). Fifty-three days later, a second surgery was performed to make a second defect, which was treated with the same type of membrane used in the first surgery. Seven days later, the animals were euthanized and samples analyzed. No differences among L1 and PTFE samples collected from sensitized and non-sensitized animals were found (P > 0.05, Kruskal-Wallis). Therefore, the results demonstrated that latex membranes presented performance

  4. Mechanisms of Guided Bone Regeneration: A Review

    PubMed Central

    Liu, Jie; Kerns, David G

    2014-01-01

    Post-extraction crestal bone resorption is common and unavoidable which can lead to significant ridge dimensional changes. To regenerate enough bone for successful implant placement, Guided Bone Regeneration (GBR) is often required. GBR is a surgical procedure that uses barrier membranes with or without particulate bone grafts or/and bone substitutes. There are two approaches of GBR in implant therapy: GBR at implant placement (simultaneous approach) and GBR before implant placement to increase the alveolar ridge or improve ridge morphology (staged approach). Angiogenesis and ample blood supply play a critical role in promoting bone regeneration. PMID:24894890

  5. Effect of GBR and fixture installation on gingiva and bone levels at adjacent teeth.

    PubMed

    Van der Zee, Erwin; Oosterveld, Paul; Van Waas, Marinus A J

    2004-02-01

    Guided bone regeneration (GBR) is frequently used in oral implantology. It is unclear to what extent GBR affects the periodontium of adjacent teeth. Therefore, the present study quantifies changes in the proximal gingiva and bone levels at these teeth in 30 patients. Staged surgery involved a standard GBR treatment, randomly using resorbable membranes with a bone substitute or non-resorbable membranes with or without a bone substitute, followed by fixture installation at 6 months and abutment connection a further 6 months later. The data were sampled at each surgery and analysed using MANOVA. Twelve months after GBR, there was on average a small but statistically significant amount of proximal gingival recession (0.75 mm) and bone resorption (0.34 mm) observed, of which 50% was the result of GBR surgery. No significant differences were found between the different GBR treatment modalities. It is concluded that GBR treatment may have a small negative effect on the levels of the free gingival margin and alveolar bone at adjacent teeth, which is in most patients not clinically relevant.

  6. Assessment of bone healing on tibial fractures treated with wire osteosynthesis associated or not with infrared laser light and biphasic ceramic bone graft (HATCP) and guided bone regeneration (GBR): Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Bastos de Carvalho, Fabíola; Aciole, Gilberth Tadeu S.; Aciole, Jouber Mateus S.; Silveira, Landulfo, Jr.; Nunes dos Santos, Jean; Pinheiro, Antônio L. B.

    2011-03-01

    The aim of this study was to evaluate, through Raman spectroscopy, the repair of complete tibial fracture in rabbits fixed with wire osteosynthesis - WO, treated or not with infrared laser light (λ 780nm, 50mW, CW) associated or not to the use of HATCP and GBR. Surgical fractures were created under general anesthesia (Ketamine 0.4ml/Kg IP and Xilazine 0.2ml/Kg IP), on the tibia of 15 rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with WO. Animals of groups III and V were grafted with hydroxyapatite + GBR technique. Animals of groups IV and V were irradiated at every other day during two weeks (16J/cm2, 4 x 4J/cm2). Observation time was that of 30 days. After animal death the specimens were kept in liquid nitrogen for further analysis by Raman spectroscopy. Raman spectroscopy showed significant differences between groups (p<0.001). It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of calcium hydroxyapatite.

  7. [Progress of researches on guided bone regeneration membrane].

    PubMed

    Wang, Xiaomin; Li, Xudong

    2008-08-01

    Guided bone regeneration (GBR) is a technique utilizing membrane as a physical barrier to separate and create a secluded space around the bone defect. This permits the regeneration of bone tissue and reduces the fast growth of connective tissues. Moreover, GBR membranes sustain a protected space during tissue-healing period. Nowadays there are many kinds of GBR membranes used in study and practice, and each of them has its characteristic merits and defects respectively. This paper reviews the studies of GBR membranes, with the emphases on the structure and properties of membrane materials as well as their biological functions.

  8. Guided Bone Regeneration with Novel Bioabsorbable Membranes

    NASA Astrophysics Data System (ADS)

    Koyama, Yoshihisa; Kikuchi, Masanori; Yamada, Takeki; Kanaya, Tomohiro; Matsumoto, Hiroko N.; Takakuda, Kazuo; Miyairi, Hiroo; Tanaka, Junzo

    Guided Bone Regeneration (GBR) is a method for bone tissue regeneration. In this method, membranes are used to cover bone defects and to block the invasion of the surrounding soft tissues. It would provide sufficient time for the osteogenic cells from bone marrow to proliferate and form new bony tissues. In spite of the potential usefulness of this method, no appropriate materials for the GBR membrane have been developed. Here we design the ideal mechanical properties of the GBR membranes and created novel materials, which is the composite of β-tricalcium phosphate and block copolymer of L-lactide, glycolide and ɛ-caplolactone. In the animal experiments with the use of the trial products, we observed significant enhancement in the bone regeneration and proved the effectiveness of the materials.

  9. Guided bone regeneration using individualized ceramic sheets.

    PubMed

    Malmström, J; Anderud, J; Abrahamsson, P; Wälivaara, D-Å; Isaksson, S G; Adolfsson, E

    2016-10-01

    Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material.

  10. Guided bone regeneration using bone grafts and collagen membranes.

    PubMed

    Wang, H L; Carroll, M J

    2001-01-01

    When nonabsorbable membranes are used for guided bone regeneration (GBR), second surgeries are required for membrane retrieval. In addition, these types of membranes show a high incidence of flap sloughing and membrane exposure that often lead to infection and unfavorable results. Absorbable barriers such as collagen membranes were developed to overcome these drawbacks. This article presents the principles and the clinical procedure of using barrier membranes composed of absorbable collagen in GBR aimed at the repair and regeneration of ridge dehiscence defects around implants. The unique properties of collagen membranes that make them ideally suited to GBR procedures are reviewed. In addition, the indications and contraindications for using collagen membranes for GBR procedures are examined. Finally, cases are presented to demonstrate details of surgical principles and techniques.

  11. Membranes for the Guided Bone Regeneration

    PubMed Central

    Lee, Sang-Woon; Kim, Seong-Gon

    2014-01-01

    Many kinds of membrane have been used for the guided bone regeneration (GBR) technique. However, most membranes do not fulfill all requirements for the ideal membrane for the GBR technique. Among them, collagen membrane has been most widely used. However, its high price and weak tensile strength in wet condition are limitations for wide clinical application. Synthetic polymers have also been used for the GBR technique. Recently, silk based membrane has been considered as a membrane for the GBR technique. Despite many promising preclinical data for use of a silk membrane, clinical data regarding the silk membrane has been limited. However, silk based material has been used clinically as vessel-tie material and an electrospun silk membrane was applied successfully to patients. No adverse effect related to the silk suture has been reported. Considering that silk membrane can be provided to patients at a cheap price, its clinical application should be encouraged. PMID:27489841

  12. Using absorbable collagen membranes for guided tissue regeneration, guided bone regeneration, and to treat gingival recession.

    PubMed

    Wang, H L; Carroll, W J

    2000-05-01

    This article reviews the role of barrier membranes in guided tissue regeneration (GTR) and guided bone regeneration (GBR), including the advantages of using absorbable barrier membranes in GTR and GBR and the unique properties of collagen membranes. The indications and contraindications for using collagen membranes for these procedures are examined, and successful cases are presented. Finally, the role of collagen membranes in the future of regenerative therapy is considered.

  13. Onlay bone graft maintenance using guided bone regeneration, platelet rich plasma, and their combination.

    PubMed

    Younis, Mohammed; Elshahat, Ahmed; Elhabbaa, Gamal; Fareed, Ahmed; Safe, Ikram

    2014-11-01

    Onlay bone grafts have a bad reputation of resorption with loss of contour and volume. Rigid fixation reduces the incidence of resorption but does not prevent it. Literature shows reduction of resorption by applying guided bone regeneration (GBR) barriers and platelet-rich plasma (PRP). Investigating the effect of combining them together to reduce resorption was the aim of this study. This study included 4 groups: control group, GBR group, PRP group, and GBR + PRP group. Twenty rabbits were used (40 mandibular halves). Onlay bone grafts were fixed by titanium miniscrews in all groups. Computed tomography scans of harvested mandibles after euthanasia allowed calculations of bone graft volume and density. Onlay bone graft volumes in all experimental groups were significantly higher than in the control group. Volume maintenance in the GBR group was significantly higher than in the PRP group. There was no significant difference in the volume of onlay bone grafts between the group of combined GBR + PRP and GBR alone. It was concluded that, to maintain the volume of onlay bone grafts, either GBR or PRP can be added. Combining them did not add any advantage over the GBR alone.

  14. Reconstruction of bone fenestration on mandiblar by the guided bone regeneration methods with beta-TCP/PLGC membranes.

    PubMed

    Koyama, Yoshihisa; Kikuchi, Masanori; Edamura, Kazuya; Nagaoka, Katsuyoshi; Tanaka, Shigeo; Tanaka, Junzo; Takakuda, Kazuo

    2007-03-01

    Guided Bone Regeneration (GBR) is a method for bone tissue regeneration. In this method, membranes are used to cover bone defects and to block the invasion of the surrounding soft tissues. It would provide sufficient time for the osteogenic cells from bone marrow to proliferate and form new bony tissues. In spite of the potential usefulness of this method, no appropriate materials for the GBR membrane have been developed. Here we design the ideal mechanical properties of the GBR membranes and created novel materials, which is the composite of beta-tricalcium phosphate (beta-TCP) and block copolymer of L-lactide, glycolide, and epsilon-caplolactone (PLGC). In the animal experiments with the use of the GBR membranes for large bone defects, we observed significant enhancement in the bone regeneration after 12 weeks implantation and proved the effectiveness of the materials.

  15. Guided Bone Regeneration: biological principle and therapeutic applications.

    PubMed

    Retzepi, Maria; Donos, N

    2010-06-01

    The Guided Bone Regeneration (GBR) treatment concept advocates that regeneration of osseous defects is predictably attainable via the application of occlusive membranes, which mechanically exclude non-osteogenic cell populations from the surrounding soft tissues, thereby allowing osteogenic cell populations originating from the parent bone to inhabit the osseous wound. The present review discusses the evolution of the GBR biological rationale and therapeutic concept over the last two decades. Further, an overview of the GBR research history is provided with specific focus on the evidence available on its effectiveness and predictability in promoting the regeneration of critical size cranio-maxillo-facial defects, the neo-osteogenesis potential and the reconstruction of atrophic alveolar ridges before, or in conjunction with, the placement of dental implants. The authors conclude that future research should focus on (a) the investigation of the molecular mechanisms underlying the wound healing process following GBR application; (b) the identification of site and patient related factors which impact on the effectiveness and predictability of GBR therapy and (c) the evaluation of the pathophysiology of the GBR healing process in the presence of systemic conditions potentially affecting the skeletal system.

  16. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

    NASA Astrophysics Data System (ADS)

    Kasai, Takao; Matsumura, Sachiko; Iizuka, Tadashi; Shiba, Kiyotaka; Kanamori, Takeshi; Yudasaka, Masako; Iijima, Sumio; Yokoyama, Atsuro

    2011-02-01

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.

  17. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect.

    PubMed

    Kasai, Takao; Matsumura, Sachiko; Iizuka, Tadashi; Shiba, Kiyotaka; Kanamori, Takeshi; Yudasaka, Masako; Iijima, Sumio; Yokoyama, Atsuro

    2011-02-11

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.

  18. Osseointegration and guided bone regeneration in ectodermal dysplasia patients.

    PubMed

    Garagiola, Umberto; Umberto, Garagiola; Maiorana, Carlo; Ghiglione, Valentino; Marzo, Giuseppe; Santoro, Franco; Szabò, Gyorgy

    2007-11-01

    Dental and surgical implant treatment for patients affected by ectodermal dysplasia syndrome can be very complicated. The guided bone regeneration (GBR) membrane technique together with bone grafting is used to facilitate the placement of osseointegrated implants in a prosthetically guided position. Two groups with the same bony anatomical features were assessed. The first consisted of 13 ectodermal dysplasia patients in whom 66 implants with bone grafts and membranes were inserted. In the second control group, 120 implants with GBR were placed in 20 patients. The implants were assessed at the second stage of surgery, and at a follow-up after 1, 2, and 3 years of functional loading. There was no statistically significant difference in the osseointegration rate between the two groups. Despite the anatomical defects associated with the decreased occlusal vertical dimension and the reduced edentulous alveolar ridges, both in height and width, osseointegrated implants together with GBR and bone grafts can be used successfully in patients with ectodermal dysplasia syndrome.

  19. Comparison of Bone Resorption Rates after Intraoral Block Bone and Guided Bone Regeneration Augmentation for the Reconstruction of Horizontally Deficient Maxillary Alveolar Ridges.

    PubMed

    Gultekin, B Alper; Bedeloglu, Elcin; Kose, T Emre; Mijiritsky, Eitan

    2016-01-01

    Purpose. Bone atrophy after tooth loss may leave insufficient bone for implant placement. We compared volumetric changes after autogenous ramus block bone grafting (RBG) or guided bone regeneration (GBR) in horizontally deficient maxilla before implant placement. Materials and Methods. In this retrospective study, volumetric changes at RBG or GBR graft sites were evaluated using cone-beam computed tomography. The primary outcome variable was the volumetric resorption rate. Secondary outcomes were bone gain, graft success, and implant insertion torque. Results. Twenty-four patients (28 grafted sites) were included (GBR, 15; RBG, 13). One patient (RBG) suffered mucosal dehiscence at the recipient site 6 weeks after surgery, which healed spontaneously. Mean volume reduction in the GBR and RBG groups was 12.48 ± 2.67% and 7.20 ± 1.40%, respectively. GBR resulted in significantly more bone resorption than RBG (P < 0.001). Mean horizontal bone gain and width after healing were significantly greater in the GBR than in the RBG group (P = 0.002 and 0.005, resp.). Implant torque was similar between groups (P > 0.05). Conclusions. Both RBG and GBR hard-tissue augmentation techniques provide adequate bone graft volume and stability for implant insertion. However, GBR causes greater resorption at maxillary augmented sites than RBG, which clinicians should consider during treatment planning.

  20. Comparison of Bone Resorption Rates after Intraoral Block Bone and Guided Bone Regeneration Augmentation for the Reconstruction of Horizontally Deficient Maxillary Alveolar Ridges

    PubMed Central

    Bedeloglu, Elcin; Kose, T. Emre

    2016-01-01

    Purpose. Bone atrophy after tooth loss may leave insufficient bone for implant placement. We compared volumetric changes after autogenous ramus block bone grafting (RBG) or guided bone regeneration (GBR) in horizontally deficient maxilla before implant placement. Materials and Methods. In this retrospective study, volumetric changes at RBG or GBR graft sites were evaluated using cone-beam computed tomography. The primary outcome variable was the volumetric resorption rate. Secondary outcomes were bone gain, graft success, and implant insertion torque. Results. Twenty-four patients (28 grafted sites) were included (GBR, 15; RBG, 13). One patient (RBG) suffered mucosal dehiscence at the recipient site 6 weeks after surgery, which healed spontaneously. Mean volume reduction in the GBR and RBG groups was 12.48 ± 2.67% and 7.20 ± 1.40%, respectively. GBR resulted in significantly more bone resorption than RBG (P < 0.001). Mean horizontal bone gain and width after healing were significantly greater in the GBR than in the RBG group (P = 0.002 and 0.005, resp.). Implant torque was similar between groups (P > 0.05). Conclusions. Both RBG and GBR hard-tissue augmentation techniques provide adequate bone graft volume and stability for implant insertion. However, GBR causes greater resorption at maxillary augmented sites than RBG, which clinicians should consider during treatment planning. PMID:27847815

  1. Nanomaterials and bone regeneration

    PubMed Central

    Gong, Tao; Xie, Jing; Liao, Jinfeng; Zhang, Tao; Lin, Shiyu; Lin, Yunfeng

    2015-01-01

    The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part. PMID:26558141

  2. Surface characteristics of implants influence their bone integration after simultaneous placement of implant and GBR membrane.

    PubMed

    Lima, Luiz A; Fuchs-Wehrle, Anita M; Lang, Niklaus P; Hämmerle, Christoph H F; Liberti, Edson; Pompeu, Eduardo; Todescan, José H

    2003-12-01

    The purpose of this study was to evaluate the influence of titanium surface characteristics on bone integration of implants, and to describe the pattern of peri-implant tissue healing after simultaneous implant placement and guided bone regeneration. In four healthy mongrel dogs mandibular premolars were extracted. Two weeks following full mouth prophylaxis and 4 months after extractions, simultaneous membrane and implant surgeries were performed. Efforts were made to produce bony defects with dimensions of 7 x 7 x 7 mm. Into these, 24 standard ITI implants (diameter = 4.1 mm; length = 8 mm) with either a titanium plasma-sprayed (TPS) or a machined surface (MS) were placed. Although implants were inserted 4 mm into cancellous bone, difficulties in achieving optimal primary stability were encountered. All dogs were maintained on a soft diet. Chlorhexidine rinses were performed three times a week. Full mouth prophylaxis was performed every 2 weeks. In the case of membrane exposure, the membranes were removed prematurely (4-6 or 14-15 weeks after surgery). Two dogs were sacrificed at 16 weeks and two at 24 weeks after surgery. Nondecalcified histologic sections were processed and histometric analyses were carried out. When membranes were removed after 4-6 weeks, a vertical bone growth (VB) of 45-61% of the original defect was noted. After membrane removal at 14-15 weeks, similar VB was observed. However, if membranes were left in situ for 24 weeks, VB was between 79% and 96%. In this group of sites, the VB was 66% at 16 weeks and 86% at 24 weeks. Osseointegration in the regenerated bone area ranged from 12% to 32% for the TPS and from 0.0% to 3.6% for the MS implants at 16 and 24 weeks combined. Osseointegration in the pristine host bone area ranged from 16% to 35% for the TPS and from 0.0% to 11% for the MS sites at 16 and 24 weeks. In conclusion, the fraction of implant-bone integration was much higher in the pristine bone compared to that in the regenerated bone

  3. Enhanced guided bone regeneration by asymmetrically porous PCL/pluronic F127 membrane and ultrasound stimulation.

    PubMed

    Oh, Se Heang; Kim, Tae Ho; Chun, So Young; Park, Eui Kyun; Lee, Jin Ho

    2012-01-01

    Recently, we developed a novel method for fabricating a guided bone regeneration (GBR) membrane with an asymmetrical pore structure and hydrophilicity by an immersion precipitation method. Results from an animal study, in a cranial defect model in rats, indicated that the unique asymmetrically porous GBR membrane would provide a good environment for bone regeneration. In the present study, we applied low intensity pulsed ultrasound as a simple and non-invasive stimulus to an asymmetrically porous polycaprolactone (PCL)/Pluronic F127 GBR membrane-implanted site transcutaneously in rats to investigate the feasibility of using ultrasound to stimulate enhanced bone regeneration through the membrane. It was observed that the ultrasound-stimulated PCL/F127 GBR membrane group had much faster bone regeneration behavior than a PCL/F127 membrane group w/o ultrasound or a control group (w/o membrane and ultrasound). The greater bone regeneration behavior in the GBR membrane/ultrasound group may be caused by a synergistic effect of the asymmetrically porous PCL/F127 membrane with unique properties (selective permeability, hydrophilicity and osteoconductivity), and the stimulatory effect of ultrasound (induction of angiogenesis and osteogenesis of cells).

  4. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    DTIC Science & Technology

    2013-01-01

    compared as experimental treatment groups to an empty untreated defect as a negative control or a defect filled with autologous bone grafts as a positive...defect site in rabbits and was a comparable synthetic alternative to autologous bone grafts in all metrics measured in this study. Acknowledgments...regeneration and repair as compared to grafting materials alone.9 Guided bone regen- eration (GBR), which refers to using barrier membrane guides, has been

  5. Guided bone regeneration using resorbable membrane and different bone substitutes: Early histological and molecular events.

    PubMed

    Elgali, Ibrahim; Turri, Alberto; Xia, Wei; Norlindh, Birgitta; Johansson, Anna; Dahlin, Christer; Thomsen, Peter; Omar, Omar

    2016-01-01

    Bone insufficiency remains a major challenge for bone-anchored implants. The combination of guided bone regeneration (GBR) and bone augmentation is an established procedure to restore the bone. However, a proper understanding of the interactions between the bone substitute and GBR membrane materials and the bone-healing environment is lacking. This study aimed to investigate the early events of bone healing and the cellular activities in response to a combination of GBR membrane and different calcium phosphate (CaP) materials. Defects were created in the trabecular region of rat femurs, and filled with deproteinized bovine bone (DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All the defects were covered with an extracellular matrix membrane. Defects were harvested after 12h, 3d and 6d for histology/histomorphometry, immunohistochemistry and gene expression analyses. Histology revealed new bone, at 6d, in all the defects. Larger amount of bone was observed in the SrHA-filled defect. This was in parallel with the reduced expression of osteoclastic genes (CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects. The observations of CD68 and periostin-expressing cells in the membrane per se indicated that the membrane may contribute to the healing process in the defect. It is concluded that the bone-promoting effects of Sr in vivo are mediated by a reduction in catabolic and osteoblast-osteoclast coupling processes. The combination of a bioactive membrane and CaP bone substitute material doped with Sr may produce early synergistic effects during GBR. The study provides novel molecular, cellular and structural evidence on the promotion of early bone regeneration in response to synthetic strontium-containing hydroxyapatite (SrHA) substitute, in combination with a resorbable, guided bone regeneration (GBR) membrane. The prevailing view, based

  6. Bioabsorbable scaffold for in situ bone regeneration.

    PubMed

    Giardino, R; Nicoli Aldini, N; Fini, M; Tanzi, M C; Faré, S; Draghi, L; Carpi, A; Nicolini, A; Giavaresi, G

    2006-09-01

    A non-porous poly-DL-lactide tubular chamber filled by demineralised bone matrix (DBM) and bone marrow stromal cells (BMSC) in combination, was evaluated as a scaffold for guided bone regeneration (GBR) in an experimental model using the rabbit radius. The tubular chamber had an internal diameter of 4.7 mm, a wall thickness of 0.4 mm and a length of 18 mm. Autologous BMSC were obtained, under general anaesthesia from rabbit iliac crest and isolated by centrifugation technique. Allogenic DBM was obtained from cortico-cancellous bone of rabbits. In general anaesthesia, a 10-mm defect was bilaterally created in the radii of 10 rabbits. On the right side (experimental side) the defect was bridged with the chamber filled with both BMSC and DBM. On the left side (control side) the defect was treated by positioning DBM and BMSC between the two stumps. At an experimental time of 4 months histology and histomorphometry demonstrated that the presence of a tubular chamber significantly improved bone regrowth in the defect The mean thickness of newly-formed bone inside the chamber was about 56.7+/-3.74% of the normal radial cortex, in comparison with 46.7+/-10.7% when DBM and BMSC without the chamber were placed in the defect, P<0.05). These results confirmed the effectiveness of the chamber as a container for factors promoting bone regeneration.

  7. Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration

    PubMed Central

    Ma, Shiqing; Adayi, Aidina; Liu, Zihao; Li, Meng; Wu, Mingyao; Xiao, Linghao; Sun, Yingchun; Cai, Qing; Yang, Xiaoping; Zhang, Xu; Gao, Ping

    2016-01-01

    Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration. PMID:27546177

  8. Collagen based barrier membranes for periodontal guided bone regeneration applications.

    PubMed

    Sheikh, Zeeshan; Qureshi, Javairia; Alshahrani, Abdullah M; Nassar, Heba; Ikeda, Yuichi; Glogauer, Michael; Ganss, Bernhard

    2017-01-01

    Certain cell populations within periodontal tissues possess the ability to induce regeneration, provided they have the opportunity to populate the wound or defect. Guided regeneration techniques have been investigated for regenerating periodontal tissues and such therapies usually utilize barrier membranes. Various natural and synthetic barrier membranes have been fabricated and tested to prevent epithelial and connective tissue cells from invading while allowing periodontal cells to selectively migrate into the defect. This paper focuses on the literature relevant to the use and potential of resorbable collagen membranes in GBR procedures, sites of periodontal and intrabony defects, in cases of socket and alveolar ridge preservation and at implant sites. The results of their use in GBR procedures has shown them to be effective and comparable with non-resorbable membranes with regards to clinical attachment gain, probing depth reduction and defect bone filling. They have also shown to prevent epithelial ingrowth into the defect space during the initial wound healing phase postsurgically. Collagen membranes have also been used for root coverage and GBR procedures and have shown good success rates comparable to subepithelial connective tissue grafts and expanded-polytetrafluoroethylene (e-PTFE) membranes. The future for periodontal tissue engineering is very exciting with the use of barrier membranes expected to continue playing a critical role. However, long-term clinical trials are required to further evaluate and confirm the efficacy of the available collagen barrier membranes for periodontal and bone regeneration use.

  9. Methyl cellulose gel obstructed bone formation by GBR: an experimental study in rats.

    PubMed

    Lioubavina-Hack, Natalia; Karring, Thorkild; Lynch, Samuel E; Lindhe, Jan

    2005-12-01

    formation under Teflon capsules placed adjacent to uninjured cortical bone in the mandibular ramus of rats. These data suggest that another material should be utilized to deliver growth factors under Teflon membranes for guided bone regeneration.

  10. Bone regeneration in dentistry

    PubMed Central

    Tonelli, Paolo; Duvina, Marco; Barbato, Luigi; Biondi, Eleonora; Nuti, Niccolò; Brancato, Leila; Rose, Giovanna Delle

    2011-01-01

    Summary The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological principles of osteogenesis, osteoinduction and osteoconduction. Several techniques combine these principles with different results, due to the condition of the bone base on which we operate changes, the surgical technique that we use, and finally for the bone metabolic conditions of the patient who can be in a state of systemic osteopenia or osteoporosis; these can also affect the result of jaw bone reconstruction. PMID:22461825

  11. Guided bone regeneration using a flexible hydroxyapatite patch.

    PubMed

    Sun, Fangfang; Kang, Hyun Gu; Ryu, Su-Chak; Kim, Ji Eun; Park, Enoch Y; Hwang, Dae Youn; Lee, Jaebeom

    2013-11-01

    Guided bone regeneration (GBR) is a new method of promoting new bone formation by blocking the proliferation of regenerated connective tissue or providing additional interventions such as direct drug delivery and mechanical support. This in vivo study of bone regeneration in radius compound fractures in rabbits was conducted using a highly flexible scaffold of nanoscale hydroxyapatite (nHAp)/chitosan, termed a "bone patch". A solidification-assisted compression (SAC) method was utilized to fabricate the bone patch, and its in vivo cytotoxicity, bio-absorption, and bone regeneration capacity were evaluated. Four weeks after implantation, new bone formation with abundant active osteoblasts and incompleted degradation of chitosan in the patch were observed without any regeneration of connective tissue, compared with the corresponding implant without a patch. X-ray images showed that the radius with the bone patch had higher opacity than that of the control, which was consistent with the results obtained via histological analysis. Evidently, the nHAp-embedded bone-patch scaffold has considerable potential for application in the field of orthopedics of bone regeneration.

  12. Nanocomposites and bone regeneration

    NASA Astrophysics Data System (ADS)

    James, Roshan; Deng, Meng; Laurencin, Cato T.; Kumbar, Sangamesh G.

    2011-12-01

    This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite (HA) and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA (reduced grain size), one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

  13. Antibacterial Nanostructured Polyhydroxybutyrate Membranes for Guided Bone Regeneration.

    PubMed

    Karahaliloğlu, Zeynep; Ercan, Batur; Taylor, Erik N; Chung, Stanley; Denkbaş, Emir B; Webster, Thomas J

    2015-12-01

    The principle of guided bone regeneration (GBR) in orthopedic, cranio-maxillofacial and dental tissue engineering applications is to create a secluded space for the treatment of large bone defects while excluding fibrous connective tissue formation at the defect area. In dental surgeries, a GBR membrane is placed near the dental implant in post-extraction sockets to grow new bone at the implant site, along with inhibiting infection due to the microbial nature of the mouth flora. Poly[(R)-3-hydroxybutyric acid] (PHB) is a natural polyester synthesized by a wide variety of microorganisms which has been proposed for various biomedical applications. In this study, to improve the performance of PHB as a GBR, a NaOH based alkaline treatment was designed to create nanofeatured PHB membranes. The newly fabricated nanofeatured PHB membranes were investigated for GBR applications. The results showed that a quick, simple, and inexpensive sodium hydroxide treatment modified the nanostructured surface morphology and chemistry of the PHB membranes by inducing hydrolysis of the ester bonds in the PHB backbone creating carboxylic surface functional groups, which increased the hydrophilicity of the PHB surfaces. Cytocompatibility studies showed increased proliferation of human osteoblasts (bone forming cells) on the NaOH treated PHB membranes compared to the untreated ones. Importantly, in vitro bacterial studies with Staphylococcus aureus (S. aureus) indicated that the NaOH-treated PHB surfaces inhibited S. aureus growth more than 60% after 48 hours of culture compared to the untreated PHB membrane. Thus, this study, for the first time, showed that nanofeatured PHB membranes modified with a NaOH treatment may be a useful anti-bacterial, osteoconductive GBR membrane for numerous orthopedic, cranio-maxillofacial and dental tissue engineering applications.

  14. GBR and autogenous cortical bone particulate by bone scraper for alveolar ridge augmentation: a 2-case report.

    PubMed

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Itro, Angelo; Calura, Giorgio

    2008-01-01

    Scientific literature describes autogenous bone as the gold standard among graft materials for alveolar reconstructive procedures. Alveolar ridge augmentation has been clinically achieved with different forms of autogenous bone, including autogenous cortical bone particulate (ACBP). However, few histologic studies demonstrating the biologic potential and healing dynamics following the use of ACBP are currently available. This case report presents 2 patients in whom atrophic edentulous alveolar crests were submitted to a vertical/lateral ridge augmentation prior to implant placement. The technique was performed through the use of a titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) membrane with an ACBP graft obtained from the retromolar region with a specially designed bone scraper. Bone biopsy specimens were harvested at 9 months after graft placement. Analysis of the reconstructed bone revealed bone with a lamellar quality characterized by a mature osteonic structure. Sparse particles of grafted bone were evident in direct contact with the regenerated bone. Marrow spaces showed a normal stromal component with limited grafted particles.

  15. Active implant peri-apical lesion: a case report treated via guided bone regeneration with a 5-year clinical and radiographic follow-up.

    PubMed

    Quaranta, Alessandro; Andreana, Sebastiano; Pompa, Giorgio; Procaccini, Maurizio

    2014-06-01

    Implant peri-apical lesion (IPL) is a periapical lesion, usually asymptomatic, in which the coronal portion of the implant achieves a normal bone to implant interface. A case of IPL following immediate implant placement and treated with guided bone regeneration (GBR) principles is described. Five-year clinical and radiographic follow-up with cone-beam assessment showed complete healing of the bone. GBR principles applied to IPL could completely solve the lesion.

  16. Vertical Guided Bone Regeneration using Titanium-reinforced d-PTFE Membrane and Prehydrated Corticocancellous Bone Graft

    PubMed Central

    Cucchi, Alessandro; Ghensi, Paolo

    2014-01-01

    Guided bone regeneration (GBR) standard protocols call for filling the space underneath the membrane with autogenous bone or a mixture composed of autogenous bone particles and allogeneic bone tissue or heterologous biomaterials. This work describes the case of a GBR performed to restore a vertical bone defect with simultaneous placement of a dental implant in the posterior mandible that was carried out using a high density d-PTFE membrane and corticocancellous porcine-derived bone without the addition of any autogenous bone. Bone regeneration was assessed by histological analysis of a biopsy sample collected from the grafted site nine months after the surgery. Intraoral radiographs taken at follow-up visits showed complete maintenance of the peri-implant bone levels for up to two years after prosthesis delivery. The regenerated site successfully supported functional loading of the implant. The present case report suggests that the use of a heterologous bone substitute alone to restore a vertical defect in a GBR procedure can be as effective as the standard protocol, while avoiding the drawbacks associated with a second surgical site opening. PMID:25419250

  17. Biodegradable effect of PLGA membrane in alveolar bone regeneration on beagle dog.

    PubMed

    Hua, Nan; Ti, Vivian Lao; Xu, Yuanzhi

    2014-11-01

    Guided bone regeneration (GBR) is a principle adopted from guided tissue regeneration (GTR). Wherein, GBR is used for the healing of peri-implant bony dehiscences, for the immediate placement of implants into extraction sockets and for the augmentation of atrophic alveolar ridges. This procedure is done by the placement of a resorbable or non-resorbable membrane that will exclude undesirable types of tissue growth between the extraction socket and the soft tissue to allow only bone cells to regenerate in the surgically treated lesion. Here, we investigated the biodegradable effect of polylactic-co-glycolic acid (PLGA) membrane in the alveolar bone on Beagle dogs. Results show that both collagen and PLGA membrane had been fully resorbed, biodegraded, at four weeks post-operative reentry into the alveolar bone. Histological results under light microscopy revealed formation of new bone trabeculae in the extraction sites on both collagen and PLGA membrane. In conclusion, PLGA membrane could be a potential biomaterials for use on GBR and GTR. Nevertheless, further studies will be necessary to elucidate the efficiency and cost effectiveness of PLGA as GBR membrane in clinical.

  18. Novel microinjector for carrying bone substitutes for bone regeneration in periodontal diseases.

    PubMed

    Tsai, Hsiao-Cheng; Li, Yi-Chen; Young, Tai-Horng; Chen, Min-Huey

    2016-01-01

    Traditionally, guide bone regeneration (GBR) was a widely used method for repairing bone lost from periodontal disease. There were some disadvantages associated with the GBR method, such as the need for a stable barrier membrane and a new creative cavity during the surgical process. To address these disadvantages, the purpose of this study was to evaluate a novel microinjector developed for dental applications. The microinjector was designed to carry bone graft substitutes to restore bone defects for bone regeneration in periodontal diseases. The device would be used to replace the GBR method. In this study, the injected force and ejected volume of substitutes (including air, water, and ethanol) were defined by Hooke's law (n = 3). The optimal particle size of bone graft substitutes was determined by measuring the recycle ratio of bone graft substitutes from the microinjector (n = 3). Furthermore, a novel agarose gel model was used to evaluate the feasibility of the microinjector. The current study found that the injected force was less than 0.4 N for obtaining the ejected volume of approximately 2 mL, and when the particle size of tricalcium phosphate (TCP) was smaller than 0.5 mm, 80% TCP could be ejected from the microinjector. Furthermore, by using an agarose model to simulate the periodontal soft tissue, it was also found that bone graft substitutes could be easily injected into the gel. The results confirmed the feasibility of this novel microinjector for dental applications to carry bone graft substitutes for the restoration of bone defects of periodontal disease. Copyright © 2015. Published by Elsevier B.V.

  19. Dental implants with versus without peri-implant bone defects treated with guided bone regeneration

    PubMed Central

    Peñarrocha-Oltra, David; Peñarrocha-Diago, Maria; Peñarrocha-Diago, Miguel

    2015-01-01

    Background The guided bone regeneration (GBR) technique is highly successful for the treatment of peri-implant bone defects. The aim was to determine whether or not implants associated with GBR due to peri-implant defects show the same survival and success rates as implants placed in native bone without defects. Material and Methods Patients with a minimum of two submerged dental implants: one suffering a dehiscence or fenestration defect during placement and undergoing simultaneous guided bone regeneration (test group), versus the other entirely surrounded by bone (control group) were treated and monitored annually for three years. Complications with the healing procedure, implant survival, implant success and peri-implant marginal bone loss were assessed. Statistical analysis was performed with non-parametric tests setting an alpha value of 0.05. Results Seventy-two patients and 326 implants were included (142 test, 184 control). One hundred and twenty-five dehiscences (average height 1.92±1.11) and 18 fenestrations (average height 3.34±2.16) were treated. At 3 years post-loading, implant survival rates were 95.7% (test) and 97.3% (control) and implant success rates were 93.6% and 96.2%, respectively. Mean marginal bone loss was 0.54 (SD 0.26 mm) for the test group and 0.43 (SD 0.22 mm) for the control group. No statistically significant differences between both groups were found. Conclusions Within the limits of this study, implants with peri-implant defects treated with guided bone regeneration exhibited similar survival and success rates and peri-implant marginal bone loss to implants without those defects. Large-scale randomized controlled studies with longer follow-ups involving the assessment of esthetic parameters and hard and soft peri-implant tissue stability are needed. Key words:Guided bone regeneration, peri-implant defects, dental implants, marginal bone level, success rate, survival rate. PMID:26330931

  20. Bone regeneration during distraction osteogenesis.

    PubMed

    Amir, Lisa R; Everts, Vincent; Bronckers, Antonius L J J

    2009-07-01

    Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connective tissues in the gap area between two separated bone segments. This procedure has received much clinical attention as a way to correct congenital growth retardation of bone tissue or to generate bone to fill skeletal defects. The process of bone regeneration involves a complex system of biological changes whereby mechanical stress is converted into a cascade of signals that activate cellular behavior resulting in (enhanced) formation of bone. Over the last decade, significant progress has been made in understanding the bone regeneration process during distraction osteogenesis. The mechanical and biological factors that are important for the success of the distraction treatment have been partially characterized and are discussed in this review.

  1. The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses.

    PubMed

    Retzepi, M; Calciolari, E; Wall, I; Lewis, M P; Donos, N

    2017-07-18

    To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR). Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis. Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38-42%) and newly formed bone (54-61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified. Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Bone Morphogenetic Proteins: Periodontal Regeneration

    PubMed Central

    Rao, Subramaniam M; Ugale, Gauri M; Warad, Shivaraj B

    2013-01-01

    Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search). All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP. PMID:23626951

  3. Improving gingival smile by means of guided bone regeneration principles

    PubMed Central

    Ferreira, Carlos Eduardo de Almeida; Brandão, Roberto Carlos Bodart; Martinelli, Carolina Borges; Pignaton, Túlio Bonna

    2016-01-01

    ABSTRACT Objective: This study evaluated the effectiveness of guided bone regeneration (GBR) carried out with xenogenic bone substitute (Bio-OssTM) and collagen resorbable membrane (Bio-GideTM) to improve gingival smile (GS) in patients with excessive vertical maxillary growth (EVMG). Methods: Twelve healthy women aged between 20 and 49 years old (mean age of 26 years), with 5 mm or more of gingival exposure during fully posed smile (FPS) due to EVMG, were included. Baseline digital photographs were taken with standardized head position at rest and FPS. In eight out of 12 cases, crown lengthening procedure was indicated and the initial incision was made 2 to 4 mm from the gingival margin. In four cases, with no indication for crown lengthening procedure, a sulcular incision was performed. GBR was performed in all cases, using micro screws and/or titanium mesh associated with Bio-OssTM and Bio-GideTM. After 10 days, sutures were removed. Recall appointments were scheduled at 1, 6, and 12 months when standardized photographs were again taken. ImageToolTM software was used to measure the gingival exposure (GE) during FPS from the standardized close-up smile photographs at baseline and 12 months. Results: GE mean at baseline was 275.44 mm2. After 12 months, patients who undergone exclusively GBR procedure, presented GE reduction of 40.7%, ∆ = 112.01 mm2 (statistically significant, p = 0.12), and patients who had crown lengthening associated with the graft had a reduction of 60%, ∆ = 167.01 mm2. Conclusion: Our results using GBR to improve GS in cases of EVMG showed an exceptionally high patient acceptance and satisfaction. One-year follow-up confirmed stable results. PMID:27409660

  4. Gene therapy for bone regeneration.

    PubMed

    Luo, Jeffrey; Sun, Michael H; Kang, Quan; Peng, Ying; Jiang, Wei; Luu, Hue H; Luo, Qing; Park, Jae Yoon; Li, Yien; Haydon, Rex C; He, Tong-Chuan

    2005-04-01

    Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone has the unique ability to regenerate and continuously remodel itself throughout life. However, clinical situations arise when bone is unable to heal itself, as with segmental bone loss, fracture non-union, and failed spinal fusion. This leads to significant morbidity and mortality. Current attempts at improved bone healing have been met with limited success, fueling the development of improved techniques. Gene therapy in many ways represents an ideal approach for augmenting bone regeneration. Gene therapy allows specific gene products to be delivered to a precise anatomic location. In addition, the level of transgene expression as well as the duration of expression can be regulated with current techniques. For bone regeneration, the gene of interest should be delivered to the fracture site, expressed at appropriate levels, and then deactivated once the fracture has healed. Delivery of biological factors, mostly bone morphogenetic proteins (BMPs), has yielded promising results both in animal and clinical studies. There has also been tremendous work on discovering new growth factors and exploring previously defined ones. Finally, significant advances are being made in the delivery systems of the genes, ranging from viral and non-viral vectors to tissue engineering scaffolds. Despite some public hesitation to gene therapy, its use has great potential to expand our ability to treat a variety of human bone and musculoskeletal disorders. It is conceivable that in the near future gene therapy can be utilized to induce bone formation in virtually any region of the body in a minimally invasive manner. As bone biology and gene therapy research progresses, the goal of successful human gene transfer for augmentation of bone regeneration draws nearer.

  5. Effects of ipriflavone on augmented bone using a guided bone regeneration procedure.

    PubMed

    Ito, Koichi; Minegishi, Tadashi; Takayama, Tadahiro; Tamura, Takanori; Yamada, Yutaka; Sato, Shuichi

    2007-02-01

    : This study investigated the effects of ipriflavone (IP) on augmented bone using a guided bone regeneration (GBR) procedure. In 15 rabbits, two titanium caps were placed into calvarial bone for GBR. The animals were divided into three groups: the No-IP (no intake of IP), Post-IP (IP orally, 10 mg/kg/day after GBR), and Pre-IP (IP intake beginning before GBR) groups. One cap was removed from each rabbit after 3 months, and the remaining site was a control. One month after one cap removal, all the animals were euthanized, and histologic and histomorphometric analyses were performed. In all of the groups, the newly generated tissue was of varying size, and it consisted of thin pieces of mineralized bone and large marrow spaces with fat cells and some hematopoietic cells. In all of the control sites, the newly generated tissue was noted and almost filled the space under the cap. There was a significant difference between groups No-IP and Pre-IP (93.8+/-4.6% vs. 98.5+/-0.8%, P<0.05). The tissue generated at the test sites in all of the groups was resorbed, and its original shape and volume were not maintained 1 month after one cap removal. In particular, the greatest percentage, approximately 20% of the newly generated tissue, was resorbed in the No-IP group (93.8+/-4.6% vs. 73.9+/-3.7%, P<0.05), and approximately 11% and 15% in groups Post-IP and Pre-IP, respectively. The relative amount of mineralized bone generated at the control and test sites was significantly larger in groups Post-IP and Pre-IP when compared with group No-IP, except for the test site between groups No-IP and Post-IP (P<0.05). Therefore, the amount of mineralized tissue generated appeared to increase with an increase in the total IP dose. Within the limitations of this rabbit experimental model, we conclude that the daily intake of IP before or after GBR inhibits the resorption of augmented tissue and would be useful for improving the quality of newly generated bone beyond the skeletal envelope.

  6. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures

    PubMed Central

    Ferroni, Letizia; Guazzo, Riccardo; Sbricoli, Luca; De Benedictis, Giulia; Finotti, Luca; Isola, Maurizio; Bressan, Eriberto; Zavan, Barbara

    2015-01-01

    The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications. PMID:26191793

  7. Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures.

    PubMed

    Gardin, Chiara; Ricci, Sara; Ferroni, Letizia; Guazzo, Riccardo; Sbricoli, Luca; De Benedictis, Giulia; Finotti, Luca; Isola, Maurizio; Bressan, Eriberto; Zavan, Barbara

    2015-01-01

    The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications.

  8. Antibacterial efficacy of triple-layered poly(lactic-co-glycolic acid)/nanoapatite/lauric acid guided bone regeneration membrane on periodontal bacteria.

    PubMed

    Saarani, Nur Najiha; Jamuna-Thevi, Kalitheerta; Shahab, Neelam; Hermawan, Hendra; Saidin, Syafiqah

    2017-01-20

    A guided bone regeneration (GBR) membrane has been extensively used in the repair and regeneration of damaged periodontal tissues. One of the main challenges of GBR restoration is bacterial colonization on the membrane, constitutes to premature membrane degradation. Therefore, the purpose of this study was to investigate the antibacterial efficacy of triple-layered GBR membrane composed of poly(lactic-co-glycolic acid) (PLGA), nanoapatite (NAp) and lauric acid (LA) with two types of Gram-negative periodontal bacteria, Fusobacterium nucleatum and Porphyromonas gingivalis through a disc diffusion and bacterial count tests. The membranes exhibited a pattern of growth inhibition and killing effect against both bacteria. The increase in LA concentration tended to increase the bactericidal activities which indicated by higher diameter of inhibition zone and higher antibacterial percentage. It is shown that the incorporation of LA into the GBR membrane has retarded the growth and proliferation of Gram-negative periodontal bacteria for the treatment of periodontal disease.

  9. Bone Repair on Fractures Treated with Osteosynthesis, ir Laser, Bone Graft and Guided Bone Regeneration: Histomorfometric Study

    NASA Astrophysics Data System (ADS)

    dos Santos Aciole, Jouber Mateus; dos Santos Aciole, Gilberth Tadeu; Soares, Luiz Guilherme Pinheiro; Barbosa, Artur Felipe Santos; Santos, Jean Nunes; Pinheiro, Antonio Luiz Barbosa

    2011-08-01

    The aim of this study was to evaluate, through the analysis of histomorfometric, the repair of complete tibial fracture in rabbits fixed with osteosynthesis, treated or not with infrared laser light (λ780 nm, 50 mW, CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical fractures were created, under general anesthesia (Ketamina 0,4 ml/Kg IP and Xilazina 0,2 ml/Kg IP), on the dorsum of 15 Oryctolagus rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with wire osteosynthesis. Animals of groups III and V were grafted with hydroxyapatite and GBR technique used. Animals of groups IV and V were irradiated at every other day during two weeks (16 J/cm2, 4×4 J/cm2). Observation time was that of 30 days. After animal death (overdose of general anesthetics) the specimes were routinely processed to wax and underwent histological analysis by light microscopy. The histomorfometric analysis showed an increased bone neoformation, increased collagen deposition, less reabsorption and inflammation when laser was associated to the HATCP. It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of CHA.

  10. Limitations and options using resorbable versus nonresorbable membranes for successful guided bone regeneration.

    PubMed

    Soldatos, Nikolaos K; Stylianou, Popi; Koidou, Vasiliki P; Angelov, Nikola; Yukna, Raymond; Romanos, Georgios E

    2017-01-01

    Deficient bony ridges often complicate the implant treatment plan. Several treatment modalities are used to regenerate bone, including guided bone regeneration (GBR). The purpose of this study was to summarize the knowledge on different types of membranes available and currently used in GBR procedures in a staged approach or with simultaneous implant placement. The primary role of the membranes is to exclude epithelial and connective tissue cells from the wound area to be regenerated, and to create and maintain the space into which pluripotential and osteogenic cells are free to migrate. A literature search was performed for articles that were published in English on the topic. A selected number of studies were chosen in order to provide a review of the main characteristics, applications, and outcomes of the different types of membranes. Resorbable membranes are made of natural or synthetic polymers like collagen and aliphatic polyesters. Collagens are the most common type used. They have similar collagen composition to the periodontal connective tissue. Other materials available include human, porcine, and bovine pericardium membranes, human amnion and chorion tissue, and human acellular freeze-dried dermal matrix. Nonresorbable membranes used in GBR include dense-polytetrafluoroethylene (d-PTFE), expanded-polytetrafluoroethylene (e-PTFE), titanium mesh, and titanium-reinforced polytetrafluoroethylene. The most common complication of nonresorbable membranes is exposure, which has detrimental effect on the final outcome with both types of membranes. For vertical bone augmentation procedures, the most appropriate membranes are the nonresorbable. For combination defects, both types result in a successful outcome.

  11. Surgical Approaches Based on Biological Objectives: GTR versus GBR Techniques

    PubMed Central

    Pagni, Giorgio; Rasperini, Giulio

    2013-01-01

    Guided tissue regenerative (GTR) therapies are performed to regenerate the previously lost tooth supporting structure, thus maintaining the aesthetics and masticatory function of the available dentition. Alveolar ridge augmentation procedures (GBR) intend to regain the alveolar bone lost following tooth extraction and/or periodontal disease. Several biomaterials and surgical approaches have been proposed. In this paper we report biomaterials and surgical techniques used for periodontal and bone regenerative procedures. Particular attention will be adopted to highlight the biological basis for the different therapeutic approaches. PMID:23843792

  12. A novel silk fibroin nanofibrous membrane for guided bone regeneration: a study in rat calvarial defects

    PubMed Central

    Lu, Shijun; Wang, Peng; Zhang, Feng; Zhou, Xichao; Zuo, Baoqi; You, Xinran; Gao, Yang; Liu, Hongchen; Tang, Hailiang

    2015-01-01

    A novel membrane for guided bone regeneration (GBR), constituting silk fibroin (SF) nanofiber from native silk nanofibril solution, was prepared by electrospinning process. Another barrier membrane, a collagen-type membrane (Bio-Gide®), was used as a comparative sample. Twelve healthy male Sprague-Dawley rats were used in this study. Bilateral round defects were created in the calvarial bone. The bone regenerative efficacy was evaluated in rat calvarial defects. Animals were killed at 4 and 12 weeks. Bone regeneration was analyzed using micro-computed tomography and histological analysis. The SF nanofibrous membrane showed superior results with regard to mechanical tensile properties. At 4 weeks, the bone volume and collagen I positive areas in the SF group were greater than in the Bio-Gide group. At 12 weeks, the defect had completely healed with new bone in both the groups. In conclusion, the SF nanofibrous membranes showed satisfactory mechanical stability, good biocompatibility, slow degradability, and improved new bone regeneration without any adverse inflammatory reactions. Considering the low cost and low risk of disease transmission, the SF nanofibrous membrane is a potential candidate for GBR therapy compared with the widely used collagen membranes. PMID:26807172

  13. Composite Hydrogels for Bone Regeneration

    PubMed Central

    Tozzi, Gianluca; De Mori, Arianna; Oliveira, Antero; Roldo, Marta

    2016-01-01

    Over the past few decades, bone related disorders have constantly increased. Among all pathological conditions, osteoporosis is one of the most common and often leads to bone fractures. This is a massive burden and it affects an estimated 3 million people only in the UK. Furthermore, as the population ages, numbers are due to increase. In this context, novel biomaterials for bone fracture regeneration are constantly under development. Typically, these materials aim at favoring optimal bone integration in the scaffold, up to complete bone regeneration; this approach to regenerative medicine is also known as tissue engineering (TE). Hydrogels are among the most promising biomaterials in TE applications: they are very flexible materials that allow a number of different properties to be targeted for different applications, through appropriate chemical modifications. The present review will focus on the strategies that have been developed for formulating hydrogels with ideal properties for bone regeneration applications. In particular, aspects related to the improvement of hydrogels’ mechanical competence, controlled delivery of drugs and growth factors are treated in detail. It is hoped that this review can provide an exhaustive compendium of the main aspects in hydrogel related research and, therefore, stimulate future biomaterial development and applications. PMID:28773392

  14. Scaffold Design for Bone Regeneration

    PubMed Central

    Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.

    2014-01-01

    The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250

  15. Infection, Inflammation, and Bone Regeneration

    PubMed Central

    Thomas, M.V.; Puleo, D.A.

    2011-01-01

    Various strategies have been developed to promote bone regeneration in the craniofacial region. Most of these interventions utilize implantable materials or devices. Infections resulting from colonization of these implants may result in local tissue destruction in a manner analogous to periodontitis. This destruction is mediated via the expression of various inflammatory mediators and tissue-destructive enzymes. Given the well-documented association among microbial biofilms, inflammatory mediators, and tissue destruction, it seems reasonable to assume that inflammation may interfere with bone healing and regeneration. Paradoxically, recent evidence also suggests that the presence of certain pro-inflammatory mediators is actually required for bone healing. Bone injury (e.g., subsequent to a fracture or surgical intervention) is followed by a choreographed cascade of events, some of which are dependent upon the presence of pro-inflammatory mediators. If inflammation resolves promptly, then proper bone healing may occur. However, if inflammation persists (which might occur in the presence of an infected implant or graft material), then the continued inflammatory response may result in suboptimal bone formation. Thus, the effect of a given mediator is dependent upon the temporal context in which it is expressed. Better understanding of this temporal sequence may be used to optimize regenerative outcomes. PMID:21248364

  16. Infrared laser light further improves bone healing when associated with bone morphogenetic proteins and guided bone regeneration: an in vivo study in a rodent model.

    PubMed

    Pinheiro, Antonio Luiz B; Martinez Gerbi, Marleny E; Carneiro Ponzi, Elizabeth Arruda; Pedreira Ramalho, Luciana Maria; Marques, Aparecida M C; Carvalho, Carolina Montagn; Santos, Rafael de Carneiro; Oliveira, Priscila Chagas; Nóia, Manuela

    2008-04-01

    This study assessed histologically the effect of laser photobiomodulation on the repair of surgical defects created in the femurs of Wistar rats treated or not treated with bone morphogenetic proteins (BMPs) and organic bovine bone graft. This paper is part of an ongoing series of works in which biomaterials and/or guided bone regeneration (GBR) are used in association with laser photobiomodulation. Several previous reports from our group have shown that the use of laser photobiomodulation improves the treatment of bone defects. Forty-eight adult male Wistar rats were divided into four randomized groups: group 1 (controls, n = 12); group 2 (laser photobiomodulation, n = 12); group 3 (BMPs + organic bovine bone graft + GBR, n = 12); and group 4 (BMPs + organic bovine bone graft + GBR + laser photobiomodulation, n = 12). The irradiated groups received seven irradiations every 48 h, the first immediately after the surgical procedure. Laser photobiomodulation (830 nm, 40 mW, CW, phi approximately 0.6 mm) consisted of a total of 16 J/cm2 per session at four points (4 J/cm2 each) equally spaced around the periphery of the defect. The animals were sacrificed after 15, 21, and 30 d, and the specimens were routinely embedded in wax and stained with hematoxylin and eosin and Sirius red stains and analyzed under light microscopy. The results showed histological evidence of increased deposition of collagen fibers (at 15 and 21 d), as well as an increased amount of well-organized bone trabeculi at the end of the experimental period (30 d) in irradiated animals compared to non-irradiated controls. We concluded that the use of laser photobiomodulation in association with BMPs, organic bovine bone grafts, and GBR increases the positive biomodulating effects of laser energy.

  17. Collagen-apatite nanocomposite membranes for guided bone regeneration.

    PubMed

    Song, Ju-Ha; Kim, Hyoun-Ee; Kim, Hae-Won

    2007-10-01

    Collagen-apatite nanocomposite is regarded as a potential biomaterial because of its composition and structure, which are similar to those of human hard tissues. However, there have been few investigations of its mechanical and biological benefits in direct comparison with a collagen equivalent. Herein, we successfully produced a biomedical membrane made of a nanocomposite, and systemically evaluated the mechanical, chemical, and biological properties of the nanocomposite in comparison with those of pure collagen. The results showed that significant improvements were achieved by the nanocomposite approach, particularly in terms of the mechanical strength and chemical stability. The present findings point to the potential usefulness of the collagen-apatite nanocomposite membrane in the field of guided bone regeneration (GBR).

  18. Fixation tack penetration into the maxillary sinus: A case report of a guided bone regeneration procedure complication

    PubMed Central

    Harrison, Kevin; Iskandar, Irma; Chien, Hua-Hong

    2013-01-01

    Summary Background: Guided bone regeneration (GBR) is an established and predictable procedure used to obtain adequate alveolar bone for the placement of dental implants. Anatomical challenges, such as the proximity of the maxillary sinus, may lead to complications during a GBR procedure. The purpose of this report is to present a unique and hitherto unreported complication of a GBR procedure, i.e., the penetration of a titanium fixation tack into the maxillary sinus. Case Report: A unique GBR is presented, where a titanium tack penetrated the maxillary sinus with subsequent migration and loss. Attempts to locate the tack visually during the procedure were unsuccessful. The GBR procedure was aborted and dental radiographs were immediately obtained. The patient was completely asymptomatic during the healing period. Eight weeks later a cone beam computed tomography revealed a non-inflamed sinus with no pathology evident. However, the tack could not be visualized. An otolaryngology consultation was requested and the ensuing sinus endoscopy did not reveal any evidence of the penetrated tack. It is thought that the loose tack migrated completely out of the sinus through the nasal passage. Conclusions: The use of a pre-operative cone beam computed tomography (CBCT) would have allowed the clinician to assess the exact thickness of the lateral wall of the maxillary sinus and better determine the ideal placement location and/or the feasibility of using a fixation tack in the posterior upper jaw. PMID:23569561

  19. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  20. Guided bone regeneration is promoted by the molecular events in the membrane compartment.

    PubMed

    Turri, Alberto; Elgali, Ibrahim; Vazirisani, Forugh; Johansson, Anna; Emanuelsson, Lena; Dahlin, Christer; Thomsen, Peter; Omar, Omar

    2016-04-01

    The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-β1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier.

  1. Development of a guided bone regeneration device using salicylic acid-poly(anhydride-ester) polymers and osteoconductive scaffolds.

    PubMed

    Mitchell, Ashley; Kim, Brian; Cottrell, Jessica; Snyder, Sabrina; Witek, Lukasz; Ricci, John; Uhrich, Kathryn E; O'Connor, J Patrick

    2014-03-01

    Successful repair of craniofacial and periodontal tissue defects ideally involves a combined therapy that includes inflammation modulation, control of soft tissue infiltration, and bone regeneration. In this study, an anti-inflammatory polymer, salicylic acid-based poly(anhydride-ester) (SAPAE) and a three-dimensional osteoconductive ceramic scaffold were evaluated as a combined guided bone regeneration (GBR) system for concurrent control of inflammation, soft tissue ingrowth, and bone repair in a rabbit cranial defect model. At time periods of 1, 3, and 8 weeks, five groups were compared: (1) scaffolds with a solid ceramic cap (as a GBR structure); (2) scaffolds with no cap; (3) scaffolds with a poly(lactide-glycolide) cap; (4) scaffolds with a slow release SAPAE polymer cap; and (5) scaffolds with a fast release SAPAE polymer cap. Cellular infiltration and bone formation in these scaffolds were evaluated to assess inflammation and bone repair capacity of the test groups. The SAPAE polymers suppressed inflammation and displayed no deleterious effect on bone formation. Additional work is warranted to optimize the anti-inflammatory action of the SAPAE, GBR suppression of soft tissue infiltration, and stimulation of bone formation in the scaffolds and create a composite device for successful repair of craniofacial and periodontal tissue defects.

  2. Horizontal bone augmentation by means of guided bone regeneration.

    PubMed

    Benic, Goran I; Hämmerle, Christoph H F

    2014-10-01

    The development of bone augmentation procedures has allowed placement of dental implants into jaw bone areas lacking an amount of bone sufficient for standard implant placement. Thus, the indications for implants have broadened to include jaw regions with bone defects and those with a bone anatomy that is unfavorable for implant anchorage. Of the different techniques, the best documented and the most widely used method to augment bone in localized alveolar defects is guided bone regeneration. A large body of evidence has demonstrated the successful use of guided bone regeneration to regenerate missing bone at implant sites with insufficient bone volume and the long-term success of implants placed simultaneously with, or after, guided bone regeneration. However, the influence of guided bone regeneration on implant survival and success rates, and the long-term stability of the augmented bone, remain unknown. Many of the materials and techniques currently available for bone regeneration of alveolar ridge defects were developed many years ago. Recently, various new materials and techniques have been introduced. Many of them have, however, not been sufficiently documented in clinical studies. The aim of this review was to present the scientific basis of guided bone regeneration and the accepted clinical procedures. A classification of bone defects has been presented, aiming at simplifying the decision-making process regarding the choice of strategy for bone augmentation. Finally, an outlook into actual research and the possible future options related to bone augmentation has been provided.

  3. Interim endodontic therapy for alveolar socket bone regeneration of infected hopeless teeth prior to implant therapy.

    PubMed

    Rass, Marwan Abou

    2010-01-01

    The immediate placement of implants in the fresh extraction sockets of infected teeth with periradicular and periapical lesions is contraindicated because of both the infection and the loss of architecture required for proper implant placement. There are 4 approaches for implant replacement of a hopeless tooth with lesions: (1) extraction and delayed implant placement; (2) extraction, debridement, guided bone regeneration (GBR), guided tissue regeneration (GTR), and delayed implant placement; (3) extraction, intrasocket debridement, and immediate implant placement; or (4) extraction, debridement, GBR, GTR, and simultaneous implant placement. The extraction of such hopeless teeth often results in large bone and soft tissue defects that are difficult to repair. This article introduces an alternative approach: interim endodontic implant site preparation, defined as a transitional, surgical, or nonsurgical endodontic treatment to regenerate the hopeless tooth bone defects and prepare the site for proper implant placement. This article describes 3 distinct interim endodontic protocols used to manage 5 patients, all of whom had severely infected hopeless teeth with large lesions and were treatment planned for implant replacement: the first, interim nonsurgical endodontic treatment to restore the normal anatomy of the infected hopeless tooth; the second, interim surgical endodontics on the hopeless tooth with preexisting endodontic treatment to regenerate apical bone for primary implant stability, thus avoiding the involvement of the maxillary sinus and other critical anatomic structures; and the third, interim surgical endodontics on the hopeless tooth with preexisting endodontic treatment to confine the size of the osseous defect and simplify the GBR and GTR procedures. The outcome of interim endodontic treatment on these 5 patients demonstrated that tooth extraction would have been a less predictable approach. The interim treatment changed the overall direction of the

  4. Reproducibility and accuracy of automated probe measurements of gingiva and bone levels on stone casts following guided bone regeneration treatment.

    PubMed

    Van der Zee, Erwin; Vogels, Marie-Faustine; Oosterveld, Paul; Van Waas, Marinus

    2004-04-01

    For evidence-based evaluation of guided bone regeneration (GBR), accurate registration of changes in gingiva and bone levels is needed. A new method is introduced and evaluated. In a clinical trial with 30 patients, alginate impressions of the surgical area including the interproximal gingiva and alveolar bone at the adjacent teeth were made in duplicate prior to and during GBR surgery, fixture installation and abutment connection. Poured in hard stone, the casts were used for repeated measurements of the level of the free gingival margin and the alveolar bone with an automated probe (Florida disc-probe(R)), using the incisal edge as a fixed reference point. The reproducibility and accuracy of these measurements were evaluated by means of the Intraclass Correlation Coefficients and Generalizability Theory. The effect of treatment was evaluated by multivariate analysis of variance. Generalizability Theory indicated a high accuracy of the gingiva- and bone-level measurements: the Intraclass Correlation Coefficients for gingiva and bone levels were 0.99 and 0.98, respectively. The intra-cast reproducibility was 0.09+/-0.07 mm (mean+/-SD) and the inter-cast reproducibility was 0.10+/-0.09 and 0.20+/-0.07 mm for gingiva and bone levels, respectively. Clinical applicability is demonstrated by the fact that manova revealed on average a small but highly significant (p=0.001) effect of the staged surgical intervention on the gingiva and bone levels at the adjacent teeth. It is concluded that the presented method makes it possible to evaluate reproducibly and accurately changes in gingiva and bone levels for GBR studies.

  5. Bone repair following bone grafting hydroxyapatite guided bone regeneration and infra-red laser photobiomodulation: a histological study in a rodent model.

    PubMed

    Pinheiro, Antonio Luiz B; Martinez Gerbi, Marleny E; de Assis Limeira, Francisco; Carneiro Ponzi, Elizabeth Arruda; Marques, Aparecida M C; Carvalho, Carolina Montagn; de Carneiro Santos, Rafael; Oliveira, Priscila Chagas; Nóia, Manuela; Ramalho, Luciana Maria Pedreira

    2009-03-01

    The aim of the investigation was to assess histologically the effect of laser photobiomodulation (LPBM) on a repair of defects surgically created in the femurs of rats. Forty-five Wistar rats were divided into four groups: group I (control); group II (LPBM); group III (hydroxyapatite guided bone regeneration; HA GBR); group IV (HA GBR LPBM). The animals in the irradiated groups were subjected to the first irradiation immediately after surgery, and it was repeated every day for 2 weeks. The animals were killed 15 days, 21 days and 30 days after surgery. When the groups irradiated with implant and membrane were compared, it was observed that the repair of the defects submitted to LPBM was also processed faster, starting from the 15th day. At the 30th day, the level of repair of the defects was similar in the irradiated groups and those not irradiated. New bone formation was seen inside the cavity, probably by the osteoconduction of the implant, and, in the irradiated groups, this new bone formation was incremental. The present preliminary data seem to suggest that LPMB therapy might have a positive effect upon early wound healing of bone defects treated with a combination of HA and GBR.

  6. Collagen for bone tissue regeneration.

    PubMed

    Ferreira, Ana Marina; Gentile, Piergiorgio; Chiono, Valeria; Ciardelli, Gianluca

    2012-09-01

    In the last decades, increased knowledge about the organization, structure and properties of collagen (particularly concerning interactions between cells and collagen-based materials) has inspired scientists and engineers to design innovative collagen-based biomaterials and to develop novel tissue-engineering products. The design of resorbable collagen-based medical implants requires understanding the tissue/organ anatomy and biological function as well as the role of collagen's physicochemical properties and structure in tissue/organ regeneration. Bone is a complex tissue that plays a critical role in diverse metabolic processes mediated by calcium delivery as well as in hematopoiesis whilst maintaining skeleton strength. A wide variety of collagen-based scaffolds have been proposed for different tissue engineering applications. These scaffolds are designed to promote a biological response, such as cell interaction, and to work as artificial biomimetic extracellular matrices that guide tissue regeneration. This paper critically reviews the current understanding of the complex hierarchical structure and properties of native collagen molecules, and describes the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of innovative techniques for scaffold and material manufacturing that are currently opening the way to the preparation of biomimetic substrates that modulate cell interaction for improved substitution, restoration, retention or enhancement of bone tissue function.

  7. Comparable efficacy of silk fibroin with the collagen membranes for guided bone regeneration in rat calvarial defects

    PubMed Central

    Kim, Jwa-Young; Yang, Byoung-Eun; Ahn, Jin-Hee; Park, Sang O

    2014-01-01

    PURPOSE Silk fibroin (SF) is a new degradable barrier membrane for guided bone regeneration (GBR) that can reduce the risk of pathogen transmission and the high costs associated with the use of collagen membranes. This study compared the efficacy of SF membranes on GBR with collagen membranes (Bio-Gide®) using a rat calvarial defect model. MATERIALS AND METHODS Thirty-six male Sprague Dawley rats with two 5 mm-sized circular defects in the calvarial bone were prepared (n=72). The study groups were divided into a control group (no membrane) and two experimental groups (SF membrane and Bio-Gide®). Each group of 24 samples was subdivided at 2, 4, and 8 weeks after implantation. New bone formation was evaluated using microcomputerized tomography and histological examination. RESULTS Bone regeneration was observed in the SF and Bio-Gide®-treated groups to a greater extent than in the control group (mean volume of new bone was 5.49 ± 1.48 mm3 at 8 weeks). There were different patterns of bone regeneration between the SF membrane and the Bio-Gide® samples. However, the absolute volume of new bone in the SF membrane-treated group was not significantly different from that in the collagen membrane-treated group at 8 weeks (8.75 ± 0.80 vs. 8.47 ± 0.75 mm3, respectively, P=.592). CONCLUSION SF membranes successfully enhanced comparable volumes of bone regeneration in calvarial bone defects compared with collagen membranes. Considering the lower cost and lesser risk of infectious transmission from animal tissue, SF membranes are a viable alternative to collagen membranes for GBR. PMID:25551015

  8. Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit.

    PubMed

    Shim, Jin-Hyung; Yoon, Min-Chul; Jeong, Chang-Mo; Jang, Jinah; Jeong, Sung-In; Cho, Dong-Woo; Huh, Jung-Bo

    2014-11-10

    We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/β-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml(-1)) was infused into pores of a PCL/PLGA/β-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/β-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks.

  9. Enhanced bioactivity of polyvinylidene chloride films using argon ion bombardment for guided bone regeneration.

    PubMed

    Kobayashi, Shuichiro; Hayashi, Tatsuhide; Asakura, Masaki; Hamajima, Soichiro; Sato, Yamato; Sasaki, Keisuke; Okabe, Eijiro; Kawase, Mayu; Ando, Masahiko; Kawai, Tatsushi; Noguchi, Toshihide

    2014-09-01

    Polyvinylidene chloride (PVDC) is a long chain carbon synthetic polymer. The objective of this study was to improve the bioactivity of PVDC films through surface modification using argon (Ar) ion bombardment to create Ar-modified PVDC films (Ar-PVDC) to address the clinical problems of guided bone regeneration (GBR), which is technique-sensitive, and low bone regenerative ability. First, the effects of Ar ion bombardment, a low temperature plasma etching technique widely used in industry, on PVDC film wettability, surface chemistry, and morphology were confirmed. Next, fibroblast-like and osteoblast-like cell attachment and proliferation on Ar-PVDC were assessed. As a preclinical in vivo study, Ar-PVDC was used to cover a critical-sized bone defect on rat calvaria and osteoconductivity was evaluated by micro-computed tomography analysis and histological examinations. We found that the contact angle of PVDC film decreased by 50° because of the production of -OH groups on the PVDC film surface, though surface morphological was unchanged at 30 min after Ar ion bombardment. We demonstrated that cell attachment increased by about 40% and proliferation by more than 140% because of increased wettability, and 2.4 times greater bone regeneration was observed at week 3 with Ar-PVDC compared with untreated PVDC films. These results suggest that Ar ion bombardment modification of PVDC surfaces improves osteoconductivity, indicating its potential to increase bone deposition during GBR.

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

    PubMed

    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.

  11. Engineered matrices for bone regeneration

    NASA Astrophysics Data System (ADS)

    Winn, Shelley R.; Hu, Yunhua; Pugh, Amy; Brown, Leanna; Nguyen, Jesse T.; Hollinger, Jeffrey O.

    2000-06-01

    Traditional therapies of autografts and allogeneic banked bone can promote reasonable clinical outcome to repair damaged bone. However, under certain conditions the success of these traditional approaches plummets, providing the incentive for researchers to develop clinical alternatives. The evolving field of tissue engineering in the musculoskeletal system attempts to mimic many of the components from the intact, healthy subject. Those components consist of a biologic scaffold, cells, extracellular matrix, and signaling molecules. The bone biomimetic, i.e., an engineered matrix, provides a porous structural architecture for the regeneration and ingrowth of osseous tissue at the site of injury. To further enhance the regenerative cascade, our strategy has involved porous biodegradable scaffolds containing and releasing signaling molecules and providing a suitable environment for cell attachment, growth and differentiation. In addition, the inclusion of genetically modified osteogenic precursor cells has brought the technology closer to developing a tissue-engineered equivalent. The presentation will describe various formulations and the methods utilized to evaluate the clinical utility of these biomimetics.

  12. The effect of bacterial cellulose membrane compared with collagen membrane on guided bone regeneration

    PubMed Central

    Lim, Youn-Mook; Jeong, Sung In; An, Sung-Jun; Kang, Seong-Soo

    2015-01-01

    PURPOSE This study was to evaluate the effects of bacterial cellulose (BC) membranes as a barrier membrane on guided bone regeneration (GBR) in comparison with those of the resorbable collagen membranes. MATERIALS AND METHODS BC membranes were fabricated using biomimetic technology. Surface properties were analyzed, Mechanical properties were measured, in vitro cell proliferation test were performed with NIH3T3 cells and in vivo study were performed with rat calvarial defect and histomorphometric analysis was done. The Mann-Whitney U test and the Wilcoxon signed rank test was used (α<.05). RESULTS BC membrane showed significantly higher mechanical properties such as wet tensile strength than collagen membrane and represented a three-dimensional multilayered structure cross-linked by nano-fibers with 60 % porosity. In vitro study, cell adhesion and proliferation were observed on BC membrane. However, morphology of the cells was found to be less differentiated, and the cell proliferation rate was lower than those of the cells on collagen membrane. In vivo study, the grafted BC membrane did not induce inflammatory response, and maintained adequate space for bone regeneration. An amount of new bone formation in defect region loaded with BC membrane was significantly similar to that of collagen membrane application. CONCLUSION BC membrane has potential to be used as a barrier membrane, and efficacy of the membrane on GBR is comparable to that of collagen membrane. PMID:26816579

  13. Vertical Bone Grafting and Periosteal Vertical Mattress Suture for the Fixation of Resorbable Membranes and Stabilization of Particulate Grafts in Horizontal Guided Bone Regeneration to Achieve More Predictable Results: A Technical Report.

    PubMed

    Urban, Istvan A; Lozada, Jaime L; Wessing, Bastian; Suárez-López del Amo, Fernando; Wang, Hom-Lay

    2016-01-01

    Osteosynthesis screws and titanium or resorbable pins have been recommended for fixing guided bone regeneration (GBR) membranes and stabilizing the graft. However, the removal of fixation screws or pins often requires an additional surgical procedure. This article presents a periosteal suturing technique with resorbable sutures for the fixation of grafts and membranes in GBR in single implant sites. This technique avoids potential complications of using fixation screws or pins, such as perforation of the roots when inserting the pins, and eliminates the need for a second retrieval surgery.

  14. Platelet-Derived Growth Factor-Mediated Guided Bone Regeneration in Immediate Implant Placement in Molar Sites with Buccal Bone Defects.

    PubMed

    Santana, Ronaldo B; Santana, Carolina Mm; Dibart, Serge

    2015-01-01

    This study compared the clinical outcomes of recombinant human platelet-derived growth factor BB and beta-tricalcium phosphate (rhPDGF-BB/βTCP) with guided bone regeneration (GBR) in immediate implant placement in molar extraction sockets with buccal bone defects versus conventional implant placement. Twenty-eight implants were placed in fourteen patients. Clinical and radiographic evaluations assessed peri-implant soft and hard tissue parameters after 12 months. No implants were lost during the 1-year observation period, yielding a survival rate of 100%. Similar clinical and radiographic parameters were observed for both treatment groups. Use of rhPDGF-BB/βTCP and GBR in immediate implants in molars was as successful as conventional implant placement in fully healed extraction sites.

  15. Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility.

    PubMed

    Norowski, Peter A; Fujiwara, Tomoko; Clem, William C; Adatrow, Pradeep C; Eckstein, Eugene C; Haggard, Warren O; Bumgardner, Joel D

    2015-05-01

    Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue infiltration into the graft space during dental procedures that involve bone grafting. Chitosan materials have shown promise as GBR barrier membranes, due to their biocompatibility and predictable biodegradability, but degradation rates may still be too high for clinical applications. In this study, chitosan GBR membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%), with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent, in order to extend the degradation to meet the clinical target time frame of 4-6 months. Membranes were evaluated for fibre diameter, tensile strength, biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5 or 10 mm, resulted in median fibre diameters 184, 144 and 154 nm for uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined by Fourier transform infrared spectroscopy, showed a decrease in N-H stretch as genipin levels were increased. Genipin-crosslinked mats exhibited only 22% degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16 weeks in vitro. The ultimate tensile strength of the mats was increased by 165% to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally, genipin-crosslinked mats supported the proliferation of SAOS-2 cells in a 5 day growth study, similar to uncrosslinked mats. These results suggest that electrospun chitosan mats may benefit from genipin crosslinking and have the potential to meet clinical degradation time frames for GBR applications.

  16. Maintaining space in localized ridge augmentation using guided bone regeneration with tenting screw technology.

    PubMed

    Chasioti, Evdokia; Chiang, Tat Fai; Drew, Howard J

    2013-01-01

    Prosthetic guided implant surgery requires adequate ridge dimensions for proper implant placement. Various surgical procedures can be used to augment deficient alveolar ridges. Studies have examined new bone formation on deficient ridges, utilizing numerous surgical techniques and biomaterials. The goal is to develop time efficient techniques, which have low morbidity. A crucial factor for successful bone grafting procedures is space maintenance. The article discusses space maintenance tenting screws, used in conjunction with bone allografts and resorbable barrier membranes, to ensure uneventful guided bone regeneration (GBR) enabling optimal implant positioning. The technique utilized has been described in the literature to treat severely resorbed alveolar ridges and additionally can be considered in restoring the vertical and horizontal component of deficient extraction sites. Three cases are presented to illustrate the utilization and effectiveness of tenting screw technology in the treatment of atrophic extraction sockets and for deficient ridges.

  17. Long-term results of implants treated with guided bone regeneration: a 5-year prospective study.

    PubMed

    Zitzmann, N U; Schärer, P; Marinello, C P

    2001-01-01

    The aim of this prospective 5-year longitudinal study was to follow endosteal implants in which guided bone regeneration (GBR) was applied during implant placement. In 75 patients, defects around implants (Branemark System) were treated with Bio-Oss and Bio-Gide (112 implants). In split-mouth patients in this group, Bio-Oss and Gore-Tex were used in the second defect site (41 implants). All 75 patients had at least 1 implant that was entirely surrounded by bone and served as the control (112 implants). After placement of the definitive prostheses (single-tooth, fixed, or removable implant prostheses), patients were recalled after 6 months and then every 12 months during a 5-year observation period. The following variables were investigated: implant survival, marginal bone level (MBL), presence of plaque, peri-implant mucosal conditions, height of keratinized mucosa (KM), and marginal soft tissue level (MSTL). The cumulative implant survival rate after 5 years varied between 93% and 97% for implants treated with or without GBR. The mean MBL after 60 months was 1.83 mm for sites treated with Bio-Oss and Bio-Gide, 2.21 mm for sites treated with Bio-Oss and Gore-Tex, and 1.73 mm for the control sites. The MBL values were found to increase significantly with time and differed significantly among the treatment groups. During the observation period, KM varied between 3.16 and 3.02 mm. A slight recession of 0.1 mm was observed, and plaque was found in 15% of all sites and was associated with inflammatory symptoms of the peri-implant mucosa. It was observed that such symptoms and recession correlated more strongly with the type of restoration than with the type of treatment. This study demonstrated that implants placed with or without GBR techniques had similar survival rates after 5 years, but that bone resorption was more pronounced in sites with GBR treatment. It was assumed that the use of GBR is indeed indicated when the initial defect size is larger than 2 mm in the

  18. Decellularized bone matrix grafts for calvaria regeneration

    PubMed Central

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

    2016-01-01

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

  19. Post traumatic immediate GBR: alveolar ridge preservation after a comminuted fracture of the anterior maxilla.

    PubMed

    Kim, Yongsoo; Leem, Dae Ho

    2015-04-01

    Without a proper intervention, a crushed alveolar process fracture can cause significant dimensional changes on affected hard and soft tissue that lead to difficult circumstances for post traumatic bone augmentation and dental implant placement. We present herein the cases of immediate guided bone regeneration (GBR) for the maxillary anterior alveolar process with comminuted fracture. Shortly after the hospital visit, guided bone regeneration was conducted for three patients using only xenograft material and bone fragments from traumatic site, without an additional donor site. Resorbable collagen membrane was used on the bone graft site, and titanium mesh was also used if significant bone loss were expected. Radiographic evaluation 6 months after GBR confirmed that all three cases had sufficiently preserved alveolar bone which is clinically required for implant placement. Dental implant installation was carried out for two patients and no specific findings were noted in follow-up after the placement. In this method, additional operation sites for bone collection are not necessary and the number of surgical steps before implant placement can be reduced. Furthermore, this immediate intervention can effectively minimize the alveolar ridge shrinkage of anterior maxilla after injury. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. In vitro and in vivo evaluation of chitosan/β-glycerol phosphate composite membrane for guided bone regeneration.

    PubMed

    Cui, Jun; Liang, Jie; Wen, Yong; Sun, Xiaoning; Li, Tiejun; Zhang, Gairong; Sun, Kangning; Xu, Xin

    2014-09-01

    Chitosan and β-glycerol phosphate (CS/β-GP) composite, with a thermosensitive sol-gel transition behavior, has been tested as one of the viable materials for barrier membrane fabrication. These studies have provided us with a new concept for a guided bone regeneration (GBR) membrane design. The composition, porous structure of the membrane, and the neutral mild preparation procedures make the CS/β-GP membrane a potentially active guide for bone regeneration. In this study, the CS/β-GP composite membrane, with different concentrations of β-GP, was studied to assess their potential utility in GBR application. The initial attachment of the ST2 stromal cell line to the CS/β-GP composite membrane was better than their attachment to the pure CS membrane. The proliferation and osteoblastic differentiation of the cells were much higher on the CS/β-GP composite membrane as compared to the pure CS membrane (p < 0.05). A mild inflammatory response was observed around the implanted CS/β-GP composite membrane without any foreign body reaction that continued up to 4 weeks of postsurgery. This primary study indicated that the in vitro and in vivo bioactivities of the CS/β-GP composite membrane fulfilled the requirements for GBR technique.

  1. Bone regeneration: current concepts and future directions

    PubMed Central

    2011-01-01

    Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis. PMID:21627784

  2. Orthopaedic tissue engineering and bone regeneration.

    PubMed

    Dickson, Glenn; Buchanan, Fraser; Marsh, David; Harkin-Jones, Eileen; Little, Uel; McCaigue, Mervyn

    2007-01-01

    Orthopaedic tissue engineering combines the application of scaffold materials, cells and the release of growth factors. It has been described as the science of persuading the body to reconstitute or repair tissues that have failed to regenerate or heal spontaneously. In the case of bone regeneration 3-D scaffolds are used as a framework to guide tissue regeneration. Mesenchymal cells obtained from the patient via biopsy are grown on biomaterials in vitro and then implanted at a desired site in the patient's body. Medical implants that encourage natural tissue regeneration are generally considered more desirable than metallic implants that may need to be removed by subsequent intervention. Numerous polymeric materials, from natural and artificial sources, are under investigation as substitutes for skeletal elements such as cartilage and bone. For bone regeneration, cells (obtained mainly from bone marrow aspirate or as primary cell outgrowths from bone biopsies) can be combined with biodegradable polymeric materials and/or ceramics and absorbed growth factors so that osteoinduction is facilitated together with osteoconduction; through the creation of bioactive rather than bioinert scaffold constructs. Relatively rapid biodegradation enables advantageous filling with natural tissue while loss of polymer strength before mass is disadvantageous. Innovative solutions are required to address this and other issues such as the biocompatibility of material surfaces and the use of appropriate scaffold topography and porosity to influence bone cell gene expression.

  3. Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

    PubMed Central

    Sheikh, Zeeshan; Javaid, Mohammad Ahmad; Hamdan, Nader; Hashmi, Raheel

    2015-01-01

    Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration. PMID:28788032

  4. [Quantitative analysis on guided bone regeneration-membrane technique with Bio-Oss in dental implantation].

    PubMed

    Wang, Guo-shi; Li, Shao-wei; Cai, Lu

    2012-06-01

    To measure the absorbed quantity of Bio-Oss by using dental CT scanning and measuring the variety of the volume of Bio-Oss. Nine patients were preformed stage I surgery of dental implants and guided bone regeneration-membrane technique (GBR) simultaneously. These patients were scanned by dental CT at the end of 1-week, 3-month and 6-month after operation, respectively. The measurements of the varied volume of Bio-Oss with dental CT scanning were conducted. Finally the remaining quantity of Bio-Oss in the patients' jaw bone was obtained. The results suggested that the remaining quantity of Bio-Oss was 32.72% ±18.35% at the end of 3-month post operatively and 15.75% ±16.73% at the end of 6-month postoperatively. It is concluded that there is a decrease in the remaining quantity of Bio-Oss in GBR along with the increase of time. As a kind of osteoconductive material, Bio-Oss can be absorbed and replaced by newly formed bone. Using dental CT scanning to measure the volume of Bio-Oss in man is predictable.

  5. Bone marrow cells and myocardial regeneration.

    PubMed

    Wang, Fu-Sheng; Trester, Cathy

    2004-05-01

    Hematopoietic stem cell (HSC) plasticity and its clinical application have been studied profoundly in the past few years. Recent investigations indicate that HSC and other bone marrow stem cells can develop into other tissues. Because of the high morbidity and mortality of myocardial infarction and other heart disorders, myocardial regeneration is a good example of the clinical application of HSC plasticity in regenerative medicine. Preclinical studies in animals suggest that the use of this kind of treatment can reconstruct heart blood vessels, muscle, and function. Some clinical study results have been reported in the past 2 years. In 2003, reports of myocardial regeneration treatment increased significantly. Other studies include observations on the cell surface markers of transplanted cells and treatment efficacy. Some investigations, such as HSC testing, have focused on clinical applications using HSC plasticity and bone marrow transplantation to treat different types of disorders. In this review, we focus on the clinical application of bone marrow cells for myocardial regeneration.

  6. Biomechanical evaluation of regenerating long bone by nanoindentation.

    PubMed

    Ishimoto, Takuya; Nakano, Takayoshi; Yamamoto, Masaya; Tabata, Yasuhiko

    2011-04-01

    It is crucial to measure the mechanical function of regenerating bone in order to assess the mechanical performance of the regenerating portion as well as the efficiency of the regeneration methods. In this study, nanoindentation was applied to regenerating and intact rabbit ulnae to determine the material properties of hardness and elasticity; viscoelasticity was also investigated to precisely evaluate the material properties. Both intact and regenerating bones exhibited remarkable viscoelasticity manifested as a creep behavior during load hold at the maximum load, and the creep was significantly greater in the regenerating bone than the intact bone. The creep resulted in an overestimation of the hardness and Young's modulus. Hence, during nanoindentation testing of bones, the effect of creep should be eliminated. Moreover, the regenerating bone had lower hardness and Young's modulus than the intact bone. The nanoindentation technique proved to be a powerful approach for understanding the mechanical properties of regenerating bone.

  7. Bone Regeneration Using Gene-Activated Matrices.

    PubMed

    D'Mello, Sheetal; Atluri, Keerthi; Geary, Sean M; Hong, Liu; Elangovan, Satheesh; Salem, Aliasger K

    2017-01-01

    Gene delivery to bone is a potential therapeutic strategy for directed, sustained, and regulated protein expression. Tissue engineering strategies for bone regeneration include delivery of proteins, genes (viral and non-viral-mediated delivery), and/or cells to the bone defect site. In addition, biomimetic scaffolds and scaffolds incorporating bone anabolic agents greatly enhance the bone repair process. Regional gene therapy has the potential of enhancing bone defect healing and bone regeneration by delivering osteogenic genes locally to the osseous lesions, thereby reducing systemic toxicity and the need for using supraphysiological dosages of therapeutic proteins. By implanting gene-activated matrices (GAMs), sustained gene expression and continuous osteogenic protein production in situ can be achieved in a way that stimulates osteogenesis and bone repair within osseous defects. Critical parameters substantially affecting the therapeutic efficacy of gene therapy include the choice of osteogenic transgene(s), selection of non-viral or viral vectors, the wound environment, and the selection of ex vivo and in vivo gene delivery strategies, such as GAMs. It is critical for gene therapy applications that clinically beneficial amounts of proteins are synthesized endogenously within and around the lesion in a sustained manner. It is therefore necessary that reliable and reproducible methods of gene delivery be developed and tested for their efficacy and safety before translating into clinical practice. Practical considerations such as the age, gender, and systemic health of patients and the nature of the disease process also need to be taken into account in order to personalize the treatments and progress towards developing a clinically applicable gene therapy for healing bone defects. This review discusses tissue engineering strategies to regenerate bone with specific focus on non-viral gene delivery systems.

  8. Hypoxia signalling manipulation for bone regeneration.

    PubMed

    Drager, Justin; Harvey, Edward J; Barralet, Jake

    2015-04-22

    Hypoxia-inducible factor (HIF) signalling is intricately involved in coupling angiogenesis and osteogenesis during bone development and repair. Activation of HIFs in response to a hypoxic bone micro-environment stimulates the transcription of multiple genes with effects on angiogenesis, precursor cell recruitment and differentiation. Substantial progress has been made in our understanding of the molecular mechanisms by which oxygen content regulates the levels and activity of HIFs. In particular, the discovery of the role of oxygen-dependent hydroxylase enzymes in modulating the activity of HIF-1α has sparked interest in potentially promising therapeutic strategies in multiple clinical fields and most recently bone healing. Several small molecules, termed hypoxia mimics, have been identified as activators of the HIF pathway and have demonstrated augmentation of both bone vascularity and bone regeneration in vivo. In this review we discuss key elements of the hypoxic signalling pathway and its role in bone regeneration. Current strategies for the manipulation of this pathway for enhancing bone repair are presented with an emphasis on recent pre-clinical in vivo investigations. These findings suggest promising approaches for the development of therapies to improve bone repair and tissue engineering strategies.

  9. Novel applications of statins for bone regeneration

    PubMed Central

    Shah, Sarita R.; Werlang, Caroline A.; Kasper, F. Kurtis; Mikos, Antonios G.

    2015-01-01

    The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID:26543666

  10. Metallic Scaffolds for Bone Regeneration

    PubMed Central

    Alvarez, Kelly; Nakajima, Hideo

    2009-01-01

    Bone tissue engineering is an emerging interdisciplinary field in Science, combining expertise in medicine, material science and biomechanics. Hard tissue engineering research is focused mainly in two areas, osteo and dental clinical applications. There is a lot of exciting research being performed worldwide in developing novel scaffolds for tissue engineering. Although, nowadays the majority of the research effort is in the development of scaffolds for non-load bearing applications, primarily using soft natural or synthetic polymers or natural scaffolds for soft tissue engineering; metallic scaffolds aimed for hard tissue engineering have been also the subject of in vitro and in vivo research and industrial development. In this article, descriptions of the different manufacturing technologies available to fabricate metallic scaffolds and a compilation of the reported biocompatibility of the currently developed metallic scaffolds have been performed. Finally, we highlight the positive aspects and the remaining problems that will drive future research in metallic constructs aimed for the reconstruction and repair of bone.

  11. High resolution films for bone regeneration evaluation.

    PubMed

    Jammal, María V; Territoriale, Erika B; Abate, Carlos M; Missana, Liliana R

    2010-01-01

    Diagnostic imaging techniques (DIxT) seem to be a useful tool for evaluating bone formation in both human and animal models. There is little evidence on the use of Soft X-Rays (sXR) with high-resolution films for studying the healing process in critical bone size defects (CSD). The aim of this study was to evaluate the ability of soft X-Ray - High Resolution Films (sXR) to distinguish bone regeneration in CSDs. A CSD was created in each of 16 Wistar rat calvariae. The animals were euthanized at 1, 3 and 6 weeks after surgery. The samples were submitted to cXR (conventional X-rays), sXR techniques and histological procedures (HP). Bone formation was observed at CSD edges at all periods of time. At 6 week there was also new bone in the central area. The CSD was not fully regenerated after any period of time. Histometric results were 0.16%; 0.75% and 0.89% new bone formed at weeks 1, 3 and 6 respectively; radiometric results at cXR were 0% in all samples. Evaluation of sXR shows 0.4%; 0.50% and 3.64% bone at weeks 1, 3 and 6. Mean and Standard Deviation were calculated. The data were submitted to statistical analysis using the Pearson product-moment correlation coefficient test. The r value was 0.581. Under these experimental conditions, sXR was found to be a suitable method for detecting new bone formation, based on the positive correlation between sXR and HP during the bone healing process of CSDs in rat calvaria. Furthermore, the sXR technique allowed us to obtain samples with appropriate spatial orientation.

  12. Guided bone regeneration using acellular bovine pericardium in a rabbit mandibular model: in-vitro and in-vivo studies.

    PubMed

    Bai, M; Zhang, T; Ling, T; Zhou, Z; Xie, H; Zhang, W; Hu, G; Jiang, C; Li, M; Feng, B; Wu, H

    2014-08-01

    To investigate the feasibility of acellular bovine pericardium (BP) for guided bone regeneration (GBR) in vitro and in vivo. The success of GBR relies on the fact that various cellular components possess different migration rates into the defect site and that a barrier membrane plays a significant role in these processes. BP membrane was isolated and decellularized using an enzymatic method. The microarchitecture, mechanical properties, cytotoxicity and cell chemotaxis properties of the acellular BP were evaluated in vitro, and the in-vivo efficacy of the acellular BP was also investigated in a rabbit mandibular model. The acellular BP membrane possessed an interconnected fibrous structure. Glutaraldehyde (GA) treatment was efficient for enhancement of the mechanical properties of the acellular BP bur and resulted in negligible cytotoxicity. After 16 wk, standardized osseous defects created in the rabbit mandible, and covered with acellular BP, were associated with an enhanced deposition of mineralized tissue when compared with defects left to spontaneous healing. GA-treated acellular BP is promising as a barrier membrane for GBR for further in-vivo and clinical studies. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Guided bone regeneration via a preformed titanium foil: clinical, histological and histomorphometric outcome of a case series

    PubMed Central

    BASSI, M. ANDREASI; ANDRISANI, C.; LICO, S.; ORMANIER, Z.; OTTRIA, L.; GARGARI, M.

    2016-01-01

    SUMMARY Purpose The aim of this paper was to evaluate the histological and histomorphometric outcome of Preformed Titanium Foil (PTF) to perform Guided Bone Regeneration (GBR) in posterior mandibular atrophies. Materials and methods 10 subjects (1 male; 9 females; mean age 58±11.37 years), with distal mandibular atrophies were selected to perform GBR by means of PTF, using a moldable allograft paste as graft material. The devices, made of a 0,2 mm thick pure titanium foil, were pre-shaped using stereolithographic models obtained from CT-scan of the patients’ recipient site. In the second stage, performed at 6.7±2.33 months, 18 cylindrical two-piece implants were placed and the devices removed, at the same time bone biopsies were harvested. At 4 months, the implants were exposed and submitted to progressive prosthetic load for a span of 4 months. The cases were finalized by means of metal-ceramic cementable restorations. The post finalization follow-up was at 12 months. Results Survival rate (i.e. SVR) was 100% since none fixtures were lost. At the one-year follow up the clinical appearance of the soft tissues was optimal and not pathological signs on probing were recorded. The success rate (i.e. SCR) was 88.2% and the average peri-implant bone reabsorption was 1.17±0.41 mm. The average rate of graft contraction was 19.4±10.55%. The mean percentage occupied by mineralized bone was 48.03±5.93%, while the bone marrow and graft material were 36.1±2.81% and 15.87±4.87 %, respectively. Conclusion The results suggest good potentialities of the method for GBR in distal mandibular atrophies, allowing to maximize the outcome and simplifying the surgical phase. PMID:28042445

  14. Cell-based therapies for regenerating bone

    PubMed Central

    GOODMAN, S. B.

    2013-01-01

    Cellular therapies to replenish bone lost due to acquired conditions such as trauma, infection, tumor, periprosthetic osteolysis and other etiologies have become widespread. Traditional, open, surgical bone grafting techniques have given way to newer cellular therapies that are potentially less invasive and have a lower complication rate and faster recovery time. These new technologies include bone marrow harvesting with concentration of osteoprogenitor cells with/without cell culture, scaffolds which are both osteoconductive and osteoinductive, attempts to facilitate mesenchymal stem cell and osteoprogenitor cell homing both locally and systemically, genetic engineering of specialized stem cells, and the use of potentially immune-privileged fetal and other types of stem cells. Some of these techniques have already been introduced into the orthopaedic clinic, whereas others are still in the pre-clinical testing phase. Given the limited supply of autologous graft, these new techniques will have a dramatic impact on bone regeneration in the future. PMID:24436510

  15. Comparative study of NMP-preloaded and dip-loaded membranes for guided bone regeneration of rabbit cranial defects.

    PubMed

    Karfeld-Sulzer, Lindsay S; Ghayor, Chafik; Siegenthaler, Barbara; Gjoksi, Bebeka; Pohjonen, Timo H; Weber, Franz E

    2017-02-01

    Guided bone regeneration (GBR) has been utilized for several decades for the healing of cranio-maxillofacial bone defects and, particularly in the dental field, by creating space with a barrier membrane to exclude soft tissue and encourage bone growth in the membrane-protected volume. Although the first membranes were non-resorbable, a new generation of GBR membranes aims to biodegrade and provide bioactivity for better overall results. The Inion GTR™ poly(lactide-co-glycolide) (PLGA) membrane is not only resorbable but also bioactive, since it includes N-methylpyrrolidone (NMP), which has been shown to promote bone regeneration. In this study, the effects of loading different amounts of NMP onto the membrane through chemical vapour deposition or dipping have been explored. In vitro release demonstrated that lower levels of NMP led to lower NMP concentrations and slower release, based on total NMP loaded in the membrane. The dipped membrane released almost all of the NMP within 15 min, leading to a high NMP concentration. For the in vivo studies in rabbits, 6 mm calvarial defects were created and left untreated or covered with an ePTFE membrane or PLGA membranes dipped in, or preloaded with, NMP. Evaluation of the bony regeneration revealed that the barrier membranes improved bony healing and that a decrease in NMP content improved the performance. Overall, we have demonstrated the potential of these PLGA membranes with a more favourable NMP release profile and the significance of exploring the effect of NMP on these PLGA membranes with regard to bone ingrowth. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Blood-filled spaces with and without deproteinized bone grafts in guided bone regeneration. A histomorphometric study of the rabbit skull using non-resorbable membrane.

    PubMed

    Okazaki, Kousuke; Shimizu, Yoshinaka; Xu, Hui; Ooya, Kiyoshi

    2005-04-01

    This experimental study evaluated the effects of deproteinized bone grafts on guided bone regeneration (GBR). A groove was made in the bone marrow of the external cortical plate of the skull. A dome of non-resorbable membrane was placed on the groove and secured with titanium pins. The secluded graft space was filled with autogenous blood clots (control group) and deproteinized bone particles (experimental group). The rabbits were sacrificed 2, 4, 8 and 12 weeks after the operation. Decalcified and paraffin-embedded, transverse 3-mum-thick sections were made and stained with hematoxylin and eosin. The proportions of newly formed bone and newly formed bone-graft particle contact surfaces were histomorphometrically measured in the basal, central, and peripheral areas from the cortical plate to the top of the dome. In the control group, the basal area showed a significant increase at 4 weeks (P<0.01) and a significant decrease at 8 weeks (P<0.01). The central and peripheral areas showed gradual increases in the proportion of newly formed bone. The experimental group showed significant increase at 4 weeks in the basal area and at 8 weeks in central and peripheral area (P<0.01). There were significant differences between both groups in basal and central area (P<0.01). The proportion of newly formed bone-graft particle contact length showed significant increases at 4 weeks (P<0.01) and no significant decreases at 8 and 12 weeks in three areas. The present study showed that deproteinized bone grafts maintain newly formed bone in extensive areas for a prolonged period during GBR.

  17. Cranial bone regeneration via BMP-2 encoding mesenchymal stem cells.

    PubMed

    Vural, Altugan Cahit; Odabas, Sedat; Korkusuz, Petek; Yar Sağlam, Atiye Seda; Bilgiç, Elif; Çavuşoğlu, Tarık; Piskin, Erhan; Vargel, İbrahim

    2017-05-01

    Cranial bone repair and regeneration via tissue engineering principles has attracted a great deal of interest from researchers during last decade. Here, within this study, 6 mm critical-sized bone defect regeneration via genetically modified mesenchymal stem cells (MSC) were monitored up to 4 months. Cranial bone repair and new bone formations were evaluated by histological staining and real time PCR analysis in five different groups including autograft and bone morphogenetic protein-2 (BMP-2) transfected MSC groups. Results presented here indicate a proper cranial regeneration in autograft groups and a prospering regeneration for hBMP-2 encoding mesenchymal stem cells.

  18. 'Pre-prosthetic use of poly(lactic-co-glycolic acid) membranes treated with oxygen plasma and TiO2 nanocomposite particles for guided bone regeneration processes'.

    PubMed

    Castillo-Dalí, Gabriel; Castillo-Oyagüe, Raquel; Terriza, Antonia; Saffar, Jean-Louis; Batista-Cruzado, Antonio; Lynch, Christopher D; Sloan, Alastair J; Gutiérrez-Pérez, José-Luis; Torres-Lagares, Daniel

    2016-04-01

    Guided bone regeneration (GBR) processes are frequently necessary to achieve appropriate substrates before the restoration of edentulous areas. This study aimed to evaluate the bone regeneration reliability of a new poly-lactic-co-glycolic acid (PLGA) membrane after treatment with oxygen plasma (PO2) and titanium dioxide (TiO2) composite nanoparticles. Circumferential bone defects (diameter: 10mm; depth: 3mm) were created on the parietal bones of eight experimentation rabbits and were randomly covered with control membranes (Group 1: PLGA) or experimental membranes (Group 2: PLGA/PO2/TiO2). The animals were euthanized two months afterwards, and a morphologic study was then performed under microscope using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone formed in the grown defects, concentration of osteoclasts, and intensity of osteosynthetic activity were assessed. Comparisons among the groups and with the original bone tissue were made using the Kruskal-Wallis test. The level of significance was set in advance at a=0.05. The experimental group recorded higher values for new bone formation, mineralised bone length, and osteoclast concentration; this group also registered the highest osteosynthetic activity. Bone layers in advanced formation stages and low proportions of immature tissue were observed in the study group. The functionalised membranes showed the best efficacy for bone regeneration. The addition of TiO2 nanoparticles onto PLGA/PO2 membranes for GBR processes may be a promising technique to restore bone dimensions and anatomic contours as a prerequisite to well-supported and natural-appearing prosthetic rehabilitations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

    PubMed

    Won, J-Y; Park, C-Y; Bae, J-H; Ahn, G; Kim, C; Lim, D-H; Cho, D-W; Yun, W-S; Shim, J-H; Huh, J-B

    2016-10-07

    Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

  20. Long-term Evaluation of Peri-implant Bone Level after Reconstruction of Severely Atrophic Edentulous Maxilla via Vertical and Horizontal Guided Bone Regeneration in Combination with Sinus Augmentation: A Case Series with 1 to 15 Years of Loading.

    PubMed

    Urban, Istvan A; Monje, Alberto; Lozada, Jaime L; Wang, Hom-Lay

    2017-02-01

    To the best of the authors' knowledge, there is very limited clinical data on the outcomes of simultaneous guided bone regeneration (GBR) for horizontal and/or vertical bone gain for the reconstruction of severely atrophic edentulous maxilla. Therefore, the purpose of the clinical series presented herein was to clinically evaluate long-term horizontal and vertical bone gain, as well as implant survival rate after reconstruction of severely atrophic edentulous maxillary ridges. Sixteen patients (mean age: 64.6 ± 14.6 years of age) were consecutively treated for vertical and/or horizontal bone augmentation via GBR in combination with bilateral sinus augmentation utilizing a mixture of autologous and anorganic bovine bone. Implant survival, bone gain, intraoperative/postoperative complications and peri-implant bone loss were calculated up to the last follow-up exam. Overall, 122 dental implants were placed into augmented sites and have been followed from 12 to 180 months (mean: 76.5 months). Implant survival was 100% (satisfactory survival rate of 97.5%). Mean bone gain was 5.6 mm (max: 9 mm; min: 3 mm) While vertical bone gain was 5.1 ± 1.8 mm; horizontal bone gain was 7.0 ± 1.5 mm. No intraoperative/postoperative complications were noted. Mean peri-implant bone loss values were consistent within the standards for implant success (1.4 ± 1.0 mm). At patient-level, only one patient who had three implants presented with severe peri-implant bone loss. Complete reconstruction of an atrophied maxilla can be successfully achieved by means of guided bone regeneration for horizontal and/or vertical bone gain including bilateral sinus augmentation using a mixture of anorganic bovine bone and autologous bone. © 2016 Wiley Periodicals, Inc.

  1. Effects of mechanical loading on the degradability and mechanical properties of the nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer composite membrane tube for guided bone regeneration

    PubMed Central

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

    2013-01-01

    Background and methods Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls. Results The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats’ femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis. Conclusions n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for critical size defects of long bones in goats for animal experiments. PMID:23946651

  2. Effects of mechanical loading on the degradability and mechanical properties of the nanocalcium-deficient hydroxyapatite-multi(amino acid) copolymer composite membrane tube for guided bone regeneration.

    PubMed

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

    2013-01-01

    Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite-multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls. The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats' femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis. n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for critical size defects of long bones in goats for animal experiments.

  3. The Efficacy of Electron Beam Irradiated Bacterial Cellulose Membranes as Compared with Collagen Membranes on Guided Bone Regeneration in Peri-Implant Bone Defects

    PubMed Central

    Lee, So-Hyoun; An, Sung-Jun; Lim, Youn-Mook; Huh, Jung-Bo

    2017-01-01

    Bacterial cellulose (BC) is a natural polysaccharide produced by some bacteria, and consists of a linear polymer linked by β-(1,4) glycosidic bonds. BC has been developed as a material for tissue regeneration purposes. This study was conducted to evaluate the efficacy of resorbable electron beam irradiated BC membranes (EI-BCMs) for guided bone regeneration (GBR). The electron beam irradiation (EI) was introduced to control the biodegradability of BC for dental applications. EI-BCMs had higher porosity than collagen membranes (CMs), and had similar wet tensile strengths to CMs. NIH3T3 cell adhesion and proliferation on EI-BCMs were not significantly different from those on CMs (p > 0.05). Micro-computed tomography (μCT) and histometric analysis in peri-implant dehiscence defects of beagle dogs showed that EI-BCMs were non-significantly different from CMs in terms of new bone area (NBA; %), remaining bone substitute volume (RBA; %) and bone-to-implant contact (BIC; %) (p > 0.05). These results suggest resorbable EI-BCMs can be used as an alternative biomaterial for bone tissue regeneration. PMID:28862689

  4. A new biological approach to guided bone and tissue regeneration.

    PubMed

    Montanari, Marco; Callea, Michele; Yavuz, Izzet; Maglione, Michele

    2013-04-09

    The purpose of this study was to determine the potential of platelet-rich fibrin (PRF) membranes used for guided bone and tissue regeneration. A patient with insufficient alveolar ridge width in aesthetic zone was enrolled. The patient's blood was centrifuged to obtain PRF membranes. Autogenous bone graft was mixed with bovine hydroxyapatite, PRF particles and applied to fill the defect. Five PRF membranes were placed over the bone mix. After 4 months a cone-beam CT was performed to evaluate bone regeneration. The use of PRF as cover membrane permitted a rapid epithelisation and represented an effective barrier versus epithelial cell penetration. After 4 months the site appeared precociously healed and the bone volume increased. This new approach represents a predictable method of augmenting deficient alveolar ridges. Guided bone regeneration with PRF showed limitation compared with guided bone regeneration using collagen membrane in terms of bone gain. The association of collagen membrane and PRF could be a good association.

  5. Alkaline phosphatase immobilization onto Bio-Gide® and Bio-Oss® for periodontal and bone regeneration.

    PubMed

    Oortgiesen, Daniël A W; Plachokova, Adelina S; Geenen, Claudia; Meijer, Gert J; Walboomers, X Frank; van den Beucken, Jeroen J J P; Jansen, John A

    2012-06-01

    To evaluate the effect of alkaline phosphatase (ALP) immobilization onto Bio-Gide(®) in vitro, and to study the in vivo performance of ALP-enriched Bio-Gide(®) and/or Bio-Oss(®) with the purpose to enhance periodontal regeneration. Alkaline phosphatase ALP was immobilized onto Bio-Gide(®) and Bio-Oss(®) . Forty-eight rats received periodontal defects, which were treated according to one of the following strategies: Bio-Gide(®), Bio-Gide(®) -ALP, Bio-Gide(®) -ALP/Bio-Oss(®), Bio-Gide(®) /Bio-Oss(®) -ALP, Bio-Gide(®) -ALP/Bio-Oss(®) -ALP, or empty. Micro-CT and histological analysis were performed. A 30 min ALP-deposition time was determined as optimal from mineralization capacity assessment and consequently used as Bio-Gide(®) -ALP membranes in the animal experiment. In vivo results showed that after 2 weeks, the defect and implanted materials were still visible, an inflammatory response was present, and membrane degradation was ongoing. Bone formation, although limited, was observed in the majority of Bio-Gide(®) -ALP specimens and all of the Bio-Gide(®) /Bio-Oss(®) -ALP specimens, and was significantly higher compared with Bio-Gide(®) and empty controls. After 6 weeks, the defects and particles were still visible, whereas membranes were completely degraded. The inflammatory response was decreased and bone formation appeared superior for Bio-Gide(®) -ALP treated defects. Immobilization of ALP onto guided tissue regeneration (GTR)/ guided bone regeneration (GBR)-materials (Bio-Gide(®) and Bio-Oss(®)) can enhance the performance of these materials in GTR/GBR procedures. © 2012 John Wiley & Sons A/S.

  6. Bioceramics: from bone regeneration to cancer nanomedicine.

    PubMed

    Vallet-Regí, María; Ruiz-Hernández, Eduardo

    2011-11-23

    Research on biomaterials has been growing in the last few years due to the clinical needs in organs and tissues replacement and regeneration. In addition, cancer nanomedicine has recently appeared as an effective means to combine nanotechnology developments towards a clinical application. Ceramic materials are suitable candidates to be used in the manufacturing of bone-like scaffolds. Bioceramic materials may also be designed to deliver biologically active substances aimed at repairing, maintaining, restoring or improving the function of organs and tissues in the organism. Several materials such as calcium phosphates, glasses and glass ceramics able to load and subsequently release in a controlled fashion drugs, hormones, growth factors, peptides or nucleic acids have been developed. In particular, to prevent post surgical infections bioceramics may be surface modified and loaded with certain antibiotics, thus preventing the formation of bacterial biofilms. Remarkably, mesoporous bioactive glasses have shown excellent characteristics as drug carrying bone regeneration materials. These bioceramics are not only osteoconductive and osteoproductive, but also osteoinductive, and have therefore been proposed as ideal components for the fabrication of scaffolds for bone tissue engineering. A recent promising development of bioceramic materials is related to the design of magnetic mediators against tumors. Magnetic composites are suitable thermoseeds for cancer treatment by hyperthermia. Moreover, magnetic nanomaterials offer a wide range of possibilities for diagnosis and therapy. These nanoparticles may be conjugated with therapeutic agents and heat the surrounding tissue under the action of alternating magnetic fields, enabling hyperthermia of cancer as an effective adjunct to chemotherapy regimens. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Biological Evaluation (In Vitro and In Vivo) of Bilayered Collagenous Coated (Nano Electrospun and Solid Wall) Chitosan Membrane for Periodontal Guided Bone Regeneration.

    PubMed

    Lotfi, Ghogha; Shokrgozar, Mohammad Ali; Mofid, Rasoul; Abbas, Fatemeh Mashhadi; Ghanavati, Farzin; Baghban, Alireza Akbarzadeh; Yavari, Seyedeh Kimia; Pajoumshariati, Seyedramin

    2016-07-01

    The application of barrier membranes in guided bone regeneration (GBR) has become a commonly used surgical technique in periodontal research. The objectives of this study were to evaluate the in vitro biocompatibility and osteogenic differentiation of mesenchymal stem cells (MSCs) on two different collagenous coatings (nano electrospun fibrous vs. solid wall) of bilayered collagen/chitosan membrane and their histological evaluation on bone regeneration in rabbit calvarial defects. It was found that chitosan-nano electrospun collagen (CNC) membranes had higher proliferation/metabolic activity compared to the chitosan-collagen (CC) and pristine chitosan membranes. The qRT-PCR analysis demonstrated the CNC membranes induced significant expression of osteogenic genes (Osteocalcin, RUNX2 and Col-α1) in MSCs. Moreover, higher calcium content and alkaline phosphatase activity of MSCs were observed compared to the other groups. Histologic and histomorphometric evaluations were performed on the uncovered (negative control) as well as covered calvarial defects of ten adult white rabbits with different membranes (CNC, CC, BioGide (BG, positive control)) at 1 and 2 months after surgery. More bone formation was detected in the defects covered with CNC and BG membranes than those covered by CC and the negative control. No inflammation and residual biomaterial particles were observed on the membrane surface or in the surrounding tissues in the surgical areas. These results suggest that bilayer CNC membrane can have the potential for use as a GBR membrane material facilitating bone formation.

  8. Does LED phototherapy influence the repair of bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration? A description of the repair process on rodents.

    PubMed

    Pinheiro, Antonio L B; Soares, Luiz G P; Barbosa, Artur F S; Ramalho, Luciana M P; dos Santos, Jean N

    2012-09-01

    This work carried out a histological analysis on bone defects grafted (MTA) treated or not with LED, BMPs, and membrane (GBR). Benefits of their isolated or combined usage on bone repair were reported, but not their association. Ninety rats were divided into ten groups and each subdivided into three. Defects on G II and I were filled with the blood clot. G II was further LED irradiated. G III and IV were filled with MTA; G IV was further LED irradiated. In G V and VI, the defects were filled with MTA and covered with a membrane (GBR). G VI was further LED irradiated. In G VII and VIII, BMPs were added to the MTA and group VIII was further LED irradiated. In G IX and X, the MTA + BMP graft was covered with a membrane (GBR). G X was further LED irradiated. LED was applied over the defect at 48-h intervals and repeated for 15 days. Specimens were processed, cut, and stained with H&E and Sirius red and underwent histological analysis. The use of LED light alone dramatically reduced inflammation. However, its use on MTA associated with BMP and/or GBR increased the severity of the inflammatory reaction. Regarding bone reabsorption, the poorest result was seen when the LED light was associated with the MTA + BMP graft. In the groups Clot and MTA + GBR, no bone reabsorption was detectable. Increased collagen deposition was observed when the LED light was associated with the use of the MTA associated with BMP and/or GBR. Increased new bone formation was observed when the LED light was used alone or associated with the use of MTA + GBR, MTA + BMP, on association of MTA + BMP + GBR and when BMP was added to the MTA. Our results indicate that the use of LED light alone or in association with MTA, MTA + BMP, MTA + GBR, and MTA + BMP + GBR caused less inflammation, and an increase of both collagen deposition and bone deposition as seen on both histological and morphometric analysis.

  9. Enhanced bioactive scaffolds for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Karnik, Sonali

    Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]. The field of tissue engineering and regenerative medicine involves the use of cells to form a new tissue on bio-absorbable or inert scaffolds. [2, 32] One of the applications of this field is to regenerate the damaged or lost bone by using stem cells or osteoprogenitor cells on scaffolds that can integrate in the host tissue without causing any harmful side effects. [2, 32] A variety of natural, synthetic materials and their combinations have been used to regenerate the damaged bone tissue. [2, 19, 30, 32, 43]. Growth factors have been supplied to progenitor cells to trigger a sequence of metabolic pathways leading to cellular proliferation, differentiation and to enhance their functionality. [56, 57] The challenge persists to supply these proteins, in the range of nano or even picograms, and in a sustained fashion over a period of time. A delivery system has yet to be developed that would mimic the body's inherent mechanism of delivering the growth factor molecules in the required amount to the target organ or tissue. Titanium is the most preferred metal for orthopedic and orthodontic implants. [28, 46, 48] Even though it has better osteogenic properties as compared to other metals and alloys, it still has drawbacks like poor integration into the surrounding host tissue leading to bone resorption and implant failure. [20, 28, 35] It also faces the problem of postsurgical infections that contributes to the implant failure. [26, 37

  10. [Guided bone regeneration beneath titanium foils].

    PubMed

    Otto, Katharina; Schopper, Christian; Ewers, Rolf; Lambrecht, J Thomas

    2004-01-01

    The aim of this study was to examine the clinical and histological bony healing process beneath titanium foils used for guided tissue regeneration as well as of the Frios Algipore graft which was applied with autologous bone. 66 sinus floor elevations were carried out and examined over a period of three years and eight months. A success rate of 64% was recorded with foil incorporation. Complications occurred in form of primary and secondary disturbances in the healing process caused by exposure of the foil. 12 of the 66 foils had to be removed early. In all but one case, the augmented bone material was macroscopically well integrated despite the loss of the foil. Primary stability of the inserted dental implants into the ossified augmented site after operations of the sinus maxillaris was reached in all cases with absence of post-operative complications, and in 94% when there was postoperative exposure of the membrane. Histologically, a thin layer of connective tissue poor in cells but rich in collagen fibers appeared underneath the titanium foil. This was followed by newly-formed bony tissue transforming into osseous lamella parallel to the membrane underneath the new periost. In 65 out of 66 cases a sufficient amount of stable bone was built up locally suggesting good bio-compatibility and barrier function. Further, the foil also provided mechanical rest and supporting function for the space underneath. However, the occurrence of healing complications in 36% of the cases showed a need to improve on the titanium foils.

  11. Mesenchymal Stem Cells and Nano-Bioceramics for Bone Regeneration.

    PubMed

    Kankilic, Berna; Köse, Sevil; Korkusuz, Petek; Timuçin, Muharrem; Korkusuz, Feza

    Orthopedic disorders and trauma usually result in bone loss. Bone grafts are widely used to replace this tissue. Bone grafts excluding autografts unfortunately have disadvantages like evoking immune response, contamination and rejection. Autografts are of limited sources and optimum biomaterials that can replace bone have been searched for several decades. Bioceramics, which have the similar inorganic structure of natural bone, are widely used to regenerate bone or coat metallic implants. As people continuously look for a higher life quality, there are developments in technology almost everyday to meet their expectations. Nanotechnology is one of such technologies and it attracts everyone's attention in biomaterial science. Nano scale biomaterials have many advantages like larger surface area and higher biocompatibility and these properties make them more preferable than micro scale. Also, stem cells are used for bone regeneration besides nano-bioceramics due to their differentiation characteristics. This review covers current research on nano-bioceramics and mesenchymal stem cells and their role in bone regeneration.

  12. Tissue Engineering Strategies for Promoting Vascularized Bone Regeneration

    PubMed Central

    Almubarak, Sarah; Nethercott, Hubert; Freeberg, Marie; Beaudon, Caroline; Jha, Amit; Jackson, Wesley; Marcucio, Ralph; Miclau, Theodore; Healy, Kevin; Bahney, Chelsea

    2016-01-01

    This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how adipose derived stem cells compare to bone marrow derived mesenchymal stem cells in the promotion of angiogenesis. We conclude this review with a discussion of a novel approach to bone regeneration through a cartilage intermediate, and discuss why it has the potential to be more effective than traditional bone grafting methods. PMID:26608518

  13. Retrospective success and survival rates of dental implants placed with simultaneous bone augmentation in partially edentulous patients.

    PubMed

    Bazrafshan, Nima; Darby, Ivan

    2014-07-01

    The aim of this study was to assess the success and survival rate of dental implants placed with simultaneous hard tissue grafting. All patients treated in Royal Dental Hospital of Melbourne who had implant placement with and without guided bone regeneration (GBR) procedures were identified. Seventy-three attended a follow-up appointment. These patients were examined recording probing depth, bleeding on probing, plaque accumulation and radiographic bone loss by one examiner. Clinical and radiographic findings were compared in grafted and non-grafted groups and also analysed for years in function. Approximately 50% of implants were placed simultaneous guided bone regeneration technique. In the majority of cases, defects were filled by deproteinized bovine bone mineral and covered with collagen membrane. The range of time in function was 20-88 months with a mean 34.8 (±1.7). Seventy-nine per cent of the implants placed in anterior maxilla were placed with GBR, while only 18% in posterior mandible needed grafting procedure. The cumulative implant survival rates at the time of examination was 97.95% for both GBR and non-GBR group. The mean PPD, BOP, and Plaque index were not statistically significantly different in GBR vs. non-GBR groups two to seven years in function. However, bone loss is significantly less in GBR group 2-7 years after function. The overall success rate was around 90% after 2-7 years in function with the GBR group slightly less than the non-GBR group, but not statistically significant. For the subjects included in this retrospective study, the data demonstrate that GBR is a predictable procedure. The survival and success rates of the implants inserted with simultaneous GBR were similar, if slightly lower, to the non-grafted implants. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Biological properties of an anti-bacterial membrane for guided bone regeneration: an experimental study in rats.

    PubMed

    Zhang, Jingchao; Xu, Qian; Huang, Cui; Mo, Anchun; Li, Jidong; Zuo, Yi

    2010-03-01

    The biosafety and efficacy of silver-hydroxyapatite-titania/polyamide nanocomposite (nAg-HA-TiO(2)/PA) membrane as a guided bone regeneration (GBR) barrier were investigated based on a rat subcutaneous and critical-size calvarial defect model. Thirty-six Sprague-Dawley albino rats were divided into nAg-HA-TiO(2)/PA membrane test, expanded polytetrafluoroethylene (e-PTFE) membrane control and blank control. Inflammatory response and bone regeneration in each group were evaluated using morphological, serological, radiographic and histological techniques at 1, 4 and 8 weeks, respectively, after implantation. For subcutaneous implantation, slight degradation of nAg-HA-TiO(2)/PA membranes was observed by scanning electron microscope at 4 and 8 weeks. Histopathologic examination demonstrated a thinner layer of granulation tissue in the vicinity of nAg-HA-TiO(2)/PA membranes than that of e-PTFE membranes. For cranial defect implantation, the serum alkaline phosphatase level was remarkably higher in nAg-HA-TiO(2)/PA group than that in e-PTFE group. Radiographic and histomorphometric analysis showed a fully closed cranial defect for both nAg-HA-TiO(2)/PA and e-PTFE groups at 8 weeks. No remarkable difference was found between the two groups regarding the integral optical density of neo-bone at each time interval. nAg-HA-TiO(2)/PA membranes demonstrated better biocompatibility and similar osteoinductive activity compared with e-PTFE membranes. nAg-HA-TiO(2)/PA composite membranes provided a good prospect for further research and development in anti-bacterial GBR membrane.

  15. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration

    PubMed Central

    Sammarco, Mimi C.; Simkin, Jennifer; Cammack, Alexander J.; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response. PMID:26452224

  16. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration.

    PubMed

    Sammarco, Mimi C; Simkin, Jennifer; Cammack, Alexander J; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.

  17. On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation.

    PubMed

    Selvakumar, M; Srivastava, Priyanka; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Sathishkumar, G; Subramanian, Bhuvaneshwaran; Jaganathan, Saravana Kumar; George, Gibin; Anandhan, S; Dhara, Santanu; Nando, Golok B; Chattopadhyay, Santanu

    2016-02-17

    Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi

  18. Biomaterials for orthopaedic implants and bone regeneration

    NASA Astrophysics Data System (ADS)

    Sargeant, Timothy David

    For bone regeneration, there is need for biodegradable, synthetic scaffolds that direct the formation of de novo mineralized tissue. Orthopaedic implants additionally require mechanical function. The work described herein attempts to address both of these needs. The general strategy involves integrating molecularly designed tissue engineering scaffolds with porous metallic foams to create hybrid materials to direct cellular behavior. Peptide amphiphiles (PAs) that self-assemble into nanofibers were designed to template hydroxyapatite mineral under biological conditions. The molecular design incorporated either serine (S) or phosphoserine S(P) and was mixed with RGDS-bearing PA to evaluate of the key parameters for mineral formation. This led to the discovery of nanoscale hydroxyapatite spheres templated on both S- and S(P)-bearing PA nanofibers. Stem cells were encapsulated in these gels and RT-PCR showed osteoblastic differentiation in all samples. Osteoblast maturation was increased in S-bearing PA compared to S(P)-bearing PA, although the reason is not yet understood. A method to create robust PA nanofiber coatings on NiTi was developed by optimizing the NiTi oxide surface chemistry, optimizing silane vapor deposition, and covalently attaching the PAs to the silanized substrate. The surfaces were characterized by XPS, SIMS, AFM, and fluorimetry. In vitro experiments demonstrated the importance of covalent attachment for cellular adhesion and proved the materials were not cytotoxic. Orthopaedic hybrid materials were created by triggering PA self-assembly within the interconnected pores of Ti foams developed by the Dunand research group. In vitro experiments demonstrate that pre-osteoblasts adhere to, proliferate on, and migrate into PA-Ti hybrids made with S(P)- and RGDS-bearing PA mixtures. The cells differentiate into mature osteoblasts and remain viable up to 28 days. In vivo studies using a rat model demonstrate osteointegration and boney ingrowth into bare

  19. Nanosized CaP-silk fibroin-PCL-PEG-PCL/PCL based bilayer membranes for guided bone regeneration.

    PubMed

    Türkkan, Sibel; Pazarçeviren, A Engin; Keskin, Dilek; Machin, Nesrin E; Duygulu, Özgür; Tezcaner, Ayşen

    2017-11-01

    Guided bone regeneration (GBR) concept has been developed to prevent the formation of non-functional scar tissue layer on defect site by undertaking barrier role. In this study, a new bilayer membrane which consisted of one layer of electrospun silk fibroin/PCL-PEG-PCL incorporating nanocalcium phosphate (SPCA)(1) and one layer of PCL membrane was developed for GBR. To improve the osteoconductivity of membranes, nanosized calcium phosphate particles synthesized by Flame Spray Pyrolysis method were incorporated into membranes at 10% (wt) (SPCA10) and 20% (wt) (SPCA20) of the polymer content. The structural and chemical analyses revealed the well-integrated two layers of membranes with a total thickness of ca 100μm. In the regenerative layer, the highly porous mesh structure had a thickness of 12.6μm with randomly oriented fibers having diameters around 760nm, and nanoparticles dispersed homogenously. The mechanical test results showed remarkable improvement on the tensile strength of membranes with incorporation of nanoparticles. Higher water affinity of nanoCaP included membranes was proved by lower contact angle values and higher percent water uptake capacity. Biomineralization assay revealed that nucleation and growth of apatites around fibers of SPCA10 and SPCA20 were apparent while on SPCA0 apatite minerals were barely detected after 10days. Human dental pulp stem cells (DPSC) were seeded on electrospun layer of the bilayer membranes for biocompatibility and osteo-compatibility study. Increasing nanoCaP amount resulted in higher cell adhesion, proliferation, ALP activity and calcium deposition on membranes. These overall results confirmed the biocompatibility and potential applicability of proposed membranes for GBR treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. In vivo bone regeneration using a novel porous bioactive composite

    NASA Astrophysics Data System (ADS)

    Xie, En; Hu, Yunyu; Chen, Xiaofeng; Bai, Xuedong; Li, Dan; Ren, Li; Zhang, Ziru

    2008-11-01

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  1. Preparation of electrospun fiber mats using siloxane-containing vaterite and biodegradable polymer hybrids for bone regeneration.

    PubMed

    Fujikura, Kie; Lin, Sen; Nakamura, Jin; Obata, Akiko; Kasuga, Toshihiro

    2013-11-01

    An electrospun fiber mat using a new composite consisting of siloxane-containing vaterite (SiV) and poly(lactic-co-glycolic acid) (PLGA) (denoted by SiPLGVH) was prepared with the aim of applying it as a membrane for use in a guided bone regeneration (GBR) system. Another electrospun fiber mat using a previously described composite consisting of SiV and poly(L-lactic acid) (denoted by SiPVH) was also prepared as a comparative sample. SiPLG VH fiber mats showed superior results in terms of mechanical tensile properties and cellular behavior. Their elongation before failure was about eight times higher than that of SiPVH. The numbers of osteoblast-like cells that proliferated on the SiPLGVH fiber mats, regardless of the hydroxyapatite coating, were comparable to that of SiPVH. The cells spread more, two dimensionally, on the SiPLGVH fiber mats, since the pores between fibers were narrowed down because of swelling of the PLGA matrix during cell culture. This two-dimensional cellular proliferation quality on the SiPLGVH fiber mats is expected to be suitable for materials used in GBR, leading to control of infiltration of the soft tissue and great tissue integration with the surrounding tissue.

  2. Preparation and preliminary in vitro evaluation of a bFGF-releasing heparin-conjugated poly(ε-caprolactone) membrane for guided bone regeneration.

    PubMed

    Cao, Cong; Song, Ying; Yao, Qianqian; Yao, Yang; Wang, Tianlu; Huang, Bo; Gong, Ping

    2015-01-01

    In an effort to improve guided bone regeneration (GBR), we successfully fabricated a novel basic fibroblast growth factor (bFGF)-releasing heparin-conjugated poly(ε-caprolactone) membrane (hep-PCL/bFGF). This material has a porous microstructure with smooth and rough pore walls before and after heparinization, respectively. Our FTIR analyses indicated that chemical bonds were formed between PCL and heparin with a new amide C=O band at 1660 cm(-1) and a band at 3400 cm(-1) that can be attributed to -OH stretching in cross-linked heparin. We showed that bFGF was released from hep-PCL/bFGF in a continuous pattern, which remained for 3 weeks. We evaluated MG63 cell proliferation and biocompatibility of GBR membrane by a CCK-8 assay and a live/dead assay. The CCK-8 results revealed that the hep-PCL/bFGF group had superiority compared to other groups. Furthermore, cell morphology of hep-PCL membrane exhibited larger projected areas than those of PCL surfaces based on scanning electron microscopy analysis and immunofluorescent staining of cell cytoskeleton and vinculin expression. Our alkaline phosphatase activity assay also confirmed better performance of the hep-PCL/bFGF group. These results suggested that this novel hep-PCL/bFGF membrane is suitable for osteoblast-like cells to attach, proliferate, and differentiate. Therefore, the hep-PCL/bFGF membrane has potential to be a biodegradable membrane for GBR and warrants further investigation.

  3. ‘Reliability of new poly (lactic-co-glycolic acid) membranes treated with oxygen plasma plus silicon dioxide layers for pre-prosthetic guided bone regeneration processes’

    PubMed Central

    Castillo-Dalí, Gabriel; Batista-Cruzado, Antonio; López-Santos, Carmen; Rodríguez-González-Elipe, Agustín; Saffar, Jean-Louis; Lynch, Christopher D.; Gutiérrez-Pérez, José-Luis; Torres-Lagares, Daniel

    2017-01-01

    Background The use of cold plasmas may improve the surface roughness of poly(lactic-co-glycolic) acid (PLGA) membranes, which may stimulate the adhesion of osteogenic mediators and cells, thus accelerating the biodegradation of the barriers. Moreover, the incorporation of metallic-oxide particles to the surface of these membranes may enhance their osteoinductive capacity. Therefore, the aim of this paper was to evaluate the reliability of a new PLGA membrane after being treated with oxygen plasma (PO2) plus silicon dioxide (SiO2) layers for guided bone regeneration (GBR) processes. Material and Methods Circumferential bone defects (diameter: 11 mm; depth: 3 mm) were created on the top of eight experimentation rabbits’ skulls and were randomly covered with: (1) PLGA membranes (control), or (2) PLGA/PO2/SiO2 barriers. The animals were euthanized two months afterwards. A micromorphologic study was then performed using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone, concentration of osteoclasts, and intensity of ostheosynthetic activity were assessed and compared with those of the original bone tissue. The Kruskal-Wallis test was applied for between-group com Asignificance level of a=0.05 was considered. Results The PLGA/PO2/SiO2 membranes achieved the significantly highest new bone formation, length of mineralised bone, concentration of osteoclasts, and ostheosynthetic activity. The percentage of regenerated bone supplied by the new membranes was similar to that of the original bone tissue. Unlike what happened in the control group, PLGA/PO2/SiO2 membranes predominantly showed bone layers in advanced stages of formation. Conclusions The addition of SiO2 layers to PLGA membranes pre-treated with PO2 improves their bone-regeneration potential. Although further research is necessary to corroborate these conclusions in humans, this could be a promising strategy to rebuild the bone architecture prior to rehabilitate

  4. Bioactive and biodegradable nanocomposites and hybrid biomaterials for bone regeneration.

    PubMed

    Allo, Bedilu A; Costa, Daniel O; Dixon, S Jeffrey; Mequanint, Kibret; Rizkalla, Amin S

    2012-06-20

    Strategies for bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix and act as templates onto which cells attach, multiply, migrate and function. Of particular interest are nanocomposites and organic-inorganic (O/I) hybrid biomaterials based on selective combinations of biodegradable polymers and bioactive inorganic materials. In this paper, we review the current state of bioactive and biodegradable nanocomposite and O/I hybrid biomaterials and their applications in bone regeneration. We focus specifically on nanocomposites based on nano-sized hydroxyapatite (HA) and bioactive glass (BG) fillers in combination with biodegradable polyesters and their hybrid counterparts. Topics include 3D scaffold design, materials that are widely used in bone regeneration, and recent trends in next generation biomaterials. We conclude with a perspective on the future application of nanocomposites and O/I hybrid biomaterials for regeneration of bone.

  5. Bioactive and Biodegradable Nanocomposites and Hybrid Biomaterials for Bone Regeneration

    PubMed Central

    Allo, Bedilu A.; Costa, Daniel O.; Dixon, S. Jeffrey; Mequanint, Kibret; Rizkalla, Amin S.

    2012-01-01

    Strategies for bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix and act as templates onto which cells attach, multiply, migrate and function. Of particular interest are nanocomposites and organic-inorganic (O/I) hybrid biomaterials based on selective combinations of biodegradable polymers and bioactive inorganic materials. In this paper, we review the current state of bioactive and biodegradable nanocomposite and O/I hybrid biomaterials and their applications in bone regeneration. We focus specifically on nanocomposites based on nano-sized hydroxyapatite (HA) and bioactive glass (BG) fillers in combination with biodegradable polyesters and their hybrid counterparts. Topics include 3D scaffold design, materials that are widely used in bone regeneration, and recent trends in next generation biomaterials. We conclude with a perspective on the future application of nanocomposites and O/I hybrid biomaterials for regeneration of bone. PMID:24955542

  6. Novel membrane for guided bone regeneration.

    PubMed

    Pirhonen, E M; Pohjonen, T H; Weber, F E

    2006-09-01

    Membranes have been clinically used for guided tissue and bone regeneration for decades, but their use in every day clinical practice is rather limited. We developed a biodegradable membrane (InionGTR) composed of polylactide, polyglycolide and trimethylene carbonate aiming to improve the properties of membrane. Before application the membrane is treated with N-methyl-pyrrolidone (NMP) to achieve a rubber like consistency, to allow easy handling and manageability in the clinical setting. After placing the membrane NMP diffuses out from the polymer phase into the water phase. The loss of NMP in the polymer stiffens the membrane up and allows space maintenance in the defect area. In addition the influx and efflux of NMP creates a porous surface on the membrane leading to an improved integration of tissues into the porous surface layers of the InionGTR membrane. Therefore, the use of NMP improves the handling in the clinical setting, and allows tissue integration and space maintenance, both important for the outcome of the treatment.

  7. Chitosan as a barrier membrane material in periodontal tissue regeneration.

    PubMed

    Xu, Chun; Lei, Chang; Meng, Liuyan; Wang, Changning; Song, Yaling

    2012-07-01

    Periodontal regeneration is defined as regeneration of the tooth-supporting tissues including cementum, periodontal ligament, and alveolar bone. Guided tissue regeneration (GTR) has been demonstrated to be an effective technique to achieve periodontal regeneration. In the GTR procedures, various kinds of membranes play important roles. Chitosan, a deacetylated derivative of chitin, is biocompatible, biodegradable, and antimicrobial. It acts as hydrating agent and possesses tissue healing and osteoinducing effect. Chitosan can be easily processed into membranes, gels, nanofibers, beads, nanoparticles, scaffolds, and sponges forms and can be used in drug delivery systems. Here, we review the bioproperties of chitosan and report the progress of application of chitosan as membranes in GTR and guided bone regeneration (GBR), which indicates that chitosan could be a good substrate candidate as the materials for the GTR/GBR membranes.

  8. Bone Regeneration Mediated by Biomimetic Mineralization of a Nanofiber Matrix

    PubMed Central

    Mata, Alvaro; Geng, Yanbiao; Henrikson, Karl; Aparicio, Conrado; Stock, Stuart; Satcher, Robert L.; Stupp, Samuel I.

    2010-01-01

    Rapid bone regeneration within a three-dimensional defect without the use of bone grafts, exogenous growth factors, or cells remains a major challenge. We report here on the use of self-assembling peptide nanostructured gels to promote bone regeneration that have the capacity to mineralize in biomimetic fashion. The main molecular design was the use of phosphoserine residues in the sequence of a peptide amphiphile known to nucleate hydroxyapatite crystals on the surfaces of nanofibers. We tested the system in a rat femoral critical size defect by placing pre-assembled nanofiber gels in a 5 mm gap and analyzed bone formation with micro-computed tomography and histology. We found within 4 weeks significantly higher bone formation relative to controls lacking phosphorylated residues and comparable bone formation to that observed in animals treated with a clinically used allogenic bone matrix. PMID:20472286

  9. On scaffold designing for bone regeneration: A computational multiscale approach.

    PubMed

    Sanz-Herrera, J A; García-Aznar, J M; Doblaré, M

    2009-01-01

    Scaffold design for bone tissue engineering applications involves many parameters that directly influence the rate of bone tissue regeneration onto its microstructural surface. To improve scaffold functionality, increasing interest is being focused on in vitro and in vivo research in order to obtain the optimal scaffold design for a specific application. However, the evaluation of the effect of each specific scaffold parameter on tissue regeneration using these techniques requires costly protocols and long-term experiments. In this paper, we elucidate the effect of some scaffold parameters on bone tissue regeneration by means of a mathematically based approach. By virtue of in silico experiments, factors such as scaffold stiffness, porosity, resorption kinetics, pore size and pre-seeding are analyzed in a specific bone tissue application found in the literature. The model predicts the in vivo rate of bone formation within the scaffold, the scaffold degradation and the interaction between the implanted scaffold and the surrounding bone. Results show an increasing rate of bone regeneration with increasing scaffold stiffness, scaffold mean pore size and pre-seeding, whereas the collapse of the scaffold occurs for a faster biomaterial resorption kinetics. Requiring further experimental validation, the model can be useful for the assessment of scaffold design and for the analysis of scaffold parameters in tissue regeneration.

  10. Dimensionally stable and bioactive membrane for guided bone regeneration: An in vitro study

    PubMed Central

    Rowe, Matthew J.; Kamocki, Krzysztof; Pankajakshan, Divya; Li, Ding; Bruzzaniti, Angela; Thomas, Vinoy; Blanchard, Steve B.; Bottino, Marco C.

    2015-01-01

    Composite fibrous electrospun membranes based on poly(DL-lactide) (PLA) and poly(ε-caprolactone) (PCL) were engineered to include borate bioactive glass (BBG) for the potential purposes of guided bone regeneration (GBR). The fibers were characterized using scanning and transmission electron microscopies, which respectively confirmed the submicron fibrous arrangement of the membranes and the successful incorporation of BBG particles. Selected mechanical properties of the membranes were evaluated using the suture pullout test. The addition of BBG at 10 wt.% led to similar stiffness, but more importantly, it led to a significantly stronger (2.37±0.51 N*mm) membrane when compared to the commercially available Epiguide® (1.06±0.24 N*mm) under hydrated conditions. Stability (shrinkage) was determined after incubation in a phosphate buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL-based membranes with or without BBG incorporation (10.07-16.08%) was similar to that of Epiguide® (14.28%). Cell proliferation assays demonstrated a higher rate of pre-osteoblasts proliferation on BBG-containing membranes (6.4-fold) over BBG-free membranes (4-5.8-fold) and EpiGuide® (4.5-fold), following 7 days of in vitro culture. Collectively, our results demonstrated the ability to synthesize, via electrospinning, stable, polymer-based submicron fibrous BBG-containing membranes capable of sustaining osteoblastic attachment and proliferation—a promising attribute in guided bone regeneration. PMID:25953329

  11. Guided bone regeneration in distal mandibular atrophy by means of a preformed titanium foil: a case series.

    PubMed

    Andreasi Bassi, M; Andrisani, C; Lopez, M A; Gaudio, R M; Lombardo, L; Lauritano, D

    2016-01-01

    The aim of this case series was to evaluate the clinical outcome of preformed titanium foil (PTF) to perform guided bone regeneration (GBR) in posterior mandibular atrophies. Thirteen patients (4 male; 9 female; mean age 58.85±10.16 years), with class II division C atrophy, according to Misch, were selected to perform GBR by means of PTF, using a moldable allograft paste as graft material. The devices, made of a 0.2mm thick pure titanium foil, were pre-shaped using stereolithographic models obtained from CT-scan of the patients’ recipient sites. In the second stage, performed at 6.35±2.15 months, 23 cylindrical two-piece implants were placed and the devices removed. At four months, the implants were exposed and submitted to progressive prosthetic load for a span of 4 months. The cases were finalized by means of metal-ceramic cementable restorations. The post finalization follow-up was at 12 months. Survival rate (i.e. SVR) was 100% since no fixtures were lost. At the one-year follow up, the clinical appearance of the soft tissues was optimal and no pathological signs on probing were recorded. The success rate (i.e. SCR) was 82.6% and the average peri-implant bone reabsorption was 0.99±0.59 mm. The results suggest good potentialities of this method for bone volume augmentation in distal mandibular atrophies, allowing to maximize the outcome and simplifying the surgical phase.

  12. Iliac crest autogenous bone graft versus alloplastic graft and guided bone regeneration in the reconstruction of atrophic maxillae: a 5-year retrospective study on cost-effectiveness and clinical outcome.

    PubMed

    Dahlin, Christer; Johansson, Anita

    2011-12-01

    Reconstruction of the atrophic maxillae with autogenous bone graft and jawbone-anchored bridges is a well-proven technique. However, the morbidity associated with the concept should not be neglected. Furthermore, the costs for such treatment, including general anesthesia and hospital stay, are significant. Little data are found in the literature with regard to a cost-benefit approach to various treatment alternates. The aim of this retrospective study was to compare from a health-economical and clinical perspective the reconstruction of the atrophic maxillae prior to oral implant treatment either with autogenous bone grafts harvested from the iliac crest or the use of demineralized freeze-dried bone (DFDB) in combination with a thermoplastic carrier (Regeneration Technologies Inc., Alachua, FL, USA) and guided bone regeneration (GBR). A total of 26 patients (13 + 13) were selected and matched with regard to indication, sex, and age. The study was performed 5 years after the completion of the treatment. Implant survival, morbidity, and complications were analyzed. Furthermore, a detailed analysis of the total cost for the respective treatment modality was performed, including material, costs for staff, sick leave, etc. The study revealed no statistical difference with regard to implant survival for the respective groups. The average total cost, per patient, for the DFDB group was 22.5% of the total cost for a patient treated with autogenous bone grafting procedures. The study concluded that reconstruction of atrophic maxillae with a bone substitute material (DFDB) in combination with GBR can be performed with an equal treatment outcome and with less resources and a significant reduced cost in selected cases compared with autogenous bone grafts from the iliac crest. © 2010 Wiley Periodicals, Inc.

  13. A new biological approach to guided bone and tissue regeneration

    PubMed Central

    Montanari, Marco; Callea, Michele; Yavuz, Izzet; Maglione, Michele

    2013-01-01

    The purpose of this study was to determine the potential of platelet-rich fibrin (PRF) membranes used for guided bone and tissue regeneration. A patient with insufficient alveolar ridge width in aesthetic zone was enrolled. The patient's blood was centrifuged to obtain PRF membranes. Autogenous bone graft was mixed with bovine hydroxyapatite, PRF particles and applied to fill the defect. Five PRF membranes were placed over the bone mix. After 4 months a cone-beam CT was performed to evaluate bone regeneration. The use of PRF as cover membrane permitted a rapid epithelisation and represented an effective barrier versus epithelial cell penetration. After 4 months the site appeared precociously healed and the bone volume increased. This new approach represents a predictable method of augmenting deficient alveolar ridges. Guided bone regeneration with PRF showed limitation compared with guided bone regeneration using collagen membrane in terms of bone gain. The association of collagen membrane and PRF could be a good association. PMID:23576648

  14. Adverse effects of hyperlipidemia on bone regeneration and strength.

    PubMed

    Pirih, Flavia; Lu, Jinxiu; Ye, Fei; Bezouglaia, Olga; Atti, Elisa; Ascenzi, Maria-Grazia; Tetradis, Sotirios; Demer, Linda; Aghaloo, Tara; Tintut, Yin

    2012-02-01

    Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild-type (WT) and hyperlipidemic (Ldlr(-/-)) mice were placed on a high-fat (HF) diet for 13 weeks. Bilateral cranial defects were introduced on each side of the sagittal suture, and 5 weeks postsurgery on the respective diets, the repair/regeneration of cranial bones and mechanical properties of femoral bones were assessed. MicroCT and histological analyses demonstrated that bone regeneration was significantly impaired by the HF diet in WT and Ldlr(-/-) mice. In femoral bone, cortical bone volume fraction (bone volume [BV]/tissue volume [TV]) was significantly reduced, whereas cortical porosity was increased by the HF diet in Ldlr(-/-) but not in WT mice. Femoral bone strength and stiffness, measured by three-point bending analysis, were significantly reduced by the HF diet in Ldlr(-/-), but not in WT mice. Serum analysis showed that the HF diet significantly increased levels of parathyroid hormone, tumor necrosis factor (TNF)-α, calcium, and phosphorus, whereas it reduced procollagen type I N-terminal propeptide, a serum marker of bone formation, in Ldlr(-/-), but not in WT mice. The serum level of carboxyl-terminal collagen crosslinks, a marker for bone resorption, was also 1.7-fold greater in Ldlr(-/-) mice. These findings suggest that hyperlipidemia induces secondary hyperparathyroidism and impairs bone regeneration and mechanical strength.

  15. Reconstruction of mandibular segmental defects using the guided-bone regeneration technique with polylactide membranes and/or autogenous bone graft: a preliminary study on the influence of membrane permeability.

    PubMed

    Sverzut, Cassio E; Faria, Paulo E P; Magdalena, Carolina M; Trivellato, Alexandre E; Mello-Filho, Francisco V; Paccola, Cleber A J; Gogolewski, Sylwester; Salata, Luiz A

    2008-04-01

    Bone maintenance after mandibular reconstruction with autogenous iliac crest may be disappointing due to extensive resorption in the long term. The potential of the guided-bone regeneration (GBR) technique to enhance the healing process in segmental defects lacks comprehensive scientific documentation. This study aimed to investigate the influence of polylactide membrane permeability on the fate of iliac bone graft (BG) used to treat mandibular segmental defects. Unilateral 10-mm-wide segmental defects were created through the mandibles of 34 mongrel dogs. All defects were mechanically stabilized, and the animals were divided into 6 treatment groups: control, BG alone, microporous membrane (poly L/DL-lactide 80/20%) (Mi); Mi plus BG; microporous laser-perforated (15 cm(2) ratio) membrane (Mip), and Mip plus BG. Calcein fluorochrome was injected intravenously at 3 months, and animal euthanasia was carried out at 6 months postoperatively. Histomorphometry showed that BG protected by Mip was consistently related to larger amounts of bone compared with other groups (P bone area and reduced the amount of grafted bone to control levels. Data from bone labeling indicated that the bone formation process was incipient in the BG group at 3 months postoperatively regardless of whether or not it was covered by membrane. In contrast, GBR with Mip tended to enhance bone formation activity at 3 months. The use of Mip alone could be a useful alternative to BG. The combination of Mip membrane and BG efficiently delivered increased bone amounts in segmental defects compared with other treatment modalities.

  16. Reliability of new poly (lactic-co-glycolic acid) membranes treated with oxygen plasma plus silicon dioxide layers for pre-prosthetic guided bone regeneration processes.

    PubMed

    Castillo-Dalí, G; Castillo-Oyagüe, R; Batista-Cruzado, A; López-Santos, C; Rodríguez-González-Elipe, A; Saffar, J-L; Lynch, C-D; Gutiérrez-Pérez, J-L; Torres-Lagares, D

    2017-03-01

    The use of cold plasmas may improve the surface roughness of poly(lactic-co-glycolic) acid (PLGA) membranes, which may stimulate the adhesion of osteogenic mediators and cells, thus accelerating the biodegradation of the barriers. Moreover, the incorporation of metallic-oxide particles to the surface of these membranes may enhance their osteoinductive capacity. Therefore, the aim of this paper was to evaluate the reliability of a new PLGA membrane after being treated with oxygen plasma (PO2) plus silicon dioxide (SiO2) layers for guided bone regeneration (GBR) processes. Circumferential bone defects (diameter: 11 mm; depth: 3 mm) were created on the top of eight experimentation rabbits' skulls and were randomly covered with: (1) PLGA membranes (control), or (2) PLGA/PO2/SiO2 barriers. The animals were euthanized two months afterwards. A micromorphologic study was then performed using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone, concentration of osteoclasts, and intensity of ostheosynthetic activity were assessed and compared with those of the original bone tissue. The Kruskal-Wallis test was applied for between-group com Asignificance level of a=0.05 was considered. The PLGA/PO2/SiO2 membranes achieved the significantly highest new bone formation, length of mineralised bone, concentration of osteoclasts, and ostheosynthetic activity. The percentage of regenerated bone supplied by the new membranes was similar to that of the original bone tissue. Unlike what happened in the control group, PLGA/PO2/SiO2 membranes predominantly showed bone layers in advanced stages of formation. The addition of SiO2 layers to PLGA membranes pre-treated with PO2 improves their bone-regeneration potential. Although further research is necessary to corroborate these conclusions in humans, this could be a promising strategy to rebuild the bone architecture prior to rehabilitate edentulous areas.

  17. Clinically applied models of bone regeneration in tissue engineering research.

    PubMed

    Einhorn, T A

    1999-10-01

    The development of new strategies for the engineering of bone regeneration requires appropriate model systems. Selection of the best model for testing a new technology depends on a host of factors. In general, the best model system is the one which most closely mimics the clinical situation for which this technology is being developed, will not heal spontaneously unless the technology is used, and will not heal when another technology is used if that technology is less advanced than the one being tested. For the purposes of developing new strategies for bone regeneration, systems which can be considered include those which model normal fracture healing, the segmental loss of bone or critical size defects, and various forms of nonunions in which fracture healing is perturbed either by mechanical, metabolic, or neurologic means. Careful experimental design and selection of the appropriate model system will enhance scientific efforts in bone regeneration research.

  18. Nell-1-Induced Bone Regeneration in Calvarial Defects

    PubMed Central

    Aghaloo, Tara; Cowan, Catherine M.; Chou, Yu-Fen; Zhang, Xinli; Lee, Haofu; Miao, Steve; Hong, Nichole; Kuroda, Shun’ichi; Wu, Benjamin; Ting, Kang; Soo, Chia

    2006-01-01

    Many craniofacial birth defects contain skeletal components requiring bone grafting. We previously identified the novel secreted osteogenic molecule NELL-1, first noted to be overexpressed during premature bone formation in calvarial sutures of craniosynostosis patients. Nell-1 overexpression significantly increases differentiation and mineralization selectively in osteoblasts, while newborn Nell-1 transgenic mice significantly increase premature bone formation in calvarial sutures. In the current study, cultured calvarial explants isolated from Nell-1 transgenic newborn mice (with mild sagittal synostosis) demonstrated continuous bone growth and overlapping sagittal sutures. Further investigation into gene expression cascades revealed that fibroblast growth factor-2 and transforming growth factor-β1 stimulated Nell-1 expression, whereas bone morphogenetic protein (BMP)-2 had no direct effect. Additionally, Nell-1-induced osteogenesis in MC3T3-E1 osteoblasts through reduction in the expression of early up-regulated osteogenic regulators (OSX and ALP) but induction of later markers (OPN and OCN). Grafting Nell-1 protein-coated PLGA scaffolds into rat calvarial defects revealed the osteogenic potential of Nell-1 to induce bone regeneration equivalent to BMP-2, whereas immunohistochemistry indicated that Nell-1 reduced osterix-producing cells and increased bone sialoprotein, osteocalcin, and BMP-7 expression. Insights into Nell-1-regulated osteogenesis coupled with its ability to stimulate bone regeneration revealed a potential therapeutic role and an alternative to the currently accepted techniques for bone regeneration. PMID:16936265

  19. Effects of bone drilling on local temperature and bone regeneration: an in vivo study.

    PubMed

    Karaca, Faruk; Aksakal, Bünyamin; Köm, Mustafa

    2014-01-01

    The aim of this study was to examine the influence of bone drilling on local bone temperature and bone regeneration and determine optimal drilling speed and pressure in an animal model. The study included 12 skeletally mature New Zealand white rabbits, weighing between 2.8 to 3.2 kg. Rabbits were divided into 2 groups and euthanized at the end of Day 21 (Group A) and Day 42 (Group B). The same drilling protocol was used in both groups. Three drill holes with different pressure (5, 10 and 20 N) were made in each rabbit tibias using 3 different rotational drill speeds (230, 370 and 570 rpm). During drilling, local temperature was recorded. Rabbit tibia underwent histopathological exam for bone regeneration. Bone temperature was affected by drilling time and depth. Lower drill speeds reduced the bone temperature and revealed better bone regeneration when compared to the drilled bones at higher drill speeds. Titanium boron nitride coating on the drill bits had no significant effects on bone temperature and structure. Bone regeneration was superior in Group B rabbits that had drilling at 230 rpm and 20 N. Our results suggested that lower drilling speed with higher pressure is necessary for better bone regeneration. The optimal drilling speed is 230 rpm and optimal drilling pressure 20 N.

  20. Regenerate bone fracture rate following femoral lengthening in paediatric patients

    PubMed Central

    Burke, N. G.; Cassar-Gheiti, A. J.; Tan, J.; McHugh, G.; O’Neil, B. J.; Noonan, M.; Moore, D.

    2017-01-01

    Abstract Purpose Femoral lengthening using a circular or mono-lateral frame is a commonly used technique. Fracture at the site of the regenerate bone is a major concern especially following removal of the external fixator. This aim of this study was to assess the rate of fracture of the regenerate bone in this single surgeon series of paediatric patients and determine potential risk factors. Methods Retrospective review of all the femoral lengthening performed by the senior author was performed. The medical and physiotherapy notes were reviewed. The gender, age at time of surgery, disease aetiology, total days in the external fixator and length of the new regenerate bone were recorded. Patients who sustained a regenerate fracture were identified. Results A total of 176 femoral lengthening procedures were performed on 108 patients. Eight regenerate fractures occurred in seven patients (4.5%). The mechanism of injury was a fall in five cases and during physiotherapy in three cases. The regenerate fracture occurred a median number of nine days following removal of frame. There was no significant difference between gender, age at time of surgery, total time in external fixator between those who sustained a regenerate fracture and those patients who did not. A significant difference was noted between the amount of lengthening between the ‘regenerate fracture group’ and the ‘no fracture group’ (50 mm vs 38 mm, respectively; p = 0.029). There was no association between disease aetiology and risk of regenerate fracture. Conclusions Femoral lengthening of more than 50 mm increases the risk of a fracture at the regenerate site regardless of the disease aetiology. We recommend avoidance of aggressive physiotherapy for the initial four weeks following external fixator removal. PMID:28828065

  1. Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

    PubMed Central

    Zhang, Xingdi; Zeng, Deliang; Li, Nan; Wen, Jin; Jiang, Xinquan; Liu, Changsheng; Li, Yongsheng

    2016-01-01

    Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process. PMID:26763311

  2. Bringing computational models of bone regeneration to the clinic.

    PubMed

    Carlier, Aurélie; Geris, Liesbet; Lammens, Johan; Van Oosterwyck, Hans

    2015-01-01

    Although the field of bone regeneration has experienced great advancements in the last decades, integrating all the relevant, patient-specific information into a personalized diagnosis and optimal treatment remains a challenging task due to the large number of variables that affect bone regeneration. Computational models have the potential to cope with this complexity and to improve the fundamental understanding of the bone regeneration processes as well as to predict and optimize the patient-specific treatment strategies. However, the current use of computational models in daily orthopedic practice is very limited or inexistent. We have identified three key hurdles that limit the translation of computational models of bone regeneration from bench to bed side. First, there exists a clear mismatch between the scope of the existing and the clinically required models. Second, most computational models are confronted with limited quantitative information of insufficient quality thereby hampering the determination of patient-specific parameter values. Third, current computational models are only corroborated with animal models, whereas a thorough (retrospective and prospective) assessment of the computational model will be crucial to convince the health care providers of the capabilities thereof. These challenges must be addressed so that computational models of bone regeneration can reach their true potential, resulting in the advancement of individualized care and reduction of the associated health care costs.

  3. Magnesium substitution in brushite cements for enhanced bone tissue regeneration.

    PubMed

    Cabrejos-Azama, Jatsue; Alkhraisat, Mohammad Hamdan; Rueda, Carmen; Torres, Jesús; Blanco, Luis; López-Cabarcos, Enrique

    2014-10-01

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p<0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Chemically modified RNA activated matrices enhance bone regeneration.

    PubMed

    Elangovan, Satheesh; Khorsand, Behnoush; Do, Anh-Vu; Hong, Liu; Dewerth, Alexander; Kormann, Michael; Ross, Ryan D; Sumner, D Rick; Allamargot, Chantal; Salem, Aliasger K

    2015-11-28

    There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation.

  5. Bone tissue regeneration: the role of scaffold geometry.

    PubMed

    Zadpoor, Amir A

    2015-02-01

    The geometry of porous scaffolds that are used for bone tissue engineering and/or bone substitution has recently been shown to significantly influence the cellular response and the rate of bone tissue regeneration. Most importantly, it has been shown that the rate of tissue generation increases with curvature and is much larger on concave surfaces as compared to convex and planar surfaces. In this work, recent discoveries concerning the effects of geometrical features of porous scaffolds such as surface curvature, pore shape, and pore size on the cellular response and bone tissue regeneration process are reviewed. In addition to reviewing the recent experimental observations, we discuss the mechanisms through which geometry affects the bone tissue regeneration process. Of particular interest are the theoretical models that have been developed to explain the role of geometry in the bone tissue regeneration process. We then follow with a section on the implications of the observed phenomena for geometrical design of porous scaffolds including the application of predictive computational models in geometrical design of porous scaffolds. Moreover, some geometrical concepts in the design of porous scaffolds such as minimal surfaces and porous structures with geometrical gradients that have not been explored before are suggested for future studies. We especially focus on the porous scaffolds manufactured using additive manufacturing techniques where the geometry of the porous scaffolds could be precisely controlled. The paper concludes with a general discussion of the current state-of-the-art and recommendations for future research.

  6. Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

    PubMed Central

    Sato, Ayako; Kajiya, Hiroshi; Mori, Nana; Sato, Hironobu; Fukushima, Tadao; Kido, Hirofumi

    2017-01-01

    The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration. PMID:28060874

  7. Guided bone regeneration for fenestration defects in dental implants.

    PubMed

    Yeh, Hwey-Chin; Hsu, Kuang-Wei

    2003-09-01

    Guided bone regeneration has been applied in implant dentistry for increasing the width and height of the alveolar ridge in areas with insufficient bone. Various materials and techniques have been used for this purpose. It refers to a surgical procedure by which utilizing a mechanical barrier to create a secluded space around the defect to permit bone regeneration without the competition of other tissues. This report presents a case with buccal fenestrations on maxillary implant sites observed during a surgical procedure. An allograft and a non-resorbable membrane were concomitantly used to increase the width of the alveolar ridge. Hard tissue regeneration was evident clinically. The implants were restored for functioning and followed for 2 years. Factors affecting outcomes are also discussed. Membrane stability and the space-making effect remain the keys to success.

  8. Organ printing: the future of bone regeneration?

    PubMed

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

    2011-12-01

    In engineered bone grafts, the combined actions of bone-forming cells, matrix and bioactive stimuli determine the eventual performance of the implant. The current notion is that well-built 3D constructs include the biological elements that recapitulate native bone tissue structure to achieve bone formation once implanted. The relatively new technology of organ/tissue printing now enables the accurate 3D organization of the components that are important for bone formation and also addresses issues, such as graft porosity and vascularization. Bone printing is seen as a great promise, because it combines rapid prototyping technology to produce a scaffold of the desired shape and internal structure with incorporation of multiple living cell types that can form the bone tissue once implanted. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges.

    PubMed

    Orciani, Monia; Fini, Milena; Di Primio, Roberto; Mattioli-Belmonte, Monica

    2017-01-01

    The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis.

  10. Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges

    PubMed Central

    Orciani, Monia; Fini, Milena; Di Primio, Roberto; Mattioli-Belmonte, Monica

    2017-01-01

    The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis. PMID:28386538

  11. Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats

    PubMed Central

    Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

    2016-01-01

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical “lock” between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy. PMID:27025260

  12. Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats.

    PubMed

    Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

    2016-03-30

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical "lock" between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy.

  13. Bioinspired Collagen-Apatite Nanocomposites for Bone Regeneration.

    PubMed

    Liu, Shuai; Sun, Yue; Fu, Yu; Chang, Datong; Fu, Cuicui; Wang, Gaonan; Liu, Yan; Tay, Franklin R; Zhou, Yanheng

    2016-08-01

    Natural bone has a complex hierarchical nanostructure composed of well-organized collagen fibrils embedded with apatite crystallites. Bone tissue engineering requires scaffolds with structural properties and functionality similar to the natural bone. Inspired by bone, a collagen-apatite (Col-Ap) nanocomposite was fabricated with bonelike subfibrillar nanostructures using a modified bottom-up biomimetic approach and has a potential role in the healing of large bone defects in unresolved apical periodontitis. The bone regeneration potential of the Col-Ap nanocomposite was investigated by comparing it with inorganic beta-tricalcium phosphate and organic pure collagen using a critical-sized rodent mandibular defect model. Micro-computed tomographic imaging and histologic staining were used to evaluate new bone formation in vivo. When compared with the beta-tricalcium phosphate and collagen scaffolds, the Col-Ap nanocomposite scaffold exhibited superior regeneration properties characterized by profuse deposition of new bony structures and vascularization at the defect center. Immunohistochemistry showed that the transcription factor osterix and vascular endothelial growth factor receptor 1 were highly expressed in the Col-Ap group. The results indicate that the Col-Ap nanocomposite activates more bone-forming cells and stimulates more vascular tissue ingrowth. Furthermore, the Col-Ap nanocomposite induces extracellular matrix secretion and mineralization of rat bone marrow stem cells. The increased expression of transforming growth factor beta 1 may contribute to the formation of a mineralized extracellular matrix. The present study lays the foundation for the development of Col-Ap nanocomposite-based bone grafts for future clinical applications in bone regeneration of large periapical lesions after apical curettage or apicoectomy. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  14. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

    PubMed Central

    Stravinskas, M.; Horstmann, P.; Ferguson, J.; Hettwer, W.; Tarasevicius, S.; Petersen, M. M.; McNally, M. A.; Lidgren, L.

    2016-01-01

    Objectives Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating

  15. [Biocompatibility of poly-L-lactic acid/Bioglass-guided bone regeneration membranes processed with oxygen plasma].

    PubMed

    Fang, Wei; Zeng, Shu-Guang; Gao, Wen-Feng

    2015-04-01

    To prepare and characterize a nano-scale fibrous hydrophilic poly-L-lactic acid/ Bioglass (PLLA/BG) composite membrane and evaluate its biocompatibility as a composite membrane for guiding bone regeneration (GBR). PLLA/BG-guided bone regeneration membrane was treated by oxygen plasma to improved its hydrophilicity. The growth of MG-63 osteoblasts on the membrane was observed using Hoechst fluorescence staining, and the biocompatibility of the membrane was evaluated by calculating the cells adhesion rate and proliferation rate. Osteogenesis of MG-63 cells was assessed by detecting alkaline phosphatase (ALP), and the formation of calcified nodules and cell morphology changes were observed using scanning electron microscope (SEM). The cell adhesion rates of PLLA/BG-guided bone regeneration membrane treated with oxygen plasma were (30.570±0.96)%, (47.27±0.78)%, and (66.78±0.69)% at 1, 3, and 6 h, respectively, significantly higher than those on PLLA membrane and untreated PLLA/BG membrane (P<0.01). The cell proliferation rates on the 3 membranes increased with time, but highest on oxygen plasma-treated PLLA/BG membrane (P<0.01). Hoechst fluorescence staining revealed that oxygen plasma treatment of the PLLA/BG membrane promoted cell adhesion. The membranes with Bioglass promoted the matrix secretion of the osteoblasts. Under SEM, the formation of calcified nodules and spindle-shaped cell morphology were observed on oxygen plasma-treated PLLA/BG membrane. Oxygen plasma-treated PLLA/BG composite membrane has good biocompatibility and can promote adhesion, proliferation and osteogenesis of the osteoblasts.

  16. Does Guided Bone Regeneration Prevent Unfavorable Bone Shapes in Distraction Gap?

    PubMed

    Demetoglu, Umut; Alkan, Alper; Kiliç, Erdem; Ozturk, Mustafa; Bilge, Suheyb

    2017-08-05

    Complications related to distraction osteogenesis can cause degradation of newly regenerated bone. Additionally, an unfavorable shape of the regenerated bone at the distraction gap can reduce the quantity of regenerated bone. The aim of the present study was to report on the prevention of unfavorable shapes of regenerated bone using guided bone regeneration during distraction. Bilateral alveolar distraction was performed in 10 beagle dog mandibles. One side of the mandible formed the experimental group and the other side served as the control group. In the experimental group, guided bone regeneration was performed simultaneously with distraction osteogenesis. In the control group, only alveolar distraction was applied. At the end of a 1-week latent period, all mandibles were distracted 10 mm (1 mm/day). After the distraction period, 3 months were allowed for consolidation. After consolidation, all the dogs were euthanized, and the shape of the regenerated bone was determined to be either favorable or unfavorable. Densitometric evaluation and area measurements were performed using computed tomography scans. Statistical evaluation was performed using the independent t test, with a significance level of P < .05. In the experimental group, no unfavorable bone shape developed in the distraction gap, and the new bone had a surface and volume similar to those of the segments. In contrast, in the control group, 4 mandibles had an unfavorable bone shape in the distraction gap and 4 showed favorable bone healing with no defect. The surface area of the regenerating bone in the experimental group was significantly greater than that in the control group. Also, the surface area differed significantly between the experimental and control groups (P < .05). However, the densitometric values did not differ between the 2 groups (P < .05). Concomitant use of guided bone regeneration with distraction osteogenesis could be an optimal method for generating a favorable bone shape

  17. Novel silk protein barrier membranes for guided bone regeneration.

    PubMed

    Smeets, Ralf; Knabe, Christine; Kolk, Andreas; Rheinnecker, Michael; Gröbe, Alexander; Heiland, Max; Zehbe, Rolf; Sachse, Manuela; Große-Siestrup, Christian; Wöltje, Michael; Hanken, Henning

    2016-10-12

    This study assesses the biocompatibility of novel silk protein membranes with and without modification, and evaluates their effect on facilitating bone formation and defect repair in guided bone regeneration. Two calvarian bone defects 12 mm in diameter were created in each of a total of 38 rabbits. Four different types of membranes, (silk-, hydroxyapatite-modified silk-, β-TCP-modified silk- and commonly clinically used collagen-membranes) were implanted to cover one of the two defects in each animal. Histologic analysis did not show any adverse tissue reactions in any of the defect sites indicating good biocompatibility of all silk protein membranes. Histomorphometric and histologic evaluation revealed that collagen and β-TCP modified silk membranes supported bone formation (collagen: bone area fraction p = 0.025; significant; β-TCP modified silk membranes bone area fraction: p = 0.24, not significant), guided bone regeneration and defect bridging. The bone, which had formed in defects covered by β-TCP modified silk membranes, displayed a more advanced stage of bone tissue maturation with restoration of the original calvarial bone microarchitecture when compared to the bone which had formed in defects, for which any of the other test membranes were used. Micro-CT analysis did not reveal any differences in the amount of bone formation between defects with and without membranes. In contrast to the collagen membranes, β-TCP modified silk membranes were visible in all cases and may therefore be advantageous for further supporting bone formation beyond 10 weeks and preventing soft tissue ingrowth from the periphery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  18. Guided bone regeneration using demineralized allogenic bone matrix with calcium sulfate: case series

    PubMed Central

    Kim, Young-Kyun; Lee, Ji-Young; Lim, Seung-Chul

    2013-01-01

    PURPOSE The purpose of this case series was to evaluate the effect of guided bone regeneration using demineralized allogenic bone matrix with calcium sulfate. MATERIALS AND METHODS Guided bone regeneration using Demineralized Allogenic Bone Matrix with Calcium Sulfate (AlloMatrix™, Wright. USA) was performed at the time of implant placement from February 2010 to April 2010. At the time of the second surgery, clinical evaluation of bone healing and histologic evaluation were performed. The study included 10 patients, and 23 implants were placed. The extent of bony defects around implants was determined by measuring the horizontal and vertical bone defects using a periodontal probe from the mesial, distal, buccal, and lingual sides and calculating the mean and standard deviation of these measurements. Wedge-shaped tissue samples were obtained from 3 patients and histologic examination was performed. RESULTS In clinical evaluation, it was observed that horizontal bone defects were completely healed with new bones, and in the vertical bone defect area, 15.1% of the original defect area remained. In 3 patients, histological tests were performed, and 16.7-41.7% new bone formation was confirmed. Bone graft materials slowly underwent resorption over time. CONCLUSION AlloMatrix™ is an allograft material that can be readily manipulated. It does not require the use of barrier membranes, and good bone regeneration can be achieved with time. PMID:23755343

  19. Nanocomposite Membranes Enhance Bone Regeneration Through Restoring Physiological Electric Microenvironment.

    PubMed

    Zhang, Xuehui; Zhang, Chenguang; Lin, Yuanhua; Hu, Penghao; Shen, Yang; Wang, Ke; Meng, Song; Chai, Yuan; Dai, Xiaohan; Liu, Xing; Liu, Yun; Mo, Xiaoju; Cao, Cen; Li, Shue; Deng, Xuliang; Chen, Lili

    2016-08-23

    Physiological electric potential is well-known for its indispensable role in maintaining bone volume and quality. Although implanted biomaterials simulating structural, morphological, mechanical, and chemical properties of natural tissue or organ has been introduced in the field of bone regeneration, the concept of restoring physiological electric microenvironment remains ignored in biomaterials design. In this work, a flexible nanocomposite membrane mimicking the endogenous electric potential is fabricated to explore its bone defect repair efficiency. BaTiO3 nanoparticles (BTO NPs) were first coated with polydopamine. Then the composite membranes are fabricated with homogeneous distribution of Dopa@BTO NPs in poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. The surface potential of the nanocomposite membranes could be tuned up to -76.8 mV by optimizing the composition ratio and corona poling treatment, which conform to the level of endogenous biopotential. Remarkably, the surface potential of polarized nanocomposite membranes exhibited a dramatic stability with more than half of original surface potential remained up to 12 weeks in the condition of bone defect. In vitro, the membranes encouraged bone marrow mesenchymal stem cells (BM-MSCs) activity and osteogenic differentiation. In vivo, the membranes sustainably maintained the electric microenvironment giving rise to rapid bone regeneration and complete mature bone-structure formation. Our findings evidence that physiological electric potential repair should be paid sufficient attention in biomaterials design, and this concept might provide an innovative and well-suited strategy for bone regenerative therapies.

  20. [Osteostimulating effect of bone xenograft on bone tissue regeneration].

    PubMed

    Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

    2015-01-01

    The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

  1. Multiscale patterned transplantable stem cell patches for bone tissue regeneration.

    PubMed

    Kim, Jangho; Bae, Won-Gyu; Choung, Han-Wool; Lim, Ki Taek; Seonwoo, Hoon; Jeong, Hoon Eui; Suh, Khap-Yang; Jeon, Noo Li; Choung, Pill-Hoon; Chung, Jong Hoon

    2014-11-01

    Stem cell-based therapy has been proposed as an enabling alternative not only for the treatment of diseases but also for the regeneration of tissues beyond complex surgical treatments or tissue transplantation. In this study, we approached a conceptual platform that can integrate stem cells into a multiscale patterned substrate for bone regeneration. Inspired by human bone tissue, we developed hierarchically micro- and nanopatterned transplantable patches as synthetic extracellular matrices by employing capillary force lithography in combination with a surface micro-wrinkling method using a poly(lactic-co-glycolic acid) (PLGA) polymer. The multiscale patterned PLGA patches were highly flexible and showed higher tissue adhesion to the underlying tissue than did the single nanopatterned patches. In response to the anisotropically multiscale patterned topography, the adhesion and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled. Furthermore, the stem cell patch composed of hMSCs and transplantable PLGA substrate promoted bone regeneration in vivo when both the micro- and nanotopography of the substrate surfaces were synergistically combined. Thus, our study concludes that multiscale patterned transplantable stem cell patches may have a great potential for bone regeneration as well as for various regenerative medicine approaches.

  2. Expression of vascular antigens by bone cells during bone regeneration in a membranous bone distraction system.

    PubMed

    Lewinson, D; Maor, G; Rozen, N; Rabinovich, I; Stahl, S; Rachmiel, A

    2001-11-01

    An in vivo system of membranous bone formation during distraction has been investigated in order to follow cells that express vascular markers with the objective of understanding the neovascularization process. Concomitantly, sustained proliferation of preskeletal cells was achieved through the application of mechanical force. New capillaries and leading edges that arose by angiogenesis from the periosteal and mucosal surfaces and invaded the central zone of the regenerating distraction tissue temporally preceded the growth of delicate woven bone trabeculae from both edges of the cut bone. Concentrically arranged 'onion-like' configurations were abundant in paracentral zones and in association with mesenchymal condensations, suggesting their de novo formation in situ. Vascular specific markers, the angiopoietin receptor Tie-2 and factor VIII-related antigen (FVIIIrAg), were localized immunohistochemically in order to follow cells of vascular origin. Endothelial cells of the new capillaries, centrally located cells of the concentric configurations, pericytes, and most of the adjacent polygonal mesenchymal cells stained positively with specific antibodies to both antigens. Moreover, preosteoblasts and osteoblasts that lie adjacent to or already embedded in the osteiod of the newly formed trabeculae were also FVIIIrAg and Tie-2 immunopositive. As the source of the bone-forming cells in regenerating tissue during distraction is not yet fully understood, this observation might support the possibility of their vascular origin.

  3. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

    PubMed

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

  4. Physiological bases of bone regeneration I. Histology and physiology of bone tissue.

    PubMed

    Fernández-Tresguerres-Hernández-Gil, Isabel; Alobera-Gracia, Miguel Angel; del-Canto-Pingarrón, Mariano; Blanco-Jerez, Luis

    2006-01-01

    Bone is the only body tissue capable of regeneration, allowing the restitutio ad integrum following trauma. In the event of a fracture or bone graft, new bone is formed, which following the remodeling process is identical to the pre-existing. Bone is a dynamic tissue in constant formation and resorption. This balanced phenomena, known as the remodeling process, allows the renovation of 5-15% of the total bone mass per year under normal conditions. Bone remodeling consists of the resorption of a certain amount of bone by osteoclasts, likewise the formation of osteoid matrix by osteoblasts, and its subsequent mineralization. This phenomenon occurs in small areas of the cortical bone or the trabecular surface, called Basic Multicellular Units (BMU). Treatment in Traumatology, Orthopedics, Implantology, and Maxillofacial and Oral Surgery, is based on the biologic principals of bone regeneration, in which cells, extracellular matrix, and osteoinductive signals are involved. The aim of this paper is to provide an up date on current knowledge on the biochemical and physiological mechanisms of bone regeneration, paying particular attention to the role played by the cells and proteins of the bone matrix.

  5. Positional vertigo afterwards maxillary dental implant surgery with bone regeneration.

    PubMed

    Rodríguez Gutiérrez, Carlos; Rodríguez Gómez, Enrique

    2007-03-01

    Benign paroxysmal positional vertigo (BPPV) is the most common form of vertigo. It is caused by loose otoconia from the utricle which, in certain positions, displaced the cupula of the posterior semicircular canal. BPPV most often is a result of aging. It also can occur after a blow to the head. Less common causes include a prolonged positioning on the back (supine) during some surgical procedures. Additionally one can include in this ethiopathogenesis the positioning required during the maxillary dental implant surgery with bone regeneration related to a forced head positioning and inner ear trauma induced by dental turbine noise working in the maxillary bone. Two cases of patients who suffered BPPV after undergoing maxillary dental implant with bone regeneration procedures are reported. Diagnosis and treatment are also described.

  6. Evaluation of Cameroonian plants towards experimental bone regeneration.

    PubMed

    Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Siddiqui, Jawed Akhtar; Tewari, Deepshikha; Nagar, Geet K; Tiwari, Satish C; Theophile, Dimo; Maurya, Rakesh; Chattopadhyay, Naibedya

    2012-05-07

    Elephantopus mollis, Spilanthes africana, Urena lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis are used in Cameroonian traditional medicine for the treatment of bone diseases and fracture repair. The aim of this study was to evaluate the effect of ethanolic extracts of six Cameroonian medicinal plants on bone regeneration following bone and marrow injury. Ethanol extract of Cameroonian medicinal plants were administered (each extract at 250, 500 and 750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of fractured bone was performed to evaluate bone regeneration (calcein labeling). Only active plant extracts were used for further experiments. Thus, callus was analyzed by microcomputed tomography. Osteogenic effects of the extracts were evaluated by assessing mineralized nodules formation of bone marrow stromal cells and osteoblast recruitment at drill hole site by immunohistochemistry. Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose significantly increased mineral deposition compared to controls. Both extracts at 500 and 750mg/kg doses improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. EM and SA extracts increased the formation of mineralized nodules from the bone marrow stromal cells. In addition, EM and SA extracts increased osteoblast recruitment at the drill hole site evident from increased Runx-2 positive cells following their treatments compared to control

  7. The effect of carrier type on bone regeneration of demineralized bone matrix in vivo.

    PubMed

    Tavakol, Shima; Khoshzaban, Ahad; Azami, Mahmoud; Kashani, Iraj Ragerdi; Tavakol, Hani; Yazdanifar, Mahbube; Sorkhabadi, Seyed Mahdi Rezayat

    2013-11-01

    Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone-repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC.

  8. Monetite granules versus particulate autologous bone in bone regeneration.

    PubMed

    Torres, Jesús; Tamimi, Iskandar; Cabrejos-Azama, Jatsue; Tresguerres, Isabel; Alkhraisat, Mohammad; López-Cabarcos, Enrique; Hernández, Gonzalo; Tamimi, Faleh

    2015-07-01

    The aim of this study was to test bone tissue response to monetite granules in comparison with intramembranous autologous bone graft in a rabbit calvaria critical size defect model. Novel monetite granules were synthesized by thermal conversion of set brushite cement. Eight female New Zealand rabbits were used for this study. Two identical 10mm diameter bicortical cranial defects were created in each animal. One of the defects was grafted with monetite granules while the contralateral was grafted with granules of intramembranous autologous bone as control. Animals were sacrificed 8 weeks after surgery and biopsies were taken for histological and histomorphometrical evaluation under light microscopy. Wilcoxon test was used for statistical analysis. The bone defects treated with either autologous bone or monetite granules were able to heal within the study period. Upon histological observation the defects treated with autologous bone granules resembled the adjacent intact calvaria, whereas the defects treated with monetite showed a high infiltration of new bone and only 13.4±8.4% of remaining granules. The percentage of bone volume in the defects of the control group (71±9%) was 16% higher than in the study group (55±10%) (p<0.05). The percentage of augmented mineralized tissue volume in the study group (68±18%) was not significantly different from the control group (p>0.05). The amount of augmented mineralized tissue in the bone defects obtained with monetite granules was not significantly different from that obtained with autologous bone. This study confirms the potential of monetite based biomaterials as an alternative to autologous bone graft. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Mesenchymal Stem Cells in Bone Regeneration

    PubMed Central

    Knight, M. Noelle; Hankenson, Kurt D.

    2013-01-01

    Significance Mesenchymal stem cells (MSCs) play a key role in fracture repair by differentiating to become bone-forming osteoblasts and cartilage-forming chondrocytes. Cartilage then serves as a template for additional bone formation through the process of endochondral ossification. Recent Advances Endogenous MSCs that contribute to healing are primarily derived from the periosteum, endosteum, and marrow cavity, but also may be contributed from the overlying muscle or through systemic circulation, depending on the type of injury. A variety of growth factor signaling pathways, including BMP, Wnt, and Notch signaling, influence MSC proliferation and differentiation. These MSCs can be therapeutically manipulated to promote differentiation. Furthermore, MSCs can be harvested, cultivated, and delivered to promote bone healing. Critical Issues Pharmacologically manipulating the number and differentiation capacity of endogenous MSCs is one potential therapeutic approach to improve healing; however, ideal agents to influence signaling pathways need to be developed and additional therapeutics that activate endogenous MSCs are needed. Whether isolated and purified, MSCs participate directly in the healing process or serve a bystander effect and indirectly influence healing is not well defined. Future Directions Studies must focus on better understanding the regulation of endogenous MSCs durings fracture healing. This will reveal novel molecules and pathways to therapeutically target. Similarly, while animal models have demonstrated efficacy in the delivery of MSCs to promote healing, more research is needed to understand ideal donor cells, cultivation methods, and delivery before stem cell therapy approaches can be utilized to repair bone. PMID:24527352

  10. Bone regeneration performance of surface-treated porous titanium.

    PubMed

    Amin Yavari, Saber; van der Stok, Johan; Chai, Yoke Chin; Wauthle, Ruben; Tahmasebi Birgani, Zeinab; Habibovic, Pamela; Mulier, Michiel; Schrooten, Jan; Weinans, Harrie; Zadpoor, Amir Abbas

    2014-08-01

    The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone

  11. Development of laminated fiber-reinforced nanocomposites for bone regeneration

    NASA Astrophysics Data System (ADS)

    Xu, Weijie

    There have been numerous efforts to develop synthetic and/or natural tissue engineering scaffolds that are suitable for bone regeneration applications to replace autograft and allograft bones. Current biomaterials as a scaffold for bone regeneration are limited by the extent of degradation concurrent with bone formation, mechanical strength, and the extent of osteogenic differentiation of marrow stromal cells migrating from the surrounding tissues. In this project, a novel laminated nanocomposite scaffold is fabricated, consisting of poly (L-lactide ethylene oxide fumarate) (PLEOF) hydrogel reinforced with poly (L-lactic acid) (PLLA) electrospun nanofibers and hydroxyapatite (HA) nanoparticles. PLEOF is a novel in situ crosslinkable macromer synthesized from biocompatible building units which can be functionalized with bioactive peptides like the cell-adhesive Arg--Gly--Asp (RGD) amino acid sequence. The hydrophilicity and degradation rate of the macromer can be tailored to a particular application by controlling the ratio of PEG to PLA blocks in the macromer and the unsaturated fumarate units can be used for in-situ crosslinking. The PLLA nanofibers were electrospun from high molecular weight PLLA. The laminated nanocomposites were fabricated by dry-hand lay up technique followed by compression molding and thermal crosslinking. The laminated nanocomposites were evaluated with respect to degradation, water uptake, mechanical strength, and the extent of osteogenic differentiation of bone marrow stromal (BMS) cells. Laminates with or without HA nanoparticles showed modulus values much higher than that of trabecular bone (50-100 MPa). The effect of laminated nanocomposites on osteogenic differentiation of BMS cells was determined in terms of cell number, ALPase activity and calcium content. Our results demonstrate that grafting RGD peptide and HA nanoparticles to a PLEOF hydrogel reinforced with PLLA nanofibers synergistically enhance osteogenic differentiation of BMS

  12. Latex use as an occlusive membrane for guided bone regeneration.

    PubMed

    Ereno, Cibele; Guimarães, Sérgio A Catanzaro; Pasetto, Silvana; Herculano, Rondinelli Donizetti; Silva, Cecília Pereira; Graeff, Carlos F O; Tavano, Orivaldo; Baffa, Oswaldo; Kinoshita, Angela

    2010-12-01

    Latex extracted from Hevea brasiliensis was used as an occlusive membrane for guided bone regeneration. Twenty-four rabbits were divided in two groups: treated and control group. Critical size bone defects (2 cm × 1 cm) were surgically made in the rabbit calvarium. Two latex membranes were implanted in each animal of the treated group, whereas the control defect was filled only with autogenous blood clot. After 15, 30, 60, and 120 days, animals from each group were euthanized, and the samples with regenerated bone were removed. No signs of allergy or rejection were noticed around the calvarial bone defect of the treated group. In the histological analysis, no foreign body inflammatory reaction was observed in the adjacent tissues in contact with the membranes demonstrating that latex can be used at injured sites as an aid in the healing process. Histological analysis, digital radiography, and electron spin resonance were used to evaluate the progress of bone repair. The results show significant differences between groups (p < 0.05) suggesting that latex membranes accelerates healing in critical bone defects.

  13. Negative pressure technology enhances bone regeneration in rabbit skull defects.

    PubMed

    Zhang, Yin-gang; Yang, Zhi; Zhang, Hong; Liu, Miao; Qiu, Yushen; Guo, Xiong

    2013-03-03

    Bone is a slowly regenerating tissue influenced by various physiological processes, including proliferation, differentiation, and angiogenesis, under the control of growth factors. Shortening this healing time is an important and popular clinical research focus in orthopedics. Negative pressure can stimulate angiogenesis, improve blood circulation, promote granulation tissue growth and accelerate tissue wound healing. We sought to determine whether negative pressure could reduce bone healing time in a rabbit cranial defect model. Four symmetrical holes (diameter, 3.5 mm) were drilled into the skulls of 42 New Zealand white rabbits, with two holes in each parietal bone. For each rabbit, the two sides were then randomly assigned into experimental and control groups. Using negative pressure suction tubes, experimental holes were treated with -50 kPa for 15 minutes, four times per day, whereas the control holes remained untreated. After 4 weeks, the negative pressure suction tubes were removed. At 2, 4, 6 and 8 weeks, three-dimensional (3D) reconstruction computed tomography (CT), X-ray radiopacity, and two-photon absorptiometry were used to evaluate new bone formation. Histological changes were determined by hematoxylin and eosin (H.E) staining. At weekly intervals until 6 weeks, the mRNA expression levels of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2 were evaluated by RT-PCR. A paired student's t-test was employed to compare X-ray radiopacity and bone density measurements between the experimental and control groups. 3D-reconstruction CT showed that new bone regeneration in the experimental group was greater than that in the control group at 4 and 6 weeks. At these time points, the experimental group presented with higher X-ray radiopacity and increased bone density (P < 0.05) as compared with the control group. Cartilage islands and new bone were observed by H.E staining at 2 weeks in the experimental group. By

  14. Excavating the Role of Aloe Vera Wrapped Mesoporous Hydroxyapatite Frame Ornamentation in Newly Architectured Polyurethane Scaffolds for Osteogenesis and Guided Bone Regeneration with Microbial Protection.

    PubMed

    Selvakumar, M; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Dhara, Santanu; Chattopadhyay, Santanu

    2016-03-09

    Guided bone regeneration (GBR) scaffolds are unsuccessful in many clinical applications due to a high incidence of postoperative infection. The objective of this work is to fabricate GBR with an anti-infective electrospun scaffold by ornamenting segmented polyurethane (SPU) with two-dimensional Aloe vera wrapped mesoporous hydroxyapatite (Al-mHA) nanorods. The antimicrobial characteristic of the scaffold has been retrieved from the prepared Al-mHA frame with high aspect ratio (∼14.2) via biosynthesis route using Aloe vera (Aloe barbadensis miller) extract. The Al-mHA frame was introduced into an unprecedented SPU matrix (solution polymerized) based on combinatorial soft segments of poly(ε-caprolactone) (PCL), poly(ethylene carbonate) (PEC), and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, pristine mHA nanorods are also ornamented into it. An enzymatic ring-opening polymerization technique was adapted to synthesize soft segment of (PCL-PEC-b-PDMS). Structure elucidation of the synthesized polymers is established by nuclear magnetic resonance spectroscopy. Sparingly, Al-mHA ornamented scaffolds exhibit tremendous improvement (175%) in the mechanical properties with promising antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast-like MG63 cells (in vitro), the scaffolds were implanted in rabbits as an animal model by subcutaneous and intraosseous (tibial) sites. Improved in vivo biocompatibilities, biodegradation, osteoconductivity, and the ability to provide an adequate biomimetic environment for biomineralization for GBR of the scaffolds (SPU and ornamented SPUs) have been found from the various histological sections. Early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks were found in the defects filled with Al-mHA ornamented

  15. Histomorphological evaluation of Compound bone of Granulated Ricinus in bone regeneration in rabbits

    NASA Astrophysics Data System (ADS)

    Pavan Mateus, Christiano; Orivaldo Chierice, Gilberto; Okamoto, Tetuo

    2011-09-01

    Histological evaluation is an effective method in the behavioral description of the qualitative and quantitative implanted materials. The research validated the performance of Compound bone of Granulated Ricinus on bone regeneration with the histomorphological analysis results. Were selected 30 rabbits, females, divided into 3 groups of 10 animals (G1, G2, G3) with a postoperative time of 45, 70 and 120 days respectively. Each animal is undergone 2 bone lesions in the ilium, one implemented in the material: Compound bone of Granulated Ricinus and the other for control. After the euthanasia, the iliac bone was removed, identified and subjected to histological procedure. The evaluation histological, histomorphological results were interpreted and described by quantitative and qualitative analysis based facts verified in the three experimental groups evaluating the rate of absorption of the material in the tissue regeneration, based on the neo-bone formation. The histomorphologic results classified as a material biocompatible and biologically active. Action in regeneration by bone resorption occurs slowly and gradually. Knowing the time and rate of absorption and neo-formation bone biomaterial, which can be determined in the bone segment applicable in the clinical surgical area.

  16. Multifunctional Chitosan-45S5 Bioactive Glass-Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Microsphere Composite Membranes for Guided Tissue/Bone Regeneration.

    PubMed

    Li, Wei; Ding, Yaping; Yu, Shanshan; Yao, Qingqing; Boccaccini, Aldo R

    2015-09-23

    Novel multifunctional chitosan-45S5 bioactive glass-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microsphere (CS-BG-MS) composite membranes were developed with applicability in guided tissue/bone regeneration (GTR/GBR). The incorporation of 45S5 BG and PHBV MS into CS membranes not only provided the membranes with favorable surface roughness, hydrophilicity, and flexibility but also slowed down their degradation rate. Moreover, the CS membranes became bioactive after the incorporation of 45S5 BG and capable of releasing drugs of different physicochemical properties in a controlled and sustained manner with the addition of PHBV MS. Cell culture tests showed that osteoblast-like MG-63 human osteosarcoma cells had significantly higher adhesion, cell proliferation, and alkaline phosphatase (ALP) activity on CS-BG and CS-BG-MS membranes than on neat CS membranes. Therefore, the developed bioactive CS-BG-MS membranes with potential multidrug (e.g., antibacterial and antiosteoporosis drugs) delivery capability are promising candidate membranes for GTR/GBR applications.

  17. Bone Regeneration from PLGA Micro-Nanoparticles

    PubMed Central

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed. PMID:26509156

  18. Bone Regeneration from PLGA Micro-Nanoparticles.

    PubMed

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

  19. Biomimetic approaches with smart interfaces for bone regeneration.

    PubMed

    Sailaja, G S; Ramesh, P; Vellappally, Sajith; Anil, Sukumaran; Varma, H K

    2016-11-05

    A 'smart tissue interface' is a host tissue-biomaterial interface capable of triggering favourable biochemical events inspired by stimuli responsive mechanisms. In other words, biomaterial surface is instrumental in dictating the interface functionality. This review aims to investigate the fundamental and favourable requirements of a 'smart tissue interface' that can positively influence the degree of healing and promote bone tissue regeneration. A biomaterial surface when interacts synergistically with the dynamic extracellular matrix, the healing process become accelerated through development of a smart interface. The interface functionality relies equally on bound functional groups and conjugated molecules belonging to the biomaterial and the biological milieu it interacts with. The essential conditions for such a special biomimetic environment are discussed. We highlight the impending prospects of smart interfaces and trying to relate the design approaches as well as critical factors that determine species-specific functionality with special reference to bone tissue regeneration.

  20. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    PubMed

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  1. Vertical bone regeneration using rhBMP-2 and VEGF.

    PubMed

    Schorn, Lara; Sproll, Christoph; Ommerborn, Michelle; Naujoks, Christian; Kübler, Norbert R; Depprich, Rita

    2017-06-07

    Sufficient vertical and lateral bone supply and a competent osteogenic healing process are prerequisities for the successful osseointegration of dental implants in the alveolar bone. Several techniques including autologous bone grafts and guided bone regeneration are applied to improve quality and quantity of bone at the implantation site. Depending on the amount of lacking bone one- or two-stage procedures are required. Vertical bone augmentation has proven to be a challenge particularly in terms of bone volume stability. This study focuses on the three dimensional vertical bone generation in a one stage procedure in vivo. Therefore, a collagenous disc-shaped scaffold (ICBM = Insoluble Collagenous Bone Matrix) containing rhBMP-2 (Bone Morphogenetic Protein-2) and/or VEGF (Vascular Endothelial Growth Factor) was applied around the coronal part of a dental implant during insertion. RhBMP-2 and VEGF released directly at the implantation site were assumed to induce the generation of new vertical bone around the implant. One hundred eight titanium implants were inserted into the mandible and the tibia of 12 mini pigs. Four experimental groups were formed: Control group, ICBM, ICBM + BMP-2, and ICBM + BMP-2 + VEGF. After 1, 4 and 12 weeks the animals were sacrificed and bone generation was investigated histologically and histomorphometrically. After 12 weeks the combination of ICBM + rhBMP2 + VEGF showed significantly more bone volume density (BVD%), a higher vertical bone gain (VBG) and more vertical bone gain around the implant (PVBG) in comparison to the control group. By using collagenous disc-shaped matrices in combination with rhBMP-2 and VEGF vertical bone can be generated in a one stage procedure without donor site morbidity. The results of the presenting study suggest that the combination of rhBMP-2 and VEGF applied locally by using a collagenous carrier improves vertical bone generation in vivo. Further research is needed to establish whether this

  2. Pulsed Electromagnetic Fields Enhance Bone Morphogenetic Protein-2 Dependent-Bone Regeneration.

    PubMed

    Yang, Hoon Joo; Kim, Ri Youn; Hwang, Soon Jung

    2015-10-01

    The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the purpose of promoting bone regeneration is emerging; however, the high dose of rhBMP-2 required in humans is accompanied by several limitations, including bone resorption and swelling. To reduce the dose of rhBMP-2 required, the applicability of pulsed electromagnetic fields (PEMF) was evaluated using a rat calvarial defect model. After creating an 8-mm-diameter calvarial bone defect, a collagen sponge soaked in different concentrations (0, 2.5, 5, 10 μg) of rhBMP-2 was implanted at the defect area. One week after surgery, PEMF was applied for 8 h/day over 5 days in an experimental group of animals (n = 28) using a width of 12 μs, a pulse frequency of 60 Hz, and a magnetic intensity of 10 G. Animals were sacrificed 4 weeks after surgery and assessed by microcomputed tomography and histological and immunohistochemical analyses. In the absence of application of PEMF, bone volume, bone mineral density, trabecular thickness, trabecular number, and trabecular separation, all showed statistically significant differences, depending on the concentration of rhBMP-2 utilized (p < 0.001). PEMF accelerated bone regeneration in the groups that received 0, 2.5, and 5 μg rhBMP-2 (p < 0.05). In contrast, administration of 10 μg rhBMP-2 resulted in no additive effect on bone regeneration in combination with PEMF. Groups receiving no rhBMP-2 showed distinct bone regeneration in the central zone of the bone defect when treated with PEMF, whereas they failed to bridge the defect space without PEMF. Among the groups without PEMF, soft tissue infiltrations from the outer surface on the skin side were common. Among groups with PEMF, the groups receiving 5 and 10 μg rhBMP-2 displayed denser bone with significantly reduced dead spaces. The application of PEMF did not result in an accelerated effect on bone regeneration in groups treated with 10 μg rhBMP-2. Therefore, our data

  3. Bacterial Cellulose-Hydroxyapatite Nanocomposites for Bone Regeneration

    PubMed Central

    Saska, S.; Barud, H. S.; Gaspar, A. M. M.; Marchetto, R.; Ribeiro, S. J. L.; Messaddeq, Y.

    2011-01-01

    The aim of this study was to develop and to evaluate the biological properties of bacterial cellulose-hydroxyapatite (BC-HA) nanocomposite membranes for bone regeneration. Nanocomposites were prepared from bacterial cellulose membranes sequentially incubated in solutions of CaCl2 followed by Na2HPO4. BC-HA membranes were evaluated in noncritical bone defects in rat tibiae at 1, 4, and 16 weeks. Thermogravimetric analyses showed that the amount of the mineral phase was 40%–50% of the total weight. Spectroscopy, electronic microscopy/energy dispersive X-ray analyses, and X-ray diffraction showed formation of HA crystals on BC nanofibres. Low crystallinity HA crystals presented Ca/P a molar ratio of 1.5 (calcium-deficient HA), similar to physiological bone. Fourier transformed infrared spectroscopy analysis showed bands assigned to phosphate and carbonate ions. In vivo tests showed no inflammatory reaction after 1 week. After 4 weeks, defects were observed to be completely filled in by new bone tissue. The BC-HA membranes were effective for bone regeneration. PMID:21961004

  4. Biomimesis and biomorphic transformations: new concepts applied to bone regeneration.

    PubMed

    Sprio, Simone; Ruffini, Andrea; Valentini, Federica; D'Alessandro, Teresa; Sandri, Monica; Panseri, Silvia; Tampieri, Anna

    2011-12-20

    In the last decades the activity of material scientists was more and more directed to the development of biomimetic scaffolds, able to drive and address cell activity towards proper differentiation and the repair of diseased human tissues. In case of bone, this requires the synthesis of three-dimensional constructs able to exchange chemical signals promoting osteogenesis and to progressively be resorbed during the formation and remodelling of new bone. Besides, particularly for the regeneration of extensive portions of bone, a morphological and mechanical biomimesis is also required, to allow cell colonization and formation of a proper vascularization tree. The healing of load-bearing bones also requires scaffolds with a hierarchically organized morphology, to provide improved biomechanical behaviour and allow a proper mechano-transduction of the mechanical stimuli down to the cell level. The present paper is an overview of the current technologies and devices developed in the last decade for the regeneration of bone tissue. In particular, novel biomimetic and biomorphic scaffolds, obtained by the controlled transformation of native ligneous structures, promise to adequately face the problem of obtaining complex hierarchical structures, not achievable otherwise by any currently existing manufacturing techniques.

  5. Mathematical Model of Bone Regeneration in a Porous Implant

    NASA Astrophysics Data System (ADS)

    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. Real-Time Assessment of Guided Bone Regeneration in Standardized Calvarial Defects in Rats Using Bio-Oss With and Without Collagen Membrane: An In Vivo Microcomputed Tomographic and Histologic Experiment.

    PubMed

    Nooh, Nasser; Ramalingam, Sundar; Al-Kindi, Mohammed; Al-Rasheed, Abdulaziz; Al-Hamdan, Khalid S; Al-Hezaimi, Khalid

    2016-01-01

    In vivo microcomputed tomography (μCT) enables real-time assessment of bone regeneration. The aim of this μCT and histologic experiment was to assess guided bone regeneration (GBR) around standardized calvarial defects in rats using particulate graft material (Bio-Oss) with and without collagen membranes (CMs). Eighteen female Sprague-Dawley rats aged 6 weeks and weighing 300 g were used. With the rats under general anesthesia, calvaria were exposed and a full-thickness standardized defect was created on the parietal bone. For treatment, rats were randomly assigned to the following three groups: (1) CM group; (2) Bio-Oss group; and (3) Bio-Oss + CM group. Bone volume and bone mineral density (BMD) of newly formed bone (NFB) and remnant bone particles were measured at baseline and 2, 4, 6, and 10 weeks after the operations using real-time in vivo μCT. At 10 weeks, all animals were sacrificed and calvarial tissues were assessed histologically. In the CM group, a significant increase in mean ± standard deviation (SD) BMD of NFB was observed at 6 weeks (0.32 ± 0.02 g/mm(3)) (P < .01) compared with baseline. In the Bio-Oss group, mean ± SD volume (3.03 ± 0.14 mm(3)) (P < .05) and BMD (0.14 ± 0.01 g/mm(3)) of NFB significantly increased at 6 weeks compared with baseline (P < .01). In the Bio-Oss + CM group, mean ± SD volume (0.98 ± 0.19 mm(3)) and BMD (0.13 ± 0.01 g/mm(3)) of NFB significantly increased at 4 weeks compared with baseline (P < .01). In th Bio-Oss + CM group, mean ± SD volume (3.5 ± 0.7 mm(3)) and BMD (0.44 ± 0.03 g/mm(3)) of remnant bone particles were significantly reduced at 10 weeks compared with baseline values (5.8 ± 0.96 mm(3) and 1.3 ± 0.02 g/mm(3)) (P < .05). Although histologic analysis revealed NFB in all the study groups, the Bio-Oss + CM group exhibited the most. The results of this study revealed that, in real time, new bone formation starts as early as 4 weeks in standardized calvarial defects undergoing GBR with Bio-Oss + CM

  7. Bone morphogenetic proteins: Signaling periodontal bone regeneration and repair.

    PubMed

    Anusuya, G Sai; Kandasamy, M; Jacob Raja, S A; Sabarinathan, S; Ravishankar, P; Kandhasamy, Balu

    2016-10-01

    Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signaling in pathological processes. A study done wherein it was found that protein extracts from bone implanted into the animals at nonbone sites induced the formation of new cartilage and bone tissue. This protein extract contained multiple factors that stimulated bone formation and was termed as "BMP." There are at least 15 different BMPs identified to date and are a part of the transforming growth factor-β super family. The most widely studied BMPs are BMP-2, BMP-3 (osteogenin), BMP-4, and BMP-7 (osteogenic protein-1). Now, any recombination type of morphogenic proteins have been synthesized, for example - recombinant human BMPs.

  8. Bone morphogenetic proteins: Signaling periodontal bone regeneration and repair

    PubMed Central

    Anusuya, G. Sai; Kandasamy, M.; Jacob Raja, S. A.; Sabarinathan, S.; Ravishankar, P.; Kandhasamy, Balu

    2016-01-01

    Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signaling in pathological processes. A study done wherein it was found that protein extracts from bone implanted into the animals at nonbone sites induced the formation of new cartilage and bone tissue. This protein extract contained multiple factors that stimulated bone formation and was termed as “BMP.” There are at least 15 different BMPs identified to date and are a part of the transforming growth factor-β super family. The most widely studied BMPs are BMP-2, BMP-3 (osteogenin), BMP-4, and BMP-7 (osteogenic protein-1). Now, any recombination type of morphogenic proteins have been synthesized, for example - recombinant human BMPs. PMID:27829744

  9. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration.

    PubMed

    Colnot, Céline

    2009-02-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. [corrected] Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment.

  10. Preparation and In Vitro Biological Evaluation of Octacalcium Phosphate/Bioactive Glass-Chitosan/ Alginate Composite Membranes Potential for Bone Guided Regeneration.

    PubMed

    Xu, Sanzhong; Chen, Xiaoyi; Yang, Xianyan; Zhang, Lei; Yang, Guojing; Shao, Huifeng; He, Yong; Gou, Zhongru

    2016-06-01

    The chitosan/alginate-trace element-codoped octacalcium phosphate/nano-sized bioactive glass (CS/ALG-teOCP/nBG) composite membranes were prepared by a layer-by-layer coating method for the functional requirement of guided bone regeneration (GBR). The morphology, mechanical properties and moisture content of the membranes was studied by scanning electron microscopy (SEM) observation, mechanical and swelling test. The results showed that the teOCP/nBG distributed uniformly in the composite membranes, and such as-prepared composite membrane exhibited an excellent tensile strength, accompanying with mechanical decay with immersion in aqueous medium. Cell culture and MTT assays showed that the surface microstructure and the ion dissolution products from teOCP/nBG components could enhance the cell proliferation, and especially the composite membranes was suitable for supporting the adhesion and growth behavior of human bone marrow mesenchymal stem cells (hBMSCs) in comparison with the CS/ALG pure polymer membranes. These results suggest that the new CS/ALG-teOCP/nBG composite membrane is highly bioactive and biodegradable, and favorable for guiding bone regeneration.

  11. Osteoinductive silk-silica composite biomaterials for bone regeneration.

    PubMed

    Mieszawska, Aneta J; Fourligas, Nikolaos; Georgakoudi, Irene; Ouhib, Nadia M; Belton, David J; Perry, Carole C; Kaplan, David L

    2010-12-01

    Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining silk fibroin with silica particles. The influence of these composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on silk/silica films. The addition of the silica to the silk films influenced gene expression leading to upregulation of bone sialoprotein (BSP) and collagen type 1 (Col 1) osteogenic markers. Evidence for early bone formation in the form of collagen fibers and apatite nodules was obtained on the silk/silica films. Collagen fibers were closely associated with apatite deposits and overall collagen content was higher for the silica containing samples. Also, smaller sized silica particles (24 nm-2 μm) with large surface area facilitated silica biodegradation in vitro through particle dissolution, leading to ∼5-fold decrease in silica content over 10 weeks. These results indicate the suitability of silk/silica composite system towards bone regeneration, where degradation/remodeling rates of the organic and inorganic components can be controlled. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Osteoinductive silk-silica composite biomaterials for bone regeneration

    PubMed Central

    Mieszawska, Aneta J.; Fourligas, Nikolaos; Georgakoudi, Irene; Ouhib, Nadia; Belton, David J.; Perry, Carole C.; Kaplan, David L.

    2010-01-01

    Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining silk fibroin with silica particles. The influence of these composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on silk/silica films. The addition of the silica to the silk films influenced gene expression leading to upregulation of bone sialoprotein (BSP) and collagen type 1 (Col 1) osteogenic markers. Evidence for early bone formation in the form of collagen fibers and apatite nodules was obtained on the silk/silica films. Collagen fibers were closely associated with apatite deposits and overall collagen content was higher for the silica containing samples. Also, smaller sized silica particles (24 nm – 2 μm) with large surface area facilitated silica biodegradation in vitro through particle dissolution, leading to ~5 fold decrease in silica content over 10 weeks. These results indicate suitability of silk/silica composite system towards bone regeneration, where degradation/remodeling rates of the organic and inorganic components can be controlled. PMID:20817293

  13. Systemic administration of lithium improves distracted bone regeneration in rats.

    PubMed

    Wang, Xuemei; Zhu, Songsong; Jiang, Xiaowen; Li, Yunfeng; Song, Donghui; Hu, Jing

    2015-06-01

    Lithium, popular in psychology field, has been recognized as an activator component of the canonical Wnt signaling pathway. The effect of lithium on osteogenesis or on the human fracture risk has been widely reported. However, little is known on its role in distraction osteogenesis to date. In this study, the effect of systematic administrated lithium on distraction osteogenesis in a rat model was investigated. The osteotomy was performed on the right tibia in 40 adult male Sprague-Dawley rats. Then they were randomly assigned into two equal groups (n = 20/group), which underwent Lithium or saline treatment through gastric gavage until the day they were killed. One week after the osteotomy, the tibias were distracted for 14 days (rate 0.6 mm/day). Following 8 weeks consolidation period, the distracted tibias in both groups were harvested and examined by X-ray plain radiography, histology, dual-energy X-ray absorptiometry, Micro-CT, and biomechanical tests. The results showed that lithium group possessed higher bone mineral density, more mature new bone tissue, and better regenerated bone mass continuity in the distraction gaps without any local or systemic adverse effects was encountered. This study suggested lithium could increase bony callus ossification volume and accelerate distracted tissue mineralization to facilitate bone regeneration in distraction gap.

  14. Use of human perivascular stem cells for bone regeneration.

    PubMed

    James, Aaron W; Zara, Janette N; Corselli, Mirko; Chiang, Michael; Yuan, Wei; Nguyen, Virginia; Askarinam, Asal; Goyal, Raghav; Siu, Ronald K; Scott, Victoria; Lee, Min; Ting, Kang; Péault, Bruno; Soo, Chia

    2012-05-25

    Human perivascular stem cells (PSCs) can be isolated in sufficient numbers from multiple tissues for purposes of skeletal tissue engineering. PSCs are a FACS-sorted population of 'pericytes' (CD146+CD34-CD45-) and 'adventitial cells' (CD146-CD34+CD45-), each of which we have previously reported to have properties of mesenchymal stem cells. PSCs, like MSCs, are able to undergo osteogenic differentiation, as well as secrete pro-osteogenic cytokines. In the present protocol, we demonstrate the osteogenicity of PSCs in several animal models including a muscle pouch implantation in SCID (severe combined immunodeficient) mice, a SCID mouse calvarial defect and a femoral segmental defect (FSD) in athymic rats. The thigh muscle pouch model is used to assess ectopic bone formation. Calvarial defects are centered on the parietal bone and are standardly 4 mm in diameter (critically sized). FSDs are bicortical and are stabilized with a polyethylene bar and K-wires. The FSD described is also a critical size defect, which does not significantly heal on its own. In contrast, if stem cells or growth factors are added to the defect site, significant bone regeneration can be appreciated. The overall goal of PSC xenografting is to demonstrate the osteogenic capability of this cell type in both ectopic and orthotopic bone regeneration models.

  15. Growth and differentiation of a long bone in limb development, repair and regeneration.

    PubMed

    Egawa, Shiro; Miura, Shinichirou; Yokoyama, Hitoshi; Endo, Tetsuya; Tamura, Koji

    2014-06-01

    Repair from traumatic bone fracture is a complex process that includes mechanisms of bone development and bone homeostasis. Thus, elucidation of the cellular/molecular basis of bone formation in skeletal development would provide valuable information on fracture repair and would lead to successful skeletal regeneration after limb amputation, which never occurs in mammals. Elucidation of the basis of epimorphic limb regeneration in amphibians would also provide insights into skeletal regeneration in mammals, since the epimorphic regeneration enables an amputated limb to re-develop the three-dimensional structure of bones. In the processes of bone development, repair and regeneration, growth of the bone is achieved through several events including not only cell proliferation but also aggregation of mesenchymal cells, enlargement of cells, deposition and accumulation of extracellular matrix, and bone remodeling. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

  16. Tracheal regeneration: evidence of bone marrow mesenchymal stem cell involvement.

    PubMed

    Seguin, Agathe; Baccari, Sonia; Holder-Espinasse, Muriel; Bruneval, Patrick; Carpentier, Alain; Taylor, Doris A; Martinod, Emmanuel

    2013-05-01

    Recent advances in airway transplantation have shown the ability of ex vivo or in vivo tracheal regeneration with bioengineered conduits or biological substitutes, respectively. Previously, we established a process of in vivo-guided tracheal regeneration using vascular allografts as a biological scaffold. We theorized that tracheal healing was the consequence of a mixed phenomenon associating tracheal contraction and regeneration. The aim of the present study was to determine the role that bone marrow stem cells play in that regenerative process. Three groups of 12 rabbits underwent a gender-mismatched aortic graft transplantation after tracheal resection. The first group received no cells (control group), the second group had previously received autologous green fluorescent protein-labeled mesenchymal stem cell transplantation, and the third group received 3 labeled mesenchymal stem cell injections on postoperative days 0, 10, and 21. The clinical results were impaired by stent complications (obstruction or migration), but no anastomotic leakage, dehiscence, or stenosis was observed. The rabbits were killed, and the trachea was excised for analysis at 1 to 18 months after tracheal replacement. In all 3 groups, microscopic examination showed an integrated aortic graft lined by metaplastic epithelium. By 12 months, immature cartilage was detected among disorganized elastic fibers. Positive SRY gene detection served as evidence for engraftment of cells derived from the male recipient. EF-green fluorescent protein detection showed bone marrow-derived mesenchymal stem cell involvement. The results of the present study imply a role for bone marrow stem cells in tracheal regeneration after aortic allografting. Studies are necessary to identify the local and systemic factors stimulating that regenerative process. Copyright © 2013 The American Association for Thoracic Surgery. All rights reserved.

  17. Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration.

    PubMed

    Tsai, Tsung-Lin; Li, Wan-Ju

    2017-02-14

    Maintaining properties of human bone marrow-derived mesenchymal stem cells (BMSCs) in culture for regenerative applications remains a great challenge. An emerging approach of constructing a culture environment mimicking the bone marrow niche to regulate BMSC activities has been developed. In this study, we have demonstrated a systematic approach to identify soluble factors of interest extracted from human bone marrow and used them in BMSC culture for tissue regeneration. We have found that lipocalin-2 and prolactin are key factors in bone marrow, involved in regulating BMSC activities. Treating the cell with lipocalin-2 and prolactin delays cellular senescence of BMSCs and primes the cell for osteogenesis and chondrogenesis. We have also demonstrated that BMSCs pretreated with lipocalin-2 and prolactin can enhance the repair of calvarial defects in mice. Together, our study provides research evidence of using a viable approach to prime BMSC properties in vitro for improving cell-based tissue regeneration in vivo.

  18. Bones of contention: marrow-derived cells in myocardial regeneration.

    PubMed

    Sussman, Mark A; Murry, Charles E

    2008-06-01

    Almost 7 years have passed since the initial publication reporting that bone marrow cells regenerate infarcted myocardium. The subsequent years produced hundreds of investigations that ran the gamut of findings from validation to disproof. Undeterred by the concurrent debate, clinical trials ensued to test the safety and efficacy of bone marrow-derived cell population for autologous therapy in clinical treatment of myocardial disease. In the following conversational exchange, two scientists with distinct perspectives weigh the pros and cons of pursuing bone marrow stem cell therapy and look toward finding a consensus of where the future lies for regenerative medicine and the heart. The conclusion is that the two camps may not be as far apart as it may seem from the rancor in literature and at meetings, and the potential of one day achieving regenerative therapy is indeed a vision that both parties enthusiastically share.

  19. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation.

    PubMed

    Kim, Ji-Beom; Lee, Dong Yeon; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-09-01

    Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest

  20. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

    PubMed Central

    Kim, Ji-Beom; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-01-01

    Background Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. Methods The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. Results The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. Conclusions DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the

  1. Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

    PubMed

    Freeman, Fiona E; McNamara, Laoise M

    2017-04-01

    Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for

  2. Bioactive glass scaffolds for bone regeneration and their hierarchical characterisation.

    PubMed

    Jones, J R; Lin, S; Yue, S; Lee, P D; Hanna, J V; Smith, M E; Newport, R J

    2010-12-01

    Scaffolds are needed that can act as temporary templates for bone regeneration and actively stimulate vascularized bone growth so that bone grafting is no longer necessary. To achieve this, the scaffold must have a suitable interconnected pore network and be made of an osteogenic material. Bioactive glass is an ideal material because it rapidly bonds to bone and degrades over time, releasing soluble silica and calcium ions that are thought to stimulate osteoprogenitor cells. Melt-derived bioactive glasses, such as the original Bioglass composition, are available commercially, but porous scaffolds have been difficult to produce because Bioglass and similar compositions crystallize on sintering. Sol-gel foam scaffolds have been developed that avoid this problem. They have a hierarchical pore structure comprising interconnected macropores, with interconnect diameters in excess of the 100 microm that is thought to be needed for vascularized bone ingrowth, and an inherent nanoporosity of interconnected mesopores (2-50 nm) which is beneficial for the attachment of osteoprogenitor cells. They also have a compressive strength in the range of cancellous bone. This paper describes the optimized sol-gel foaming process and illustrates the importance of optimizing the hierarchical structure from the atomic through nano, to the macro scale with respect to biological response.

  3. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2

    PubMed Central

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn

    2015-01-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation. PMID:25813520

  4. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2.

    PubMed

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn; O'Connor, J Patrick

    2015-07-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.

  5. Bone regeneration at dental implant sites with suspended stem cells.

    PubMed

    Zheng, R C; Park, Y K; Cho, J J; Kim, S K; Heo, S J; Koak, J Y; Lee, J H

    2014-10-01

    primary BMMSC isolation have bone regeneration capacity like that of BMMSCs, not only in vitro but also in vivo. ECM was valuable for propagation of MSCs for cell-based bone regeneration. Therefore, the suspended cells could also be useful tools for bone regeneration after implant surgery. © International & American Associations for Dental Research.

  6. CCN3 Protein Participates in Bone Regeneration as an Inhibitory Factor*

    PubMed Central

    Matsushita, Yuki; Sakamoto, Kei; Tamamura, Yoshihiro; Shibata, Yasuaki; Minamizato, Tokutaro; Kihara, Tasuku; Ito, Masako; Katsube, Ken-ichi; Hiraoka, Shuichi; Koseki, Haruhiko; Harada, Kiyoshi; Yamaguchi, Akira

    2013-01-01

    CCN3, a member of the CCN protein family, inhibits osteoblast differentiation in vitro. However, the role of CCN3 in bone regeneration has not been well elucidated. In this study, we investigated the role of CCN3 in bone regeneration. We identified the Ccn3 gene by microarray analysis as a highly expressed gene at the early phase of bone regeneration in a mouse bone regeneration model. We confirmed the up-regulation of Ccn3 at the early phase of bone regeneration by RT-PCR, Western blot, and immunofluorescence analyses. Ccn3 transgenic mice, in which Ccn3 expression was driven by 2.3-kb Col1a1 promoter, showed osteopenia compared with wild-type mice, but Ccn3 knock-out mice showed no skeletal changes compared with wild-type mice. We analyzed the bone regeneration process in Ccn3 transgenic mice and Ccn3 knock-out mice by microcomputed tomography and histological analyses. Bone regeneration in Ccn3 knock-out mice was accelerated compared with that in wild-type mice. The mRNA expression levels of osteoblast-related genes (Runx2, Sp7, Col1a1, Alpl, and Bglap) in Ccn3 knock-out mice were up-regulated earlier than those in wild-type mice, as demonstrated by RT-PCR. Bone regeneration in Ccn3 transgenic mice showed no significant changes compared with that in wild-type mice. Phosphorylation of Smad1/5 was highly up-regulated at bone regeneration sites in Ccn3 KO mice compared with wild-type mice. These results indicate that CCN3 is up-regulated in the early phase of bone regeneration and acts as a negative regulator for bone regeneration. This study may contribute to the development of new strategies for bone regeneration therapy. PMID:23653360

  7. Surgically-induced mouse models in the study of bone regeneration: Current models and future directions

    PubMed Central

    Ning, Bin; Zhao, Yunpeng; Buza, John A.; Li, Wei; Wang, Wenzhao; Jia, Tanghong

    2017-01-01

    Bone regeneration has been extensively studied over the past several decades. The surgically-induced mouse model is the key animal model for studying bone regeneration, of the various research strategies used. These mouse models mimic the trauma and recovery processes in vivo and serve as carriers for tissue engineering and gene modification to test various therapies or associated genes in bone regeneration. The present review introduces a classification of surgically induced mouse models in bone regeneration, evaluates the application and value of these models and discusses the potential development of further innovations in this field in the future. PMID:28138711

  8. Strontium borate glass: potential biomaterial for bone regeneration.

    PubMed

    Pan, H B; Zhao, X L; Zhang, X; Zhang, K B; Li, L C; Li, Z Y; Lam, W M; Lu, W W; Wang, D P; Huang, W H; Lin, K L; Chang, J

    2010-07-06

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones.

  9. Cardiomyocyte regeneration from circulating bone marrow cells in mice.

    PubMed

    Kuramochi, Yukio; Fukazawa, Ryuji; Migita, Makoto; Hayakawa, Jun; Hayashida, Mari; Uchikoba, Yohko; Fukumi, Daichi; Shimada, Takashi; Ogawa, Shunichi

    2003-09-01

    We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 +/- 5.9%) and at 3 mo (45.3 +/- 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 +/- 45 cells/50 sections; 3 mo: 458 +/- 100 cells/50 sections; p < 0.05 versus noninfarct, infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

  10. A biocomposite of collagen nanofibers and nanohydroxyapatite for bone regeneration.

    PubMed

    Ribeiro, Nilza; Sousa, Susana R; van Blitterswijk, Clemens A; Moroni, Lorenzo; Monteiro, Fernando J

    2014-09-01

    This work aims to design a synthetic construct that mimics the natural bone extracellular matrix through innovative approaches based on simultaneous type I collagen electrospinning and nanophased hydroxyapatite (nanoHA) electrospraying using non-denaturating conditions and non-toxic reagents. The morphological results, assessed using scanning electron microscopy and atomic force microscopy (AFM), showed a mesh of collagen nanofibers embedded with crystals of HA with fiber diameters within the nanometer range (30 nm), thus significantly lower than those reported in the literature, over 200 nm. The mechanical properties, assessed by nanoindentation using AFM, exhibited elastic moduli between 0.3 and 2 GPa. Fourier transformed infrared spectrometry confirmed the collagenous integrity as well as the presence of nanoHA in the composite. The network architecture allows cell access to both collagen nanofibers and HA crystals as in the natural bone environment. The inclusion of nanoHA agglomerates by electrospraying in type I collagen nanofibers improved the adhesion and metabolic activity of MC3T3-E1 osteoblasts. This new nanostructured collagen-nanoHA composite holds great potential for healing bone defects or as a functional membrane for guided bone tissue regeneration and in treating bone diseases.

  11. Strontium borate glass: potential biomaterial for bone regeneration

    PubMed Central

    Pan, H. B.; Zhao, X. L.; Zhang, X.; Zhang, K. B.; Li, L. C.; Li, Z. Y.; Lam, W. M.; Lu, W. W.; Wang, D. P.; Huang, W. H.; Lin, K. L.; Chang, J.

    2010-01-01

    Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones. PMID:20031984

  12. Comparative study of chitosan/fibroin–hydroxyapatite and collagen membranes for guided bone regeneration in rat calvarial defects: micro-computed tomography analysis

    PubMed Central

    Song, Jae Min; Shin, Sang Hun; Kim, Yong Deok; Lee, Jae Yeol; Baek, Young Jae; Yoon, Sang Yong; Kim, Hong Sung

    2014-01-01

    This study aimed to utilize micro-computed tomography (micro-CT) analysis to compare new bone formation in rat calvarial defects using chitosan/fibroin–hydroxyapatite (CFB–HAP) or collagen (Bio-Gide) membranes. Fifty-four (54) rats were studied. A circular bony defect (8 mm diameter) was formed in the centre of the calvaria using a trephine bur. The CFB–HAP membrane was prepared by thermally induced phase separation. In the experimental group (n=18), the CFB–HAP membrane was used to cover the bony defect, and in the control group (n=18), a resorbable collagen membrane (Bio-Gide) was used. In the negative control group (n=18), no membrane was used. In each group, six animals were euthanized at 2, 4 and 8 weeks after surgery. The specimens were then analysed using micro-CT. There were significant differences in bone volume (BV) and bone mineral density (BMD) (P<0.05) between the negative control group and the membrane groups. However, there were no significant differences between the CFB–HAP group and the collagen group. We concluded that the CFB–HAP membrane has significant potential as a guided bone regeneration (GBR) membrane. PMID:24722582

  13. Comparative study of chitosan/fibroin-hydroxyapatite and collagen membranes for guided bone regeneration in rat calvarial defects: micro-computed tomography analysis.

    PubMed

    Song, Jae Min; Shin, Sang Hun; Kim, Yong Deok; Lee, Jae Yeol; Baek, Young Jae; Yoon, Sang Yong; Kim, Hong Sung

    2014-06-01

    This study aimed to utilize micro-computed tomography (micro-CT) analysis to compare new bone formation in rat calvarial defects using chitosan/fibroin-hydroxyapatite (CFB-HAP) or collagen (Bio-Gide) membranes. Fifty-four (54) rats were studied. A circular bony defect (8 mm diameter) was formed in the centre of the calvaria using a trephine bur. The CFB-HAP membrane was prepared by thermally induced phase separation. In the experimental group (n=18), the CFB-HAP membrane was used to cover the bony defect, and in the control group (n=18), a resorbable collagen membrane (Bio-Gide) was used. In the negative control group (n=18), no membrane was used. In each group, six animals were euthanized at 2, 4 and 8 weeks after surgery. The specimens were then analysed using micro-CT. There were significant differences in bone volume (BV) and bone mineral density (BMD) (P<0.05) between the negative control group and the membrane groups. However, there were no significant differences between the CFB-HAP group and the collagen group. We concluded that the CFB-HAP membrane has significant potential as a guided bone regeneration (GBR) membrane.

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

    PubMed Central

    Huh, Jung-Bo; Yang, June-Jip; Choi, Kyung-Hee; Bae, Ji Hyeon; Lee, Jeong-Yeol; Kim, Sung-Eun; Shin, Sang-Wan

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. PMID:26184187

  15. Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

    PubMed Central

    Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

    2013-01-01

    Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. PMID:23836972

  16. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects.

    PubMed

    Osugi, Masashi; Katagiri, Wataru; Yoshimi, Ryoko; Inukai, Takeharu; Hibi, Hideharu; Ueda, Minoru

    2012-07-01

    Tissue engineering has recently become available as a treatment procedure for bone augmentation. However, this procedure has several problems, such as high capital investment and expensive cell culture, complicated safety and quality management issues regarding cell handling, and patient problems with the invasive procedure of cell collection. Moreover, it was reported that stem cells secrete many growth factors and chemokines during their cultivation, which could affect cellular characteristics and behavior. This study investigated the effect of stem-cell-cultured conditioned media on bone regeneration. Cultured conditioned media from human bone marrow-derived mesenchymal stem cells (MSC-CM) enhanced the migration, proliferation, and expression of osteogenic marker genes, such as osteocalcin and Runx2, of rat MSCs (rMSCs) in vitro. MSC-CM includes cytokines such as insulin-like growth factor-1 and vascular endothelial growth factor. In vivo, a prepared bone defect of a rat calvarial model was implanted in five different rat groups using one of the following graft materials: human MSCs/agarose (MSCs), MSC-CM/agarose (MSC-CM), Dulbecco's modified Eagle's medium without serum [DMEM(-)]/agarose [DMEM(-)], PBS/agarose (PBS), and defect only (Defect). After 4 and 8 weeks, implant sections were evaluated using microcomputed tomography (micro-CT) and histological analysis. Micro-CT analysis indicated that the MSC-CM group had a greater area of newly regenerated bone compared with the other groups (p<0.05) and histological analysis at 8 weeks indicated that the newly regenerated bone bridge almost covered the defect. Interestingly, the effects of MSC-CM were stronger than those of the MSC group. In vivo imaging and immunohistochemical staining of transgenic rats expressing green fluorescent protein also showed that migration of rMSCs to the bone defect in the MSC-CM group was greater than in the other groups. These results demonstrated that MSC-CM can regenerate bone

  17. Conditioned Media from Mesenchymal Stem Cells Enhanced Bone Regeneration in Rat Calvarial Bone Defects

    PubMed Central

    Osugi, Masashi; Yoshimi, Ryoko; Inukai, Takeharu; Hibi, Hideharu; Ueda, Minoru

    2012-01-01

    Tissue engineering has recently become available as a treatment procedure for bone augmentation. However, this procedure has several problems, such as high capital investment and expensive cell culture, complicated safety and quality management issues regarding cell handling, and patient problems with the invasive procedure of cell collection. Moreover, it was reported that stem cells secrete many growth factors and chemokines during their cultivation, which could affect cellular characteristics and behavior. This study investigated the effect of stem-cell-cultured conditioned media on bone regeneration. Cultured conditioned media from human bone marrow–derived mesenchymal stem cells (MSC-CM) enhanced the migration, proliferation, and expression of osteogenic marker genes, such as osteocalcin and Runx2, of rat MSCs (rMSCs) in vitro. MSC-CM includes cytokines such as insulin-like growth factor-1 and vascular endothelial growth factor. In vivo, a prepared bone defect of a rat calvarial model was implanted in five different rat groups using one of the following graft materials: human MSCs/agarose (MSCs), MSC-CM/agarose (MSC-CM), Dulbecco's modified Eagle's medium without serum [DMEM(−)]/agarose [DMEM(−)], PBS/agarose (PBS), and defect only (Defect). After 4 and 8 weeks, implant sections were evaluated using microcomputed tomography (micro-CT) and histological analysis. Micro-CT analysis indicated that the MSC-CM group had a greater area of newly regenerated bone compared with the other groups (p<0.05) and histological analysis at 8 weeks indicated that the newly regenerated bone bridge almost covered the defect. Interestingly, the effects of MSC-CM were stronger than those of the MSC group. In vivo imaging and immunohistochemical staining of transgenic rats expressing green fluorescent protein also showed that migration of rMSCs to the bone defect in the MSC-CM group was greater than in the other groups. These results demonstrated that MSC-CM can regenerate bone

  18. Investigation of potential injectable polymeric biomaterials for bone regeneration

    PubMed Central

    Dreifke, Michael B.; Ebraheim, Nabil A.; Jayasuriya, Ambalangodage C.

    2014-01-01

    This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(l-lactide-co-glycolide)-PLGA, poly (propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behaviorin vitro andin vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects. PMID:23401336

  19. Bone marrow-derived stem cells initiate pancreatic regeneration.

    PubMed

    Hess, David; Li, Li; Martin, Matthew; Sakano, Seiji; Hill, David; Strutt, Brenda; Thyssen, Sandra; Gray, Douglas A; Bhatia, Mickie

    2003-07-01

    We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

  20. Silk fibroin membrane used for guided bone tissue regeneration.

    PubMed

    Cai, Yurong; Guo, Junmao; Chen, Cen; Yao, Chenxue; Chung, Sung-Min; Yao, Juming; Lee, In-Seop; Kong, Xiangdong

    2017-01-01

    With the aim to develop a novel membrane with an appropriate mechanical property and degradation rate for guided bone tissue regeneration, lyophilized and densified silk fibroin membrane was fabricated and its mechanical behavior as well as biodegradation property were investigated. The osteoconductive potency of the silk fibroin membranes were evaluated in a defect rabbit calvarial model. Silk fibroin membrane showed the modulated biodegradable and mechanical properties via ethanol treatment with different concentration. The membrane could prevent soft tissue invasion from normal tissue healing, and the amounts of new bone and defect closure with silk fibroin membrane were similar to those of commercially available collagen membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Investigation of potential injectable polymeric biomaterials for bone regeneration.

    PubMed

    Dreifke, Michael B; Ebraheim, Nabil A; Jayasuriya, Ambalangodage C

    2013-08-01

    This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(L-lactide-co-glycolide)-PLGA, poly(propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behavior in vitro and in vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects.

  2. [Evaluation of reparative regeneration of the jaw bone by microfocus roentgenography in an experiment].

    PubMed

    Vasil'ev, A Iu; Bulanova, I M; Mal'ginov, N N; Tarasenko, I V; Tarasenko, S V; Kiseleva, E V; Drobyshev, A Iu; Volozhin, A I

    2009-01-01

    In experiment on 16 grown-up chinchilla rabbits the dynamic of reparative regeneration was evaluated by digital microfocal rontgenography in the terms of 1, 2 and 4 months. Bone defect of the 8capital CHE, Cyrillic8 mm size in the region of mandible angle was caused by surgical laser Smart 2940 D+ on the right side and by physiodespenser Surgec XT on the left side. Surgical laser use let to reduce intact mother bone traumatisation and to improve remote results of bone tissue regeneration. After bone defect creation bone tissue regeneration was put into effect by all 3 callus types - endosteal, periosteal and intermediary.

  3. Generation of clinical grade human bone marrow stromal cells for use in bone regeneration.

    PubMed

    Robey, Pamela G; Kuznetsov, Sergei A; Ren, Jiaqiang; Klein, Harvey G; Sabatino, Marianna; Stroncek, David F

    2015-01-01

    In current orthopaedic practice, there is a need to increase the ability to reconstruct large segments of bone lost due to trauma, resection of tumors and skeletal deformities, or when normal regenerative processes have failed such as in non-unions and avascular necrosis. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells), when used in conjunction with appropriate carriers, represent a means by which to achieve bone regeneration in such cases. While much has been done at the bench and in pre-clinical studies, moving towards clinical application requires the generation of clinical grade cells. What is described herein is an FDA-approved cell manufacturing procedure for the ex vivo expansion of high quality, biologically active human BMSCs. This article is part of a Special Issue entitled Stem Cells and Bone.

  4. Mechanical properties of a biodegradable bone regeneration scaffold

    NASA Technical Reports Server (NTRS)

    Porter, B. D.; Oldham, J. B.; He, S. L.; Zobitz, M. E.; Payne, R. G.; An, K. N.; Currier, B. L.; Mikos, A. G.; Yaszemski, M. J.

    2000-01-01

    Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

  5. Mechanical properties of a biodegradable bone regeneration scaffold.

    PubMed

    Porter, B D; Oldham, J B; He, S L; Zobitz, M E; Payne, R G; An, K N; Currier, B L; Mikos, A G; Yaszemski, M J

    2000-06-01

    Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

  6. Mechanical properties of a biodegradable bone regeneration scaffold

    NASA Technical Reports Server (NTRS)

    Porter, B. D.; Oldham, J. B.; He, S. L.; Zobitz, M. E.; Payne, R. G.; An, K. N.; Currier, B. L.; Mikos, A. G.; Yaszemski, M. J.

    2000-01-01

    Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

  7. Improvement of bone regeneration capability of ceramic scaffolds by accelerated release of their calcium ions.

    PubMed

    Seol, Young-Joon; Park, Ju Young; Jung, Jin Woo; Jang, Jinah; Girdhari, Rijal; Kim, Sung Won; Cho, Dong-Woo

    2014-11-01

    To regenerate the bone tissue, the fabrication of scaffolds for better tissue regeneration has attracted a great deal of attention. In fact, growth factors are already used in clinical practice and are being investigated for enhancing the capacity for bone tissue regeneration. However, despite their strong osteoinductive activity, these growth factors have several limitations: safety issues, high treatment costs, and the potential for ectopic bone formation. The aim of this study was therefore to develop ceramic scaffolds that could promote the capacity for bone regeneration without growth factors. Three-dimensional ceramic scaffolds were successfully fabricated from hydroxyapatite (HA) and tricalcium phosphate (TCP) using projection-based microstereolithography, which is an additive manufacturing technology. The effects of calcium ions released from ceramic scaffolds on osteogenic differentiation and bone regeneration were evaluated in vitro and in vivo. The osteogenesis-related gene expression and area of new bone formation in the HA/TCP scaffolds was higher than those in the HA scaffolds. Moreover, regenerated bone tissue in HA/TCP scaffolds were more matured than that in HA scaffolds. Through this study, we were able to enhance the bone regeneration capacity of scaffolds not by growth factors but by calcium ions released from the scaffolds. Ceramic scaffolds developed in this study might be useful for enhancing the capacity for regeneration in complex bone defects.

  8. Improvement of Bone Regeneration Capability of Ceramic Scaffolds by Accelerated Release of Their Calcium Ions

    PubMed Central

    Seol, Young-Joon; Park, Ju Young; Jung, Jin Woo; Jang, Jinah; Girdhari, Rijal; Kim, Sung Won

    2014-01-01

    To regenerate the bone tissue, the fabrication of scaffolds for better tissue regeneration has attracted a great deal of attention. In fact, growth factors are already used in clinical practice and are being investigated for enhancing the capacity for bone tissue regeneration. However, despite their strong osteoinductive activity, these growth factors have several limitations: safety issues, high treatment costs, and the potential for ectopic bone formation. The aim of this study was therefore to develop ceramic scaffolds that could promote the capacity for bone regeneration without growth factors. Three-dimensional ceramic scaffolds were successfully fabricated from hydroxyapatite (HA) and tricalcium phosphate (TCP) using projection-based microstereolithography, which is an additive manufacturing technology. The effects of calcium ions released from ceramic scaffolds on osteogenic differentiation and bone regeneration were evaluated in vitro and in vivo. The osteogenesis-related gene expression and area of new bone formation in the HA/TCP scaffolds was higher than those in the HA scaffolds. Moreover, regenerated bone tissue in HA/TCP scaffolds were more matured than that in HA scaffolds. Through this study, we were able to enhance the bone regeneration capacity of scaffolds not by growth factors but by calcium ions released from the scaffolds. Ceramic scaffolds developed in this study might be useful for enhancing the capacity for regeneration in complex bone defects. PMID:24784792

  9. Novel bioceramic-reinforced hydrogel for alveolar bone regeneration.

    PubMed

    Iviglia, Giorgio; Cassinelli, Clara; Torre, Elisa; Baino, Francesco; Morra, Marco; Vitale-Brovarone, Chiara

    2016-10-15

    The osseointegration of dental implants and their consequent long-term success is guaranteed by the presence, in the extraction site, of healthy and sufficient alveolar bone. Bone deficiencies may be the result of extraction traumas, periodontal disease and infection. In these cases, placement of titanium implants is contraindicated until a vertical bone augmentation is obtained. This goal is achieved using bone graft materials, which should simulate extracellular matrix (ECM), in order to promote osteoblast proliferation and fill the void, maintaining the space without collapsing until the new bone is formed. In this work, we design, develop and characterize a novel, moldable chitosan-pectin hydrogel reinforced by biphasic calcium phosphate particles with size in the range of 100-300μm. The polysaccharide nature of the hydrogel mimics the ECM of natural bone, and the ceramic particles promote high osteoblast proliferation, assessed by Scanning Electron Microscopy analysis. Swelling properties allow significant adsorption of water solution (up to 200% of solution content) so that the bone defect space can be filled by the material in an in vivo scenario. The incorporation of ceramic particles makes the material stable at different pH and increases the compressive elastic modulus, toughness and ultimate tensile strength. Furthermore, cell studies with SAOS-2 human osteoblastic cell line show high cell proliferation and adhesion already after 72h, and the presence of ceramic particles increases the expression of alkaline phosphatase activity after 1week. These results suggest a great potential of the developed moldable biomaterials for the regeneration of the alveolar bone. The positive fate of a surgical procedure involving the insertion of a titanium screw still depends on the quality and quantity of alveolar bone which is present in the extraction site. Available materials are basically hard scaffold materials with un-predictable behavior in different condition

  10. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    PubMed Central

    Walker, John A.; Singleton, Brian M.; Hernandez, Jesus W.; Son, Jun-Sik; Kim, Su-Gwan; Oh, Daniel S.; Appleford, Mark R.; Ong, Joo L.; Wenke, Joseph C.

    2013-01-01

    There are few synthetic graft alternatives to treat large long-bone defects resulting from trauma or disease that do not incorporate osteogenic or osteoinductive factors. The aim of this study was to test the additional benefit of including a permeable collagen membrane guide in conjunction with a preformed porous hydroxyapatite bone graft to serve as an improved osteoconductive scaffold for bone regeneration. A 10-mm-segmental long-bone defect model in the rabbit radius was used. The hydroxyapatite scaffolds alone or with a collagen wrap were compared as experimental treatment groups to an empty untreated defect as a negative control or a defect filled with autologous bone grafts as a positive control. All groups were evaluated after 4 and 8 weeks of in vivo implantation using microcomputed tomography, mechanical testing in flexure, and histomorphometry. It was observed that the use of the wrap resulted in an increased bone volume regenerated when compared to the scaffold-only group (59% greater at 4 weeks and 27% greater after 8 weeks). Additionally, the increase in density of the regenerated bone from 4 to 8 weeks in the wrap group was threefold than that in the scaffold group. The use of the collagen wrap showed significant benefits of increased interfacial bone in-growth (149% greater) and periosteal remodeling (49%) after 4 weeks compared to the scaffold-alone with the two groups being comparable after 8 weeks, by when the collagen membrane showed close-to-complete resorption. While the autograft and wrap groups showed significantly greater flexural strength than the defect group after 8 weeks, the scaffold-alone group was not significantly different from the other three groups. It is most likely that the wrap shows improvement of function by acting like a scaffold for periosteal callus ossification, maintaining the local bone-healing environment while reducing fibrous infiltration (15% less than scaffold only at 4 weeks). This study indicates that the use of

  11. Enhancing dermal and bone regeneration in calvarial defect surgery

    PubMed Central

    Zanotti, Bruno; Zingaretti, Nicola; Almesberger, Daria; Verlicchi, Angela; Stefini, Roberto; Ragonese, Mauro; Guarneri, Gianni Franco; Parodi, Pier Camillo

    2014-01-01

    Introduction: To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. Objectives: The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. Materials and Methods: The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT) scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI) was used to confirm dermal integrity. Results: Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were used to fill gaps

  12. Enhancing dermal and bone regeneration in calvarial defect surgery.

    PubMed

    Zanotti, Bruno; Zingaretti, Nicola; Almesberger, Daria; Verlicchi, Angela; Stefini, Roberto; Ragonese, Mauro; Guarneri, Gianni Franco; Parodi, Pier Camillo

    2014-01-01

    To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT) scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI) was used to confirm dermal integrity. Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were used to fill gaps between the implant and skull appeared to show more rapid

  13. Bone regeneration using the pouch-and-tunnel technique.

    PubMed

    Azzi, Robert; Etienne, Daniel; Takei, Henry; Carranza, Fermin

    2009-10-01

    Several surgical techniques, such as the papilla preservation flap, the modified papilla preservation flap, and the sulcular incision flap, have attempted to achieve clot stabilization and graft coverage in an attempt to regenerate lost tissue due to periodontal disease. This case report focuses on soft tissue root coverage and bone regeneration in a one-wall osseous defect using the pouch-and-tunnel surgical procedure. The pouch-and-tunnel surgical technique is a minimally invasive periodontal plastic surgical procedure that uses subepithelial connective tissue as a free graft in a pouch beneath the gingival margin, created by sulcular incisions around the involved teeth. The autogenous bone graft placed in this one-wall osseous defect through a sulcular incision after root planing is protected in a stable pouch-like recipient site with an abundant blood supply. The free connective tissue graft also prevents epithelial migration into the recipient site. The use of Emdogain may help with cementogenesis around the planed root surface. This technique warrants further evaluation of cases with similar defects using this surgical procedure. (Int J Periodontics Restorative Dent 2009;29:515-521.).

  14. Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.

    PubMed

    Li, Chen-Shuang; Yang, Pu; Ting, Kang; Aghaloo, Tara; Lee, Soonchul; Zhang, Yulong; Khalilinejad, Kambiz; Murphy, Maxwell C; Pan, Hsin Chuan; Zhang, Xinli; Wu, Benjamin; Zhou, Yan-Heng; Zhao, Zhihe; Zheng, Zhong; Soo, Chia

    2016-03-01

    Pluripotent or multipotent cell-based therapeutics are vital for skeletal reconstruction in non-healing critical-sized defects since the local endogenous progenitor cells are not often adequate to restore tissue continuity or function. However, currently available cell-based regenerative strategies are hindered by numerous obstacles including inadequate cell availability, painful and invasive cell-harvesting procedures, and tumorigenesis. Previously, we established a novel platform technology for inducing a quiescent stem cell-like stage using only a single extracellular proteoglycan, fibromodulin (FMOD), circumventing gene transduction. In this study, we further purified and significantly increased the reprogramming rate of the yield multipotent FMOD reprogrammed (FReP) cells. We also exposed the 'molecular blueprint' of FReP cell osteogenic differentiation by gene profiling. Radiographic analysis showed that implantation of FReP cells into a critical-sized SCID mouse calvarial defect, contributed to the robust osteogenic capability of FReP cells in a challenging clinically relevant traumatic scenario in vivo. The persistence, engraftment, and osteogenesis of transplanted FReP cells without tumorigenesis in vivo were confirmed by histological and immunohistochemical staining. Taken together, we have provided an extended potency, safety, and molecular profile of FReP cell-based bone regeneration. Therefore, FReP cells present a high potential for cellular and gene therapy products for bone regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Graphene oxide as a scaffold for bone regeneration.

    PubMed

    Holt, Brian D; Wright, Zoe M; Arnold, Anne M; Sydlik, Stefanie A

    2017-05-01

    Graphene oxide (GO), the oxidized form of graphene, holds great potential as a component of biomedical devices, deriving utility from its ability to support a broad range of chemical functionalities and its exceptional mechanical, electronic, and thermal properties. GO composites can be tuned chemically to be biomimetic, and mechanically to be stiff yet strong. These unique properties make GO-based materials promising candidates as a scaffold for bone regeneration. However, questions still exist as to the compatibility and long-term toxicity of nanocarbon materials. Unlike other nanocarbons, GO is meta-stable, water dispersible, and autodegrades in water on the timescale of months to humic acid-like materials, the degradation products of all organic matter. Thus, GO offers better prospects for biological compatibility over other nanocarbons. Recently, many publications have demonstrated enhanced osteogenic performance of GO-containing composites. Ongoing work toward surface modification or coating strategies could be useful to minimize the inflammatory response and improve compatibility of GO as a component of medical devices. Furthermore, biomimetic modifications could offer mechanical and chemical environments that encourage osteogenesis. So long as care is given to assure their safety, GO-based materials may be poised to become the next generation scaffold for bone regeneration. WIREs Nanomed Nanobiotechnol 2017, 9:e1437. doi: 10.1002/wnan.1437 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  16. A Novel Nanosilver/Nanosilica Hydrogel for Bone Regeneration in Infected Bone Defects.

    PubMed

    Zhang, Shiwen; Guo, Yuchen; Dong, Yuliang; Wu, Yunshu; Cheng, Lei; Wang, Yongyue; Xing, Malcolm; Yuan, Quan

    2016-06-01

    Treating bone defects in the presence of infection is a formidable clinical challenge. The use of a biomaterial with the dual function of bone regeneration and infection control is a novel therapeutic approach to this problem. In this study, we fabricated an innovative, dual-function biocomposite hydrogel containing nanosilver and nanosilica (nAg/nSiO2) particles and evaluated its characteristics using FT-IR, SEM, swelling ratio, and stiffness assays. The in vitro antibacterial analysis showed that this nAg/nSiO2 hydrogel inhibited both Gram-positive and Gram-negative bacteria. In addition, this nontoxic material could promote osteogenic differentiation of rat bone marrow stromal cells (BMSCs). We then created infected bone defects in rat calvaria in order to evaluate the function of the hydrogel in vivo. The hydrogel demonstrated effective antibacterial ability while promoting bone regeneration in these defects. Our results indicate that this nAg/nSiO2 hydrogel has the potential to both control infection and to promote bone healing in contaminated defects.

  17. Guided orthodontic regeneration: A tool to enhance conventional regenerative techniques in implant surgery.

    PubMed

    Kaitsas, Roberto; Paolone, Maria Giacinta; Paolone, Gaetano

    2015-12-01

    A hopeless upper central incisor was subjected to forced eruption before implant substitution to improve and develop the amount of soft tissue. This involved a GBR to insert the implant and a GTR to regenerate the tissue around the dehiscence of the nearby lateral using a "Guided Orthodontic Regeneration" (GOR) approach. The extrusion was performed esthetically in lingual orthodontics. The GOR technique included a Guided Orthodontic "Bone" Regeneration (GOBR) and a Guided Orthodontic "Soft Tissue" Regeneration (GOTR). This developed a 3D implant site while correcting the osseous defects and increasing the amount of soft tissue, which was used for a subsequent regenerative technique.

  18. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area

    PubMed Central

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID:27279797

  19. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area.

    PubMed

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications.

  20. Effects of fibrinogen concentration on fibrin glue and bone powder scaffolds in bone regeneration.

    PubMed

    Kim, Beom-Su; Sung, Hark-Mo; You, Hyung-Keun; Lee, Jun

    2014-10-01

    Fibrin polymers are widely used in the tissue engineering field as biomaterials. Although numerous researchers have studied the fabrication of scaffolds using fibrin glue (FG) and bone powder, the effects of varied fibrinogen content during the fabrication of scaffolds on human mesenchymal stem cells (hMSCs) and bone regeneration remain poorly understood. In this study, we formulated scaffolds using demineralized bone powder and various fibrinogen concentrations and analyzed the microstructure and mechanical properties. Cell proliferation, cell viability, and osteoblast differentiation assays were performed. The ability of the scaffold to enhance bone regeneration was evaluated using a rabbit calvarial defect model. Micro-computed tomography (micro-CT) showed that bone powders were uniformly distributed on the scaffolds, and scanning electron microscopy (SEM) showed that the fibrin networks and flattened fibrin layers connected adjacent bone powder particles. When an 80 mg/mL fibrinogen solution was used to formulate scaffolds, the porosity decreased 41.6 ± 3.6%, while the compressive strength increased 1.16 ± 0.02 Mpa, when compared with the values for the 10 mg/mL fibrinogen solution. Proliferation assays and SEM showed that the scaffolds prepared using higher fibrinogen concentrations supported and enhanced cell adhesion and proliferation. In addition, mRNA expression of alkaline phosphatase and osteocalcin in cells grown on the scaffolds increased with increasing fibrinogen concentration. Micro-CT and histological analysis revealed that newly formed bone was stimulated in the scaffold implantation group. Our results demonstrate that optimization of the fibrinogen content of fibrin glue/bone powder scaffolds will be beneficial for bone tissue engineering. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. [Effect of opiod peptides on free radical oxidation in a bone regenerate after fracture].

    PubMed

    Liashev, Iu D; Kniazev, A I; Solin, A V

    2005-01-01

    Opioid peptides (DSLET and DAGO) stimulating bone tissue regeneration were studied for effects on content of free radical products in regenerate tissue from the region of leg fracture in mice at various terms of reparative osteogenesis. These opioids reduce concentration of malonic dialdehyde and dienic conjugastes in bone for 10 days after fracture.

  2. Monolithic and assembled polymer-ceramic composites for bone regeneration.

    PubMed

    Nandakumar, Anandkumar; Cruz, Célia; Mentink, Anouk; Tahmasebi Birgani, Zeinab; Moroni, Lorenzo; van Blitterswijk, Clemens; Habibovic, Pamela

    2013-03-01

    The rationale for the use of polymer-ceramic composites for bone regeneration stems from the natural composition of bone, with collagen type I and biological apatite as the main organic and inorganic constituents, respectively. In the present study composite materials of PolyActive™ (PA), a poly(ethylene oxide terephthalate)/poly(butylene terephtalate) co-polymer, and hydroxyapatite (HA) at a weight ratio of 85:15 were prepared by rapid prototyping (RP) using two routes. In the first approach pre-extruded composite filaments of PA-HA were processed using three-dimensional fibre deposition (3DF) (conventional composite scaffolds). In the second approach PA scaffolds were fabricated using 3DF and combined with HA pillars produced inside stereolithographic moulds that fitted inside the pores of the PA three-dimensional structure (assembled composite scaffolds). Analysis of calcium and phosphate release in a simulated physiological solution, not containing calcium or phosphate, revealed significantly higher values for the HA pillars compared with other scaffolds. Release in simulated body fluid saturated with respect to HA did not show significant differences among the different scaffolds. Human mesenchymal stromal cells were cultured on polymer (3DF), conventional composite (3DF-HA) and assembled composite (HA assembled in 3DF) scaffolds and assessed for morphology, metabolic activity, DNA amount and gene expression of osteogenic markers using real time quantitative polymerase chain reaction (PCR). Scanning electron microscopy images showed that the cells attached to and infiltrated all the scaffolds. Assembled composites had a higher metabolic activity compared with 3DF-HA scaffolds while no significant differences were observed in DNA amounts. Gene expression of osteopontin in the assembled composite was significantly higher compared with the conventional composites. The strategy of composite fabrication by assembly appears to be a promising alternative to the

  3. Use of osteoplastic material to guide bone tissue regeneration deffect.

    PubMed

    Machavariani, A; Mazmishvili, K; Grdzelidze, T; Menabde, G; Amiranashvili, I

    2011-12-01

    The goal of research was study of restoration processes in jaw-teeth bone defects by application of osteoplastic materials in the experiment. The experiment was performed over 32 white (6-12 month old) rats; the animals were divided into 2 groups; 16 animals were enrolled in the first group; the section was performed in the edge of lower jaw; the lower jaw body was revealed. Under the effect of the dental drilling machine and the # 1 cooling mean by the fissure bohrium (distilled water) the defect of the dimension of 2x2 mm was created; the defect was washed by 0/9% saline to remove the bone sawdust; the wound was sutured tightly, in layers. The second group of the experiment was staffed with 16 animals (main group); the similar bone defect of the size 2 x 2mm was created on the rat's jaw's body. After washing of modeled defect we inserted osteopathic materials PORESORB-TCP crystals with the size of 0,6-1.0 mm the wound was sutured tightly, in layers. After the 3-rd, 15-th, 30-th and 90-th days from the date of operation there was performed X-ray and morphological examination over the animals in the control as well as the main group. The analysis of the examination performed over the experimental materials showed that in the control group in samples taken at 90th day the defects were not completely restored. In the test group in samples taken at 90th day reparative regeneration is confirmed. This is stimulated by the factor that within the main group's animals the defect regeneration process is supported with the osteoplastic material PORESORB-TCP.

  4. The efficacy of the use of IR laser phototherapy associated to biphasic ceramic graft and guided bone regeneration on surgical fractures treated with miniplates: a histological and histomorphometric study on rabbits.

    PubMed

    Pinheiro, Antonio L B; Aciole, Gilberth Tadeu Santos; Ramos, Thais Andrade; Gonzalez, Tayná Assunção; da Silva, Laís Nogueira; Soares, Luiz G Pinheiro; Aciole, Jouber Mateus Santos; dos Santos, Jean Nunes

    2014-01-01

    The aim of the present study was to assess, by light microscopy and histomorphometry, the repair of surgical fractures fixed with internal rigid fixation (IRF) treated or not with IR laser (λ780 nm, 50 mW, 4 × 4 J/cm(2) = 16 J/cm(2), ϕ = 0.5 cm(2), CW) associated or not to the use of hydroxyapatite and guided bone regeneration. Surgical tibial fractures were created under general anesthesia on 15 rabbits that were divided into 5 groups, maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet, and had water ad libidum. The fractures in groups II, III, IV, and V were fixed with miniplates. Animals in groups III and V were grafted with hydroxyapatite and GBR technique used. Animals in groups IV and V were irradiated at every other day during two weeks (4 × 4 J/cm(2), 16 J/cm(2) = 112 J/cm(2)). Observation time was that of 30 days. After animal death, specimens were taken, routinely processed to wax, cut and stained with HA and Sirius red, and used for histological assessment. The results of both analyses showed a better bone repair on all irradiated subjects especially when the biomaterial and GBR were used. In conclusion, the results of the present investigation are important clinically as they are suggestive that the association of hydroxyapatite, and laser light resulted in a positive and significant repair of complete tibial fractures treated with miniplates.

  5. Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2.

    PubMed

    Mediero, Aránzazu; Wilder, Tuere; Perez-Aso, Miguel; Cronstein, Bruce N

    2015-04-01

    Promoting bone regeneration and repair of bone defects is a need that has not been well met to date. We have previously found that adenosine, acting via A2A receptors (A2AR) promotes wound healing and inhibits inflammatory osteolysis and hypothesized that A2AR might be a novel target to promote bone regeneration. Therefore, we determined whether direct A2AR stimulation or increasing endogenous adenosine concentrations via purine transport blockade with dipyridamole regulates bone formation. We determined whether coverage of a 3 mm trephine defect in a mouse skull with a collagen scaffold soaked in saline, bone morphogenetic protein-2 (BMP-2; 200 ng), 1 μM CGS21680 (A2AR agonist, EC50 = 160 nM), or 1 μM dipyridamole (EC50 = 32 nM) promoted bone regeneration. Microcomputed tomography examination demonstrated that CGS21680 and dipyridamole markedly enhanced bone regeneration as well as BMP-2 8 wk after surgery (60 ± 2%, 79 ± 2%, and 75 ± 1% bone regeneration, respectively, vs. 32 ± 2% in control, P < 0.001). Blockade by a selective A2AR antagonist (ZM241385, 1 μM) or deletion of A2AR abrogated the effect of CGS21680 and dipyridamole on bone regeneration. Both CGS21680 and dipyridamole treatment increased alkaline phosphatase-positive osteoblasts and diminished tartrate resistance acid phosphatase-positive osteoclasts in the defects. In vivo imaging with a fluorescent dye for new bone formation revealed a strong fluorescent signal in treated animals that was equivalent to BMP-2. In conclusion, stimulation of A2AR by specific agonists or by increasing endogenous adenosine levels stimulates new bone formation as well as BMP-2 and represents a novel approach to stimulating bone regeneration. © FASEB.

  6. Induction of fully stabilized cortical bone defects to study intramembranous bone regeneration

    PubMed Central

    McGee-Lawrence, Meghan E.; Razidlo, David F.

    2015-01-01

    Summary Bone is a regenerative tissue with an innate ability to self-remodel in response to environmental stimuli and the need to repair damage. Rodent models of fracture healing, and in particular genetic mouse models, can be used to study the contributions of specific molecular switches to skeletal repair, as well as to recreate and exacerbate biological development and repair mechanisms in postnatal skeletons. Here, we describe methodology for producing fully stabilized, single-cortex defects in mouse femurs to study mechanisms of intramembranous bone regeneration. PMID:25331051

  7. Double-layered cell transfer technology for bone regeneration.

    PubMed

    Akazawa, Keiko; Iwasaki, Kengo; Nagata, Mizuki; Yokoyama, Naoki; Ayame, Hirohito; Yamaki, Kazumasa; Tanaka, Yuichi; Honda, Izumi; Morioka, Chikako; Kimura, Tsuyoshi; Komaki, Motohiro; Kishida, Akio; Izumi, Yuichi; Morita, Ikuo

    2016-09-14

    For cell-based medicine, to mimic in vivo cellular localization, various tissue engineering approaches have been studied to obtain a desirable arrangement of cells on scaffold materials. We have developed a novel method of cell manipulation called "cell transfer technology", enabling the transfer of cultured cells onto scaffold materials, and controlling cell topology. Here we show that using this technique, two different cell types can be transferred onto a scaffold surface as stable double layers or in patterned arrangements. Various combinations of adherent cells were transferred to a scaffold, amniotic membrane, in overlapping bilayers (double-layered cell transfer), and transferred cells showed stability upon deformations of the material including folding and trimming. Transplantation of mesenchymal stem cells from periodontal ligaments (PDLSC) and osteoblasts, using double-layered cell transfer significantly enhanced bone formation, when compared to single cell type transplantation. Our findings suggest that this double-layer cell transfer is useful to produce a cell transplantation material that can bear two cell layers. Moreover, the transplantation of an amniotic membrane with PDLSCs/osteoblasts by cell transfer technology has therapeutic potential for bone defects. We conclude that cell transfer technology provides a novel and unique cell transplantation method for bone regeneration.

  8. Double-layered cell transfer technology for bone regeneration

    PubMed Central

    Akazawa, Keiko; Iwasaki, Kengo; Nagata, Mizuki; Yokoyama, Naoki; Ayame, Hirohito; Yamaki, Kazumasa; Tanaka, Yuichi; Honda, Izumi; Morioka, Chikako; Kimura, Tsuyoshi; Komaki, Motohiro; Kishida, Akio; Izumi, Yuichi; Morita, Ikuo

    2016-01-01

    For cell-based medicine, to mimic in vivo cellular localization, various tissue engineering approaches have been studied to obtain a desirable arrangement of cells on scaffold materials. We have developed a novel method of cell manipulation called “cell transfer technology”, enabling the transfer of cultured cells onto scaffold materials, and controlling cell topology. Here we show that using this technique, two different cell types can be transferred onto a scaffold surface as stable double layers or in patterned arrangements. Various combinations of adherent cells were transferred to a scaffold, amniotic membrane, in overlapping bilayers (double-layered cell transfer), and transferred cells showed stability upon deformations of the material including folding and trimming. Transplantation of mesenchymal stem cells from periodontal ligaments (PDLSC) and osteoblasts, using double-layered cell transfer significantly enhanced bone formation, when compared to single cell type transplantation. Our findings suggest that this double-layer cell transfer is useful to produce a cell transplantation material that can bear two cell layers. Moreover, the transplantation of an amniotic membrane with PDLSCs/osteoblasts by cell transfer technology has therapeutic potential for bone defects. We conclude that cell transfer technology provides a novel and unique cell transplantation method for bone regeneration. PMID:27624174

  9. Synchrotron X-ray bioimaging of bone regeneration by artificial bone substitute of MegaGen Synthetic Bone and hyaluronate hydrogels.

    PubMed

    Yeom, Junseok; Chang, Soeun; Park, Jung Kyu; Je, Jung Ho; Yang, Dong Jun; Choi, Seok Kyu; Shin, Hong-In; Lee, Seung-Jae; Shim, Jin-Hyung; Cho, Dong-Woo; Hahn, Sei Kwang

    2010-10-01

    Synchrotron X-ray bioimaging was successfully carried out to observe bone regeneration by a novel artificial bone substitute of bioactive MegaGen Synthetic Bone (MGSB) and hyaluronate (HA) hydrogels. A biphasic calcium phosphate of MGSB was prepared by chemical precipitation method, with a porous spherical morphology. On the basis of the fact that HA plays important roles in bone regeneration and promotes the differentiation, vascularization, and migration of stem cells, HA-cystamine (CYS) hydrogels with cleavable disulfide linkages were prepared to supply HA continuously for effective bone regeneration by their controlled degradation in vivo. Among seven different samples using Bio-OSS®, MGSB, and/or several kinds of HA hydrogels, MGSB/HA-CYS hydrogels resulted in the most significant bone regeneration in the calvarial critical bone defect of New Zealand white rabbits. Histological and histomorphometric analyses revealed that the bone regeneration by MGSB/HA-CYS hydrogels was as high as 43%, occupying 71% of the bone defect area with MGSB in the form of a calvarial bone plate in 4 weeks. After that, MGSB was bioabsorbed and replaced gradually with regenerated bones as observed in 8 weeks. Synchrotron X-ray imaging clearly confirmed the effective bone regeneration by MGSB/HA-CYS hydrogels, showing three-dimensional micron-scale morphologies of regenerated bones interconnected with MGSB. In addition, sequential nondestructive synchrotron X-ray tomographic analysis results from anterior to posterior of the samples were well matched with the histomorphometric analysis results. The clinically feasible artificial bone substitutes of MGSB/HA-CYS hydrogels will be investigated further for various bone tissue engineering applications using the synchrotron X-ray bioimaging systems.

  10. Poly(glycerol sebacate) elastomer: a novel material for mechanically loaded bone regeneration.

    PubMed

    Zaky, Samer Helal; Lee, Kee-Won; Gao, Jin; Jensen, Adrianna; Close, John; Wang, Yadong; Almarza, Alejandro J; Sfeir, Charles

    2014-01-01

    The selection criteria for potential bone engineering scaffolds are based chiefly on their relative mechanical comparability to mature bone. In this study, we challenge this notion by obtaining full regeneration of a rabbit ulna critical size defect by employing the elastomeric polymer, poly(glycerol sebacate) (PGS). We tested the regeneration facilitated by PGS alone, PGS in combination with hydroxyapatite particles, or PGS seeded with bone marrow stromal cells. We investigated the quantity and quality of the regenerated bone histologically, by microcomputed tomography and by four-point bending flexural mechanical testing at 8 weeks postimplantation. We conclude that the relatively lower stiffness of this biocompatible elastomer allows a load-transducing milieu in which osteogenesis, matrix deposition, and eventual bone maturation can take place. This study's results suggest that PGS elastomer is an auspicious osteoconductive material for the regeneration of bony defects. These results call for an innovative reassessment of the current art of selection for novel bone scaffold materials.

  11. Bone regeneration strategy inspired by the study of calcification behavior in deer antler.

    PubMed

    Shi, Haishan; Yu, Tao; Li, Zhaoyang; Lu, William; Zhang, Ming; Ye, Jiandong

    2015-12-01

    Bone regeneration has attracted much attention from various researchers and inspired numerous strategies for bone formation. In this study, rapid calcification of deer antlers was studied to unravel bone biology by investigating mineral composition, morphology and microstructure. Calcification model was hypothesized and preliminarily established by in vitro experiments. In our model, mineral deposition and phase conversions in the gel matrix were mimicked. Results revealed that mineral metabolism including deposition and phase conversion plays key roles in calcification in vivo, which inspired the bone regeneration strategy with three main components, i.e. enhanced mineral nucleation, mineral ions sources and crystals habits. Rapid mineral metabolism of implant apatite biomaterials was supposed as the critical aspect of bone regeneration. This study will provide a relatively ideal model for peer bone regeneration studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities

    PubMed Central

    Xie, Hui; Wang, Zhenxing; Zhang, Liming; Lei, Qian; Zhao, Aiqi; Wang, Hongxiang; Li, Qiubai; Cao, Yilin; Jie Zhang, Wen; Chen, Zhichao

    2017-01-01

    Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering. PMID:28367979

  13. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities.

    PubMed

    Xie, Hui; Wang, Zhenxing; Zhang, Liming; Lei, Qian; Zhao, Aiqi; Wang, Hongxiang; Li, Qiubai; Cao, Yilin; Jie Zhang, Wen; Chen, Zhichao

    2017-04-03

    Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering.

  14. Synthetic Bone Substitute Engineered with Amniotic Epithelial Cells Enhances Bone Regeneration after Maxillary Sinus Augmentation

    PubMed Central

    Barboni, Barbara; Mangano, Carlo; Valbonetti, Luca; Marruchella, Giuseppe; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mauro, Annunziata; Bedini, Rossella; Turriani, Maura; Pecci, Raffaella; Nardinocchi, Delia; Zizzari, Vincenzo Luca; Tetè, Stefano; Piattelli, Adriano; Mattioli, Mauro

    2013-01-01

    Background Evidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined. Aim In the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC), loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT) technique, was evaluated in an animal study. Material And Methods Two blocks of synthetic bone substitute (∼0.14 cm3), alone or engineered with 1×106 ovine AEC (oAEC), were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.). Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT), morphological, morphometric and biochemical analyses. Results And Conclusions The obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation), data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their ability to switch

  15. Bioactive glasses: Importance of structure and properties in bone regeneration

    NASA Astrophysics Data System (ADS)

    Hench, Larry L.; Roki, Niksa; Fenn, Michael B.

    2014-09-01

    This review provides a brief background on the applications, mechanisms and genetics involved with use of bioactive glass to stimulate regeneration of bone. The emphasis is on the role of structural changes of the bioactive glasses, in particular Bioglass, which result in controlled release of osteostimulative ions. The review also summarizes the use of Raman spectroscopy, referred to hereto forward as bio-Raman spectroscopy, to obtain rapid, real time in vitro analysis of human cells in contact with bioactive glasses, and the osteostimulative dissolution ions that lead to osteogenesis. The bio-Raman studies support the results obtained from in vivo studies of bioactive glasses, as well as extensive cell and molecular biology studies, and thus offers an innovative means for rapid screening of new bioactive materials while reducing the need for animal testing.

  16. Bone regeneration in surgically created defects filled with autogenous bone: an epifluorescence microscopy analysis in rats

    PubMed Central

    GUSKUMA, Marcos Heidy; HOCHULI-VIEIRA, Eduardo; PEREIRA, Flávia Priscila; RANGEL-GARCIA JUNIOR, Idelmo; OKAMOTO, Roberta; OKAMOTO, Tetuo; MAGRO FILHO, Osvaldo

    2010-01-01

    Although the search for the ideal bone substitute has been the focus of a large number of studies, autogenous bone is still the gold standard for the filling of defects caused by pathologies and traumas, and mainly, for alveolar ridge reconstruction, allowing the titanium implants installation. Objectives The aim of this study was to evaluate the dynamics of autogenous bone graft incorporation process to surgically created defects in rat calvaria, using epifluorescence microscopy. Material and methods Five adult male rats weighing 200-300 g were used. The animals received two 5-mm-diameter bone defects bilaterally in each parietal bone with a trephine bur under general anesthesia. Two groups of defects were formed: a control group (n=5), in which the defects were filled with blood clot, and a graft group (n=5), in which the defects were filled with autogenous bone block, removed from the contralateral defect. The fluorochromes calcein and alizarin were applied at the 7th and 30th postoperative days, respectively. The animals were killed at 35 days. Results The mineralization process was more intense in the graft group (32.09%) and occurred mainly between 7 and 30 days, the period labeled by calcein (24.66%). Conclusions The fluorochromes showed to be appropriate to label mineralization areas. The interfacial areas between fluorochrome labels are important sources of information about the bone regeneration dynamics. PMID:20835568

  17. T cell regeneration after allogenic bone marrow transplantation

    PubMed Central

    Favrot, Marie; Janossy, G.; Tidman, N.; Blacklock, Hilary; Lopez, Elisa; Bofill, Margarita; Lampert, I.; Morgenstein, G.; Powles, R.; Prentice, H. G.; Hoffbrand, A. V.

    1983-01-01

    Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0·7±0·2 vs 1·5±0·3×109/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was <1. A sizeable subset of circulating T cells expressed the phenotype T8+,T10+,HNK-1+,DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+,T1-,T10-,HNK-1-,DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM. PMID:6352107

  18. Engineering Pre-vascularized Scaffolds for Bone Regeneration.

    PubMed

    Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

    2015-01-01

    Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.

  19. Cell-to-cell communication in guided bone regeneration: molecular and cellular mechanisms.

    PubMed

    Gruber, Reinhard; Stadlinger, Bernd; Terheyden, Hendrik

    2016-08-23

    This overview provides insights into the molecular and cellular mechanisms involved in guided bone regeneration, in particular focusing on aspects presented in the 3D movie, Cell-To-Cell Communication in Guided Bone Regeneration. The information presented here is based almost exclusively on genetic mouse models in which single genes can be deleted or overexpressed, even in a specific cell type. This information needs to be extrapolated to humans and related to aspects relevant to graft consolidation under the clinical parameters of guided bone regeneration. The overview follows the ground tenor of the Cell-To-Cell Communication series and focuses on aspects of cell-to-cell communication in bone regeneration and guided bone regeneration. Here, we discuss (1) the role of inflammation during bone regeneration, including (2) the importance of the fibrin matrix, and (3) the pleiotropic functions of macrophages. We highlight (4) the origin of bone-forming osteoblasts and bone-resorbing osteoclasts as well as (5) what causes a progenitor cell to mature into an effector cell. (6) We touch on the complex bone adaptation and maintenance after graft consolidation and (7) how osteocytes control this process. Finally, we speculate on (8) how barrier membranes and the augmentation material can modulate graft consolidation.

  20. Mathematical model for osteobstruction in bone regeneration mechanisms: a headway in skeletal tissue engineering.

    PubMed

    Ogunsalu, C; Arunaye, F I; Ezeokoli, C; Gardner, M; Rohrer, M; Prasad, H

    2012-11-01

    In this paper, we formulate a mathematical model for the evaluation of parameters responsible for the retardation and eventual acceleration of bone regeneration on the contralateral side of the mandible of experimental animals, following the discovery of a new mechanism of bone regeneration called the osteobstruction mechanism (a negative mechanism of bone regeneration as opposed to the well established and extensively documented positive mechanisms such as osteogenesis, osteoinduction and osteoconduction). This osteobstructive mechanism was demonstrated by episodes of overtaking and reovertaking on single photon emission computed tomography (SPECT) following evaluation of osteoblastic activities in a sequential animal experiment to validate both the Ogunsalu sandwich technique (a double guided tissue technique; D-GTR) and the interceed membrane technique (a single guided tissue regeneration technique; S-GTR) utilizing SPECT, histological and histomorphometric evaluation. This work is now given special attention in terms of mathematical analysis because of limited experimental observations since experiments cannot be observed infinitely. Mathematical modelling is as such essential to generalize the results of this osteobstructive mechanism in bone regeneration. We utilize the Fisher's equation to describe bone cell mobilization during bone regeneration by two different techniques: the Ogunsalu sandwich bone regeneration technique (D-GTR) and the S-GTR.

  1. Bovine bone matrix/poly(l-lactic-co-ε-caprolactone)/gelatin hybrid scaffold (SmartBone(®)) for maxillary sinus augmentation: A histologic study on bone regeneration.

    PubMed

    D'Alessandro, Delfo; Perale, Giuseppe; Milazzo, Mario; Moscato, Stefania; Stefanini, Cesare; Pertici, Gianni; Danti, Serena

    2016-10-18

    The ideal scaffold for bone regeneration is required to be highly porous, non-immunogenic, biostable until the new tissue formation, bioresorbable and osteoconductive. This study aimed at investigating the process of new bone formation in patients treated with granular SmartBone(®) for sinus augmentation, providing an extensive histologic analysis. Five biopsies were collected at 4-9 months post SmartBone(®) implantation and processed for histochemistry and immunohistochemistry. Histomorphometric analysis was performed. Bone-particle conductivity index (BPCi) was used to assess SmartBone(®) osteoconductivity. At 4 months, SmartBone(®) (12%) and new bone (43.9%) were both present and surrounded by vascularized connective tissue (37.2%). New bone was grown on SmartBone(®) (BPCi=0.22). At 6 months, SmartBone(®) was almost completely resorbed (0.5%) and new bone was massively present (80.8%). At 7 and 9 months, new bone accounted for a large volume fraction (79.3% and 67.4%, respectively) and SmartBone(®) was resorbed (0.5% and 0%, respectively). Well-oriented lamellae and bone scars, typical of mature bone, were observed. In all the biopsies, bone matrix biomolecules and active osteoblasts were visible. The absence of inflammatory cells confirmed SmartBone(®) biocompatibility and non-immunogenicity. These data indicate that SmartBone(®) is osteoconductive, promotes fast bone regeneration, leading to mature bone formation in about 7 months.

  2. Chitosan and alginate scaffolds for bone tissue regeneration.

    PubMed

    Olmez, S S; Korkusuz, P; Bilgili, H; Senel, S

    2007-06-01

    Polymeric scaffold for tissue regeneration was developed for veterinary applications. Oxytetracycline hydrochloride (OTC), which is a widely used antibiotic in veterinary medicine was chosen as the model compound. Gel formulations using chitosan and alginate were prepared in distilled water or in 1% (v/v) acetic acid solution. Sponges were also prepared by a freeze-drying process. Tripolyphosphate was used for cross-linking. Viscosity was decreased in the presence of OTC in chitosan gels whereas no difference was found with alginate gels. All gels showed pseudoplastic behaviour. Water absorption capacity was highest with chitosan/alginate sponges. The solvent used for preparation of the chitosan gels was found to affect the release of OTC. The release of OTC from the sponges was increased by cross-linking. Chitosan/alginate sponges showed the slowest and lowest drug release among the developed sponge formulations in this study. The formulations were found to be biocompatible, inducing no adverse reaction in vivo on surgically formed bone defects of radius of rabbits. The level of organization of the remodelled new bone in the treatment groups was better than that of control. Incorporation of OTC into formulations did not show any considerable enhancing effect.

  3. Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration.

    PubMed

    Hur, Woojune; Park, Min; Lee, Jae Yeon; Kim, Myung Hun; Lee, Seung Ho; Park, Chun Gwon; Kim, Se-Na; Min, Hye Sook; Min, Hye Jeong; Chai, Jin Ho; Lee, Sang Jeong; Kim, Sukwha; Choi, Tae Hyun; Choy, Young Bin

    2016-01-28

    We prepared a bone plate enabled with the local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at an average rate of 4.03μg/day for 63days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8mm cranial critical size defect in living rats and the newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at scheduled times over 8weeks. At week 8, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78±6.84%) than the groups implanted with the plates without drug (23.6±3.81%) (p<0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system with the combined functionality of bone fixation and its expedited repair. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    SciTech Connect

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    2013-12-16

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  5. Imaging regenerating bone tissue based on neural networks applied to micro-diffraction measurements

    NASA Astrophysics Data System (ADS)

    Campi, G.; Pezzotti, G.; Fratini, M.; Ricci, A.; Burghammer, M.; Cancedda, R.; Mastrogiacomo, M.; Bukreeva, I.; Cedola, A.

    2013-12-01

    We monitored bone regeneration in a tissue engineering approach. To visualize and understand the structural evolution, the samples have been measured by X-ray micro-diffraction. We find that bone tissue regeneration proceeds through a multi-step mechanism, each step providing a specific diffraction signal. The large amount of data have been classified according to their structure and associated to the process they came from combining Neural Networks algorithms with least square pattern analysis. In this way, we obtain spatial maps of the different components of the tissues visualizing the complex kinetic at the base of the bone regeneration.

  6. Silk-based anisotropical 3D biotextiles for bone regeneration.

    PubMed

    Ribeiro, Viviana P; Silva-Correia, Joana; Nascimento, Ana I; da Silva Morais, Alain; Marques, Alexandra P; Ribeiro, Ana S; Silva, Carla J; Bonifácio, Graça; Sousa, Rui A; Oliveira, Joaquim M; Oliveira, Ana L; Reis, Rui L

    2017-04-01

    Bone loss in the craniofacial complex can been treated using several conventional therapeutic strategies that face many obstacles and limitations. In this work, novel three-dimensional (3D) biotextile architectures were developed as a possible strategy for flat bone regeneration applications. As a fully automated processing route, this strategy as potential to be easily industrialized. Silk fibroin (SF) yarns were processed into weft-knitted fabrics spaced by a monofilament of polyethylene terephthalate (PET). A comparative study with a similar 3D structure made entirely of PET was established. Highly porous scaffolds with homogeneous pore distribution were observed using micro-computed tomography analysis. The wet state dynamic mechanical analysis revealed a storage modulus In the frequency range tested, the storage modulus values obtained for SF-PET scaffolds were higher than for the PET scaffolds. Human adipose-derived stem cells (hASCs) cultured on the SF-PET spacer structures showed the typical pattern for ALP activity under osteogenic culture conditions. Osteogenic differentiation of hASCs on SF-PET and PET constructs was also observed by extracellular matrix mineralization and expression of osteogenic-related markers (osteocalcin, osteopontin and collagen type I) after 28 days of osteogenic culture, in comparison to the control basal medium. The quantification of convergent macroscopic blood vessels toward the scaffolds by a chick chorioallantoic membrane assay, showed higher angiogenic response induced by the SF-PET textile scaffolds than PET structures and gelatin sponge controls. Subcutaneous implantation in CD-1 mice revealed tissue ingrowth's accompanied by blood vessels infiltration in both spacer constructs. The structural adaptability of textile structures combined to the structural similarities of the 3D knitted spacer fabrics to craniofacial bone tissue and achieved biological performance, make these scaffolds a possible solution for tissue

  7. Strontium-rich injectable hybrid system for bone regeneration.

    PubMed

    Neves, Nuno; Campos, Bruno B; Almeida, Isabel F; Costa, Paulo C; Cabral, Abel Trigo; Barbosa, Mário A; Ribeiro, Cristina C

    2016-02-01

    Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium(Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% (w/v) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35%w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N.Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation.

  8. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    PubMed

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  9. The role of vasculature in bone development, regeneration and proper systemic functioning.

    PubMed

    Filipowska, Joanna; Tomaszewski, Krzysztof A; Niedźwiedzki, Łukasz; Walocha, Jerzy A; Niedźwiedzki, Tadeusz

    2017-02-13

    Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

  10. Bone Regeneration in Rat Cranium Critical-Size Defects Induced by Cementum Protein 1 (CEMP1)

    PubMed Central

    Serrano, Janeth; Romo, Enrique; Bermúdez, Mercedes; Narayanan, A. Sampath; Zeichner-David, Margarita; Santos, Leticia; Arzate, Higinio

    2013-01-01

    Gene therapy approaches to bone and periodontal tissue engineering are being widely explored. While localized delivery of osteogenic factors like BMPs is attractive for promotion of bone regeneration; method of delivery, dosage and side effects could limit this approach. A novel protein, Cementum Protein 1 (CEMP1), has recently been shown to promote regeneration of periodontal tissues. In order to address the possibility that CEMP1 can be used to regenerate other types of bone, experiments were designed to test the effect of hrCEMP1 in the repair/regeneration of a rat calvaria critical-size defect. Histological and microcomputed tomography (µCT) analyses of the calvaria defect sites treated with CEMP1 showed that after 16 weeks, hrCEMP1 is able to induce 97% regeneration of the defect. Furthermore, the density and characteristics of the new mineralized tissues were normal for bone. This study demonstrates that hrCEMP1 stimulates bone formation and regeneration and has therapeutic potential for the treatment of bone defects and regeneration of mineralized tissues. PMID:24265720

  11. A novel in vivo platform for studying alveolar bone regeneration in rat

    PubMed Central

    Kim, Joong-Hyun; Moon, Ho-Jin; Kim, Tae-Hyun; Jo, Jong-Min; Yang, Sung Hee; Naskar, Deboki; Kundu, Subhas C; Chrzanowski, Wojciech

    2013-01-01

    Alveolar bone regeneration is a significant challenge in dental implantation. Novel biomaterials and tissue-engineered constructs are under extensive development and awaiting in vivo animal tests to find clinical endpoint. Here, we establish a novel in vivo model, modifying gingivoperiosteoplasty in rat for the alveolar bone regeneration. Rat premaxillary bone defects were filled with silk scaffold or remained empty during the implantation period (up to 6 weeks), and harvested samples were analyzed by micro-computed tomography and histopathology. Empty defects showed increased but limited new bone formation with increasing implantation period. In defects implanted with silk sponge, the bone formation was significantly greater than that of empty defect, indicating an effective role of silk scaffold in the defect model. The modified premaxillary defect model in rat is simple to perform, while mimicking the clinical conditions, finding usefulness for the development of biomaterials and tissue-engineered constructs targeting alveolar bone regeneration in dental implantation. PMID:24555013

  12. Bioactive behavior of silicon substituted calcium phosphate based bioceramics for bone regeneration.

    PubMed

    Khan, Ather Farooq; Saleem, Muhammad; Afzal, Adeel; Ali, Asghar; Khan, Afsar; Khan, Abdur Rahman

    2014-02-01

    Bone graft substitutes are widely used for bone regeneration and repair in defect sites resulting from aging, disease, trauma, or accident. With invariably increasing clinical demands, there is an urgent need to produce artificial materials, which are readily available and are capable of fast and guided skeletal repair. Calcium phosphate based bioactive ceramics are extensively utilized in bone regeneration and repair applications. Silicon is often utilized as a substituent or a dopant in these bioceramics, since it significantly enhances the ultimate properties of conventional biomaterials such as surface chemical structure, mechanical strength, bioactivity, biocompatibility, etc. This article presents an overview of the silicon substituted bioceramics, which have emerged as efficient bone replacement and bone regeneration materials. Thus, the role of silicon in enhancing the biological performance and bone forming capabilities of conventional calcium phosphate based bioceramics is identified and reviewed.

  13. Cranial bone regeneration after cranioplasty using cryopreserved autogenous bone by a programmed freezer with a magnetic field in rats.

    PubMed

    Kaku, Masato; Koseki, Hiroyuki; Kojima, Shunich; Sumi, Hiromi; Shikata, Hanaka; Kojima, Shotoku; Motokawa, Masahide; Fujita, Tadashi; Tanimoto, Kotaro; Tanne, Kazuo

    2014-01-01

    The purpose of this study was to develop a bone tissue bank using a programmed freezer with a magnetic field. Parietal bones were removed from rats and used for organ culture examination (non-cryopreserved, cryopreserved with a magnetic field (CAS) and cryopreserved without a magnetic field group). Next, other parietal bones were used for histological examination. The cryopreserved bones by a CAS freezer and dried bones were transplanted respectively. Control bones were replanted without cryopreservation. Animals were sacrificed at 4, 8, 12 and 24 weeks after surgery. After organ culture, the isolated osteoblasts from parietal bones which were cryopreserved by a CAS freezer can survive and proliferate as much as non-cryopreserved group. Histological examinations showed new bone formation in control and CAS group. These results suggest that bone tissue cryopreservation by CAS freezer can be successfully used for bone grafting which may be a novel option for regeneration medicine.

  14. Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs.

    PubMed

    McCusker, Catherine D; Diaz-Castillo, Carlos; Sosnik, Julian; Q Phan, Anne; Gardiner, David M

    2016-08-01

    The Mexican Axolotl is one of the few tetrapod species that is capable of regenerating complete skeletal elements in injured adult limbs. Whether the skeleton (bone and cartilage) plays a role in the patterning and contribution to the skeletal regenerate is currently unresolved. We tested the induction of pattern formation, the effect on cell proliferation, and contributions of skeletal tissues (cartilage, bone, and periosteum) to the regenerating axolotl limb. We found that bone tissue grafts from transgenic donors expressing GFP fail to induce pattern formation and do not contribute to the newly regenerated skeleton. Periosteum tissue grafts, on the other hand, have both of these activities. These observations reveal that skeletal tissue does not contribute to the regeneration of skeletal elements; rather, these structures are patterned by and derived from cells of non-skeletal connective tissue origin. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Adult stem cell mobilization enhances intramembranous bone regeneration: a pilot study.

    PubMed

    McNulty, Margaret A; Virdi, Amarjit S; Christopherson, Kent W; Sena, Kotaro; Frank, Robin R; Sumner, Dale R

    2012-09-01

    Stem cell mobilization, which is defined as the forced egress of stem cells from the bone marrow to the peripheral blood (PB) using chemokine receptor agonists, is an emerging concept for enhancing tissue regeneration. However, the effect of stem cell mobilization by a single injection of the C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 on intramembranous bone regeneration is unclear. We therefore asked: Does AMD3100 mobilize adult stem cells in C57BL/6 mice? Are stem cells mobilized to the PB after marrow ablation? And does AMD3100 enhance bone regeneration? Female C57BL/6 mice underwent femoral marrow ablation surgery alone (n = 25), systemic injection of AMD3100 alone (n = 15), or surgery plus AMD3100 (n = 57). We used colony-forming unit assays, flow cytometry, and micro-CT to investigate mobilization of mesenchymal stem cells, endothelial progenitor cells, and hematopoietic stem cells to the PB and bone regeneration. AMD3100 induced mobilization of stem cells to the PB, resulting in a 40-fold increase in mesenchymal stem cells. The marrow ablation injury mobilized all three cell types to the PB over time. Administration of AMD3100 led to a 60% increase in bone regeneration at Day 21. A single injection of a CXCR4 antagonist lead to stem cell mobilization and enhanced bone volume in the mouse marrow ablation model of intramembranous bone regeneration.

  16. The effect of the association of NIR laser therapy BMPs, and guided bone regeneration on tibial fractures treated with wire osteosynthesis: Raman spectroscopy study.

    PubMed

    Lopes, C B; Pacheco, M T T; Silveira, L; Duarte, J; Cangussú, M C T; Pinheiro, A L B

    2007-12-14

    Bone fractures are lesions of different etiology; may be associated or not to bone losses; and have different options for treatment, such as the use of biomaterials, guided bone regeneration, techniques considered effective on improving bone repair. Laser therapy has also been shown to improve bone healing on several models. The association of these three techniques has been well documented by our group using different models. This study aimed to assess, through Raman spectroscopy, the incorporation of calcium hydroxyapatite (CHA approximately 958 cm(-1)) on the repair of complete tibial fractures in rabbits treated with wire osteosynthesis (WO); treated or not with laser therapy; and associated or not with the use of BMPs and/or Guided Bone Regeneration. Complete tibial fractures were created in 12 animals that were divided into four groups: WO; WO+BMPs; WO+laser therapy; and WO+BMPs+laser therapy. Irradiation started immediately after surgery; was repeated at every other day during 2 weeks; and was carried out with lambda 790 nm laser light (4 J/cm(2) per point, 40 mW, phi approximately 0.5 cm(2), 16J per session). Animal death occurred after 30 days. Raman spectroscopy was performed at both the surface and the depth of the fracture site. Statistical analysis showed significant difference on the concentrations of CHA between surface and depth. The analysis in each of the areas showed at the depth of the fracture significant differences between all treatment groups (p<0.0001). Significant differences were also seen between WO+BMPs+laser therapy and WO (p<0.001) and WO+laser therapy (p<0.001). At the surface, significant difference was seen only between the treatment groups and the non-fractured subjects (p=0.0001). However, no significant difference was seen between the treatment groups (p=0.14). It is concluded that the use of NIR laser therapy associated to BMPs and GBR was effective in improving bone healing on the fractured bones as a result of the increasing

  17. Optimal scaffold design and effective progenitor cell identification for the regeneration of vascularized bone.

    PubMed

    Nukavarapu, Syam P; Amini, Ami R

    2011-01-01

    Bone tissue engineering offers perhaps the most attractive treatment option for bone repair/regeneration as it eliminates complications of other bone grafting options (i.e., availability and immunogenicity issues of autografts and allografts, respectively). However, scaffold-based bone tissue engineering is largely limited by inadequate vascaularization, and as a result, bone formation is often restricted to the construct's periphery. In this study, we offer a two-pronged approach to overcome periphery-limited bone and vascular formation. We have developed optimally designed, mechanically strong, biodegradable scaffolds with increased porosity and interconnectivity. We have also identified and isolated superior, clinically-relevant cell populations (peripheral blood-derived endothelial progenitor cells (EPCs), and bone marrow-derived mesenchymal stem cells (MSCs)). In combination, we have developed a synthetic graft system suitable for the regeneration of vascularized bone.

  18. Systemically transplanted human gingiva-derived mesenchymal stem cells contributing to bone tissue regeneration.

    PubMed

    Xu, Quan-Chen; Wang, Zhi-Guo; Ji, Qiu-Xia; Yu, Xin-Bo; Xu, Xiao-Yan; Yuan, Chang-Qing; Deng, Jing; Yang, Pi-Shan

    2014-01-01

    As novel postnatal stem cells, gingiva-derived mesenchymal stem cells (GMSCs) have been considered as an ideal candidate cell resource for tissue engineering and cell-based therapies. GMSCs implanted into sites of injury have been confirmed to promote the injury repair. However, no studies have demonstrated whether systemically transplanted GMSCs can home to the bone injuries and contribute to the new bone formation in vivo. In this study, we transplanted human GMSCs into C57BL/6J mice with defects in mandibular bone via the tail vein to explore the capacity of transplanted GMSCs to promote bone regeneration. Results showed that the transplanted GMSCs were detected in the bone defects and employed in new bone formation. And the newly formed bone area in mice with GMSCs transplantation was significantly higher than that in control mice. Our findings indicate that systemically transplanted GMSCs can not only home to the mandibular defect but also promote bone regeneration.

  19. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.

    PubMed

    García, José R; Clark, Amy Y; García, Andrés J

    2016-04-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple-helical, α2 β1 integrin-specific peptide GGYGGGP(GPP)5 GFOGER(GPP)5 GPC (GFOGER) or an αv β3 integrin-targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. © 2016 Wiley Periodicals, Inc.

  20. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects

    PubMed Central

    García, José R.; Clark, Amy Y.; García, Andrés J.

    2016-01-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded polyethylene glycol (PEG) hydrogels functionalized with either a triple-helical, α2β1 integrin-specific peptide (GFOGER) or an αvβ3 integrin-targeting peptide (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. PMID:26662727

  1. The application of nanomaterials in controlled drug delivery for bone regeneration.

    PubMed

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part.

  2. Presence of interleukin-4-producing cells for human bone regeneration after application of guided tissue regeneration membranes.

    PubMed

    Kabashima, H; Nagata, K

    2001-07-01

    To study the process of bone regeneration we examined three samples of periapical regenerative tissue obtained from two patients under a guided tissue regeneration treatment in endodontic surgery by the immunohistochemical and enzyme histochemical methods. The regenerative tissue consisted of a large number of fibroblast-like cells and a small number of mononuclear cells. Fibroblast-like cells stained positively for alkaline phosphatase and osteopontin, whereas mononuclear cells stained positively for CD4. Interleukin-4-producing cells could be detected in adjacent sections. However, interferon-y-producing cells could not be detected. These findings suggest that interleukin-4-producing cells may be one of the elements associated with success in the human bone regeneration process in vivo.

  3. Bioinspired Design of Polycaprolactone Composite Nanofibers as Artificial Bone Extracellular Matrix for Bone Regeneration Application.

    PubMed

    Gao, Xiang; Song, Jinlin; Zhang, Yancong; Xu, Xiao; Zhang, Siqi; Ji, Ping; Wei, Shicheng

    2016-10-07

    The design and development of functional biomimetic systems for programmed stem cell response is a field of topical interest. To mimic bone extracellular matrix, we present an innovative strategy for constructing drug-loaded composite nanofibrous scaffolds in this study, which could integrate multiple cues from calcium phosphate mineral, bioactive molecule, and highly ordered fiber topography for the control of stem cell fate. Briefly, inspired by mussel adhesion mechanism, a polydopamine (pDA)-templated nanohydroxyapatite (tHA) was synthesized and then surface-functionalized with bone morphogenetic protein-7-derived peptides via catechol chemistry. Afterward, the resulting peptide-loaded tHA (tHA/pep) particles were blended with polycaprolactone (PCL) solution to fabricate electrospun hybrid nanofibers with random and aligned orientation. Our research demonstrated that the bioactivity of grafted peptides was retained in composite nanofibers. Compared to controls, PCL-tHA/pep composite nanofibers showed improved cytocompatibility. Moreover, the incorporated tHA/pep particles in nanofibers could further facilitate osteogenic differentiation potential of human mesenchymal stem cells (hMSCs). More importantly, the aligned PCL-tHA/pep composite nanofibers showed more osteogenic activity than did randomly oriented counterparts, even under nonosteoinductive conditions, indicating excellent performance of biomimetic design in cell fate decision. After in vivo implantation, the PCL-tHA/pep composite nanofibers with highly ordered structure could significantly promote the regeneration of lamellar-like bones in a rat calvarial critical-sized defect. Accordingly, the presented strategy in our work could be applied for a wide range of potential applications in not only bone regeneration application but also pharmaceutical science.

  4. Locally delivered salicylic acid from a poly(anhydride-ester): impact on diabetic bone regeneration.

    PubMed

    Wada, Keisuke; Yu, Weiling; Elazizi, Mohamad; Barakat, Sandrine; Ouimet, Michelle A; Rosario-Meléndez, Roselin; Fiorellini, Joseph P; Graves, Dana T; Uhrich, Kathryn E

    2013-10-10

    Diabetes mellitus (DM) involves metabolic changes that can impair bone repair, including a prolonged inflammatory response. A salicylic acid-based poly(anhydride-ester) (SA-PAE) provides controlled and sustained release of salicylic acid (SA) that locally resolves inflammation. This study investigates the effect of polymer-controlled SA release on bone regeneration in diabetic rats where enhanced inflammation is expected. Fifty-six Sprague-Dawley rats were randomly assigned to two groups: diabetic group induced by streptozotocin (STZ) injection or normoglycemic controls injected with citrate buffer alone. Three weeks after hyperglycemia development or vehicle injection, 5mm critical sized defects were created at the rat mandibular angle and treated with SA-PAE/bone graft mixture or bone graft alone. Rats were euthanized 4 and 12weeks after surgery, then bone fill percentage in the defect region was assessed by micro-computed tomography (CT) and histomorphometry. It was observed that bone fill increased significantly at 4 and 12weeks in SA-PAE/bone graft-treated diabetic rats compared to diabetic rats receiving bone graft alone. Accelerated bone formation in normoglycemic rats caused by SA-PAE/bone graft treatment was observed at 4weeks but not at 12weeks. This study shows that treatment with SA-PAE enhances bone regeneration in diabetic rats and accelerates bone regeneration in normoglycemic animals.

  5. Locally Delivered Salicylic Acid from a Poly(anhydride-ester): Impact on Diabetic Bone Regeneration

    PubMed Central

    Wada, Keisuke; Yu, Weiling; Elazizi, Mohamad; Barakat, Sandrine; Ouimet, Michelle A.; Rosario-Meléndez, Roselin; Fiorellini, Joseph P.; Graves, Dana T.; Uhrich, Kathryn E.

    2013-01-01

    Diabetes mellitus (DM) involves metabolic changes that can impair bone repair, including a prolonged inflammatory response. A salicylic acid-based poly(anhydride-ester) (SA-PAE) provides controlled and sustained release of salicylic acid (SA) that locally resolves inflammation. This study investigates the effect of polymer-controlled SA release on bone regeneration in diabetic rats where enhanced inflammation is expected. Fifty-six Sprague-Dawley rats were randomly assigned to two groups: diabetic group induced by streptozotocin (STZ) injection or normoglycemic controls injected with citrate buffer alone. Three weeks after hyperglycemia development or vehicle injection, 5 mm critical sized defects were created at the rat mandibular angle and treated with SA-PAE/bone graft mixture or bone graft alone. Rats were euthanized 4 and 12 weeks after surgery, then bone fill percentage in the defect region was assessed by micro-computed tomography (CT) and histomorphometry. It was observed that bone fill increased significantly at 4 and 12 weeks in SA-PAE/bone graft-treated diabetic rats compared to diabetic rats receiving bone graft alone. Accelerated bone formation in normoglycemic rats caused by SA-PAE/bone graft treatment was observed at 4 weeks but not at 12 weeks. This study shows that treatment with SA-PAE enhances bone regeneration in diabetic rats and accelerates bone regeneration in normoglycemic animals. PMID:23827476

  6. Effects of parathyroid hormone on bone mass, bone strength, and bone regeneration in male rats with type 2 diabetes mellitus.

    PubMed

    Hamann, Christine; Picke, Ann-Kristin; Campbell, Graeme M; Balyura, Mariya; Rauner, Martina; Bernhardt, Ricardo; Huber, Gerd; Morlock, Michael M; Günther, Klaus-Peter; Bornstein, Stefan R; Glüer, Claus-C; Ludwig, Barbara; Hofbauer, Lorenz C

    2014-04-01

    Type 2 diabetes mellitus (T2DM) is associated with increased skeletal fragility and impaired fracture healing. Intermittent PTH therapy increases bone strength; however, its skeletal and metabolic effects in diabetes are unclear. We assessed whether PTH improves skeletal and metabolic function in rats with T2DM. Subcritical femoral defects were created in diabetic fa/fa and nondiabetic +/+ Zucker Diabetic Fatty (ZDF) rats and internally stabilized. Vehicle or 75 μg/kg/d PTH(1-84) was sc administered over 12 weeks. Skeletal effects were evaluated by μCT, biomechanical testing, histomorphometry, and biochemical markers, and defect regeneration was analyzed by μCT. Glucose homeostasis was assessed using glucose tolerance testing and pancreas histology. In diabetic rats, bone mass was significantly lower in the distal femur and vertebrae, respectively, and increased after PTH treatment by up to 23% in nondiabetic and up to 18% in diabetic rats (P < .0001). Diabetic rats showed 23% lower ultimate strength at the spine (P < .0005), which was increased by PTH by 36% in normal and by 16% in diabetic rats (P < .05). PTH increased the bone formation rate by 3-fold in normal and by 2-fold in diabetic rats and improved defect regeneration in normal and diabetic rats (P < .01). PTH did not affect serum levels of undercarboxylated osteocalcin, glucose tolerance, and islet morphology. PTH partially reversed the adverse skeletal effects of T2DM on bone mass, bone strength, and bone defect repair in rats but did not affect energy metabolism. The positive skeletal effects were generally more pronounced in normal compared with diabetic rats.

  7. Synthesis and enhanced bone regeneration of carbonate substituted octacalcium phosphate.

    PubMed

    Shen, Donghe; Horiuchi, Naohiro; Nozaki, Sosuke; Miyashin, Michiyo; Yamashita, Kimihiro; Nagai, Akiko

    2017-01-01

    Using a wet method, we have synthesized octacalcium phosphate carbonate, in which HPO42- in octacalcium phosphate is replaced with CO32-. The physical, crystal, and chemical properties of this new material were compared to octacalcium phosphate, Ca-deficient hydroxyapatite, and Ca-deficient carbonate apatite using X-ray diffraction, Fourier-transform infrared spectroscopy, inductively coupled plasma spectroscopy, and scanning electron microscopy. Surface roughness and morphology were also characterized, along with the ability to support proliferation and differentiation of MG63 cells, as measured by MTT and alkaline phosphatase assay. We found that octacalcium phosphate carbonate enhanced osteoblast proliferation more strongly than all other materials tested. Similarly, Ca-deficient carbonate apatite, a hydrolysate of octacalcium phosphate carbonate, stimulated osteoblast differentiation to a better extent than Ca-deficient hydroxyapatite, a carbonate-free hydrolysate of octacalcium phosphate. These results indicate that octacalcium phosphate carbonate has good biocompatibility and osteoconduction, and incorporation of carbonate into octacalcium phosphate and apatite enhances bone regeneration.

  8. Effective Bone Regeneration Using Thermosensitive Poly(N-Isopropylacrylamide) Grafted Gelatin as Injectable Carrier for Bone Mesenchymal Stem Cells.

    PubMed

    Ren, Zhiwei; Wang, Yang; Ma, Shiqing; Duan, Shun; Yang, Xiaoping; Gao, Ping; Zhang, Xu; Cai, Qing

    2015-09-02

    In this study, thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) was grafted onto gelatin via atom transfer radical polymerization (ATRP). The chemical structure of PNIPAAm-grafted gelatin (Gel-PNIPAAm) was confirmed by XPS, ATR-IR, and (1)H NMR characterizations. Gel-PNIPAAm aqueous solution exhibited sol-to-gel transformation at physiological temperature, and was studied as injectable hydrogel for bone defect regeneration in a cranial model. The hydrogel was biocompatible and demonstrated the ability to enhance bone regeneration in comparison with the untreated group (control). With the incorporation of rat bone mesenchymal stem cells (BMSCs) into the hydrogel, the bone regeneration rate was further significantly enhanced. As indicated by micro-CT, histological (H&E and Masson) and immunohistochemical (osteocalcin and osteopontin) staining, newly formed woven bone tissue was clearly detected at 12 weeks postimplantation in the hydrogel/BMSCs treated group, showing indistinguishable boundary with surrounding host bone tissues. The results suggested that the thermosensitive Gel-PNIPAAm hydrogel was an excellent injectable delivery vehicle of BMSCs for in vivo bone defect regeneration.

  9. A new recombinant human bone morphogenetic protein-2 carrier for bone regeneration.

    PubMed

    Yokota, S; Sonohara, S; Yoshida, M; Murai, M; Shimokawa, S; Fujimoto, R; Fukushima, S; Kokubo, S; Nozaki, K; Takahashi, K; Uchida, T; Yokohama, S; Sonobe, T

    2001-07-31

    A gelatin sponge was formed by foaming and heat treating a gelatin solution, followed by coating the solid with poly(D,L-lactic-co-glycolic acid) to reinforce the gelatin framework. This sponge was tested for its suitability as a biodegradable porous, recombinant human bone morphogenetic protein (rhBMP)-2 carrier. Incorporation of rhBMP-2 into the sponge was closely related to its bulk density of gelatin sponge. The calcium content in the sponges, as assessed by an ectopic bone formation assay in rats, increased with the increasing sponge bulk density. Histologic and peripheral quantitative computed tomography analysis of implants in this ectopic assay system revealed cell growth throughout the carrier in 4 weeks after implantation regardless gelatin bulk density. The carrier containing rhBMP-2 maintained its three-dimensional structure after implantation; the carrier resisted collapse caused by soft tissue pressure during rapid bone formation as assessed by soft X-ray photographs. These results indicate that this newly developed sponge has excellent carrier characteristics to introduce rhBMP-2 into areas needed for bone regeneration.

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

    PubMed

    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.

  11. Optimization of regenerated bone char for fluoride removal in drinking water: a case study in Tanzania.

    PubMed

    Kaseva, M E

    2006-03-01

    This paper presents findings of a study on optimization and application of the regenerated bone char media for the defluoridation of drinking water in Tanzania where more than 30% of all water sources have fluoride concentrations above the 1.50 mg/I which is recommended by the World Heath Organization (WHO). In this study, regeneration temperature, regeneration duration, contact time, regenerated bone char dosage and particle size were investigated. Results indicate that the highest fluoride removal and adsorption capacity were 70.64% and 0.75 mg-F/g-bc, respectively, for a sample with bone char material that was regenerated at 500 degrees C. In this study the optimum burning duration was found to be 120 min, which resulted in residual fluoride that varied from a maximum value of 17.43 mg/I for a 2 min contact time to a minimum value of 8.53 mg/I for a contact time of 180 min. This study further indicated that the smallest size of regenerated bone char media (0.5-1.0 mm diameter) had the highest defluoridation capacity, with residual fluoride which varied from 17.82 mg/I at 2 min contact time to 11.26 mg/I at 120 min contact time. In terms of dosage of the regenerated bone char media it was established that the optimum dosage was 25g of bone char media with a grain size of 0.50-1.0 mm. This had a fluoride removal capacity of 0.55 mg-F/g-BC. Column filter experiments indicated that regenerated bone media is capable of removing fluoride from dinking water to meet both WHO and Tanzania recommended values.

  12. Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration.

    PubMed

    McDermott, Anna M; Mason, Devon E; Lin, Angela S P; Guldberg, Robert E; Boerckel, Joel D

    2016-09-01

    A common design constraint in functional tissue engineering is that scaffolds intended for use in load-bearing sites possess similar mechanical properties to the replaced tissue. Here, we tested the hypothesis that in vivo loading would enhance bone morphogenetic protein-2 (BMP-2)-mediated bone regeneration in the presence of a load-bearing PLDL scaffold, whose pores and central core were filled with BMP-2-releasing alginate hydrogel. First, we evaluated the effects of in vivo mechanical loading on bone regeneration in the structural scaffolds. Second, we compared scaffold-mediated bone regeneration, independent of mechanical loading, with alginate hydrogel constructs, without the structural scaffold, that have been shown previously to facilitate in vivo mechanical stimulation of bone formation. Contrary to our hypothesis, mechanical loading had no effect on bone formation, distribution, or biomechanical properties in structural scaffolds. Independent of loading, the structural scaffolds reduced bone formation compared to non-structural alginate, particularly in regions in which the scaffold was concentrated, resulting in impaired functional regeneration. This is attributable to a combination of stress shielding by the scaffold and inhibition of cellular infiltration and tissue ingrowth. Collectively, these data question the necessity of scaffold similarity to mature tissue at the time of implantation and emphasize development of an environment conducive to cellular activation of matrix production and ultimate functional regeneration.

  13. Clinical, Morphological, and Molecular Evaluations of Bone Regeneration With an Additive Manufactured Osteosynthesis Plate.

    PubMed

    Thor, Andreas; Palmquist, Anders; Hirsch, Jan-Michaél; Rännar, Lars-Erik; Dérand, Per; Omar, Omar

    2016-10-01

    There is limited information on the biological status of bone regenerated with microvascular fibula flap combined with biomaterials. This paper describes the clinical, histological, ultrastructural, and molecular picture of bone regenerated with patient-customized plate, used for mandibular reconstruction in combination with microvascular osteomyocutaneous fibula flap. The plate was virtually planned and additively manufactured using electron beam melting. This plate was retrieved from the patient after 33 months. Microcomputed tomography, backscattered-scanning electron microscopy, histology, and quantitative-polymerase chain reaction were employed to evaluate the regenerated bone and the flap bone associated with the retrieved plate. At retrieval, the posterior two-thirds of the plate were in close adaptation with the underlying flap, whereas soft tissue was observed between the native mandible and the anterior one-third. The histological and structural analyses showed new bone regeneration, ingrowth, and osseointegration of the posterior two-thirds. The histological observations were supported by the gene expression analysis showing higher expression of bone formation and remodeling genes under the posterior two-thirds compared with the anterior one-third of the plate. The observation of osteocytes in the flap indicated its viability. The present data endorse the suitability of the customized, additively manufactured plate for the vascularized fibula mandibular reconstruction. Furthermore, the combination of the analytical techniques provides possibilities to deduce the structural and molecular characteristics of bone regenerated using this procedure.

  14. Calcium Sulfate and Platelet-Rich Plasma make a novel osteoinductive biomaterial for bone regeneration

    PubMed Central

    Intini, Giuseppe; Andreana, Sebastiano; Intini, Francesco E; Buhite, Robert J; Bobek, Libuse A

    2007-01-01

    Background With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. Methods First, we tested CS-Platelet in heterotopic (muscle) and orthotopic (bone) bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. Results The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS-Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. Conclusion This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost-effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments. PMID:17343737

  15. [The value of selected imaging techniques in evaluation of bone regeneration during limb lengthening].

    PubMed

    Synder, M; Hussein, A A; Niedzielski, K; Grzegorzewski, A

    2000-01-01

    The paper presents the value of different imaging techniques, including X-rays, ultrasonography, computed tomography and densitometry in the evaluation of bone regenerates during limb lengthening. Material consisted of 60 children, age ranging from 4 to 18 years who underwent surgery using the Ilizarov technique because of limb inequality. During of limb lengthening different imaging techniques were employed for monitoring regenerate growth and remodeling. The study showed that all the employed imaging techniques play an important role in monitoring bone regenerate remodeling at different stages of limb lengthening.

  16. Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs

    PubMed Central

    Boix, Damien; Gauthier, Olivier; Guicheux, Jérôme; Pilet, Paul; Weiss, Pierre; Grimandi, Gaël; Daculsi, Guy

    2004-01-01

    Background The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. Methods Third and fourth mandibular premolars were extracted from 3 Beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, immediate placements of titanium implants were performed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and a biphasic calcium phosphate ceramic. As a control, the right defects were left unfilled. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. Results No post surgical complication was observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (p<0.05) increase in term of thread numbers in contact with bone (TN), bone-to-implant contact (BIC) and peri-implant bone density (PBD), of about 8.6%, 11.0% and 14.7%, respectively. In addition, no significant difference was observed when TN, BIC and PBD in filled defects were compared to no-defect sites. Conclusion It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increase bone regeneration around immediate implants. PMID:15212348

  17. Drug loaded homogeneous electrospun PCL/gelatin hybrid nanofiber structures for anti-infective tissue regeneration membranes.

    PubMed

    Xue, Jiajia; He, Min; Liu, Hao; Niu, Yuzhao; Crawford, Aileen; Coates, Phil D; Chen, Dafu; Shi, Rui; Zhang, Liqun

    2014-11-01

    Infection is the major reason for guided tissue regeneration/guided bone regeneration (GTR/GBR) membrane failure in clinical application. In this work, we developed GTR/GBR membranes with localized drug delivery function to prevent infection by electrospinning of poly(ε-caprolactone) (PCL) and gelatin blended with metronidazole (MNA). Acetic acid (HAc) was introduced to improve the miscibility of PCL and gelatin to fabricate homogeneous hybrid nanofiber membranes. The effects of the addition of HAc and the MNA content (0, 1, 5, 10, 20, 30, and 40 wt.% of polymer) on the properties of the membranes were investigated. The membranes showed good mechanical properties, appropriate biodegradation rate and barrier function. The controlled and sustained release of MNA from the membranes significantly prevented the colonization of anaerobic bacteria. Cells could adhere to and proliferate on the membranes without cytotoxicity until the MNA content reached 30%. Subcutaneous implantation in rabbits for 8 months demonstrated that MNA-loaded membranes evoked a less severe inflammatory response depending on the dose of MNA than bare membranes. The biodegradation time of the membranes was appropriate for tissue regeneration. These results indicated the potential for using MNA-loaded PCL/gelatin electrospun membranes as anti-infective GTR/GBR membranes to optimize clinical application of GTR/GBR strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effects of demineralized bone matrix and a 'Ricinus communis' polymer on bone regeneration: a histological study in rabbit calvaria.

    PubMed

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

    2009-09-01

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

  19. Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones

    PubMed Central

    Ignjatović, Nenad; Ajduković, Zorica; Savić, Vojin; Najman, Stevo; Mihailović, Dragan; Vasiljević, Perica; Stojanović, Zoran; Uskoković, Vuk; Uskoković, Dragan

    2012-01-01

    Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of six months after the implantation of the material containing different amounts of cobalt, ranging from 5 – 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study. PMID:23090835

  20. Survival and regeneration of deep-freeze preserved autologous cranial bones after cranioplasty.

    PubMed

    Lu, Yi; Hui, Guozhen; Liu, Fengqiang; Wang, Zhengan; Tang, Yuming; Gao, Shuxing

    2012-04-01

    After decompressive craniectomy, a deep-freeze-preserved autologous cranial bone graft can be used for cranioplasty to avoid immunoreaction against an artificial patch material. Autologous cranial bone grafts not only have better physical properties, such as heat conduction, compared to artificial patch materials, but they also have the advantages of a lower medical cost and satisfactory physical flexibility. The discussion over (99)Tc(m)-MDP SPECT static cranial bone tomography in the diagnosis of survival and regeneration in deep-freeze preservation autologous cranial bones after cranioplasty is valuable. Objective. To investigate whether deep-freeze-preserved autologous cranial bone grafts could survive and regenerate after autologous reimplantation. The method of cranial bone preservation involved removing the cranial graft and sealing it in a double-layer sterile plastic bag under sterile surgical conditions. On the day of the cranioplasty operation, the cranial bone graft was disinfected by immersing it in 3% povidone-iodine for 30 minutes. At short-term (2 weeks), medium-term (3 months), and long-term (12 months) postoperative follow-up visits, (99)Tc(m)-MDP SPECT static cranial bone tomography was used to examine the reimplanted cranial bone. Results. There were no postoperative infections or seromas in all 16 cases. Two weeks following cranial bone graft reimplantation, the SPECT tomography showed some radioactivity uptake in the reimplanted cranial bone graft, which was lower than that in the cranial bone on the healthy side. At 3 months and 12 months after the operation, the radioactivity uptake in the reimplanted cranial bone graft was the same as that in the cranial bone on the healthy side. X-ray films showed blurred sutures in the reimplanted cranial bone graft at 12 months after surgery. Reimplanted deep-freeze-preserved autologous cranial bone can survive in the short term and regenerate in the medium and long terms.

  1. New nano-hydroxyapatite in bone defect regeneration: A histological study in rats.

    PubMed

    Kubasiewicz-Ross, Paweł; Hadzik, Jakub; Seeliger, Julia; Kozak, Karol; Jurczyszyn, Kamil; Gerber, Hanna; Dominiak, Marzena; Kunert-Keil, Christiane

    2017-09-01

    Many types of bone substitute materials are available on the market. Researchers are refining new bone substitutes to make them comparable to autologous grafting materials in treatment of bone defects. The purpose of the study was to evaluate the osseoconductive potential and bone defect regeneration in rat calvaria bone defects treated with new synthetic nano-hydroxyapatite. The study was performed on 30 rats divided into 5 equal groups. New preproduction of experimental nano-hydroxyapatite material by NanoSynHap (Poznań, Poland) was tested and compared with commercially available materials. Five mm critical size defects were created and filled with the following bone grafting materials: 1) Geistlich Bio-Oss(®); 2) nano-hydroxyapatite+β-TCP; 3) nano-hydroxyapatite; 4) nano-hydroxyapatite+collagen membrane. The last group served as controls without any augmentation. Bone samples from calvaria were harvested for histological and micro-ct evaluation after 8 weeks. New bone formation was observed in all groups. Histomorphometric analysis revealed an amount of regenerated bone between 34.2 and 44.4% in treated bone defects, whereas only 13.0% regenerated bone was found in controls. Interestingly, in group 3, no significant particles of the nano-HA material were found. In contrast, residual bone substitute material could be detected in all other test groups. Micro-CT study confirmed the results of the histological examinations. The new nano-hydroxyapatite provides comparable results to other grafts in the field of bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Noni leaf and black tea enhance bone regeneration in estrogen-deficient rats.

    PubMed

    Shalan, Nor Aijratul Asikin Mohd; Mustapha, Noordin M; Mohamed, Suhaila

    2017-01-01

    Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats. Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh). The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density. The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The roles of vascular endothelial growth factor in bone repair and regeneration.

    PubMed

    Hu, Kai; Olsen, Bjorn R

    2016-10-01

    Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors.

  4. Bone regeneration by octacalcium phosphate collagen composites in a dog alveolar cleft model.

    PubMed

    Matsui, K; Matsui, A; Handa, T; Kawai, T; Suzuki, O; Kamakura, S; Echigo, S

    2010-12-01

    Octacalcium phosphate (OCP) and porcine atelocollagen sponge composites (OCP/Col) markedly enhanced bone regeneration in a rat cranial defect model. To assess clinical application, the authors examined whether OCP/Col would enhance bone regeneration in an alveolar cleft model in an adult dog, which was assumed to reflect patients with alveolar cleft. Disks of OCP/Col or collagen were implanted into the defect and bone regeneration by OCP/Col or collagen was investigated 4 months after implantation. Macroscopically, the OCP/Col-treated alveolus was obviously augmented and occupied by radio-opacity, and the border between the original bone and the defect was indistinguishable. Histological analysis revealed it was filled and bridged with newly formed bone; a small quantity of the remaining implanted OCP was observed. X-ray diffraction patterns of the area of implanted OCP/Col indicated no difference from those of dog bone. In the collagen-treated alveolus, the hollowed alveolus was mainly filled with fibrous connective tissue, and a small amount of new bone was observed at the defect margin. These results suggest that bone was obviously repaired when OCP/Col was implanted into the alveolar cleft model in a dog, and OCP/Col would be a significant bone regenerative material to substitute for autogeneous bone. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  5. Cotton-wool-like bioactive glasses for bone regeneration.

    PubMed

    Poologasundarampillai, G; Wang, D; Li, S; Nakamura, J; Bradley, R; Lee, P D; Stevens, M M; McPhail, D S; Kasuga, T; Jones, J R

    2014-08-01

    Inorganic sol-gel solutions were electrospun to produce the first bioactive three-dimensional (3-D) scaffolds for bone tissue regeneration with a structure like cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for packing into complex defects. It also has large inter-fiber spaces to promote vascularization, penetration of cells and transport of nutrients throughout the scaffold. The 3-D fibrous structure was obtained by electrospinning, where the applied electric field and the instabilities exert tremendous force on the spinning jet, which is required to be viscoelastic to prevent jet break up. Previously, polymer binding agents were used with inorganic solutions to produce electrospun composite two-dimensional fibermats, requiring calcination to remove the polymer. This study presents novel reaction and processing conditions for producing a viscoelastic inorganic sol-gel solution that results in fibers by the entanglement of the intermolecularly overlapped nanosilica species in the solution, eliminating the need for a binder. Three-dimensional cotton-wool-like structures were only produced when solutions containing calcium nitrate were used, suggesting that the charge of the Ca(2+) ions had a significant effect. The resulting bioactive silica fibers had a narrow diameter range of 0.5-2μm and were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within the first 12h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells cultured on the fibers showed no adverse cytotoxic effect and they were observed to attach to and spread in the material.

  6. Bone regeneration after removal of a mandibular cyst and following prosthetic rehabilitation with implants. Case report.

    PubMed

    Di Dio, M; De Luca, M; Cammarata, L; Pierazzi, G

    2005-06-01

    This study shows the spontaneous bone regeneration after a Partch II surgical operation without using filling materials. The following functional and esthetic rehabilitation was made with overdenture on implants even in the recovery zone. A male patient, 59 years old, with a cystic lesion of 3.5 mm diameter in the mandibular bone was submitted to surgical enucleation of this neoformation. Postoperative radiological examinations, orthopantomography and TC DentaScan were performed to value the bone regeneration. Four implants of 10 mm diameter and 4.1 mm length were subsequently fixed in the mandibular bone and also in the regeneration area. Then, the rehabilitation of the patient with an overdenture on implants was possible. Radiographic controls after cystic enucleation showed a good recovery of the region occupied by the neoformation. The implants fixed proved to be solid and it was possible to carry out an overdenture on them. The cystectomy alone, performed with conservative technique, without subsequent filling of the remaining cavity with biointegrative materials, permitted bone regeneration also in a large remaining cavity. This regeneration was sufficient to guarantee the success of the subsequent overdenture on implants, and very good functional and esthetic results in a patient totally edentulous in the mandibular bone.

  7. Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

    PubMed

    Waki, Tomonori; Kan, Joseph Y K

    2016-01-01

    Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations.

  8. Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects.

    PubMed

    Ribeiro, F V; Suaid, F F; Ruiz, K G S; Rodrigues, T L; Carvalho, M D; Nociti, F H; Sallum, E A; Casati, M Z

    2012-01-01

    This study investigated the effect of bone marrow-derived cells associated with guided bone regeneration in the treatment of dehiscence bone defects around dental implants. Iliac-derived bone marrow cells were harvested from dogs and phenotypically characterized with regard to their osteogenic properties. After teeth extraction, three implant sites were drilled, dehiscences created and implants placed. Dehiscences were randomly assigned to: bone marrow-derived cells, bone marrow-derived cells+guided bone regeneration, and control (no treatment). After 3 months, implants with adjacent tissues were processed histologically, bone-to-implant contact, bone fill within the threads, new bone area in a zone lateral to the implant, new bone height, and new bone weight at the bottom of the defect were determined. Phenotypic characterization demonstrated that bone marrow-derived cells presented osteogenic potential. Statistically higher bone fill within the threads was observed in both bone marrow-derived cells+guided bone regeneration bone marrow-derived cell groups compared with the control group (P<0.05), with no difference between the groups treated with cells (P>0.05). For the other parameters (new bone area, bone-to-implant contact, new bone height and new bone weight), only the bone marrow-derived cells+guided bone regeneration group presented higher values compared with the non-treated control (P<0.05). Bone marrow-derived cells provided promising results for peri-implantar bone regeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads.

  9. Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1α Promote Bone Regeneration via Recruiting Endogenous Stem Cells.

    PubMed

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

    2016-10-07

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

  10. Hydroxyapatite-calcium sulfate-hyaluronic acid composite encapsulated with collagenase as bone substitute for alveolar bone regeneration.

    PubMed

    Subramaniam, Sadhasivam; Fang, Yen-Hsin; Sivasubramanian, Savitha; Lin, Feng-Huei; Lin, Chun-pin

    2016-01-01

    Periodontitis is a very severe inflammatory condition of the periodontium that progressively damages the soft tissue and destroys the alveolar bone that supports the teeth. The bone loss is naturally irreversible because of limited reparability of the teeth. Advancement in tissue engineering provides an effective regeneration of osseous defects with suitable dental implants or tissue-engineered constructs. This study reports a hydroxyapatite, calcium sulfate hemihydrate and hyaluronic acid laden collagenase (HAP/CS/HA-Col) as a bone substitute for the alveolar bone regeneration. The composite material was mechanically tested and the biocompatibility was evaluated by WST-1 assay. The in vivo bone formation was assessed in rat with alveolar bone defects and the bone augmentation by the HAP/CS/HA-Col composite was confirmed by micro-CT images and histological examination. The mechanical strength of 6.69 MPa with excellent biocompatibility was obtained for the HAP/CS/HA-Col composite. The collagenase release profile had facilitated the acceleration of bone remodeling process and it was confirmed by the findings of micro-CT and H&E staining. The bone defects implanted with HAP/CS/HA composite containing 2 mg/mL type I collagenase have shown improved new bone formation with matured bone morphology in comparison with the HAP/CS/HA composite that lacks the collagenase and the porous hydroxyapatite (p-HAP) granules. The said findings demonstrated that the collagenase inclusion in HAP/CS/HA composite is a feasible approach for the alveolar bone regeneration and the same design can also be applied to other defective tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Periodontal Bone Regeneration and the Er,Cr:YSGG Laser: A Case Report

    PubMed Central

    Perio, Douglas N. Dederich Cert

    2013-01-01

    Background: Traditional methods of regenerating bone in periodontal bone defects have been partially successful and have involved numerous protocols and materials. More recently, it has been proposed that Er,Cr:YSGG laser energy may also be beneficial in the treatment of periodontal pockets, particularly in the regeneration of bone lost due to periodontal disease. Case Description: The purpose of this paper is to present a case report of the Er,Cr:YSGG laser being used to conservatively treat a recalcitrant periodontal pocket in the presence of a periodontal bone defect and that resulted in successful resolution of the pocket and significant radiographic bone fill at the 1 year recall visit. Clinical Implications: This protocol using the Er,Cr:YSGG laser for the treatment of periodontal loss of attachment and periodontal bone loss may represent a less invasive alternative than traditional open-flap periodontal surgery or the intrasulcular use of other more penetrating laser wavelengths. PMID:23524914

  12. Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cells in scaffold

    PubMed Central

    Im, Jin-Young; Min, Woo-Kie; You, Changkook; Kim, Hyun-Ok; Jin, Hee-Kyung

    2013-01-01

    Combination of tissue engineering and cell therapy represents a promising approach for bone regeneration. Human mesenchymal stem cells (hMSCs) have properties that include low immunogenicity, high proliferation rate, and multi-differentiation potential; therefore, they are an attractive seeding source for tissue engineering therapy. Here we found that hMSCs with a scaffold did not affect cell viability and osteogenic differentiation. We also investigated regenerative effect of hMSCs with the scaffold in a calvarial bone defect model. Formation of new bone was evaluated by micro-CT, histology and expression of osteogenic markers. The results clearly showed interesting evidence indicating that hMSCs with scaffold increased the formation of new bone and expression of osteogenic markers, compared to the empty and scaffold only groups. Overall, our results suggest that hMSCs with scaffold are suitable for stimulation of intense bone regeneration in critical-sized bone defects. PMID:24396384

  13. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis

    PubMed Central

    Qin, Yunhao; Sun, Ruixin; Wu, Chuanlong; Wang, Lian; Zhang, Changqing

    2016-01-01

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current “gold standard” treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration. PMID:27213355

  14. Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis.

    PubMed

    Qin, Yunhao; Sun, Ruixin; Wu, Chuanlong; Wang, Lian; Zhang, Changqing

    2016-05-19

    The clinical need for effective bone regeneration therapy remains in huge demands. However, the current "gold standard" treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration.

  15. Delayed bone regeneration is linked to chronic inflammation in murine muscular dystrophy.

    PubMed

    Abou-Khalil, Rana; Yang, Frank; Mortreux, Marie; Lieu, Shirley; Yu, Yan-Yiu; Wurmser, Maud; Pereira, Catia; Relaix, Frédéric; Miclau, Theodore; Marcucio, Ralph S; Colnot, Céline

    2014-02-01

    Duchenne muscular dystrophy (DMD) patients exhibit skeletal muscle weakness with continuous cycles of muscle fiber degeneration/regeneration, chronic inflammation, low bone mineral density, and increased risks of fracture. Fragility fractures and associated complications are considered as a consequence of the osteoporotic condition in these patients. Here, we aimed to establish the relationship between muscular dystrophy and fracture healing by assessing bone regeneration in mdx mice, a model of DMD with absence of osteoporosis. Our results illustrate that muscle defects in mdx mice impact the process of bone regeneration at various levels. In mdx fracture calluses, both cartilage and bone deposition were delayed followed by a delay in cartilage and bone remodeling. Vascularization of mdx fracture calluses was also decreased during the early stages of repair. Dystrophic muscles are known to contain elevated numbers of macrophages contributing to muscle degeneration. Accordingly, we observed increased macrophage recruitment in the mdx fracture calluses and abnormal macrophage accumulation throughout the process of bone regeneration. These changes in the inflammatory environment subsequently had an impact on the recruitment of osteoclasts and the remodeling phase of repair. Further damage to the mdx muscles, using a novel model of muscle trauma, amplified both the chronic inflammatory response and the delay in bone regeneration. In addition, PLX3397 treatment of mdx mice, a cFMS (colony stimulating factor receptor 1) inhibitor in monocytes, partially rescued the bone repair defect through increasing cartilage deposition and decreasing the number of macrophages. In conclusion, chronic inflammation in mdx mice contributes to the fracture healing delay and is associated with a decrease in angiogenesis and a transient delay in osteoclast recruitment. By revealing the role of dystrophic muscle in regulating the inflammatory response during bone repair, our results

  16. Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

    PubMed

    Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

    2015-07-01

    The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation.

  17. Hard tissue regeneration using bone substitutes: an update on innovations in materials

    PubMed Central

    Sarkar, Swapan Kumar

    2015-01-01

    Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues. PMID:25995658

  18. The importance of densitometric testing in the evaluation of regenerated bone during long bone lengthening by the Ilizarov method.

    PubMed

    Hussein, Abdulwahab; Faflik, Jakub; Bik, Krzysztof

    2002-06-30

    Background. Lengthening a long bone by cutting it surgically and then stretching it a process laden with numerous complications. Among the greatest threats is surely the insufficient support strength of the lengthening limb due to inadequate calcification of the newly generated bone tissue. This leads to fractures, distortion of the axis, or lack of osseous consolidation around the newly formed bone. In order to reduce the number of such complications constant diligent monitoring of the entire process is necessary, from the moment treatment is commenced until the distraction apparatus is removed. The purpose of the present study was to evaluate the usefulness of densitometric testing at various stages in the process of lengthening long bones.
    Material and method. The testing involved 17 children, in 20 limbs were lengthened by the Ilizarov method. The average shortening was 4,70 cm (range 3,5-13 cm). the article compares the results of density assessments of regenerated bone using ultrasonographic testing and densitometry.
    Conclusions. Densinometric testing constitutes an important supplement to the evaluation of regenerated bone. This is an easy test to perform and repeat, enabling the physician to evaluate the degree of mineralization of the regenerated bone, reach conclusions regarding its consolidation and mechanical strength, and make a decision regarding the removal of the external stabilizer.

  19. Administration of tauroursodeoxycholic acid enhances osteogenic differentiation of bone marrow-derived mesenchymal stem cells and bone regeneration.

    PubMed

    Cha, Byung-Hyun; Jung, Moon-Joo; Moon, Bo-Kyung; Kim, Jin-Su; Ma, Yoonji; Arai, Yoshie; Noh, Myungkyung; Shin, Jung-Youn; Kim, Byung-Soo; Lee, Soo-Hong

    2016-02-01

    It is known that osteogenic differentiation of mesenchymal stem cells (MSCs) can be promoted by suppression of adipogenesis of MSCs. We have recently found that the chemical chaperone tauroursodeoxycholic acid (TUDCA) significantly reduces adipogenesis of MSCs. In the present study, we examined whether TUDCA can promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) by regulating Integrin 5 (ITGA5) associated with activation of ERK1/2 signal pathway and thereby enhance bone tissue regeneration by reducing apoptosis and the inflammatory response. TUDCA treatment promoted in vitro osteogenic differentiation of BMMSCs and in vivo bone tissue regeneration in a calvarial defect model, as confirmed by micro-computed tomography, histological staining, and immunohistochemistry for osteocalcin. In addition, TUDCA treatment significantly decreased apoptosis and the inflammatory response in vivo and in vitro, which is important to enhance bone tissue regeneration. These results indicate that TUDCA plays a critical role in enhancing osteogenesis of BMMSCs, and is therefore a potential alternative drug for bone tissue regeneration.

  20. [Experimental study of poly-DL-lactic acid membrane guided bone regeneration in rabbit radii bone defects].

    PubMed

    Duan, Hong; Fan, Yubo; Dou, Jun; Pei, Fuxing

    2004-10-01

    This study was conducted to observe bone regeneration guided by poly-DL-latic acid (PDLLA) membrane in rabbit radii bone defects and to explore the mechanism of the membrane guided bone regeneration (MGBR). The animal models of bony and periosteous defects were established in both radii of 40 adult New Zealand white rabbits. The left defect as the experimental side was bridged with PDLLA membrane tube, the right side as the controlled side was untreated. The specimens were collected at 2, 4, 8 and 12 weeks postoperatively. General observation, X-ray, histological observation and biomechanical examination were applied to the repair of the models of MGBR in both groups. Two weeks after operation, with much new bony callus formed outside the tube at both fragments, the membrane tube covered with connective tissues was filled with haematoma and fibrous callus. Twelve weeks after operation, the PDLLA membrane became white and its tube shape was still maintained. However, new bone callus outside the tube almost completely disappeared, and inside the tubes all radii bone defects were successfully repaired with bony union. On the controlled sides, bone defects were filled with connective tissues 2 weeks postoperatively. And 12 weeks after operation, the typical nonunion that had been formed after bone marrow canals were sealed with cortical bone. On the experimental side, the strength of the newly formed bone at the 12th week was higher than that at the 8th week (P<0.05), whereas the biomechanical examination could not be done on the controlled side. Therefore, these findings suggested that the bone regeneration could be successfully guided by PDLLA membrane, and this MGBR technique might be generally used in the treatment of bone defects and nonunion.

  1. Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration.

    PubMed

    Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio

    2016-03-01

    The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

  2. Physiological bases of bone regeneration II. The remodeling process.

    PubMed

    Fernández-Tresguerres-Hernández-Gil, Isabel; Alobera-Gracia, Miguel Angel; del-Canto-Pingarrón, Mariano; Blanco-Jerez, Luis

    2006-03-01

    Bone remodeling is the restructuring process of existing bone, which is in constant resorption and formation. Under normal conditions, this balanced process allows the renewal of 5-10% of bone volume per year. At the microscopic level, bone remodeling is produced in basic multicellular units, where osteoclasts resorb a certain quantity of bone and osteoblasts form the osteoid matrix and mineralize it to fill the previously created cavity. These units contain osteoclasts, macrophages, preosteoblasts and osteoblasts, and are controlled by a series of factors, both general and local, allowing normal bone function and maintaining the bone mass. When this process becomes unbalanced then bone pathology appears, either in excess (osteopetrosis) or deficit (osteoporosis). The purpose of this study is to undertake a revision of current knowledge on the physiological and biological mechanisms of the bone remodeling process; highlighting the role played by the regulating factors, in particular that of the growth factors.

  3. Alveolar bone regeneration using poly-(lactic acid-co-glycolic acid-co-ε-caprolactone) porous membrane with collagen sponge containing basic fibroblast growth factor: an experimental study in the dog.

    PubMed

    Matsumoto, Goichi; Hoshino, Jyunichi; Kinoshita, Yasuhiko; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Ikada, Yoshito; Kinoshita, Yukihiko

    2012-11-01

    The aim of this study was to evaluate the effects of combining porous poly-lactic acid-co-glycolic acid-co-ε-caprolactone (PLGC) as a barrier membrane and collagen sponge containing basic fibroblast growth factor (bFGF) to promote bone regeneration in the canine mandible. In six beagle dogs, two lateral bone defects per side were created in the mandible. The lateral bone defects on the left side were treated with a PLGC membrane plus a collagen sponge containing bFGF. In half of these, the collagen sponge contained 50 µg of bFGF. In the other half, it contained 250 µg of bFGF. As a control, we treated the right-side bone defects in each animal with the same PLGC membrane but with a collagen sponge containing phosphate buffered saline. Computed tomography (CT) images were recorded at 3 and 6 months post-op to evaluate regeneration of the bone defects. After a healing period of 6 months, whole mandibles were removed for micro-CT and histological analyses. The post-op CT images showed that more bone had formed at all experimental sites than at control sites. At 3 months post-op, the volume of bone at defect sites covered with PLGC membrane plus 250 µg of bFGF was significantly greater than it was at defect sites covered with PLGC membrane plus 50 µg of bFGF. At 6 months post-op, however, this difference was smaller and not statistically significant. Micro-CT measurement showed that the volume of new bone regenerated at bone-defect sites, covered with PLGC membrane plus bFGF, was significantly greater than that of control sites. However, the presence or absence of bFGF in the collagen sponge did not significantly affect the bone density of new bone. These results suggest that the macroporous bioresorbable PLGC membrane plus collagen sponge containing bFGF effectively facilitates healing in GBR procedures.

  4. Biodegradable composite scaffolds of bioactive glass/chitosan/carboxymethyl cellulose for hemostatic and bone regeneration.

    PubMed

    Chen, Chen; Li, Hong; Pan, Jianfeng; Yan, Zuoqin; Yao, Zhenjun; Fan, Wenshuai; Guo, Changan

    2015-02-01

    Hemostasis in orthopedic osteotomy or bone cutting requires different methods and materials. The bleeding of bone marrow can be mostly stopped by bone wax. However, the wax cannot be absorbed, which leads to artificial prosthesis loosening, foreign matter reaction, and infection. Here, a bioactive glass/chitosan/carboxymethyl cellulose (BG/CS/CMC) composite scaffold was designed to replace traditional wax. WST-1 assay indicated the BG/CS/CMC composite resulted in excellent biocompatibility with no cytotoxicity. In vivo osteogenesis assessment revealed that the BG/CS/CMC composite played a dominant role in bone regeneration and hemostasis. The BG/CS/CMC composite had the same hemostasis effect as bone wax; in addition its biodegradation also led to the functional reconstruction of bone defects. Thus, BG/CS/CMC scaffolds can serve as a potential material for bone repair and hemostasis in critical-sized bone defects.

  5. Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

    NASA Astrophysics Data System (ADS)

    Gheith, Mostafa E.; Khairy, Maggie A.

    2014-02-01

    Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

  6. Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating the Distal Phalanx

    PubMed Central

    Sheehy, Eamon J.; Mesallati, Tariq; Kelly, Lara; Vinardell, Tatiana; Buckley, Conor T.; Kelly, Daniel J.

    2015-01-01

    Abstract Novel strategies are urgently required to facilitate regeneration of entire bones lost due to trauma or disease. In this study, we present a novel framework for the regeneration of whole bones by tissue engineering anatomically shaped hypertrophic cartilaginous grafts in vitro that subsequently drive endochondral bone formation in vivo. To realize this, we first fabricated molds from digitized images to generate mesenchymal stem cell-laden alginate hydrogels in the shape of different bones (the temporomandibular joint [TMJ] condyle and the distal phalanx). These constructs could be stimulated in vitro to generate anatomically shaped hypertrophic cartilaginous tissues that had begun to calcify around their periphery. Constructs were then formed into the shape of the distal phalanx to create the hypertrophic precursor of the osseous component of an engineered long bone. A layer of cartilage engineered through self-assembly of chondrocytes served as the articular surface of these constructs. Following chondrogenic priming and subcutaneous implantation, the hypertrophic phase of the engineered phalanx underwent endochondral ossification, leading to the generation of a vascularized bone integrated with a covering layer of stable articular cartilage. Furthermore, spatial bone deposition within the construct could be modulated by altering the architecture of the osseous component before implantation. These findings open up new horizons to whole limb regeneration by recapitulating key aspects of normal bone development. PMID:26309799

  7. Calcitonin in bone-guided regeneration of mandibles in ovariectomized rats: densitometric, histologic and histomorphometric analysis.

    PubMed

    Arisawa, E A L; Brandão, A A H; Almeida, J D; da Rocha, R F

    2008-01-01

    The aim of the present study was to investigate bone promotion in surgical defects created in the mandible of normal and ovariectomized female rats using calcitonin associated with a polytetrafluoroethylene barrier. The 100 female rats were divided into four groups: control (C), control treated with calcitonin (CM), ovariectomized control (OV) and ovariectomized treated with calcitonin (OVM). A circumscribed bone defect 4mm in diameter was created in the region of the mandibular angle, and covered with the barrier. Groups CM and OVM received 2 IU/kg of synthetic salmon calcitonin intramuscularly three times a week. The animals were killed 3, 7, 14, 21 and 28 days after surgery. The bone defects were submitted to densitometric, histologic and histomorphometric analysis. Groups C and CM showed higher levels of bone formation after 7 days compared to the OV and OVM groups. A significant difference was observed between groups C and OV at 3-14 days. The OV group presented slower bone regeneration of the surgical bone defect created in the mandibular angle than group C. Synthetic salmon calcitonin accelerated regeneration of the bone defect in the mandibles of OVM animals similarly to group C, and also increased the formation of new bone during the regeneration process in CM.

  8. Bone regeneration assessment by optical coherence tomography and MicroCT synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Negrutiu, Meda L.; Sinescu, Cosmin; Canjau, Silvana; Manescu, Adrian; Topalá, Florin I.; Hoinoiu, Bogdan; Romînu, Mihai; Márcáuteanu, Corina; Duma, Virgil; Bradu, Adrian; Podoleanu, Adrian G.

    2013-06-01

    Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of orthopaedic and maxillofacial procedures, with autologous bone being considered as the "gold standard" bone-grafting material, as it combines all properties required in a bone-graft material: osteoinduction (bone morphogenetic proteins - BMPs - and other growth factors), osteogenesis (osteoprogenitor cells) and osteoconduction (scaffold). The problematic elements of bone regenerative materials are represented by their quality control methods, the adjustment of the initial bone regenerative material, the monitoring (noninvasive, if possible) during their osteoconduction and osteointegration period and biomedical evaluation of the new regenerated bone. One of the research directions was the interface investigation of the regenerative bone materials and their behavior at different time periods on the normal femoral rat bone. 12 rat femurs were used for this investigation. In each ones a 1 mm diameter hole were drilled and a bone grafting material was inserted in the artificial defect. The femurs were removed after one, three and six months. The defects repaired by bone grafting material were evaluated by optical coherence tomography working in Time Domain Mode at 1300 nm. Three dimensional reconstructions of the interfaces were generated. The validations of the results were evaluated by microCT. Synchrotron Radiation allows achieving high spatial resolution images to be generated with high signal-to-noise ratio. In addition, Synchrotron Radiation allows acquisition of volumes at different energies and volume subtraction to enhance contrast. Evaluation of the bone grafting material/bone interface with noninvasive methods such as optical coherence tomography could act as a valuable procedure that can be use in the future in the usual clinical techniques. The results were confirmed by microCT. Optical coherence tomography can be performed in vivo and can provide a

  9. The efficacy of the use of IR laser phototherapy associated to biphasic ceramic graft and guided bone regeneration on surgical fractures treated with miniplates: a Raman spectral study on rabbits.

    PubMed

    Pinheiro, Antonio L B; Santos, Nicole Ribeiro Silva; Oliveira, Priscila Chagas; Aciole, Gilberth Tadeu Santos; Ramos, Thais Andrade; Gonzalez, Tayná Assunção; da Silva, Laís Nogueira; Barbosa, Artur Felipe Santos; Silveira, Landulfo

    2013-02-01

    The aim of the present study was to assess, by Raman spectroscopy, the repair of surgical fractures fixed with internal rigid fixation (IRF) treated or not with IR laser (λ780 nm, 50 mW, 4 × 4 J/cm(2) = 16 J/cm(2), ϕ = 0.5 cm(2), CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical tibial fractures were created under general anesthesia on 15 rabbits that were divided into five groups, maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libitum. The fractures in groups II, III, IV and V were fixed with miniplates. Animals in groups III and V were grafted with hydroxyapatite and GBR technique used. Animals in groups IV and V were irradiated at every other day during 2 weeks (4 × 4 J/cm(2), 16 J/cm(2) = 112 J/cm(2)). Observation time was that of 30 days. After animal death, specimens were taken and kept in liquid nitrogen and used for Raman spectroscopy. Raman spectroscopy showed significant differences between groups (p < 0.001). Basal readings showed mean value of 1,234 ± 220.1. Group internal rigid fixation + biomaterial + laser showed higher readings (3,521 ± 2,670) and group internal rigid fixation + biomaterial the lowest (212.2 ± 119.8). In conclusion, the results of the present investigation are important clinically as spectral analysis of bone component evidenced increased levels of CHA on fractured sites by using the association of laser light to a ceramic graft.

  10. Endogenous Bone Regeneration Is Dependent Upon a Dynamic Oxygen Event

    DTIC Science & Technology

    2014-01-01

    media (20% FBS, 60% high glucose DMEM, 40% HBSS). Digits were glued to the sample platform with the lateral plane parallel to the direction of motion of...osseous obliteration in vitro. J Bone Miner Res. 1995; 10: 1978-87. 32. Doube M, Klosowski MM, Arganda- Carreras I, et al. BoneJ: Free and extensible bone

  11. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

    PubMed Central

    Henkel, Jan; Woodruff, Maria A.; Epari, Devakara R.; Steck, Roland; Glatt, Vaida; Dickinson, Ian C.; Choong, Peter F. M.; Schuetz, Michael A.; Hutmacher, Dietmar W.

    2013-01-01

    The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts. PMID:26273505

  12. Synergistic effects of dimethyloxalylglycine and butyrate incorporated into α-calcium sulfate on bone regeneration.

    PubMed

    Woo, Kyung Mi; Jung, Hong-Moon; Oh, Joung-Hwan; Rahman, Saeed Ur; Kim, Soung Min; Baek, Jeong-Hwa; Ryoo, Hyun-Mo

    2015-01-01

    Osteogenesis is closely related to angiogenesis, and the combined delivery of angiogenic and osteogenic factors has been suggested to enhance bone regeneration. Small molecules have been explored as alternatives to growth factors for tissue regeneration applications. In this study, we examined the effects of the combined application of angiogenic and osteogenic small molecules on bone regeneration using a prolyl hydroxylase, dimethyloxalylglycine (DMOG), and a histone deacetylase inhibitor, butyrate. In a critical size bone defect model in rats, DMOG and butyrate, which were incorporated into α calcium sulfate (αCS), resulted in synergistic enhancements in bone and blood vessel formation, eventually leading to bone healing, as confirmed by micro-CT and histological analyses. In MC4 pre-osteoblast cultures, DMOG and butyrate enhanced the pro-angiogenic responses and osteoblast differentiation, respectively, which were evaluated based on the levels of hypoxia inducible factor (HIF)-1α protein and the expression of pro-angiogenic molecules (VEGF, home oxidase-1, glucose transporter-1) and by alkaline phosphatase (ALP) activity and the expression of osteoblast phenotype marker molecules (ALP, α1(I)col, osteocalcin, and bone sialoprotein). DMOG combined with butyrate synergistically improved osteoblast differentiation and pro-angiogenic responses, the levels of which were drastically increased in the cultures on αCS disks. Furthermore, it was demonstrated that αCS increased the level of HIF-1α and as a consequence VEGF expression, and supported osteoblast differentiation through the release of calcium ions from the αCS. Altogether, the results of this study provide evidence that a combination treatment with the small molecules DMOG and butyrate can expedite the process of bone regeneration and that αCS can be an efficient delivery vehicle for the small molecules for bone regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Circulating Progenitor Cells in Regenerative Technologies: A Realistic Strategy in Bone Regeneration?

    PubMed

    Chang, Jessica B; Lee, Justine C

    Strategies in skeletal regeneration research have been primarily focused on optimization of three components: cellular progenitors, biomaterials, and growth factors. With the increased understanding that circulating progenitor cells exist in peripheral blood, the question arises whether such cell types would allow for adequate osteogenesis and mineralization. In this review, we discuss the current literature on circulating progenitor cells in in vitro and in vivo studies on bone regeneration.

  14. Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration

    PubMed Central

    Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping

    2014-01-01

    Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. PMID:24646912

  15. Investigation of peri-implant tissue conditions and peri-implant tissue stability in implants placed with simultaneous augmentation procedure: a 3-year retrospective follow-up analysis of a newly developed bone level implant system.

    PubMed

    Lorenz, Jonas; Lerner, Henriette; Sader, Robert A; Ghanaati, Shahram

    2017-09-05

    Guided bone regeneration (GBR) has been proven to be a reliable therapy to regenerate missing bone in cases of atrophy of the alveolar crest. The aim of the present retrospective analysis was to assess peri-implant tissue conditions and document peri-implant tissue stability in C-Tech implants when placed simultaneously with a GBR augmentation procedure. A total of 47 implants, which were placed simultaneously with a GBR procedure with a synthetic bone substitute material in 20 patients, were investigated clinically and radiologically at least 3 years after loading. Implant survival, the width and thickness of peri-implant keratinized gingiva, probing depth, bleeding on probing (BOP), the Pink Esthetic Score (PES), peri-implant bone loss, and the presence of peri-implant osteolysis were determined. The follow-up investigation revealed a survival rate of 100% and only low median rates for probing depths (2.7 mm) and BOP (30%). The mean PES was 10.1 from the maximum value of 14. No osseous peri-implant defects were obvious, and the mean bone loss was 0.55 mm. In conclusion, implants placed in combination with a GBR procedure can achieve long-term stable functionally and esthetically satisfying results for replacing missing teeth in cases of atrophy of the alveolar crest.

  16. Poly-N-acetyl glucosamine fibers activate bone regeneration in a rabbit femur injury model.

    PubMed

    Muise-Helmericks, Robin C; Demcheva, Marina; Vournakis, John N; Seth, Arun

    2011-08-01

    The purpose of this study was to evaluate the ability of a membrane material, consisting only of short poly-N-acetyl glucosamine (sNAG) nanofibers, to regenerate bone tissue after implantation into circular holes in the rabbit femur. Three circular holes were created in the femurs of five male New Zealand white rabbits. The holes were ∼ 2.0 mm in diameter. Three holes in the left femur were implanted with the comparative control substance (Bone Wax; Ethicon, Inc.); three holes in the right femur were implanted with the sNAG membrane test article. Animals were killed 4 weeks after surgery, and macroscopic evaluation of the implant sites was made. Hematoxylin and eosin histology was performed on both control and test sites. All control (bone wax) sites had visible holes (defects) at the 28-day end point of the study and showed no evidence of new bone formation. All the 15 sNAG test sites were found to have new bone tissue present in the bone hole defects. Hematoxylin and eosin histology of the sNAG-treated test sites showed the presence of osteoblasts, osteocytes, and trabecula of new bone formation at the 28-day end point of the study. The sNAG membrane test material activated the regeneration of new bone tissue in a rabbit femur bone model after 28 days of implantation, whereas the control bone wax material did not.

  17. Review: gene- and stem cell-based therapeutics for bone regeneration and repair.

    PubMed

    Kimelman, Nadav; Pelled, Gadi; Helm, Gregory A; Huard, J; Schwarz, Edward M; Gazit, Dan

    2007-06-01

    Many clinical conditions require regeneration or implantation of bone. This is one focus shared by neurosurgery and orthopedics. Current therapeutic options (bone grafting and protein-based therapy) do not provide satisfying solutions to the problem of massive bone defects. In the past few years, gene- and stem cell-based therapy has been extensively studied to achieve a viable alternative to current solutions offered by modern medicine for bone-loss repair. The use of adult stem cells for bone regeneration has gained much focus. This unique population of multipotential cells has been isolated from various sources, including bone marrow, adipose, and muscle tissues. Genetic engineering of adult stem cells with potent osteogenic genes has led to fracture repair and rapid bone formation in vivo. It is hypothesized that these genetically modified cells exert both an autocrine and a paracrine effects on host stem cells, leading to an enhanced osteogenic effect. The use of direct gene delivery has also shown much promise for in vivo bone repair. Several viral and nonviral methods have been used to achieve substantial bone tissue formation in various sites in animal models. To advance these platforms to the clinical setting, it will be mandatory to overcome specific hurdles, such as control over transgene expression, viral vector toxicity, and prolonged culture periods of therapeutic stem cells. This review covers a prospect of cell and gene therapy for bone repair as well as some very recent advancements in stem cell isolation, genetic engineering, and exogenous control of transgene expression.

  18. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: An In Vivo Microcomputed Tomographic Analysis.

    PubMed

    Basudan, Amani; Babay, Nadir; Ramalingam, Sundar; Nooh, Nasser; Al-Kindi, Mohammed; Al-Rasheed, Abdulaziz; Al-Hezaimi, Khalid

    2016-01-01

    The aim of this in vivo microcomputed tomographic (μCT) study was to compare the efficacy of Mucograft (MG) vs resorbable collagen membranes (RCMs) in facilitating guided bone regeneration (GBR) around standardized calvarial defects in rats. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A standardized calvarial defect with a 4.6-mm diameter was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) defects covered with MG (MG group); (2) defects covered with an RCM (RCM group); (3) defects filled with xenograft bone particles and covered by MG (MG + bone group); and (4) defects filled with xenograft bone particles and covered by an RCM (RCM + bone group). Primary closure was achieved using interrupted resorbable sutures. The animals underwent high-resolution, three-dimensional μCT scans at baseline and at 2, 4, 6, and 8 weeks after the surgical procedures. Data regarding volume and bone mineral density (BMD) of newly formed bone (NFB) and bone particles revealed an increase in the volume of NFB in all the groups from baseline to 8 weeks. The MG group had the lowest volume of NFB (mean ± standard deviation [SD], 1.32 ± 0.22 mm(3)). No significant differences in mean ± SD values for volume of NFB were observed between the RCM (3.50 ± 0.24 mm(3)) and MG + bone (3.87 ± 0.36 mm(3)) groups, but their values were significantly lower than that of the RCM + bone group (2.95 ± 0.15 mm(3), F = 131.91, dfN = 2, dfD = 27, P < .001). Significant differences in BMD of NFB between the groups (F = 332.46, dfN = 3, dfD = 36, P < .001) and during different data collection periods (F = 97.04, dfN = 3, dfD = 36, P < .01) were observed, with the RCM group having the highest mean ± SD BMD of NFB (0.42 ± 0.05 g/mm(3)). Significant

  19. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls.

  20. Guided tissue regeneration using a collagen barrier and bone swaging technique in noncontained infrabony defects.

    PubMed

    Kodama, Toshiro; Minabe, Masato; Sugiyama, Takashi; Mitarai, Eiko; Fushimi, Hajime; Kitsugi, Daisuke; Tsutsumi, Kouji; Katsuki, Makiko

    2013-01-01

    This clinical study evaluated the effectiveness of guided tissue regeneration using a resorbable collagen membrane and bone swaging in noncontained infrabony defects by assessing changes in probing pocket depth, probing attachment level, and radiographic bone level after 6 months, 1 year, and 2 years. Postsurgical clinical and radiographic measurements were statistically significantly different from presurgical measurements. The rate of bone fill was positively associated with the baseline depth of the bone defect but not associated with the width. The noncontained infrabony defects treated with this combined regenerative method improved clinically and radiographically.

  1. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury.

    PubMed

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-05-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 10(6) rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

  2. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  3. Comparison of silkworm-cocoon-derived silk membranes of two different thicknesses for guided bone regeneration.

    PubMed

    Seok, Hyun; Kim, Min Keun; Kim, Seong-Gon; Kweon, HaeYong

    2014-11-01

    The objective of this study was to compare the effectiveness of silk membranes (SMs) of different thicknesses for guided bone regeneration. Two kinds of SMs were prepared (SM1: 0.01 mm thickness, SM2: 0.5 mm thickness). Before use in animal experiments, scanning electron microscope images were taken to examine the gross morphology of each membrane. Ten New Zealand white rabbits were used for this study. Bilateral round-shaped defects were created in the parietal bone (diameter: 8.0 mm) and each defect was covered with SM1 or SM2. Animals were killed at 4 weeks and 8 weeks. Bone regeneration was analyzed in each specimen by micro-computed tomography (μ-CT) and histological analysis. In the μ-CT analysis, the average amount of newly formed bone in the SM2 group was greater than that in the SM1 group. There was a significant difference at 4 weeks after surgery (P = 0.004). In the histological analysis, the amount of formed lamellar bone was much greater in the SM2 group than in the SM1 group at 8 weeks after surgery (P = 0.021). In conclusion, the thick SM was much more effective for bone regeneration of bone defects than the thin SM.

  4. Modeling vascularized bone regeneration within a porous biodegradable CaP scaffold loaded with growth factors.

    PubMed

    Sun, Xiaoqiang; Kang, Yunqing; Bao, Jiguang; Zhang, Yuanyuan; Yang, Yunzhi; Zhou, Xiaobo

    2013-07-01

    Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors.

  5. The efficacy of the use of IR laser phototherapy associated to biphasic ceramic graft and guided bone regeneration on surgical fractures treated with wire osteosynthesis: a comparative laser fluorescence and Raman spectral study on rabbits.

    PubMed

    Pinheiro, Antônio Luiz Barbosa; Santos, Nicole Ribeiro Silva; Oliveira, Priscila Chagas; Aciole, Gilberth Tadeu Santos; Ramos, Thais Andrade; Gonzalez, Tayná Assunção; da Silva, Laís Nogueira; Barbosa, Artur Felipe Santos; Silveira, Landulfo

    2013-05-01

    The aim of the present study was to assess, by Raman spectroscopy and laser fluorescence, the repair of surgical fractures fixed with wire osteosynthesis treated or not with infrared laser (λ780 nm, 50 mW, 4 × 4 J/cm(2) =16 J/cm(2), ϕ=0.5 cm(2), CW) associated or not to the use of hydroxyapatite and guided bone regeneration. Surgical tibial fractures were created under general anesthesia on 15 rabbits that were divided into five groups, maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet, and had water ad libitum. The fractures in groups II, III, IV, and V were fixed with wires. Animals in groups III and V were grafted with hydroxyapatite (HA) and guided bone regeneration (GBR) technique used. Animals in groups IV and V were irradiated at every other day during 2 weeks (4 × 4 J/cm(2), 16 J/cm(2) =112 J/cm(2)). Observation time was that of 30 days. After animal death, specimens were taken and kept in liquid nitrogen and used for Raman spectroscopy. The Raman results showed basal readings of 1,234.38 ± 220. Groups WO+B+L showed higher readings (1,680.22 ± 822) and group WO+B the lowest (501.425 ± 328). Fluorescence data showed basal readings of 5.83333 ± 0.7. Groups WO showed higher readings (6.91667 ± 0.9) and group WO+B+L the lowest (1.66667 ± 0.5). There were significant differences between groups on both cases (p<0.05). Pearson correlation was negative and significant (R (2)   = -0.60; p<0.001), and it was indicative that, when the Raman peaks of calcium hydroxyapatite (CHA) are increased, the level of fluorescence is reduced. It is concluded that the use of near-infrared lasertherapy associated to HA graft and GBR was effective in improving bone healing on fractured bones as a result of the increasing deposition of CHA measured by Raman spectroscopy and decrease of the organic components as shown by the fluorescence readings.

  6. Bone Regeneration Induced by Bone Porcine Block with Bone Marrow Stromal Stem Cells in a Minipig Model of Mandibular “Critical Size” Defect

    PubMed Central

    Di Benedetto, Adriana; Cozzolino, Valerio; Podaliri Vulpiani, Michele; Grano, Maria; Kalemaj, Zamira; Grassi, Felice Roberto

    2017-01-01

    Introduction. Adding stem cells to biodegradable scaffolds to enhance bone regeneration is a valuable option. Different kinds of stem cells with osteoblastic activity were tested, such as bone marrow stromal stem cells (BMSSCs). Aim. To assess a correct protocol for osteogenic stem cell differentiation, so BMSSCs were seeded on a bone porcine block (BPB). Materials and Methods. Bone marrow from six minipigs was extracted from tibiae and humeri and treated to isolate BMSSCs. After seeding on BPB, critical-size defects were created on each mandible of the minipigs and implanted with BPB and BPB/BMSSCs. After three months, histomorphometric analysis was performed. Results. Histomorphometric analysis provided percentages of the three groups. Tissues present in control defects were 23 ± 2% lamellar bone, 28 ± 1% woven bone, and 56 ± 4% marrow spaces; in BPB defects were 20 ± 5% BPB, 32 ± 2% lamellar bone, 24 ± 1% woven bone, and 28 ± 2% marrow spaces; in BPB/BMSSCs defects were 17 ± 4% BPB/BMSSCs, 42 ± 2% lamellar bone, 12 ± 1% woven bone, and 22 ± 3% marrow spaces. Conclusion. BPB used as a scaffold to induce bone regeneration may benefit from the addition of BDPSCs in the tissue-engineered constructs. PMID:28553359

  7. Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Halima Shamaz, Bibi; Anitha, A.; Vijayamohan, Manju; Kuttappan, Shruthy; Nair, Shantikumar; Nair, Manitha B.

    2015-10-01

    Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

  8. Periosteal Distraction Osteogenesis: An Effective Method for Bone Regeneration

    PubMed Central

    Zhao, Danyang; Wang, Yu

    2016-01-01

    The treatment of bone defects is challenging and controversial. As a new technology, periosteal distraction osteogenesis (PDO) uses the osteogenicity of periosteum, which creates an artificial space between the bone surface and periosteum to generate new bone by gradually expanding the periosteum with no need for corticotomy. Using the newly formed bone of PDO to treat bone defects is effective, which can not only avoid the occurrence of immune-related complications, but also solve the problem of insufficient donor. This review elucidates the availability of PDO in the aspects of mechanisms, devices, strategies, and measures. Moreover, we also focus on the future prospects of PDO and hope that PDO will be applied to the clinical treatment of bone defects in the future. PMID:28078283

  9. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic analysis of regenerated bone

    NASA Astrophysics Data System (ADS)

    Benetti, Carolina; Kazarain, Sergei G.; Alves, Marco A. V.; Blay, Alberto; Correa, Luciana; Zezell, Denise M.

    2014-03-01

    The cutting of bone is routinely required in medical procedures, especially in dental applications. In such cases, bone regeneration and new bone quality can determine the success of the treatment. This study investigated the main spectral differences of undamaged and healed bone using the ATR-FTIR spectroscopy technique. Three rabbits were submitted to a surgical procedure; a small piece of bone (3x3 mm2) was removed from both sides of their jaws using a high speed drill. After 15 days, the rabbits were euthanized and the jaws were removed. A bone slice was cut from each side of the jaw containing regions of undamaged and newly formed bone, resulting in six samples which were polished for spectroscopic comparison. The samples were analyzed by FTIR spectroscopy using a diamond ATR accessory. Spectral characteristics were compared and particular attention was paid to the proportion of phosphate to amide I bands and the width of the phosphate band. The results show that the ratio of phosphate to amide I is smaller in new bone tissue than in the undamaged bone, indicating a higher organic content in the newly formed bone. The analysis of the width of the phosphate band suggests a crystallinity difference between both tissues, since the width was higher in the new bone than in the natural bone. These results suggest that the differences observed in bone aging processes by FTIR spectroscopic can be applied to the study of healing processes.

  10. Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics

    PubMed Central

    Barrère, Florence; van Blitterswijk, Clemens A; de Groot, Klaas

    2006-01-01

    Calcium phosphate bioceramics are widely used in orthopedic and dental applications and porous scaffolds made of them are serious candidates in the field of bone tissue engineering. They have superior properties for the stimulation of bone formation and bone bonding, both related to the specific interactions of their surface with the extracellular fluids and cells, ie, ionic exchanges, superficial molecular rearrangement and cellular activity. PMID:17717972

  11. Hydrogels That Allow and Facilitate Bone Repair, Remodeling, and Regeneration

    PubMed Central

    Short, Aaron R.; Koralla, Deepthi; Deshmukh, Ameya; Wissel, Benjamin; Stocker, Benjamin; Calhoun, Mark; Dean, David; Winter, Jessica O.

    2015-01-01

    Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current “gold standard” treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock. There is thus a critical need for the development of new, engineered materials for bone repair. This review describes the use of natural and synthetic hydrogels as scaffolds for bone tissue engineering. We discuss many of the advantages that hydrogels offer as bone repair materials, including their potential for osteoconductivity, biodegradability, controlled growth factor release, and cell encapsulation. We also discuss the use of hydrogels in composite devices with metals, ceramics, or polymers. These composites are useful because of the low mechanical moduli of hydrogels. Finally, the potential for thermosetting and photo-cross-linked hydrogels as three-dimensionally (3D) printed, patient-specific devices is highlighted. Three-dimensional printing enables controlled spatial distribution of scaffold materials, cells, and growth factors. Hydrogels, especially natural hydrogels present in bone matrix, have great potential to augment existing bone tissue engineering devices for the treatment of critical size bone defects. PMID:26693013

  12. The Promotional Effect of Mesenchymal Stem Cell Homing on Bone Tissue Regeneration.

    PubMed

    Zhou, Qi; Yang, Chengzhe; Yang, Pishan

    2017-01-01

    Background & Objective: Bone defects caused by bone fractures, malformations, postoperation on tumor and even periodontitis have became serious clinical problems. Although the exact origin of osteoblast precursors is still obscure, mesenchymal stem cells (MSCs) that originate from local bone marrow, periosteum, endosteum, mineralized bone or systemic circulation play key roles in osteoblastic differentiation and secretion of multiple factors during spontaneous healing of bone trauma or defect. Substantial evidences have shown that systemically infused MSCs can home and participate in bone tissue repair or regeneration. Applying pharmacological molecules to promote MSC homing or to mobilize MSCs in bone marrow niche to increase the amount of MSCs in the peripheral blood has been demonstrated to be important strategies to enhance MSC homing. However, there are some systemic conditions which influence MSC homing. In this paper, we review both systemic and local homing of MSCs during bone regeneration, and discuss strategies for enhancing the recruitment of MSCs to the injured bone tissues. Systemic influences of MSC homing are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Spontaneous Bone Regeneration in an Open Segmental Fracture of the Forearm with Extruded Middle Segment

    PubMed Central

    Rai, Bibek K; Vaishya, Raju

    2016-01-01

    Open segmental fractures of both bones of the forearm with the loss of the middle segment of the radius is a rare injury in children. An eight-year-old boy presented to our clinic four days following a road traffic accident. The child’s mother was carrying a 12-cm long extruded and soiled segment of the radius bone. The extruded bone segment seemed necrotic, and we decided not to use it for replantation. The wound over the forearm fracture was infected. It was debrided and regularly dressed until it became healthy. We planned to use a fibular graft for the gap and to fix the graft with a Kirschner wire (K-wire). The operation was delayed due to the poor wound condition. At the four-week follow-up, we noticed unexpected signs of bone regeneration in the bone defect of the radius. After eight weeks, a complete spontaneous reconstruction of the bone was noted. This case highlights the excellent healing potential of the bones in children, where even if a long segment of the bone is lost, we can expect spontaneous complete regeneration of the bone if the periosteum is intact and continuous. PMID:27738571

  14. Influence of platelet-rich plasma on bone regeneration: a histomorphometric study in rabbit calvaria.

    PubMed

    Torres, Jesús; Tresguerres, Isabel; Tamimi, Faleh; Clemente, Celia; Niembro, Enrique; Blanco, Luis

    2007-01-01

    The aim of this study was to evaluate whether local application of platelet-rich plasma (PRP) would induce bone regeneration in cranial defects on rabbits. Twelve female New Zealand rabbits were used for this study. Two identical 10-mm-diameter bicortical cranial defects were created in each animal. One of the defects was grafted with PRP, while the contralateral was left unfilled as a negative control. Animals were sacrificed at 2, 4, 6, and 8 weeks after surgery, and biopsy specimens were evaluated histologically and histomorphometrically under light microscopy. Analysis of variance was used for statistical analysis. The histomorphometric evaluation showed more regenerated bone after local administration of PRP at 2 weeks (P > .05), 4 weeks (P < .05), and 6 weeks (P > .05). At week 8, new bone formation was comparable in both groups. In this animal model, local application of PRP in bone defects enhances healing significantly at 4 weeks.

  15. Peri-implant bone regeneration with calcium sulfate: a light and transmission electron microscopy case report.

    PubMed

    Scarano, Antonio; Orsini, Giovanna; Pecora, Gabriele; Iezzi, Giovanna; Perrotti, Vittoria; Piattelli, Adriano

    2007-06-01

    Calcium sulfate is a simple, biocompatible material with a very long, safe clinical history in several different fields of medicine. It is a rapidly resorbing material that leaves behind calcium phosphate lattice, which promotes bone regeneration. The aim of this study was a histological and ultrastructural evaluation of the tissues in a peri-implant site regenerated with calcium sulfate. The specimens were processed for observation under light and transmission electron microscopes. In light microscopy, trabecular bone was present. No remnants of calcium sulfate were present. Transmission electron microscopy showed, in the areas of the interface with the implant surface, features of mature bone with many osteocytes. An amorphous layer and/or osteoid seam separated this mature bone from the metal surface. The results confirm the high biocompatibility and rapid resorption of calcium sulfate.

  16. Temporally controlled multiple-gene delivery in scaffolds: A promising strategy to enhance bone regeneration.

    PubMed

    Liu, Jinsong; Xu, Lihua; Li, Yiming; Ma, Jianfeng

    2011-02-01

    Bone defects sometimes require more effective repair regimens than conventional clinical therapies can provide. On account of this, tissue-engineered scaffolds have emerged as a promising alternative. Scaffolds that release genes encoding growth factors (GFs) offer additional benefits for bone regeneration in comparison with scaffolds providing protein delivery. The present gene delivery systems focus on unitary or dual genes delivery without controlled release. In the meantime, evidences indicate that bone formation is a complex cascade of events, in which time-dependent expression of multiple growth factors is involved. In our hypothesis, a temporally controlled, multi-gene delivery system embedded in a scaffold matrix can be fabricated; such a system is capable of mimicking the expression of growth factor profile in osteogenesis. Consequently, bone regeneration can be promoted by sequential gene expression of multiple growth factors.

  17. Role of Osteogenic Growth Peptide (OGP) and OGP(10-14) in Bone Regeneration: A Review.

    PubMed

    Pigossi, Suzane C; Medeiros, Marcell C; Saska, Sybele; Cirelli, Joni A; Scarel-Caminaga, Raquel M

    2016-11-22

    Bone regeneration is a process that involves several molecular mediators, such as growth factors, which directly affect the proliferation, migration and differentiation of bone-related cells. The osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP(10-14) have been shown to stimulate the proliferation, differentiation, alkaline phosphatase activity and matrix mineralization of osteoblastic lineage cells. However, the exact molecular mechanisms that promote osteoblastic proliferation and differentiation are not completely understood. This review presents the main chemical characteristics of OGP and/or OGP(10-14), and also discusses the potential molecular pathways induced by these growth factors to promote proliferation and differentiation of osteoblasts. Furthermore, since these peptides have been extensively investigated for bone tissue engineering, the clinical applications of these peptides for bone regeneration are discussed.

  18. Role of Osteogenic Growth Peptide (OGP) and OGP(10–14) in Bone Regeneration: A Review

    PubMed Central

    Pigossi, Suzane C.; Medeiros, Marcell C.; Saska, Sybele; Cirelli, Joni A.; Scarel-Caminaga, Raquel M.

    2016-01-01

    Bone regeneration is a process that involves several molecular mediators, such as growth factors, which directly affect the proliferation, migration and differentiation of bone-related cells. The osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP(10–14) have been shown to stimulate the proliferation, differentiation, alkaline phosphatase activity and matrix mineralization of osteoblastic lineage cells. However, the exact molecular mechanisms that promote osteoblastic proliferation and differentiation are not completely understood. This review presents the main chemical characteristics of OGP and/or OGP(10–14), and also discusses the potential molecular pathways induced by these growth factors to promote proliferation and differentiation of osteoblasts. Furthermore, since these peptides have been extensively investigated for bone tissue engineering, the clinical applications of these peptides for bone regeneration are discussed. PMID:27879684

  19. Optimizing Segmental Bone Regeneration Using Functionally Graded Scaffolds

    DTIC Science & Technology

    2012-10-01

    Williams RJ, Henderson B. 2000. Advances in our understand- ing of the bone and joint pathology caused by Staphylococcus aureus infection. Rheumatology... Radiology , The Methodist Hospital Research Institute, Weil Cornell Medical College, Houston, TX 77030, USA b School of Mathematical Science, Beijing...dimensional FIG. 1. Bone anatomy (Copyright ª 2004 Pearson Educa- tion, Inc., publishing as Benjamin Cummings). Color images available online at

  20. Modulating endochondral ossification of multipotent stromal cells for bone regeneration.

    PubMed

    Gawlitta, Debby; Farrell, Eric; Malda, Jos; Creemers, Laura B; Alblas, Jacqueline; Dhert, Wouter J A

    2010-08-01

    For years it has been recognized that engineering of large bone constructs will be feasible only if the hurdle of vascularization is overcome. Attempts to engineer bone tissue have predominantly focused on intramembranous (direct) bone formation. A relatively new and most likely more physiological approach in this line is endochondral bone formation, comprising an intermediate cartilaginous stage. Cartilage in nature is an avascular tissue and its cells are equipped to survive the poor oxygenation and nutritional conditions inherent to implanted tissues. Subsequent terminal differentiation (hypertrophy) of the chondrocytes initiates the formation of a mineralized matrix that will then be converted into bone. Through this mechanism, our long bones grow and most fractures heal through the process of secondary fracture healing. The feasibility of the attractive concept of endochondral bone tissue engineering has already been shown. Most emphasis has gone to the multipotent stromal cells because of their great potential for expansion and differentiation and immunoprivileged nature. This review will focus on the promises and current status of this new field. Further, potent modulators of endochondral bone tissue engineering, including oxygen tension and mechanical stimuli, will be discussed.

  1. Bone marrow mesenchymal stem cells, platelet-rich plasma and nanohydroxyapatite-type I collagen beads were integral parts of biomimetic bone substitutes for bone regeneration.

    PubMed

    Lin, Bo-Nian; Whu, Shu Wen; Chen, Chih-Hwa; Hsu, Fu-Yin; Chen, Jyh-Cheng; Liu, Hsia-Wei; Chen, Chien-Hao; Liou, Hau-Min

    2013-11-01

    Platelet rich plasma (PRP), which includes many growth factors, can activate osteoid production, collagen synthesis and cell proliferation. Nanohydroxyapatite-type I collagen beads (CIB), which mimetic natural bone components, are not only flexible fillers for bone defect but also encourage osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) are often used as an abundant cell source for tissue engineering. We used a rabbit model to combine PRP, CIB and BMSCs (CIB+PRP+BMSC) into a bone-like substitute to study its impact on bone regeneration, when compared to defect alone, PRP, CIB+PRP, and PRP+BMSC. CIB+PRP upregulated more alkaline phosphatase (ALP) activity in BMSCs than PRP alone at 4 weeks postoperation. CIB+PRP+BMSC and PRP+BMSC did not differ significantly in DNA content, total collagen content, and ALP activity at 8 weeks. In histological assay, both CIB+PRP+BMSC and PRP+BMSC showed more bone regeneration at 4 and 8 weeks. Higher trabecular bone volume in tissue volume (BV/TV) (31.15±2.67% and 36.93±1.01%), fractal dimension (FD) (2.30±0.18 and 2.65±0.02) and lower trabecular separation (Tb.Sp) (2.30±0.18 and 1.35±0.16) of CIB+PRP+BMSC than of other groups at 4 and 8 weeks, and approach to of bone tissue (BV/TV=24.35±2.13%; FD=2.65±0.06; Tb.Sp=4.19±0.95). CIB+PRP+BMSC significantly enhanced new bone formation at 4 week. Therefore, nanohydroxyapatite-type I collagen beads combined with PRP and BMSCs produced a bone substitute with efficiently improved bone regeneration that shows promise to repair bone defects.

  2. Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2.

    PubMed

    Krishnan, Laxminarayanan; Priddy, Lauren B; Esancy, Camden; Klosterhoff, Brett S; Stevens, Hazel Y; Tran, Lisa; Guldberg, Robert E

    2017-02-01

    Bone morphogenetic protein-2 (BMP-2), delivered on absorbable collagen sponge, is frequently used to treat bone defects. However, supraphysiological BMP-2 doses are common and often associated with complications such as heterotopic ossification and inflammation, causing pain and impaired mobility. This has prompted investigations into strategies to spatially control bone regeneration, for example growth factor delivery in appropriate scaffolds. Our objective was to investigate the spatiotemporal effects of high dose BMP-2 on bone regeneration as a function of the delivery vehicle. We hypothesized that an alginate delivery system would spatially restrict bone formation compared to a collagen sponge delivery system. In vitro, BMP-2 release was accelerated from collagen sponge compared to alginate constructs. In vivo, bone regeneration was evaluated over 12weeks in critically sized rat femoral segmental defects treated with 30μg rhBMP-2 in alginate hydrogel or collagen sponge, surrounded by perforated nanofiber meshes. Total bone volume, calculated from micro-CT reconstructions, was higher in the alginate group at 12weeks. Though bone volume within the central defect region was greater in the alginate group at 8 and 12weeks, heterotopic bone volume was similar between groups. Likewise, mechanical properties from ex vivo torsional testing were comparable between groups. Histology corroborated these findings and revealed heterotopic mineralization at 2weeks post-surgery in both groups. Overall, this study recapitulated the heterotopic ossification associated with high dose BMP-2 delivery, and demonstrated that the amount and spatial pattern of bone formation was dependent on the delivery matrix.

  3. Cellular therapy in bone-tendon interface regeneration

    PubMed Central

    Rothrauff, Benjamin B; Tuan, Rocky S

    2014-01-01

    The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

  4. Biological efficacy of silk fibroin nanofiber membranes for guided bone regeneration.

    PubMed

    Kim, Kyoung-Hwa; Jeong, Lim; Park, Ho-Nam; Shin, Seung-Yun; Park, Won-Ho; Lee, Sang-Chul; Kim, Tae-Il; Park, Yoon-Jeong; Seol, Yang-Jo; Lee, Yong-Moo; Ku, Young; Rhyu, In-Chul; Han, Soo-Boo; Chung, Chong-Pyoung

    2005-11-21

    The favorable biological properties of silk fibroin (SF) nanofiber membrane make it a good candidate for clinical applications as a device in bone and periodontal regenerative therapy. The purpose of this study is to evaluate the biocompatibility of the SF nanofiber membrane, and to examine its effect on bone regeneration in a rabbit calvarial model. To examine the biocompatibility of the electrospun SF membrane, we investigated cell proliferation, morphology, and differentiation. The bone regenerative efficacy of the membrane was evaluated in the calvarial defect of rabbits. The cell numbers and osteocalcin production labels were significantly increased in accordance with culture period. Cells had a stellate shape and broad cytoplasmic extensions on the membrane. The cells showed activity of ALPase that was comparable to culture dishes, and were calcified similarly to culture dishes. In in vivo tests, a complete bony union across the defects was observed after 8 weeks. At 12 weeks, the defect had completely healed with new bone. In conclusion, the SF nanofiber membrane was shown to possess good biocompatibility with enhanced bone regeneration and no evidence of any inflammatory reaction. These results strongly suggest that the SF membrane should be useful as a tool for guided bone regeneration.

  5. Unique microstructural design of ceramic scaffolds for bone regeneration under load.

    PubMed

    Roohani-Esfahani, S I; Dunstan, C R; Li, J J; Lu, Zufu; Davies, B; Pearce, S; Field, J; Williams, R; Zreiqat, H

    2013-06-01

    During the past two decades, research on ceramic scaffolds for bone regeneration has progressed rapidly; however, currently available porous scaffolds remain unsuitable for load-bearing applications. The key to success is to apply microstructural design strategies to develop ceramic scaffolds with mechanical properties approaching those of bone. Here we report on the development of a unique microstructurally designed ceramic scaffold, strontium-hardystonite-gahnite (Sr-HT-gahnite), with 85% porosity, 500μm pore size, a competitive compressive strength of 4.1±0.3MPa and a compressive modulus of 170±20MPa. The in vitro biocompatibility of the scaffolds was studied using primary human bone-derived cells. The ability of Sr-HT-gahnite scaffolds to repair critical-sized bone defects was also investigated in a rabbit radius under normal load, with β-tricalcium phosphate/hydroxyapatite scaffolds used in the control group. Studies with primary human osteoblast cultures confirmed the bioactivity of these scaffolds, and regeneration of rabbit radial critical defects demonstrated that this material induces new bone defect bridging, with clear evidence of regeneration of original radial architecture and bone marrow environment.

  6. Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects

    PubMed Central

    Chen, Wenchuan; Liu, Jun; Manuchehrabadi, Navid; Weir, Michael D.; Zhu, Zhimin; Xu, Hockin H.K.

    2014-01-01

    Human umbilical cord mesenchymal stem cells (hUCMSCs) are inexhaustible and can be harvested at a low cost without an invasive procedure. However, there has been no report on comparing hUCMSCs with human bone marrow MSCs (hBMSCs) for bone regeneration in vivo. The aim of this study was to investigate hUCMSC and hBMSC seeding on macroporous calcium phosphate cement (CPC), and to compare their bone regeneration in critical-sized cranial defects in rats. Cell attachment, osteogenic differentiation and mineral synthesis on RGD-modified macroporous CPC were investigated in vitro. Scaffolds with cells were implanted in 8-mm defects of athymic rats. Bone regeneration was investigated via micro-CT and histological analysis at 4, 12, and 24 weeks. Three groups were tested: CPC with hUCMSCs, CPC with hBMSCs, and CPC control without cells. Percentage of live cells and cell density on CPC in vitro were similarly good for hUCMSCs and hBMSCs. Both cells had high osteogenic expressions of alkaline phosphatase, osteocalcin, collagen I, and Runx2. Bone mineral density and trabecular thickness in hUCMSC and hBMSC groups in vivo were greater than those of CPC control group. New bone amount for hUCMSC-CPC and hBMSC-CPC constructs was increased by 57% and 88%, respectively, while blood vessel density was increased by 15% and 20%, than CPC control group at 24 weeks. hUCMSC-CPC and hBMSC-CPC groups generally had statistically similar bone mineral density, new bone amount and vessel density. In conclusion, hUCMSCs seeded on CPC were shown to match the bone regeneration efficacy of hBMSCs in vivo for the first time. Both hUCMSC-CPC and hBMSC-CPC constructs generated much more new bone and blood vessels than CPC without cells. Macroporous RGD-grafted CPC with stem cell seeding is promising for craniofacial and orthopedic repairs. PMID:24054499

  7. Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects.

    PubMed

    Chen, Wenchuan; Liu, Jun; Manuchehrabadi, Navid; Weir, Michael D; Zhu, Zhimin; Xu, Hockin H K

    2013-12-01

    Human umbilical cord mesenchymal stem cells (hUCMSCs) are inexhaustible and can be harvested at a low cost without an invasive procedure. However, there has been no report on comparing hUCMSCs with human bone marrow MSCs (hBMSCs) for bone regeneration in vivo. The aim of this study was to investigate hUCMSC and hBMSC seeding on macroporous calcium phosphate cement (CPC), and to compare their bone regeneration in critical-sized cranial defects in rats. Cell attachment, osteogenic differentiation and mineral synthesis on RGD-modified macroporous CPC were investigated in vitro. Scaffolds with cells were implanted in 8-mm defects of athymic rats. Bone regeneration was investigated via micro-CT and histological analysis at 4, 12, and 24 weeks. Three groups were tested: CPC with hUCMSCs, CPC with hBMSCs, and CPC control without cells. Percentage of live cells and cell density on CPC in vitro were similarly good for hUCMSCs and hBMSCs. Both cells had high osteogenic expressions of alkaline phosphatase, osteocalcin, collagen I, and Runx2. Bone mineral density and trabecular thickness in hUCMSC and hBMSC groups in vivo were greater than those of CPC control group. New bone amount for hUCMSC-CPC and hBMSC-CPC constructs was increased by 57% and 88%, respectively, while blood vessel density was increased by 15% and 20%, than CPC control group at 24 weeks. hUCMSC-CPC and hBMSC-CPC groups generally had statistically similar bone mineral density, new bone amount and vessel density. In conclusion, hUCMSCs seeded on CPC were shown to match the bone regeneration efficacy of hBMSCs in vivo for the first time. Both hUCMSC-CPC and hBMSC-CPC constructs generated much more new bone and blood vessels than CPC without cells. Macroporous RGD-grafted CPC with stem cell seeding is promising for craniofacial and orthopedic repairs.

  8. Pilot in vivo animal study of bone regeneration by fractional Er: YAG-laser

    NASA Astrophysics Data System (ADS)

    Altshuler, Gregory B.; Belikov, Andrey V.; Shatilova, Ksenia V.; Yaremenko, Andrey I.; Zernitskiy, Alexander Y.; Zernitckaia, Ekaterina A.

    2016-04-01

    The histological structure of the rabbit parietal bone during its regeneration after fractional Er: YAG-laser (λ=2.94μm) treatment was investigated by hematoxylin and eosin (H&E) stain. In 48 days after fractional laser treatment, bone samples contained micro-cavities and fragments of necrotic tissue with empty cellular lacuna and coagulated protein of bone matrix. In this case, necrotic lesions appeared around the periphery of micro-cavities created by laser radiation. Fragmentation of detrital mass and partial substitution of micro-cavities with fatty bone marrow were observed in bone samples in 100 days after fractional laser treatment, in contrast to the earlier period. Partial filling of micro-cavities edges by fibrous tissue with presence of osteoblasts on their inner surface was observed in 100 days also, that indicates regenerative processes in the bone.

  9. Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration.

    PubMed

    Ambrosi, Thomas H; Scialdone, Antonio; Graja, Antonia; Gohlke, Sabrina; Jank, Anne-Marie; Bocian, Carla; Woelk, Lena; Fan, Hua; Logan, Darren W; Schürmann, Annette; Saraiva, Luis R; Schulz, Tim J

    2017-06-01

    Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application

    PubMed Central

    Wu, Chengtie; Chang, Jiang

    2012-01-01

    The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition–structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models. PMID:23741607

  11. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    SciTech Connect

    Shrivastava, Pragya; Dalai, Sridhar; Vijayalakshmi, S.; Sudera, Prerna; Sivam, Santosh Param; Sharma, Pratibha

    2013-02-05

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO{sub 2} 70 mol%, CaO 26 mol % and P{sub 2}O{sub 5} 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  12. Development of high strength hydroxyapatite for bone tissue regeneration using nanobioactive glass composites

    NASA Astrophysics Data System (ADS)

    Shrivastava, Pragya; Dalai, Sridhar; Sudera, Prerna; Sivam, Santosh Param; Vijayalakshmi, S.; Sharma, Pratibha

    2013-02-01

    With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO2 70 mol%, CaO 26 mol % and P2O5 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.

  13. Periodontal regeneration by autologous bone marrow mononuclear cells embedded in a novel thermo reversible gelation polymer.

    PubMed

    Sankaranarayanan, Seshadri; Jetty, Nadeem; Gadagi, Jayaprakash S; Preethy, Senthilkumar; Abraham, Samuel J K

    2013-01-01

    Regeneration of bony defects caused by periodontal disease continues to be a challenge for clinicians. Application of stem cells from different tissue sources and scaffolds for regeneration have been reported in animal models but clinical studies with long term follow-ups are limited. Herein we report the three years follow-up of the application of autologous bone marrow mononuclear cells (BMMNCs) embedded in a thermo-reversible gelation polymer (TGP) for periodontal regeneration. A 23-year female patient with advanced periodontitis (class IV gingival recession, probing pocket depth (PPD) of 5 mm and 6 mm in relation to mandibular lateral and central incisors respectively, and clinical attachment level (CAL) of 13 mm) correlated with radiographic evidence of severe horizontal bone loss extending up to the apex of mandibular incisors was selected for the treatment. After debridement, the defect was implanted with BMMNCs impregnated in TGP. Then the clinical parameters and radiographic evaluation were made at periodic intervals of 6, 12, 24 and 36 months. At six months, significant improvement with the clinical parameters (PPD had reduced to 2 mm, clinical attachment level had improved by 6 mm) was observed. At 36 months, the radiograph revealed bone regeneration with improvement in vertical and horizontal bone height. Transplantation of BMMNCs in a novel TGP is safe and results in a relatively significant and stable clinical outcome in horizontal alveolar bony defects.

  14. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

    PubMed

    Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

    2017-08-01

    Endothelial cells and leptin receptor(+) (LepR(+)) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER(+) progenitors, which represent ∼5% of LepR(+) cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR(+) cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

  15. [Isotopic studies on the regeneration of stapedial bone in otosclerosis].

    PubMed

    Konarska, A

    1997-01-01

    The aim of the study was determining the bone rebuilding activity in stapes and otosclerotic focus and comparison the relation between bone rebuilding activity with some clinical features such as the patient's sex and age, duration of the disease and the degree of hearing impairment. The study covered 98 patients aged from 18 to 68 years (X = 37 years) in whom, due to otosclerosis, stapedectomy was performed at the Clinic of Otolaryngology--PAM in Szczecin. The rebuilding activity was estimated in bone fragments having been removed during the operation, i.e. in 98 specimens of canal wall bone, 97 specimens of stapedial crura, 88 fragments from posterior and 18 fragments from anterior parts of footplate as well as in 15 otosclerotic foci, using isotopic method implementing a complex of pyrophosphate labelled with technetium Tc-99m. The degree of bone rebuilding activity was defined by the amount of absorbed isotopic index. The "control group" was made up of 9 cases, in which stapedectomy was carried out for therapeutical purpose in consequence of other ailments, namely: in 3 cases of congenital stapedial ankylosis, 5 cases of stapedial tympanosclerosis, and 1 case of Menier's disease. It has been disclosed that otosclerosis is an active pathological process, involving the bone of the entire stapes with the strongest manifestation in the disease focus. An essential fact was linked with the very low bone rebuilding activity in the stapedial footplate and crura in the "control group". The bone rebuilding activity in otosclerotic foci and footplate of stapes was somewhat higher in males than in females. It was the highest in patients whose disease duration was the longest. In general the bone rebuilding activity didn't influence the degree of hearing impairment.

  16. Effects of single or combination therapy of teriparatide and anti-RANKL monoclonal antibody on bone defect regeneration in mice.

    PubMed

    Kitaguchi, Kazuma; Kashii, Masafumi; Ebina, Kosuke; Kaito, Takashi; Okada, Rintaro; Makino, Takahiro; Noguchi, Takaaki; Ishimoto, Takuya; Nakano, Takayoshi; Yoshikawa, Hideki

    2017-10-01

    The purpose of this study is to investigate the effects of a single or combination therapy of teriparatide (TPTD) and anti-RANKL Ab (anti-murine receptor activator of nuclear factor κB ligand monoclonal antibody) on the regeneration of both cancellous and cortical bone. Nine-week-old mice underwent bone defect surgery on the left femoral metaphysis (cancellous-bone healing model) and right femoral mid-diaphysis (cortical-bone healing model). After surgery, the mice were assigned to 1 of 4 groups to receive 1) saline (5 times a week; CNT group), 2) TPTD (40μg/kg 5 times a week; TPTD group), 3) anti-RANKL Ab (5mg/kg once; Ab group), or 4) a combination of TPTD and anti-RANKL Ab (COMB group). The following analyses were performed: Time-course microstructural analysis of healing in both cancellous and cortical bone in the bone defect, the volumetric bone mineral density of the tibia with micro-computed tomography, histological, histomorphometrical, and biomechanical analysis of regenerated bone. Regeneration of cancellous bone volume in the COMB group was the highest among the 4 groups, and this combined administration prompted medullary callus formation in the early phase of bone regeneration. On the other hand, regeneration of cortical bone volume in the COMB group was significantly higher than in the Ab group and was almost same as in the TPTD group. Histological analysis showed remaining woven bones, cartilage matrix, and immature lamellar bone in the COMB and Ab groups. However, biomechanical analysis showed that hardness and Young's modulus of regenerated cortical bone in the COMB group was not lower than in both the CNT and TPTD groups. Volumetric bone mineral density in the tibia was significantly increased in the COMB group compared with the other 3 groups. In the early phase of bone regeneration, the combination of TPTD and anti-RANKL Ab accelerates regeneration of cancellous bone in bone defects and increases cancellous bone mass in the tibia more

  17. Botulinum toxin induces muscle paralysis and inhibits bone regeneration in zebrafish.

    PubMed

    Recidoro, Anthony M; Roof, Amanda C; Schmitt, Michael; Worton, Leah E; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J; Srinivasan, Sundar; Moon, Randall T; Gardiner, Edith M; Kaminsky, Werner; Bain, Steven D; Allan, Christopher H; Gross, Ted S; Kwon, Ronald Y

    2014-11-01

    Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (eg, development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study, we developed a model of BTx-induced muscle paralysis in adult zebrafish, and we examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders.

  18. Effect of cell-seeded hydroxyapatite scaffolds on rabbit radius bone regeneration.

    PubMed

    Rathbone, C R; Guda, T; Singleton, B M; Oh, D S; Appleford, M R; Ong, J L; Wenke, J C

    2014-05-01

    Highly porous hydroxyapatite (HA) scaffolds were developed as bone graft substitutes using a template coating process, characterized, and seeded with bone marrow-derived mesenchymal stem cells (BMSCs). To test the hypothesis that cell-seeded HA scaffolds improve bone regeneration, HA scaffolds without cell seeding (HA-empty), HA scaffolds with 1.5 × 10(4) BMSCs (HA-low), and HA scaffolds with 1.5 × 10(6) BMSCs (HA-high) were implanted in a 10-mm rabbit radius segmental defect model for 4 and 8 weeks. Three different fluorochromes were administered at 2, 4, and 6 weeks after implantation to identify differences in temporal bone growth patterns. It was observed from fluorescence histomorphometry analyses that an increased rate of bone infiltration occurred from 0 to 2 weeks (p < 0.05) of implantation for the HA-high group (2.9 ± 0.5 mm) as compared with HA-empty (1.8 ± 0.8 mm) and HA-low (1.3 ± 0.2 mm) groups. No significant differences in bone formation within the scaffold or callus formation was observed between all groups after 4 weeks, with a significant increase in bone regenerated for all groups from 4 to 8 weeks (28.4% across groups). Although there was no difference in bone formation within scaffolds, callus formation was significantly higher in HA-empty scaffolds (100.9 ± 14.1 mm(3) ) when compared with HA-low (57.8 ± 7.3 mm(3) ; p ≤ 0.003) and HA-high (69.2 ± 10.4 mm(3) ; p ≤ 0.02) after 8 weeks. These data highlight the need for a better understanding of the parameters critical to the success of cell-seeded HA scaffolds for bone regeneration.

  19. Glucocorticoid inhibits bone regeneration after osteonecrosis of the femoral head in aged female rats.

    PubMed

    Takano-Murakami, Reiko; Tokunaga, Kunihiko; Kondo, Naoki; Ito, Tomoyuki; Kitahara, Hiroshi; Ito, Masayuki; Endo, Naoto

    2009-01-01

    Idiopathic osteonecrosis of the femoral head (ION) is a painful disease of the hip, the pathogenic mechanism of which is still unclear. The most common extraneous factor is steroid treatment. Steroids have inhibiting effects on bone formation and resorption. When bone regenerative treatments are indicated for ION patients who are exposed to steroids, we cannot ignore the effects of corticosteroid itself on bone healing. The aim of this study was to investigate the effects of glucocorticoid on bone regeneration after osteonecrosis of the femoral head in a rat model. Osteonecrosis was induced surgically on the left femoral heads of aged female rats (about 6 months old) on day 0. Methylprednisolone sodium succinate (MPSS) or normal saline was administrated at a dose of 100 mg/kg/day from day 7 to 11. Femoral heads were analyzed histologically. There were no pathological findings in the right femoral heads of the MPSS-treated and saline-treated rats, as control for the contralateral injury. The newly formed bone volume and the osteoclast number were significantly smaller in the MPSS-treated group. The normal bone marrow was regenerated in the saline-treated group, whereas most of the bone marrow space still contained fibroblast-like spindle-shaped cells in the MPSS-treated group on day 42. Alkaline phosphatase-positive cells were only seen in the areas around the regenerated bone marrow cavities. Thus, MPSS inhibits bone formation by suppressing osteoblast proliferation and resorption by suppressing the recruitment of osteoclast precursors. These findings may be useful when designing treatments for ION patients exposed to steroids.

  20. Effects of Two Types of Anorganic Bovine Bone on Bone Regeneration: A Histological and Histomorphometric Study of Rabbit Calvaria

    PubMed Central

    Paknejad, Mojgan; Rokn, Amir Reza; Yaghobee, Siamak; Moradinejad, Pantea; Heidari, Mohadeseh; Mehrfard, Ali

    2014-01-01

    Objective: The purpose of this study was to evaluate the efficacy of two types of bone substitutes, Bio-Oss and NuOss, for repair of bone defects. Materials and Methods: This study was performed on the calvaria of 14 New Zealand rabbits. The 6mm critical size defect (CSD) models of bone regeneration were used. Three CSDs were created in each surgical site. The first defect was filled with NuOss, the second one with Bio-Oss and the third one remained unfilled as the control. After healing periods of one and two months (seven animal for each time point), histological and histomorphometric analyses were carried out to assess the amount of new bone formation, presence of inflammation, foreign body reaction and type of new bone. Qualitative variables were analyzed by multiple comparisons, Wilcoxon, Friedman and Mann Whitney tests. Quantitative variables were analyzed using the Mann-Whitney and Wilcoxon tests. Level of statistical significance was set at 0.05. Results: The level of inflammation was not significantly different at four and eight weeks in the Bio-Oss (P=0.944), NuOss (P=1.000) and control groups (P=0.71). At four weeks, foreign body reaction was not observed in Bio-Oss, NuOss and control groups. There was no significant difference in the type of the newly formed bone at four and eight weeks in any group (P=0.141 for Bio-Oss, P=0.06 for NuOss and P=0.389 for the control group). Conclusion: Deproteinized bovine bone mineral can be used as a scaffold in bone defects to induce bone regeneration. PMID:25628699

  1. Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics.

    PubMed

    Lin, Kaili; Xia, Lunguo; Li, Haiyan; Jiang, Xinquan; Pan, Haobo; Xu, Yuanjin; Lu, William W; Zhang, Zhiyuan; Chang, Jiang

    2013-12-01

    The regeneration capacity of the osteoporotic bones is generally lower than that of the normal bones. Current methods of bone defect treatment for osteoporosis are not always satisfactory. Recent studies have shown that the silicate based biomaterials can stimulate osteogenesis and angiogenesis due to the silicon (Si) ions released from the materials, and enhance bone regeneration in vivo. Other studies showed that strontium (Sr) plays a distinct role on inhibiting bone resorption. Based on the hypothesis that the combination of Si and Sr may have synergetic effects on osteoporotic bone regeneration, the porous Sr-substituted calcium silicate (SrCS) ceramic scaffolds combining the functions of Sr and Si elements were developed with the goals to promote osteoporotic bone defect repair. The effects of the ionic extract from SrCS on osteogenic differentiation of bone marrow mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX), angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) were investigated. The in vitro results showed that Sr and Si ions released from SrCS enhanced cell viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteoblast-related genes of rBMSCs-OVX and expression of vascular endothelial growth factor (VEGF) without addition of extra osteogenic and angiogenic reagents. The activation in extracellular signal-related kinases (ERK) and p38 signaling pathways were observed in rBMSCs-OVX cultured in the extract of SrCS, and these effects could be blocked by ERK inhibitor PD98059, and P38 inhibitor SB203580, respectively. Furthermore, the ionic extract of SrCS stimulated HUVECs proliferation, differentiation and angiogenesis process. The in vivo experiments revealed that SrCS dramatically stimulated bone regeneration and angiogenesis in a critical sized OVX calvarial defect model, and the enhanced bone regeneration might be attributed to the modulation of osteogenic differentiation of

  2. Guided bone regeneration to repair an osseous defect.

    PubMed

    Carvalho, Roberto S; Nelson, Donald; Kelderman, Hans; Wise, Roger

    2003-04-01

    The ultimate goal of orthodontic therapy is to establish functional and esthetic dental relationships in a balanced facial pattern. In patients with compromised periodontal support, the use of multidisciplinary treatment plans is essential in attaining these goals. This case report includes a thorough documentation of the orthodontic and periodontal treatments to demonstrate the effectiveness of guided bone regenerative procedures combined with a bone allograft to aid in correcting a dental malocclusion.

  3. Novel Therapy for Bone Regeneration in Large Segmental Defects

    DTIC Science & Technology

    2014-10-01

    standard for normal tibia mineralization (Toshiba Infinix VC with Vitrea 2 work station) and to exclude animals with pre-existing bone pathology . 4...JC, Corona BT, McKinley TO, Kacena MA. Muscle-bone interactions during fracture healing. J Musculoskeletal Neuronal Interactions, accepted as long as...score of 0 till 12 weeks. One rat received a score of 1 at 15 weeks (Table 1).Fig. 2. Representative serial radiological images of segmental defects in

  4. Macroporous bioceramics: a remarkable material for bone regeneration.

    PubMed

    Lew, Kien-Seng; Othman, Radzali; Ishikawa, Kunio; Yeoh, Fei-Yee

    2012-09-01

    This review summarises the major developments of macroporous bioceramics used mainly for repairing bone defects. Porous bioceramics have been receiving attention ever since their larger surface area was reported to be beneficial for the formation of more rigid bonds with host tissues. The study of porous bioceramics is important to overcome the less favourable bonds formed between dense bioceramics and host tissues, especially in healing bone defects. Macroporous bioceramics, which have been studied extensively, include hydroxyapatite, tricalcium phosphate, alumina, and zirconia. The pore size and interconnections both have significant effects on the growth rate of bone tissues. The optimum pore size of hydroxyapatite scaffolds for bone growth was found to be 300 µm. The existence of interconnections between pores is critical during the initial stage of tissue ingrowth on porous hydroxyapatite scaffolds. Furthermore, pore formation on β-tricalcium phosphate scaffolds also allowed the impregnation of growth factors and cells to improve bone tissues growth significantly. The formation of vascularised tissues was observed on macroporous alumina but did not take place in the case of dense alumina due to its bioinert nature. A macroporous alumina coating on scaffolds was able to improve the overall mechanical properties, and it enabled the impregnation of bioactive materials that could increase the bone growth rate. Despite the bioinertness of zirconia, porous zirconia was useful in designing scaffolds with superior mechanical properties after being coated with bioactive materials. The pores in zirconia were believed to improve the bone growth on the coated system. In summary, although the formation of pores in bioceramics may adversely affect mechanical properties, the advantages provided by the pores are crucial in repairing bone defects.

  5. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats.

    PubMed

    Gredes, Tomasz; Kunath, Franziska; Gedrange, Tomasz; Kunert-Keil, Christiane

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  6. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    PubMed Central

    Gedrange, Tomasz

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions. PMID:27597965

  7. Platelet-rich plasma for bone healing and regeneration.

    PubMed

    Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali

    2016-01-01

    Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose. Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties. As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP.

  8. Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration.

    PubMed

    Yao, Qingqing; Liu, Yangxi; Tao, Jianning; Baumgarten, Keith M; Sun, Hongli

    2016-11-30

    Utilizing biomimetic materials to potentiate endogenous cell growth or signaling is superior to relying on exogenous cells or signals for bone formation. Desferoxamine (DFO), which is a hypoxia-mimetic agent that chelates iron (Fe(3+)), mimics hypoxia to encourage bone healing. However, high cytotoxicity, off-target effects, and the short half-life of DFO have significantly impeded its further applications. We mitigated these side effects by locally immobilizing DFO onto a gelatin nanofibrous (GF) scaffold that retained DFO's ability to chelate Fe(3+). Moreover, DFO-functionalized GF (GF-DFO) scaffolds, which have similar micro/macrostructures to GF scaffolds, not only demonstrated decreased cytotoxicity on both human umbilical vein endothelial cells and human mesenchymal stem cells but also significantly increased vascular endothelial growth factor (VEGF) expression in vitro. Most importantly, in our in vivo experiments on a critical-sized cranial bone defect mouse model, a significant amount of bone was formed in most of the GF-DFO scaffolds after six weeks, while very little new bone was observed in the GF scaffolds. These data suggest that use of a hypoxia-mimicking nanofibrous scaffold is a promising strategy for promoting endogenous bone formation.

  9. Proceedings: Using Stem Cell Therapies to Reestablish Osteogenic Capability for Bone Regeneration

    PubMed Central

    Littman, Neil

    2015-01-01

    Summary The California Institute for Regenerative Medicine (CIRM) has invested approximately $70 million in programs targeting various orthopedic indications, including osteoporosis, bone fracture healing, vertebral compression fractures, and several others. The present article serves to outline the current state of CIRM’s more advanced programs, comparing and contrasting them with the current standard of care and several other novel approaches under development. Significance This report describes CIRM bone programs that are in contrast to current cell therapy approaches. These projects aim to enhance stem cell activity for bone regeneration. PMID:26483540

  10. Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model.

    PubMed

    Liu, Weiqing; Kang, Ning; Dong, Yuliang; Guo, Yuchen; Zhao, Dan; Zhang, Shiwen; Zhou, Liyan; Seriwatanachai, Dutmanee; Liang, Xing; Yuan, Quan

    2016-04-01

    The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical-size defects. About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (μCT) and histological analysis. The μCT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Masson's trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair.

  11. Chemical inhibitors of c-Met receptor tyrosine kinase stimulate osteoblast differentiation and bone regeneration.

    PubMed

    Kim, Jung-Woo; Nam Lee, Mi; Jeong, Byung-Chul; Oh, Sin-Hye; Kook, Min-Suk; Koh, Jeong-Tae

    2017-03-16

    The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice. Treatment with SYN1143 or SGX523 inhibited HGF-induced c-Met phosphorylation in MC3T3-E1 and C3H10T1/2 cells. Cell proliferation of MC3T3-E1 or C3H10T1/2 was not significantly affected by the concentrations of these inhibitors. Co-treatment with chemical inhibitor of c-Met and osteogenic inducing media enhanced osteoblast-specific genes expression and calcium nodule formation accompanied by increased Runx2 expression via c-Met receptor-dependent but Erk-Smad signaling independent pathway. Notably, the administration of these c-Met inhibitors significantly repaired critical-sized calvarial bone defects. Collectively, our results suggest that chemical inhibitors of c-Met receptor tyrosine kinase might be used as novel therapeutics to induce bone regeneration.

  12. Incorporation of copper into chitosan scaffolds promotes bone regeneration in rat calvarial defects

    PubMed Central

    D'Mello, Sheetal; Elangovan, Satheesh; Hong, Liu; Ross, Ryan D.; Sumner, D. Rick; Salem, Aliasger K.

    2015-01-01

    The objective of this study was to investigate the effects of a copper loaded chitosan scaffold on bone regeneration in critical-sized calvarial defects in rats. Chitosan scaffolds and copper-chitosan scaffolds were fabricated and characterized by scanning electron microscopy (SEM). Chitosan and copper-chitosan scaffolds were implanted into 5 mm diameter critical-sized calvarial defects in Fisher 344 male rats. Empty defects (no scaffolds) were included as a control. After 4 weeks, the rats were sacrificed for micro-computed tomography (micro-CT) and histological analysis of new bone tissue development. Microscopy images revealed the uniformly porous structure of chitosan and copper-chitosan scaffolds. Significant bone regeneration was noted in the defects treated with copper-chitosan scaffolds when evaluated using micro-CT and histological analysis, when compared to other groups tested. On analysis of the micro-CT scans, an eleven-fold and a two-fold increase in the new bone volume/total volume (BV/TV) % was found in defects treated with the copper-chitosan scaffolds, when compared to empty defects and chitosan scaffolds, respectively. This study demonstrated the suitability of copper-crosslinked chitosan scaffolds for bone tissue engineering and provides the first evidence that inclusion of copper ions in scaffolds can enhance tissue regeneration. PMID:25230382

  13. Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane.

    PubMed

    Tejeda-Montes, Esther; Klymov, Alexey; Nejadnik, M Reza; Alonso, Matilde; Rodriguez-Cabello, J Carlos; Walboomers, X Frank; Mata, Alvaro

    2014-09-01

    The search for alternative therapies to improve bone regeneration continues to be a major challenge for the medical community. Here we report on the enhanced mineralization, osteogenesis, and in vivo bone regeneration properties of a bioactive elastin-like recombinamer (ELR) membrane. Three bioactive ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion (RGDS), mineralization (DDDEEKFLRRIGRFG), and both cell adhesion and mineralization were synthesized using standard recombinant protein techniques. The ELR materials were then used to fabricate membranes comprising either a smooth surface (Smooth) or channel microtopographies (Channels). Mineralization and osteoblastic differentiation of primary rat mesenchymal stem cells (rMSCs) were analyzed in both static and dynamic (uniaxial strain of 8% at 1 Hz frequency) conditions. Smooth mineralization membranes in static condition exhibited the highest quantity of calcium phosphate (Ca/P of 1.78) deposition with and without the presence of cells, the highest Young's modulus, and the highest production of alkaline phosphatase on day 10 in the presence of cells growing in non-osteogenic differentiation medium. These membranes were tested in a 5 mm-diameter critical-size rat calvarial defect model and analyzed for bone formation on day 36 after implantation. Animals treated with the mineralization membranes exhibited the highest bone volume within the defect as measured by micro-computed tomography and histology with no significant increase in inflammation. This study demonstrates the possibility of using bioactive ELR membranes for bone regeneration applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Sequential and Opposing Activities of Wnt and BMP Coordinate Zebrafish Bone Regeneration

    PubMed Central

    Stewart, Scott; Gomez, Alan W.; Armstrong, Benjamin E.; Henner, Astra; Stankunas, Kryn

    2014-01-01

    SUMMARY Zebrafish fully regenerate lost bone, including after fin amputation, through a process mediated by dedifferentiated, lineage-restricted osteoblasts. Mechanisms controlling the osteoblast regenerative program from its initiation through reossification are poorly understood. We show that fin amputation induces a Wnt/β-catenin-dependent epithelial to mesenchymal transformation (EMT) of osteoblasts in order to generate proliferative Runx2+ preosteoblasts. Localized Wnt/β-catenin signaling maintains this progenitor population toward the distal tip of the regenerative blastema. As they become proximally displaced, preosteoblasts upregulate sp7 and subsequently mature into re-epithelialized Runx2−/sp7+ osteoblasts that extend preexisting bone. Auto-crine bone morphogenetic protein (BMP) signaling promotes osteoblast differentiation by activating sp7 expression and counters Wnt by inducing Dickkopf-related Wnt antagonists. As such, opposing activities of Wnt and BMP coordinate the simultaneous demand for growth and differentiation during bone regeneration. This hierarchical signaling network model provides a conceptual framework for understanding innate bone repair and regeneration mechanisms and rationally designing regenerative therapeutics. PMID:24485659

  15. Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy.

    PubMed

    Picke, A-K; Gordaliza Alaguero, I; Campbell, G M; Glüer, C-C; Salbach-Hirsch, J; Rauner, M; Hofbauer, L C; Hofbauer, C

    2016-01-01

    Zucker Diabetic Fatty (ZDF) rats represent an established model of type 2 diabetes mellitus (T2DM) and display several features of human diabetic bone disease, including impaired osteoblast function, decreased bone strength, and delayed bone healing. Here, we determined whether glycemic control by insulin treatment prevents skeletal complications associated with diabetes. Subcritical femur defects were created in diabetic (fa/fa) and non-diabetic (+/+) ZDF rats. Diabetic rats were treated once daily with long-lasting insulin glargin for 12weeks for glycemic control. Insulin treatment successfully maintained serum levels of glycated hemoglobin, while untreated diabetic rats showed a 2-fold increase. Trabecular and cortical bone mass measured by μCT were decreased in diabetic rats. Insulin treatment increased bone mass of the cortical, but not of the trabecular bone compartment. Dynamic histomorphometry revealed a lower bone formation rate at the trabecular and periosteal cortical bone in diabetic animals and decreased serum procollagen type 1 N-terminal propeptide (P1NP, -49%) levels. Insulin treatment partially improved these parameters. In T2DM, serum levels of tartrate-resistant acid phosphatase (TRAP, +32%) and C-terminal telopeptide (CTX, +49%) were increased. Insulin treatment further elevated TRAP levels, but did not affect CTX levels. While diabetes impaired bone defect healing, glycemic control with insulin fully reversed these negative effects. In conclusion, insulin treatment reversed the adverse effects of T2DM on bone defect regeneration in rats mainly by improving osteoblast function and bone formation. This article is part of a Special Issue entitled Bone and diabetes.

  16. Surface Functionalization of Titanium Alloy with miR-29b Nanocapsules To Enhance Bone Regeneration.

    PubMed

    Meng, Yubin; Li, Xue; Li, Zhaoyang; Liu, Chaoyong; Zhao, Jin; Wang, Jianwei; Liu, Yunde; Yuan, Xubo; Cui, Zhenduo; Yang, Xianjin

    2016-03-09

    Titanium and its alloys have been widely used over the past 3 decades as implants for healing bone defects. Nevertheless, the bioinert property of titanium alloy limits its clinical application and surface modification method is frequently performed to improve the biological and chemical properties. Recently, the delivery of microRNA with osteogenesis capability has been recognized as a promising tool to enhance bone regeneration of implants. Here, we developed a biodegradable coating to modify the titanium surface in order to enhance osteogenic bioactivity. The previous developed nanocapsules were used as the building blocks, and then a bioactive titanium coating was designed to entrap the miR-29b nanocapsules. This coating was not only favorable for cell adhesion and growth but also provided sufficient microRNA transfection efficacy and osteoinductive potential, resulting in a significant enhancement of bone regeneration on the surface of bioinert titanium alloy.

  17. [The possibilities and perspectives of using scaffold technology for bone regeneration].

    PubMed

    Ivanov, A N; Norkin, I A; Puchin'ian, D M

    2014-01-01

    The article deals with the one of the topical problem of tissue engineering--the design and implementation of biomaterials that could replace and repair bone defects. This review presents the recent studies of the potential of scaffold technology in bone tissue regeneration. This article contains information about the basic parameters and properties of modern scaffold systems. The results of experimental in vitro and in vivo studies on the use of matrices made of various materials are shown. Advantages and disadvantages of various materials used for the production of scaffolds are discussed. Attention is paid to the advantages combinations of different materials to achieve the desired structural and functional properties. Particular attention is paid to technologies and systems of targeted delivery and controlled release of factors that stimulate bone tissue regeneration. Different strategies for modulating tissue reactions and immune responses that take place during scaffold implantation are presented.

  18. Dried and free flowing granules of Spinacia oleracea accelerate bone regeneration and alleviate postmenopausal osteoporosis.

    PubMed

    Adhikary, Sulekha; Choudhary, Dharmendra; Ahmad, Naseer; Kumar, Sudhir; Dev, Kapil; Mittapelly, Naresh; Pandey, Gitu; Mishra, Prabhat Ranjan; Maurya, Rakesh; Trivedi, Ritu

    2017-06-01

    The aim of this study was to demonstrate the efficacy of extract derived from Spinacia oleracea extract (SOE) in reversing bone loss induced by ovariectomy and bone healing properties in a drill-hole fracture model in rats. SOE was administered orally for 12 weeks in adult ovariectomized Sprague Dawley rats after inducing osteopenic condition. Bone micro-architecture, expressions of osteogenic and resorptive gene markers, biomechanical strength, new bone formation, and bone turnover markers were studied. Uterine histomorphometry was used to assess estrogenicity. Bone regeneration potential of SOE was assessed in a drill-hole fracture model. Fracture healing was assessed by calcein intensity and micro-CT analysis of callus at fracture region. SOE prevented ovariectomy-induced bone loss as evident from 122% increase in bone volume/tissue volume (BV/TV) and 29% decline in Tb.Sp in femoral trabecular micro-architecture. This was corroborated by the more than twofold stimulation in the expression of osteogenic genes runt-related transcription factor 2, osterix, osteocalcin, bone morphogenetic protein 2, collagen-1. Furthermore in the fracture healing model, we observed a 25% increase in BV/TV and enhancement in calcein intensity at the fractured site. The extract when converted into dried deliverable Spinaceae oleracea granule (SOG) form accelerated bone regeneration at fracture site, which was more efficient as evident by a 39% increase in BV/TV. Transforming SOE into dried granules facilitated prolonged systemic availability, thus providing enhanced activity for a period of 14 days. SOE treatment effectively prevents ovariectomy-induced bone loss and stimulated fracture healing in adult rats. The dried granular form of the extract of Spinaceae oleracea was effective in fracture healing at the same dose.

  19. Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices

    PubMed Central

    Fisher, James N.; Peretti, Giuseppe M.; Scotti, Celeste

    2016-01-01

    Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates. PMID:26997959

  20. Experimental model for bone regeneration in oral and cranio-maxillo-facial surgery.

    PubMed

    Mardas, Nikos; Dereka, Xanthippi; Donos, Nikolaos; Dard, Michel

    2014-02-01

    Bone and tooth loss, as a result of trauma, anatomical or congenital reasons, cancer, and periodontal disease, is a common therapeutic problem in the fields of cranio-maxillo-facial surgery and periodontics. The proposed techniques for the treatment of various bone defects encountered include bone grafts, bone substitutes, guided tissue regeneration, and distraction osteogenesis as well as their combinations. In addition, dental implants have been successfully utilized for the restoration of full or partial edentulism. The introduction and development of new therapeutic approaches and devices demand the use of appropriate animal models that present bone anatomy and healing comparable to human. Among other animal models, the pig is extensively documented in several biomedical areas and has been largely used in maxillo-facial surgery and implants dentistry-related research. Anatomical and physiological similarities with human in size, physiology, and bone biology contribute to a successful involvement of this animal to understand and treat various osseous lesions. However, improvements and standardization are requested with respect to consistency and discrimination abilities. The aim of this review is to provide a critical appraisal of the literature related to swine models for the evaluation of cranio-maxillo-facial osseous defect healing, regeneration, and bone-implant interface. This review should assist researchers in the field to select the most appropriate model for each dedicated purpose and also contribute to stimulate an innovative thinking on the use of porcine models.

  1. Angiogenic and Osteogenic Potential of Bone Repair Cells for Craniofacial Regeneration

    PubMed Central

    Pagni, Giorgio; Park, Chan-Ho; Tarle, Susan A.; Bartel, Ronnda L.; Giannobile, William V.

    2010-01-01

    There has been increased interest in the therapeutic potential of bone marrow derived cells for tissue engineering applications. Bone repair cells (BRCs) represent a unique cell population generated via an ex vivo, closed-system, automated cell expansion process, to drive the propagation of highly osteogenic and angiogenic cells for bone engineering applications. The aims of this study were (1) to evaluate the in vitro osteogenic and angiogenic potential of BRCs, and (2) to evaluate the bone and vascular regenerative potential of BRCs in a craniofacial clinical application. BRCs were produced from bone marrow aspirates and their phenotypes and multipotent potential characterized. Flow cytometry demonstrated that BRCs were enriched for mesenchymal and vascular phenotypes. Alkaline phosphatase and von Kossa staining were performed to assess osteogenic differentiation, and reverse transcriptase–polymerase chain reaction was used to determine the expression levels of bone specific factors. Angiogenic differentiation was determined through in vitro formation of tube-like structures and fluorescent labeling of endothelial cells. Finally, 6 weeks after BRC transplantation into a human jawbone defect, a biopsy of the regenerated site revealed highly vascularized, mineralized bone tissue formation. Taken together, these data provide evidence for the multilineage and clinical potential of BRCs for craniofacial regeneration. PMID:20412009

  2. Leptin receptor deficient diabetic (db/db) mice are compromised in postnatal bone regeneration.

    PubMed

    Rőszer, Tamás; Józsa, Tamás; Kiss-Tóth, Eva D; De Clerck, Nora; Balogh, Lajos

    2014-04-01

    Increased fragility fracture risk with improper healing is a frequent and severe complication of insulin resistance (IR). The mechanisms impairing bone health in IR are still not fully appreciated, which gives importance to studies on bone pathologies in animal models of diabetes. Mice deficient in leptin signaling are widely used models of IR and its comorbidities. Leptin was first recognized as a hormone, regulating appetite and energy balance; however, recent studies have expanded its role showing that leptin is a link between insulin-dependent metabolism and bone homeostasis. In the light of these findings, it is intriguing to consider the role of leptin resistance in bone regeneration. In this study, we show that obese diabetic mice lacking leptin receptor (db/db) are deficient in postnatal regenerative osteogenesis. We apply an ectopic osteogenesis and a fracture healing model, both showing that db/db mice display compromised bone acquisition and regeneration capacity. The underlying mechanisms include delayed periosteal mesenchymatic osteogenesis, premature apoptosis of the cartilage callus and impaired microvascular invasion of the healing tissue. Our study supports the use of the db/db mouse as a model of IR associated bone-healing deficits and can aid further studies of mesenchymatic cell homing and differentiation, microvascular invasion, cartilage to bone transition and callus remodeling in diabetic fracture healing.

  3. Characterization of Scaffold Carriers for BMP9-Transduced Osteoblastic Progenitor Cells in Bone Regeneration

    PubMed Central

    Shui, Wei; Zhang, Wenwen; Yin, Liangjun; Nan, Guoxin; Liao, Zhan; Zhang, Hongmei; Wang, Ning; Wu, Ningning; Chen, Xian; Wen, Sheng; He, Yunfeng; Deng, Fang; Zhang, Junhui; Luu, Hue H.; Shi, Lewis L; Hu, Zhenming; Haydon, Rex C.; Mok, James; He, Tong-Chuan

    2015-01-01

    Successful bone tissue engineering at least requires sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We have demonstrated that BMP9 is one of the most potent factors in inducing osteogenic differentiation of mesenchymal progenitors. To facilitate the potential use of cell-based BMP9 gene therapy for bone regeneration, we characterize the in vivo osteoconductive activities and bone regeneration potential of three clinically-used scaffold materials, type I collagen sponge, hydroxyapatite-tricalcium phosphate (HA-TCP) and demineralized bone matrix (DBM), using BMP9-expressing C2C12 osteoblastic progenitor cells. We find that recombinant adenovirus-mediated BMP9 expression effectively induces osteogenic differentiation in C2C12 cells. Although direct subcutaneous injection of BMP9-transduced C2C12 cells forms ectopic bony masses, subcutaneous implantation of BMP9-expressing C2C12 cells with collagen sponge or HA-TCP scaffold yields the most robust and mature cancellous bone formation, whereas the DBM carrier group forms no or minimal bone masses. Our results suggest that collagen sponge and HA-TCP scaffold carriers may provide more cell-friendly environment to support the survival, propagation, and ultimately differentiation of BMP9-expressing progenitor cells. This line of investigation should provide important experimental evidence for further pre-clinical studies in BMP9-mediated cell based approach to bone tissue engineering. PMID:24133046

  4. Bone regeneration by periosteal elevation using conventional orthodontic wire and uHA/PLLA mesh.

    PubMed

    Sotobori, Megumi; Ueki, Koichiro; Ishihara, Yuri; Moroi, Akinori; Marukawa, Kohei; Nakazawa, Ryuichi; Higuchi, Masatoshi; Iguchi, Ran; Ikawa, Hiroumi; Kosaka, Akihiko

    2014-12-01

    This study evaluated bone regeneration by periosteal elevation using conventional orthodontic wire and an unsintered hydroxyapatite (u-HA)/poly-L-lactic acid (PLLA) mesh in rabbit frontal bone. Thirty two rabbits (12-16 weeks: 2.5-3.0 kg) were used in this study. In the experimental group, 1 week after the mesh was inserted under the periosteal membrane, it was elevated by traction using the mesh connected with wire and two anchor screws. In the control group, the mesh was kept inserted under the periosteal membrane. Four animals were killed in each period in both groups, at 2, 3, 5 and 9 weeks postoperatively. Operated parts in the frontal bone were removed and prepared for radiological and histological assessment. The distance between the mesh and pristine bone (elevation length), the bone area and the expression of BMP-2 were evaluated. The value in the experimental group was significantly higher when compared to the control group (length P < 0.0001, bone area P < 0.0010, BMP-2 P = 0.0015). The BMP-2 labelling index after 3 weeks tended to be the largest in both groups. This study suggests that bone regeneration can be induced by periosteal elevation using a conventional orthodontic wire and an uHA/PLLA mesh.

  5. Bone regeneration following the in vivo bioreactor principle: is in vitro manipulation of exogenous elements still needed?

    PubMed

    Huang, Ru-Lin; Liu, Kai; Li, Qingfeng

    2016-07-01

    Large bone defect treatment is a key challenge due to the difficulty of functional and aesthetic reconstruction. A promising approach for bone regeneration is bone tissue engineering which is based on in vitro manipulation of seed cells, growth factors and bioscaffolds. However, many formidable conceptual and technical challenges impede clinical translation of experimental successes into clinical practices. An emerging strategy for bone regeneration is using the body as a bioreactor to cultivate the traditional triad and leveraging the body's own regenerative capacity to create new bone tissue. Based on the understanding of bone regeneration and in vivo bioreactor principle, we hypothesize that functional bone tissue may be eventually generated in vivo only using autologous costal periosteum, without participation of any exogenous elements.

  6. Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds

    NASA Astrophysics Data System (ADS)

    Resurreccion-Magno, Maria Hanshella C.

    Tyrosine-derived polycarbonates (TyrPC) are a versatile class of polymers highly suitable for bone tissue engineering. Among the tyrosine-derived polycarbonates, poly(DTE carbonate) has an FDA masterfile that documents its biocompatibility and non-toxicity and has shown potential utility in orthopedics due to its osteoconductive properties and strength. DTE stands for desaminotyrosyl-tyrosine ethyl ester and is the most commonly used tyrosine-derived monomer. However, in vitro degradation studies showed that poly(DTE carbonate) did not completely resorb even after four years of incubation in phosphate buffered saline. Thus for bone regeneration, which only requires a temporary implant until the bone heals, poly(DTE carbonate) would not be the best choice. The goal of the present research was to optimize a scaffold composition for bone regeneration that is based on desaminotyrosyl-tyrosine alkyl ester (DTR), desaminotyrosyl-tyrosine (DT) and poly(ethylene glycol) (PEG). Five areas of research were presented: (1) synthesis and characterization of a focused library of TyrPC terpolymers; (2) evaluation of the effects of how small changes on the composition affected the mechanism and kinetics of polymer degradation and erosion; (3) fabrication of bioactive three-dimensional porous scaffold constructs for bone regeneration; (4) assessment of osteogenic properties in vitro using pre-osteoblasts; and (5) evaluation of bone regeneration potential, with or without recombinant human bone morphogenetic protein-2 (rhBMP-2), in vivo using a critical sized defect (CSD) rabbit calvaria (cranium) model. Small changes in the composition, such as changing the R group of DTR from ethyl to methyl, varying the mole percentages of DT and PEG, and using a different PEG block length, affected the overall properties of these polymers. Porous scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. Calcium phosphate was coated on the

  7. The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration.

    PubMed

    Yamano, Seiichi; Haku, Ken; Yamanaka, Takuto; Dai, Jisen; Takayama, Tadahiro; Shohara, Ryutaro; Tachi, Keita; Ishioka, Mika; Hanatani, Shigeru; Karunagaran, Sanjay; Wada, Keisuke; Moursi, Amr M

    2014-03-01

    Regenerative procedures using barrier membrane technology are presently well established in periodontal/endodontic surgery. The objective of this study was to compare the subsequent effects of the released platelet-derived growth factor (PDGF) and growth/differentiation factor 5 (GDF-5) from collagen membranes (CMs) on bone regeneration in vitro and in vivo. In vitro studies were conducted using MC3T3-E1 mouse preosteoblasts cultured with or without factors. Cell viability, cell proliferation, alkaline phosphatase (ALP) activity and bone marker gene expression were then measured. In vivo studies were conducted by placing CMs with low or high dose PDGF or GDF-5 in rat mandibular defects. At 4 weeks after surgery new bone formation was measured using μCT and histological analysis. The results of in vitro studies showed that CM/GDF-5 significantly increased ALP and cell proliferation activities without cytotoxicity in MC3T3-E1 cells when compared to CM/PDGF or CM alone. Gene expression analysis revealed that Runx2 and Osteocalcin were significantly increased in CM/GDF-5 compared to CM/PDGF or control. Quantitative and qualitative μCT and histological analysis for new bone formation revealed that although CM/PDGF significantly enhanced bone regeneration compared to CM alone or control, CM/GDF-5 significantly accelerated bone regeneration to an even greater extent than CM/PDGF. The results also showed that GDF-5 induced new bone formation in a dose-dependent manner. These results suggest that this strategy, using a CM carrying GDF-5, might lead to an improvement in the current clinical treatment of bone defects for periodontal and implant therapy.

  8. Guided bone regeneration using chitosan-collagen membranes in dog dehiscence-type defect model.

    PubMed

    Li, Xiaojing; Wang, Xinmu; Zhao, Tengfei; Gao, Bo; Miao, Yuwen; Zhang, Dandan; Dong, Yan

    2014-02-01

    The purpose of the present study was to compare a newly developed chitosan-collagen membrane (CCM) with a standard collagen membrane (SCM) regarding their effects on guided bone regeneration. The right mandibular premolars and first molar were extracted from 12 beagle dogs. Four months later, acute buccal dehiscence-type defects (4 × 3 mm in height and width) were surgically created after implant site preparation. The defects were randomly assigned to 4 different groups: CCM-1 (weight ratio of chitosan to collagen of 40:1), CCM-2 (weight ratio of chitosan to collagen of 20:1), SCM, and vehicle control. The dogs were sacrificed after 4, 8, and 12 weeks of healing for radiographic examination, histologic observation, and histometric analysis. The membrane-treated sites showed more bone formation than the control sites, although no statistically significant differences were found between the membrane-treated sites and the control sites for new bone-to-implant contact and new bone-filled area at any point. At 8 weeks, the new bone height for the membrane-treated sites was significantly greater statistically than that of the untreated group (P < .05). At 12 weeks, the CCM-1 group showed significantly greater new bone height (1.91 ± 0.25 mm) than the untreated group (1.20 ± 0.34 mm; P < .05). However, the CCMs did not show any statistically significant differences compared with the SCMs for any assessed parameter. The results of the present study have shown that the developed CCMs can enhance bone regeneration and could be a candidate for use in guided bone regeneration. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-06-01

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

  10. Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

    PubMed Central

    Dennis, S. Connor; Berkland, Cory J.; Bonewald, Lynda F.

    2015-01-01

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

  11. In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Yue, Xinxin; Niu, Mao; Zhang, Te; Wang, Cheng; Wang, Zhonglei; Wu, Wangxi; Zhang, Qi; Lai, Chunhua; Zhou, Lei

    2016-03-01

    Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

  12. 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications

    PubMed Central

    Asa'ad, Farah; Giannì, Aldo Bruno; Giannobile, William V.; Rasperini, Giulio

    2016-01-01

    To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on “3D-printed” ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration. PMID:27366149

  13. Bone regeneration using a synthetic matrix containing enamel matrix derivate.

    PubMed

    Schneider, David; Weber, Franz E; Hämmerle, Christoph H F; Feloutzis, Andreas; Jung, Ronald E

    2011-02-01

    The aim of the present study was to test whether the delivery of enamel matrix derivate (EMD) via synthetic polyethylene glycol (PEG)-based hydrogels with and without RGD sequences enhances bone formation in vivo. In each of 10 rabbits, four titanium cylinders were placed on the external cortical bones of their calvaria. The following four treatment modalities were randomly allocated: One of the four cylinders was left empty (control), the other three were filled with a combination of PEG matrix with hydroxyapatite/tricalciumphosphate (HA/TCP) granules and EMD in a concentration of 100 μg/ml (test 1) or 500 μg/ml (test 2) or 500 μg/ml and RGD peptide (test 3). After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis, the Kruskal-Wallis test was applied (P<0.05). The histomorphometric analysis revealed a statistically larger area fraction of newly formed bone in the EMD 500/RGD group (54.8±14.5%) compared with the control group (28.7±10.3%) and the EMD 500 group (31.2±14.1%) and non-significantly higher area fraction compared with the EMD 100 group (38.2±10.4%). The percentage of mineralized bone showed no statistically significant differences among the four groups. The mean percentage of mineralized bone was 13.6±3.3% in the control group, 14.2±5.8% in the EMD 100 group, 11.69±5.9% in the EMD 500 group and 15.66±5.2% in the EMD 500/RGD group. No statistically significant difference regarding the bone-to-graft contact between the EMD 100 group (23±15.7%), the EMD 500 group (22.2±14.6%) and the EMD 500/RGD group (21.6±8.8%) was observed. The combination of a PEG matrix containing EMD with HA/TCP granules had no effect on the formation of mineralized bone tissue in rabbit calvaria. The addition of RGD peptide to the PEG/EMD 500 combination increased the area fraction of newly formed bone compared with the other treatment groups. Further studies are indicated to study a possible

  14. High-density polytetrafluoroethylene membranes in guided bone and tissue regeneration procedures: a literature review.

    PubMed

    Carbonell, J M; Martín, I Sanz; Santos, A; Pujol, A; Sanz-Moliner, J D; Nart, J

    2014-01-01

    Expanded polytetrafluoroethylene (e-PTFE) has been used successfully as a membrane barrier for regeneration procedures. However, when exposed to the oral cavity, its high porosity increases the risk of early infection, which can affect surgical outcomes. An alternative to e-PTFE is non-expanded and dense polytetrafluoroethylene (n-PFTE), which results in lower levels of early infection following surgical procedures. The aim of this literature review was to analyze and describe the available literature on n-PFTE, report the indications for use, advantages, disadvantages, surgical protocols, and complications. The medical databases Medline-PubMed and Cochrane Library were searched and supplemented with a hand search for reports published between 1980 and May 2012 on n-PTFE membranes. The search strategy was limited to animal, human, and in vitro studies in dental journals published in English. Twenty-four articles that analyzed the use of n-PTFE as a barrier membrane for guided tissue regeneration and guided bone regeneration around teeth and implants were identified: two in vitro studies, seven experimental studies, and 15 clinical studies. There is limited clinical and histological evidence for the use of n-PTFE membranes at present, with some indications in guided tissue regeneration and guided bone regeneration in immediate implants and fresh extraction sockets.

  15. Recent Strategies Combining Biomaterials and Stem Cells for Bone, Liver and Skin Regeneration.

    PubMed

    Morelli, Sabrina; Salerno, Simona; Ahmed, Haysam Mohamed Magdy; Piscioneri, Antonella; Bartolo, Loredana De

    2016-01-01

    This review is focused on the combination of biomaterials with stem cells as a promising strategy for bone, liver and skin regeneration. At first, we describe stem cell-based constructs for bone tissue engineering with special attention to recent advanced approaches based on the use of biomaterial scaffolds with renewable stem cells that have been used for bone regeneration. We illustrate the strategies to improve liver regeneration by using liver stem cells and biomaterials and/or devices as therapeutic approaches. In particular, examples of biomaterials in combination with other technologies are presented since they allow the differentiation of stem cells in hepatocytes. After a description of the role and the benefit of MSCs in wound repair and in skin substitutes we highlight the suitability of biomaterials in guiding stem cell differentiation for skin regeneration and cutaneous repair in both chronic and acute wounds. Finally, an overview of the types of bioreactors that have been developed for the differentiation of stem cells and are currently in use, is also provided. The examples of engineered microenvironments reported in this review indicate that a detailed understanding of the various factors and mechanisms that control the behavior of stem cells in vivo has provided useful information for the development of advanced bioartificial systems able to control cell fate.

  16. Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

    PubMed

    Shen, Yue; Yang, Shizhou; Liu, Jianli; Xu, Huazi; Shi, Zhongli; Lin, Zhongqing; Ying, Xiaozhou; Guo, Peng; Lin, Tiao; Yan, Shigui; Huang, Qing; Peng, Lei

    2014-08-13

    Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.

  17. Novel Therapy for Bone Regeneration in Large Segmental Defects

    DTIC Science & Technology

    2016-10-01

    with pre-existing bone pathology . 4. KEY RESEARCH ACCOMPLISHMENTS: Key accomplishments from the previous reporting period: We completed surgeries...the difference between TPO and saline treated animals was not significant. Preliminary blood and pathology analyses have not raised any safety...contralateral tibia. • No adverse effects from TPO treatment have been identified from blood measurements, organ pathology , or veterinary inspection

  18. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence.

    PubMed

    Dimitriou, Rozalia; Mataliotakis, George I; Calori, Giorgio Maria; Giannoudis, Peter V

    2012-07-26

    Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a single-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.

  19. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

    PubMed Central

    2012-01-01

    Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465

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

    PubMed

    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.

  1. Investigating the Potential of Amnion-Based Scaffolds as a Barrier Membrane for Guided Bone Regeneration.

    PubMed

    Li, Wuwei; Ma, Guowu; Brazile, Bryn; Li, Nan; Dai, Wei; Butler, J Ryan; Claude, Andrew A; Wertheim, Jason A; Liao, Jun; Wang, Bo

    2015-08-11

    Guided bone regeneration is a new concept of large bone defect therapy, which employs a barrier membrane to afford a protected room for osteogenesis and prevent the invasion of fibroblasts. In this study, we developed a novel barrier membrane made from lyophilized multilayered acellular human amnion membranes (AHAM). After decellularization, the AHAM preserved the structural and biomechanical integrity of the amnion extracellular matrix (ECM). The AHAM also showed minimal toxic effects when cocultured with mesenchymal stem cells (MSCs), as evidenced by high cell density, good cell viability, and efficient osteogenic differentiation after 21-day culturing. The effectiveness of the multilayered AHAM in guiding bone regeneration was evaluated using an in vivo rat tibia defect model. After 6 weeks of surgery, the multilayered AHAM showed great efficiency in acting as a shield to avoid the invasion of the fibrous tissues, stabilizing the bone grafts and inducing the massive bone growth. We hence concluded that the advantages of the lyophilized multilayered AHAM barrier membrane are as follows: preservation of the structural and mechanical properties of the amnion ECM, easiness for preparation and handling, flexibility in adjusting the thickness and mechanical properties to suit the application, and efficiency in inducing bone growth and avoiding fibrous tissues invasion.

  2. Bio-Inspired Nano-Featured Substrates: Suitable Environment for Bone Regeneration.

    PubMed

    Rammal, Hassan; Dubus, Marie; Aubert, Léa; Reffuveille, Fany; Laurent Maquin, Dominique; Terryn, Christine; Schaaf, Pierre; Alem, Halima; Francius, Grégory; Quilès, Fabienne; Gangloff, Sophie C; Boulmedais, Fouzia; Kerdjoudj, Halima

    2017-03-16

    Bone mimicking coatings provide a complex microenvironment in which material, through its inherent properties (such as nanostructure and composition), affects the commitment of stem cells into bone lineage and the production of bone tissue regulating factors, required for bone healing and regeneration. Herein, a bioactive mineral/biopolymers composite made of calcium phosphate/chitosan and hyaluronic acid (CaP-CHI-HA) was elaborated using a versatile simultaneous spray coating of interacting species. The resulting CaP-CHI-HA coating was mainly constituted of bioactive, carbonated and crystalline hydroxyapatite, with 277 ± 98 nm of roughness, 1 μm of thickness and 2.3 ± 1 GPa of stiffness. After five days of culture, CaP-CHI-HA suggested a synergistic effect of intrinsic biophysical features and biopolymers on stem cells mechanobiology and nuclear organization, leading to the expression of an early osteoblast-like phenotype and the production of bone tissue regulating factors such as osteoprotegerin and vascular endothelial growth factor. More interestingly, amalgamation with biopolymers, conferred to mineral a bacterial anti-adhesive property. These significant data shed light on the potential regenerative application of CaP-CHI-HA bio-inspired coating in providing a suitable environment for stem cells bone regeneration and an ideal strategy to prevent implant-associated infections.

  3. The Role of NELL-1, a Growth Factor Associated with Craniosynostosis, in Promoting Bone Regeneration

    PubMed Central

    Zhang, X.; Zara, J.; Siu, R.K.; Ting, K.; Soo, C.

    2010-01-01

    Efforts to enhance bone regeneration in orthopedic and dental cases have grown steadily for the past decade, in line with increasingly sophisticated regenerative medicine. To meet the unprecedented demand for novel osteospecific growth factors with fewer adverse effects compared with those of existing adjuncts such as BMPs, our group has identified a craniosynostosis-associated secreted molecule, NELL-1, which is a potent growth factor that is highly specific to the osteochondral lineage, and has demonstrated robust induction of bone in multiple in vivo models from rodents to pre-clinical large animals. NELL-1 is preferentially expressed in osteoblasts under direct transcriptional control of Runx2, and is well-regulated during skeletal development. NELL-1/Nell-1 can promote orthotopic bone regeneration via either intramembranous or endochondral ossification, both within and outside of the craniofacial complex. Unlike BMP-2, Nell-1 cannot initiate ectopic bone formation in muscle, but can induce bone marrow stromal cells (BMSCs) to form bone in a mouse muscle pouch model, exhibiting specificity that BMPs lack. In addition, synergistic osteogenic effects of Nell-1 and BMP combotherapy have been observed, and are likely due to distinct differences in their signaling pathways. NELL-1's unique role as a novel osteoinductive growth factor makes it an attractive alternative with promise for future clinical applications. [Note: NELL-1 and NELL-1 indicate the human gene and protein, respectively; Nell-1 and Nell-1 indicate the mouse gene and protein, respectively.] PMID:20647499

  4. Functionalized d-form self-assembling peptide hydrogels for bone regeneration

    PubMed Central

    He, Bin; Ou, Yunsheng; Zhou, Ao; Chen, Shuo; Zhao, Weikang; Zhao, Jinqiu; Li, Hong; Zhu, Yong; Zhao, Zenghui; Jiang, Dianming

    2016-01-01

    Bone defects are very common in orthopedics, and there is great need to develop suitable bone grafts for transplantation in vivo. However, current bone grafts still encounter some limitations, including limited availability, immune rejection, poor osteoinduct