ONO-1301 loaded nanocomposite scaffolds modulate cAMP mediated signaling and induce new bone formation in critical sized bone defect

2020 ◽  
Vol 8 (3) ◽  
pp. 884-896 ◽  
Author(s):  
Shruthy Kuttappan ◽  
Jun-ichiro Jo ◽  
Deepthy Menon ◽  
Takuya Ishimoto ◽  
Takayoshi Nakano ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Formation ◽  
Bone Defect ◽  
Small Molecule ◽  
Bone Defects ◽  
New Bone Formation ◽  
Osteoinductive Potential ◽  
Nanocomposite Scaffolds

Small molecule ONO-1301 displayed chemotactic and osteoinductive potential in critical sized bone defects and suggested as a replacement for high cost and unstable protein based growth factors.

scholarly journals Poly(POG)n loaded with recombinant human bone morphogenetic protein-2 accelerates new bone formation in a critical-sized bone defect mouse model

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ryo Tazawa ◽  
Kentaro Uchida ◽  
Hiroaki Minehara ◽  
Terumasa Matsuura ◽  
Tadashi Kawamura ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Bone Defect ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Morphogenetic Protein ◽  
Large Bone ◽  
Large Bone Defects

Abstract Background Delivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects. However, the administration of bovine proteins to humans is associated with the risk of zoonotic complications. We therefore examined the effect of combining BMP-2 with collagen-like peptides, poly(POG)n, in a critical-sized bone defect mouse model. Methods A 2-mm critical-sized bone defect was created in the femur of 9-week-old male C57/BL6J mice. Mice were randomly allocated into one of four treatment groups (n = 6 each): control (no treatment), poly(POG)n only, 0.2 μg, or 2.0 μg BMP-2 with poly(POG)n. New bone formation was monitored using soft X-ray radiographs, and bone formation at the bone defect site was examined using micro-computed tomography and histological examination at 4 weeks after surgery. Results Administration of 2.0 μg of BMP-2 with poly(POG)n promoted new bone formation and resulted in greater bone volume and bone mineral content than that observed in the control group and successfully achieved consolidation. In contrast, bone formation in all other groups was scarce. Conclusions Our findings suggest the potential of BMP-2 with poly(POG)n as a material, free from animal-derived collagen, for the treatment of large bone defects.

scholarly journals Synthetic Scaffold/Dental Pulp Stem Cell (DPSC) Tissue Engineering Constructs for Bone Defect Treatment: An Animal Studies Literature Review

2020 ◽  
Vol 21 (24) ◽  
pp. 9765
Author(s):  
Felice Lorusso ◽  
Francesco Inchingolo ◽  
Gianna Dipalma ◽  
Francesca Postiglione ◽  
Stefania Fulle ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Formation ◽  
Bone Defect ◽  
Dental Pulp ◽  
Animal Studies ◽  
Meta Analysis ◽  
Bone Defects ◽  
New Bone Formation ◽  
Synthetic Scaffold ◽  
Bone Defect Treatment

Background: Recently a greater interest in tissue engineering for the treatment of large bone defect has been reported. The aim of the present systematic review and meta-analysis was to investigate the effectiveness of dental pulp stem cells and synthetic block complexes for bone defect treatment in preclinical in vivo articles. Methods: The electronic database and manual search was conducted on Pubmed, Scopus, and EMBASE. The papers identified were submitted for risk-of-bias assessment and classified according to new bone formation, bone graft characteristics, dental pulp stem cells (DPSCs) culture passages and amount of experimental data. The meta-analysis assessment was conducted to assess new bone formation in test sites with DPSCs/synthetic blocks vs. synthetic block alone. Results: The database search identified a total of 348 papers. After the initial screening, 30 studies were included, according to the different animal models: 19 papers on rats, 3 articles on rabbits, 2 manuscripts on sheep and 4 papers on swine. The meta-analysis evaluation showed a significantly increase in new bone formation in favor of DPSCs/synthetic scaffold complexes, if compared to the control at 4 weeks (Mean Diff: 17.09%, 95% CI: 15.16–18.91%, p < 0.01) and at 8 weeks (Mean Diff: 14.86%, 95% CI: 1.82–27.91%, p < 0.01) in rats calvaria bone defects. Conclusion: The synthetic scaffolds in association of DPSCs used for the treatment of bone defects showed encouraging results of early new bone formation in preclinical animal studies and could represent a useful resource for regenerative bone augmentation procedures

scholarly journals Strategies for stimulation of new bone formation: a critical review

2011 ◽  
Vol 22 (6) ◽  
pp. 443-448 ◽  
Author(s):  
Juliana Alves Peres ◽  
Teresa Lamano
Keyword(s):  
Gene Therapy ◽  
Growth Factors ◽  
Bone Formation ◽  
Critical Review ◽  
Bone Defects ◽  
Autogenous Bone ◽  
Graft Material ◽  
New Bone Formation ◽  
Advantages And Disadvantages ◽  
Dental Practices

Large bone defects, congenital or caused by diseases, trauma or surgery, do not heal spontaneously and are usually a clinical challenge in the orthopedic and dental practices. A critical review concerning strategies to substitute lost bone or stimulate osteogenesis was undertaken. Pivotal concepts ranging from traditional bone grafting and use of biomaterials to local application of growth factors and gene therapy were addressed, including critical comments on the efficacy and safety, difficulties, advantages and disadvantages of each method. The most predictable results are still obtained with autogenous bone graft, despite the inconveniences of morbidity and limited availability of graft material. Satisfactory results have been reported for recombinant bone morphogenetic proteins (rhBMPs)-2 and -7, which distinguish for their osteoinductive property, the difficulty being the need for a degradable carrier that allows its continuous release in a rate compatible to that of new bone formation. Other bone growth factors are currently under evaluation in preclinical models of bone defects; however their efficacy is also dependent on the competence of a delivery strategy and on an appropriate delineation of “which one”, “which dose” and “when”. Parameters of efficiency and safety for gene therapy are still being established. In conclusion, given the variety of growth factors involved in the complex cascade of bone repair and the biological interactions between them, it remains a challenge to accomplish the ideal strategy to stimulate reparational bone formation in specific conditions of the medical as in the dental practices.

scholarly journals Cyclodextrin-Based Supramolecular Complexes of Osteoinductive Agents for Dental Tissue Regeneration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 136
Author(s):  
Masahiko Terauchi ◽  
Atsushi Tamura ◽  
Yoshinori Arisaka ◽  
Hiroki Masuda ◽  
Tetsuya Yoda ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Formation ◽  
Small Molecule ◽  
Tissue Regeneration ◽  
Alveolar Bone ◽  
Inclusion Complexation ◽  
Dental Tissue ◽  
Polyelectrolyte Complexes ◽  
Small Molecule Drugs

Oral tissue regeneration has received growing attention for improving the quality of life of patients. Regeneration of oral tissues such as alveolar bone and widely defected bone has been extensively investigated, including regenerative treatment of oral tissues using therapeutic cells and growth factors. Additionally, small-molecule drugs that promote bone formation have been identified and tested as new regenerative treatment. However, treatments need to progress to realize successful regeneration of oral functions. In this review, we describe recent progress in development of regenerative treatment of oral tissues. In particular, we focus on cyclodextrin (CD)-based pharmaceutics and polyelectrolyte complexation of growth factors to enhance their solubility, stability, and bioactivity. CDs can encapsulate hydrophobic small-molecule drugs into their cavities, resulting in inclusion complexes. The inclusion complexation of osteoinductive small-molecule drugs improves solubility of the drugs in aqueous solutions and increases in vitro osteogenic differentiation efficiency. Additionally, various anionic polymers such as heparin and its mimetic polymers have been developed to improve stability and bioactivity of growth factors. These polymers protect growth factors from deactivation and degradation by complex formation through electrostatic interaction, leading to potentiation of bone formation ability. These approaches using an inclusion complex and polyelectrolyte complexes have great potential in the regeneration of oral tissues.

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 Physical and Histological Comparison of Hydroxyapatite, Carbonate Apatite, and β-Tricalcium Phosphate Bone Substitutes

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1993 ◽  
Author(s):  
Kunio Ishikawa ◽  
Youji Miyamoto ◽  
Akira Tsuchiya ◽  
Koichiro Hayashi ◽  
Kanji Tsuru ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Defect ◽  
Tricalcium Phosphate ◽  
Bone Substitutes ◽  
Physiological Solution ◽  
Tissue Response ◽  
Histological Evaluation ◽  
Carbonate Apatite ◽  
Artificial Bone ◽  
New Bone Formation

Three commercially available artificial bone substitutes with different compositions, hydroxyapatite (HAp; Neobone®), carbonate apatite (CO3Ap; Cytrans®), and β-tricalcium phosphate (β-TCP; Cerasorb®), were compared with respect to their physical properties and tissue response to bone, using hybrid dogs. Both Neobone® (HAp) and Cerasorb® (β-TCP) were porous, whereas Cytrans® (CO3Ap) was dense. Crystallite size and specific surface area (SSA) of Neobone® (HAp), Cytrans® (CO3Ap), and Cerasorb® (β-TCP) were 75.4 ± 0.9 nm, 30.8 ± 0.8 nm, and 78.5 ± 7.5 nm, and 0.06 m2/g, 18.2 m2/g, and 1.0 m2/g, respectively. These values are consistent with the fact that both Neobone® (HAp) and Cerasorb® (β-TCP) are sintered ceramics, whereas Cytrans® (CO3Ap) is fabricated in aqueous solution. Dissolution in pH 5.3 solution mimicking Howship’s lacunae was fastest in CO3Ap (Cytrans®), whereas dissolution in pH 7.3 physiological solution was fastest in β-TCP (Cerasorb®). These results indicated that CO3Ap is stable under physiological conditions and is resorbed at Howship’s lacunae. Histological evaluation using hybrid dog mandible bone defect model revealed that new bone was formed from existing bone to the center of the bone defect when reconstructed with CO3Ap (Cytrans®) at week 4. The amount of bone increased at week 12, and resorption of the CO3Ap (Cytrans®) was confirmed. β-TCP (Cerasorb®) showed limited bone formation at week 4. However, a larger amount of bone was observed at week 12. Among these three bone substitutes, CO3Ap (Cytrans®) demonstrated the highest level of new bone formation. These results indicate the possibility that bone substitutes with compositions similar to that of bone may have properties similar to those of bone.

scholarly journals BMSCs Seeding in Different Scaffold Incorporation with Hyperbaric Oxygen Treat Seawater Immersed Bony Defect

2021 ◽  
Author(s):  
gan zhang ◽  
Xiaosong Chen ◽  
Xunsheng Cheng ◽  
Xiuwu Ma ◽  
Congcong Chen
Keyword(s):  
Bone Formation ◽  
Bone Defect ◽  
Medullary Canal ◽  
Bony Defect ◽  
New Bone Formation ◽  
X Ray ◽  
New Zealand White Rabbits ◽  
Group A ◽  
Group B ◽  
Group D

Abstract Introduction: The experiment was undertaken to estimate the effect of BMSCs seeding in different scaffold incorporation with HBO on the repair of seawater immersed bone defect. And future compared n-HA/PLGA with β-TCP/PLGA as scaffold in treatment effect of seawater immersed bone defect.Methods: 60 New Zealand White rabbits with standard seawater defect in radius were randomly divided to group A (implant with nothing), group B (implanted with atuogenous bone), group C (implanted with n-HA/PLGA/BMSCs, and Group D ( implanted with β-TCP/PLGA/BMSCs). After implant, each rabbit receive HBO treatment at 2.4 ATA 100% oxygen for 120 minutes per day for 2 weeeks. Radiograph, histological and biomechanical examination were used to analyze osteogenesis.Result: X-ray analysis show that n-HA/PLGA/BMSCs and β-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was lager than in group D or group A, and close to group B (P<0.05). After 12 weeks, in group A, defect without scaffold show a loose connect tissue filled in the areas. The medullary canal in group B was recanalizated. Defect in group C and D show a larger number of wove bone formation. The new wove bone formation in defect areas in group C was lager than D. The mechanical examination revealed ultimate strength at 12 weeks were group D>group C>group B>group A(P<0.05).Conclusion: Scaffold of n-HA/PLGA and β-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater immersed bone defect, and n-HA/PLGA was more excellent than β-TCP/PLGA.

Bioactivity of the Two Kinds of Biodegradable Composite Membrane Containing Oriented Needle-Like Apatite

2005 ◽  
Vol 284-286 ◽  
pp. 811-814 ◽  
Author(s):  
Toshiki Itoh ◽  
Seiji Ban ◽  
T. Watanabe ◽  
Shozo Tsuruta ◽  
Takahiro Kawai ◽  
...  
Keyword(s):  
Bone Formation ◽  
Composite Membrane ◽  
Composite Membranes ◽  
Bone Defects ◽  
Thigh Muscle ◽  
Poly Lactic Acid ◽  
New Bone Formation ◽  
Biodegradable Composite ◽  
Morphogenetic Protein ◽  
Old Mice

It is well known that bone morphogenetic protein (BMP) induces bone formation and requires for carriers. Poly-lactic acid / poly-glycolic acid (PLGA) is frequently used as the carriers of BMP. We developed a biodegradable composite PLGA membrane, which was containing oriented needle-like apatite with BMP. The composite membranes were implanted into the thigh muscle pouch of 3-week-old-mice. At 3 weeks after implantation, the implanted area was observed by optical microscopy. The composite membrane containing oriented needle-like apatite with BMP induced new bone formation. It seems that this composite membrane might be a scaffold of BMP and promoting the healing of bone defects.

Bone Regenerative Properties of Injectable Calcium Phosphate/PLGA Cement in an Alveolar Bone Defect

2012 ◽  
Vol 529-530 ◽  
pp. 300-303 ◽  
Author(s):  
R.P. Félix Lanao ◽  
J.W.M. Hoekstra ◽  
Joop G.C. Wolke ◽  
Sander C.G. Leeuwenburgh ◽  
A.S. Plachokova ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Calcium Phosphate ◽  
Bone Formation ◽  
Bone Substitute ◽  
Alveolar Bone ◽  
Bone Defects ◽  
Plga Microspheres ◽  
Bone Substitute Material ◽  
Substitute Material

Periodontitis is one of the most common inflammatory diseases, which can lead to early tooth loss. The conventional treatment of periodontitis is to arrest the disease progression. Most reconstructive procedures involve application of bone substitutes, barrier membranes or a combination of both into the bony defects. Calcium phosphate cements (CPCs) are the predominant type of bone substitute material used for reasons of injectability and hence perfect filling potential for bone defects. Recently, injectable apatitic CPCs demonstrated to be more rapidly degradable when combined with poly (lactic-co-glycolic) acid (PLGA) microspheres. Further, PLGA microspheres can be used as a delivery vehicle for growth factors. In this study, the performance of injectable CPCs as a bone substitute material for alveolar bone defects created in Beagle dogs was evaluated. Four CPC-formulations were generated by incorporating hollow or dense PLGA microspheres, either or not loaded with the growth factors (platelet derived growth factor (PDGF) and insulin-like growth factor (IGF). Implantation period was 8 weeks. Bone formation was based on histological and histomorphometrical evaluation. The results demonstrated that filling alveolar bone defects with CPC-dense PLGA revealed significant more bone formation compared to CPC-hollow PLGA either or not loaded with IGF and PDGF. In summary, we conclude that injectable CPC-dense PLGA composites proved to be the most suitable material for a potential use as off the shelf material due to its good biocompatibility, enhanced degradability and subsequent bone formation.

scholarly journals Histologic, Histomorphometric, and Clinical Analysis of the Effects of Growth Factors in a Fibrin Network Used in Maxillary Sinus Augmentation

2020 ◽  
Vol 17 (6) ◽  
pp. 1918
Author(s):  
Ihsan Caglar Cinar ◽  
Bahattin Alper Gultekin ◽  
Alper Saglanmak ◽  
Serdar Yalcin ◽  
Vakur Olgac ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Formation ◽  
Maxillary Sinus ◽  
Clinical Analysis ◽  
Controlled Clinical Trial ◽  
New Bone Formation ◽  
Sinus Augmentation ◽  
Volume Stability ◽  
Fibrin Network ◽  
Significant Difference

This randomized controlled clinical trial evaluated the effect of mineralized plasmatic matrix (MPM), comprised of synthetic graft and platelet concentrates, on new bone formation and volume stability over time in maxillary sinus lifting (MSL). Unilateral MSL was performed in 20 patients with either beta-tricalcium phosphate (β-TCP) or MPM grafts (10 sinuses each). Six months postsurgery, specimens were obtained with a trephine bur prior to implant placement in 39 cases. Volumetric changes in sinus augmentation were analyzed between 1 week (T-I) and 6 months (T-II) postsurgery. Histomorphometric and histological analyses of biopsy samples revealed mean new bone percentages of 35.40% ± 9.09% and 26.92% ± 7.26% and residual graft particle areas of 23.13% ± 6.16% and 32.25% ± 8.48% in the MPM and β-TCP groups, respectively (p < 0.05). The mean soft-tissue areas in the MPM and β-TCP groups were 41.48% ± 8.41% and 40.83% ± 8.86%, respectively (p > 0.05). Graft reductions between baseline and 6-months postprocedure in the β-TCP and MPM groups were 17.12% ± 13.55% and 14.41% ± 12.87%, respectively, with significant graft volume reduction observed in both groups (p < 0.05) while there is no significant difference between MPM and β-TCP groups (p > 0.05). Thus, MPM, representing growth factors in a fibrin network, increases new bone formation and has acceptable volume stability in MSL procedures

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