New bone formation by murine osteoprogenitor cells cultured on corticocancellous allograft bone

2008 ◽  
Vol 26 (12) ◽  
pp. 1660-1664 ◽  
Author(s):  
Ehren R. Nelson ◽  
Zhinong Huang ◽  
Ting Ma ◽  
Derek Lindsey ◽  
Christopher Jacobs ◽  
...  
Keyword(s):  
Bone Formation ◽  
Allograft Bone ◽  
New Bone Formation ◽  
Osteoprogenitor Cells ◽  
Cells Cultured

STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis

Rheumatology ◽  
2020 ◽  
Author(s):  
Sungsin Jo ◽  
Eun Jeong Won ◽  
Moon-Ju Kim ◽  
Yu Jeong Lee ◽  
So-Hee Jin ◽  
...  
Keyword(s):  
Bone Formation ◽  
Chronic Inflammation ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Micro Ct ◽  
New Bone Formation ◽  
Osteoprogenitor Cells ◽  
Suppression Effect ◽  
Stat3 Phosphorylation

Abstract Objective AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. Methods Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. Results In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). Conclusion Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.

scholarly journals Periosteal Augmentation of Allograft Bone and its Effect on Implant Fixation - An Experimental Study on 12 Dogs§

2013 ◽  
Vol 7 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Jeppe Barckman ◽  
Jorgen Baas ◽  
Mette Sørensen ◽  
Joan E Bechtold ◽  
Kjeld Soballe
Keyword(s):  
Bone Formation ◽  
Bone Graft ◽  
Bone Repair ◽  
Fibrous Tissue ◽  
Titanium Implants ◽  
Allograft Bone ◽  
New Bone Formation ◽  
Implant Fixation ◽  
Implant Surface ◽  
Cambium Layer

Purpose: Periosteum provides essential cellular and biological components necessary for fracture healing and bone repair. We hypothesized that augmenting allograft bone by adding fragmented autologous periosteum would improve fixation of grafted implants. Methods: In each of twelve dogs, we implanted two unloaded cylindrical (10 mm x 6 mm) titanium implants into the distal femur. The implants were surrounded by a 2.5-mm gap into which morselized allograft bone with or without addition of fragmented autologous periosteum was impacted. After four weeks, the animals were euthanized and the implants were evaluated by histomorphometric analysis and mechanical push-out test. Results: Although less new bone was found on the implant surface and increased volume of fibrous tissue was present in the gap around the implant, no difference was found between treatment groups regarding the mechanical parameters. Increased new bone formation was observed in the immediate vicinity of the periosteum fragments within the bone graft. Conclusion: The method for periosteal augmentation used in this study did not alter the mechanical fixation although osseointegration was impaired. The observed activity of new bone formation at the boundary of the periosteum fragments may indicate maintained bone stimulating properties of the transplanted cambium layer. Augmenting the bone graft by smaller fragments of periosteum, isolated cambium layer tissue or cultured periosteal cells could be studied in the future.

scholarly journals Osteoprogenitor cells can enhance early bone formation in critical bone defects in dogs

2017 ◽  
Vol 47 (7) ◽  
Author(s):  
Endrigo Gabellini Leonel Alves ◽  
Rogéria Serakides ◽  
Isabel Rodrigues Rosado ◽  
Omar Leonardo Aristizabal Paez ◽  
Jéssica Alejandra Castro Varon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Bone Formation ◽  
Bone Defects ◽  
Autogenous Bone ◽  
Control Group ◽  
New Bone Formation ◽  
Osteoprogenitor Cells ◽  
Critical Bone Defects

ABSTRACT: The aim of this study was to evaluate the effect of osteoprogenitor cells derived from mesenchymal stem cells from adipose tissue (OC-AD-MSCs), and differentiated into osteoblasts, in the treatment of critical bone defects in dogs. Adipose tissue derived mesenchymal stem cells (AD-MSCs) were subjected to osteogenic differentiation for 21 days and used in the treatment of bone defects in dogs radius. Either three experimental groups were bone defects treated with OC-AD-MSCs (OC), defects filled with autogenous bone (Control- C +), or empty defects (Control- C -). Bone regeneration was assessed by radiology, densitometry, and histomorphometry. The area of new bone formation was higher in the OC group compared to the control group (C-) on postoperative day 15. Defects treated with OC-AD-MSCs showed greater neovascularization than the other two groups at 90 days. We concluded that treatment with OC-AD-MSCs increased the area of new bone formation 15 days after surgery; however, it didn’t complete the bone union in critical bone defects in the radius of dogs at 90 days.

scholarly journals In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 381
Author(s):  
Hyunmin Choi ◽  
Kyu-Hyung Park ◽  
Narae Jung ◽  
June-Sung Shim ◽  
Hong-Seok Moon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Formation ◽  
Alveolar Bone ◽  
Human Mesenchymal Stem Cells ◽  
Titanium Implants ◽  
Osteogenic Potential ◽  
Induction Medium ◽  
Radiographic Analysis ◽  
New Bone Formation

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

scholarly journals Mechanistic Illustration: How Newly-Formed Blood Vessels Stopped by the Mineral Blocks of Bone Substitutes Can Be Avoided by Using Innovative Combined Therapeutics

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 952
Author(s):  
Fabien Bornert ◽  
François Clauss ◽  
Guoqiang Hua ◽  
Ysia Idoux-Gillet ◽  
Laetitia Keller ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Bone Formation ◽  
Medicinal Product ◽  
Blood Vessels ◽  
Bone Substitute ◽  
Bone Substitutes ◽  
Bone Defects ◽  
New Bone Formation ◽  
Polymeric Component ◽  
Bone Filling

One major limitation for the vascularization of bone substitutes used for filling is the presence of mineral blocks. The newly-formed blood vessels are stopped or have to circumvent the mineral blocks, resulting in inefficient delivery of oxygen and nutrients to the implant. This leads to necrosis within the implant and to poor engraftment of the bone substitute. The aim of the present study is to provide a bone substitute currently used in the clinic with suitably guided vascularization properties. This therapeutic hybrid bone filling, containing a mineral and a polymeric component, is fortified with pro-angiogenic smart nano-therapeutics that allow the release of angiogenic molecules. Our data showed that the improved vasculature within the implant promoted new bone formation and that the newly-formed bone swapped the mineral blocks of the bone substitutes much more efficiently than in non-functionalized bone substitutes. Therefore, we demonstrated that our therapeutic bone substitute is an advanced therapeutical medicinal product, with great potential to recuperate and guide vascularization that is stopped by mineral blocks, and can improve the regeneration of critical-sized bone defects. We have also elucidated the mechanism to understand how the newly-formed vessels can no longer encounter mineral blocks and pursue their course of vasculature, giving our advanced therapeutical bone filling great potential to be used in many applications, by combining filling and nano-regenerative medicine that currently fall short because of problems related to the lack of oxygen and nutrients.

scholarly journals Maxillary Sinus Augmentation Using Ceramic Alloplastic Granules or Paste: An Experimental Study in Rabbits

2021 ◽  
Vol 9 (6) ◽  
pp. 65
Author(s):  
Michael Medeiros Costa ◽  
Daniele Botticelli ◽  
Ofer Moses ◽  
Yuki Omori ◽  
Shigeo Fujiwara ◽  
...  
Keyword(s):  
Bone Formation ◽  
Maxillary Sinus ◽  
Biological Behavior ◽  
Collagen Membrane ◽  
Alloplastic Material ◽  
New Bone Formation ◽  
Sinus Augmentation ◽  
Beta Tricalcium Phosphate ◽  
Sinus Lifting ◽  
Points Of View

Background: Due to the lack of data comparing the biological behavior of two formulations, granules and paste, of alloplastic graft from microtomographic and histomorphometric points of view, the aim of the present experiment was to compare the histomorphometric and microtomographic healing of two formulations, i.e., granules (MR sites) or paste (MR-inject sites) of an alloplastic graft composed of a combination of beta-tricalcium phosphate and hydroxyapatite used for maxillary sinus lifting. Methods: A sinus lifting procedure was carried out bilaterally in 20 rabbits, and the elevated space was filled with either paste or granules of an alloplastic material. A collagen membrane was placed on the antrostomy and the animals were euthanized after 2 or 10 weeks, 10 animals each group. Microtomographic and histological analyses were performed. Results: Higher proportions of new bone formation were found at the MR, compared to the MR-inject sites both after 2 weeks (2.65 ± 2.89% vs. 0.08 ± 0.12%; p < 0.01) and 10 weeks of healing (34.20 ± 13.86 vs. 23.28 ± 10.35%; p = 0.022). Conclusions: It was concluded that new bone formation was faster in the MR sites, compared to the MR-inject. However, a longer time of healing should be allowed to make final conclusions about the efficiency in bone formation of the paste formulation of the biomaterial used in the present study.

scholarly journals AB1087 DETECTING AXIAL AND PERIPHERAL NEW BONE FORMATION IN SPONDYLOARTHRITIS PATIENTS USING [18F]FLUORIDE PET-CT IMAGING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1832.2-1833
Author(s):  
J. De Jongh ◽  
R. Hemke ◽  
G. C. J. Zwezerijnen ◽  
M. Yaqub ◽  
I. Van der Horst-Bruinsma ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Ct Imaging ◽  
Whole Body ◽  
Therapeutic Effects ◽  
New Bone Formation ◽  
Research Support ◽  
Patella Tendon ◽  
Pet Ct ◽  
18F Fluoride

Background:Bone formation in spondyloarthritis (SpA) is presumably related to local enthesitis/peri-articular inflammation and ultimately may lead to functional limitation (1,2). X-rays only allow long-term monitoring of bone formation (≥2 years) (3). Imaging techniques that can visualize bone formation at an early stage would therefore be valuable. Positron Emission Tomography (PET) using [18F]Fluoride can visualize and quantify (early changes in) bone formation at molecular level (4).Objectives:To investigate the feasibility of [18F]Fluoride to assess new bone formation at axial and peripheral enthesial sites in SpA patients.Methods:Thus far, 5 of the total of 15 patients with clinically active ankylosing spondylitis (AS) (according to modified New York criteria and BASDAI ≥4) and 8 of the 25 patients with active psoriatic arthritis (PsA) (according to CASPAR criteria and ≥1 clinically active enthesitis) were included. Of each patient, a whole body [18F]Fluoride PET-CT scan was performed. All scans were visually judged and scored dichotomously by one reader (blinded for clinical data) for PET-positive lesions in the spine, peripheral enthesis sites and joints. Low dose CT was used for anatomical reference.Results:The study is ongoing, with whole body [18F]Fluoride PET-CT scans available in five AS patients and eight PsA patients. In 4/5 AS scans, at least (≥1) PET positive lesions were found in the cervical, thoracic and/or lumbar vertebrae. These were mainly found in anterior corners of vertebrae and bridging syndesmophytes (Fig. 1A). In all eight PsA patients, at least 1 PET positive lesion was visualized, projected either at the site of a tendon attachment (fascia plantaris, achilles- and patella tendon (Fig 1B)) or peri-articularly (in the ankle or wrist).Fig 1.[18F]Fluoride uptake in the cervical, thoracic and lumbar spine in a clinically active AS patient (A) and in the patella tendon of the right knee in a clinically active PsA patient (B)Conclusion:[18F]Fluoride PET uptake, reflecting new bone formation, can be visualized at heterogeneously distributed enthesis and (peri-)articular sites in AS- and PsA patients. The technique therefore is sensitive to visualize new bone formation and may reflect local disease activity. Additional scans will be collected and analyzed quantitatively, also after anti-TNF or Secukinumab treatment, to further investigate the applicability of [18F]Fluoride PET for monitoring of therapeutic effects on bone formation in SpA.References: :[1]Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53.[2]Rezvani A, Bodur H, Ataman S, Kaya T, Bugdayci DS, Demir SE, et al. Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24(4):651-6.[3]Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52:1000-8..[4]Bruijnen ST, Verweij NJF, van Duivenvoorde L, Bravenboer N, Baeten D, van Denderen JC, et al. [18F]Fluoride PET-CT imaging of bone formation in ankylosing spondylitis before and after 12 weeks of anti-TNF treatment. 2017.Acknowledgments:We thank EULAR Foreum, Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of Interests:Jerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Marleen G.H. van de Sande Grant/research support from: Novartis, Eli lily, UCB, Jansen, Consultant of: Abbvie, Novartis, Eli lily, MSD, Arno Van Kuijk: None declared, Irene Bultink: None declared, Lot Burgemeister: None declared, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared

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