Nonenzymatic Transformation of Amorphous CaCO3into Calcium Phosphate Mineral after Exposure to Sodium Phosphate in Vitro: Implications for in Vivo Hydroxyapatite Bone Formation

ChemBioChem ◽  
2015 ◽  
Vol 16 (9) ◽  
pp. 1323-1332 ◽  
Author(s):  
Werner E. G. Müller ◽  
Meik Neufurth ◽  
Jian Huang ◽  
Kui Wang ◽  
Qingling Feng ◽  
...  
2011 ◽  
Vol 5 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Oliver D Schneider ◽  
Dirk Mohn ◽  
Roland Fuhrer ◽  
Karina Klein ◽  
Käthi Kämpf ◽  
...  

Background: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Materials and Methods: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Results: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. Conclusions: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.


2010 ◽  
Vol 654-656 ◽  
pp. 2065-2070
Author(s):  
Ho Yeon Song ◽  
Young Hee Kim ◽  
Jyoti M. Anirban ◽  
In Seon Byun ◽  
Kyung A Kwak ◽  
...  

Calcium phosphate ceramics such as hydroxy apatite (HA), β-tricalcium phosphate (β-TCP) and bicalcium phosphate (BCP) have been used as a bone graft biomaterial because of their good biocompatibility and similarity of chemical composition to natural bones. To increase the mechanical and osteoconductive properties, the granules and spongy type porous bone graft substitutes were prepared by fibrous monolithic process and polyurethane foam replica methods, respectively. The pore sizes obtained using these approaches ranged between 100-600 µm. The cytotoxicity, cellular proliferation, differentiation and ECM deposition on the bone graft substitutes were observed by SEM and confocal microscopy. Moreover, the scaffolds were implanted in the rabbit femur. New bone formation and biodegradation of bone graft were observed through follow-up X-ray, micro-CT analysis and histological findings. After several months (2, 3, 6, 12 and 24 months) of implantation, new bone formation and ingrowths were observed in defect sites of the animal by CaP ceramics and 2 to 3 times higher bone ingrowths were confirmed than that of the normal trabecular bones in terms of total bone volume (BV).


2016 ◽  
Vol 30 ◽  
pp. 319-333 ◽  
Author(s):  
Patrina S.P. Poh ◽  
Dietmar W. Hutmacher ◽  
Boris M. Holzapfel ◽  
Anu K. Solanki ◽  
Molly M. Stevens ◽  
...  

2018 ◽  
Vol 32 (10) ◽  
pp. 1406-1420 ◽  
Author(s):  
Mirana Taz ◽  
Sang Ho Bae ◽  
Hae Il Jung ◽  
Hyun-Deuk Cho ◽  
Byong-Taek Lee

A variety of synthetic materials are currently in use as bone substitutes, among them a new calcium phosphate-based multichannel, cylindrical, granular bone substitute that is showing satisfactory biocompatibility and osteoconductivity in clinical applications. These cylindrical granules differ in their mechanical and morphological characteristics such as size, diameter, surface area, pore size, and porosity. The aim of this study is to investigate whether the sizes of these synthetic granules and the resultant inter-granular spaces formed by their filling critical-sized bone defects affect new bone formation characteristics and to determine the best formulations from these individual types by combining the granules in different proportions to optimize the bone tissue regeneration. We evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in diameter, combined the granules in two different proportions (wt%), and compared their different mechanical, morphological, and in vitro and in vivo biocompatibility characteristics. We assessed in vitro biocompatibility and cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal imaging. In vivo investigation in a rabbit model indicated that all four samples formed significantly better bone than the control after four weeks and eight weeks of implantation. Micro-computed tomography analysis showed more bone formation by the 1 mm cylindrical granules with 160 ± 10 µm channeled pore and 50% porosity than the other three samples ( p<.05), which we confirmed by histological analysis.


2020 ◽  
Vol 7 ◽  
Author(s):  
Haitao Peng ◽  
Jianxiao Li ◽  
Yanan Xu ◽  
Guoyu Lv

Adequate bone tissue regeneration has been challenging to achieve at critical-sized bone defects caused by disease. Bone tissue engineering using a combination of scaffolds and bioactive factors provides new hope for the treatment of this extreme condition. Icaritin, a herb-derived chemical, has shown its ability to enhance bone formation both in vitro and in vivo, and it has been found that sub-micron surface structure instructs bone formation in calcium phosphate ceramics (CaPs). Here, we evaluated the possibility of using a submicron surface structured CaP ceramic as the carrier of icaritin for bone tissue regeneration in critical-sized bone defects. Icaritin, an herb-derived chemical, was loaded into a submicron surface structured porous calcium phosphate ceramic (Ø12.8 × 3 mm) to get samples with 0, 10, 50, 250, and 1,250 µg icaritin per CaP disc (M0, M10, M50, M250, M1250 groups, respectively). In vitro evaluation with the certain dosages correlated to those released from the samples showed a dose-dependent enhancement of osteogenic differentiation and mineralization of human bone marrow stromal cells with the presence of osteogenic factors in the culture medium, indicating icaritin is an osteopromotive factor. After intramuscular implantation of the samples in dogs for 8 weeks, a dose-dependent of bone formation was seen with enhanced bone formation at the dosage of 50 and 250 µg. To evaluate the in vivo osteogenic potentials of icaritin-containing CaP ceramic scaffolds in the orthopedic site, a 12.8 mm calvarial defect model in rabbits was established. Micro-computed tomography (micro-CT) and histology results at weeks 4, 8 and 12 post-surgery showed more newly formed bone in M250 group, with correspondingly more new vessel ingrowth. The results presented herein suggested that being osteopromotive, icaritin could enhance bone formation initiated by sub-microstructured CaP ceramics and the CaP ceramics scaffold incorporating icaritin is a promising biomaterial for the treatment of critical-sized defect.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meadhbh Á. Brennan ◽  
Mario Barilani ◽  
Francesco Rusconi ◽  
Julien de Lima ◽  
Luciano Vidal ◽  
...  

AbstractBone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, however they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. Conversely, cord blood can be collected non-invasively after birth and contains MSCs (CBMSCs) that can be stored for future use. However, whether CBMSCs can replace BMSCs targeting bone repair is unknown. This study evaluates the in vitro osteogenic potential of unprimed, osteogenically primed, or chondrogenically primed CBMSCs and BMSCs and their in vivo bone forming capacity following ectopic implantation on biphasic calcium phosphate ceramics in nude mice. In vitro, alkaline phosphatase (intracellular, extracellular, and gene expression), and secretion of osteogenic cytokines (osteoprotegerin and osteocalcin) was significantly higher in BMSCs compared with CBMSCs, while CBMSCs demonstrated superior chondrogenic differentiation and secretion of interleukins IL-6 and IL-8. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. However, priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs.


2021 ◽  
Vol 22 (3) ◽  
pp. 1169
Author(s):  
Yuhan Chang ◽  
Chih-Chien Hu ◽  
Ying-Yu Wu ◽  
Steve W. N. Ueng ◽  
Chih-Hsiang Chang ◽  
...  

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.


2021 ◽  
Vol 14 (4) ◽  
pp. 289
Author(s):  
Sana Ansari ◽  
Bregje W. M. de de Wildt ◽  
Michelle A. M. Vis ◽  
Carolina E. de de Korte ◽  
Keita Ito ◽  
...  

Bone is a complex organ maintained by three main cell types: osteoblasts, osteoclasts, and osteocytes. During bone formation, osteoblasts deposit a mineralized organic matrix. Evidence shows that bone cells release extracellular vesicles (EVs): nano-sized bilayer vesicles, which are involved in intercellular communication by delivering their cargoes through protein–ligand interactions or fusion to the plasma membrane of the recipient cell. Osteoblasts shed a subset of EVs known as matrix vesicles (MtVs), which contain phosphatases, calcium, and inorganic phosphate. These vesicles are believed to have a major role in matrix mineralization, and they feature bone-targeting and osteo-inductive properties. Understanding their contribution in bone formation and mineralization could help to target bone pathologies or bone regeneration using novel approaches such as stimulating MtV secretion in vivo, or the administration of in vitro or biomimetically produced MtVs. This review attempts to discuss the role of MtVs in biomineralization and their potential application for bone pathologies and bone regeneration.


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