Bone regeneration strategy by different sized multichanneled biphasic calcium phosphate granules: In vivo evaluation in rabbit model

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 444
Author(s):  
Alaa Mahran ◽  
Sayed Ismail ◽  
Ayat A. Allam

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.


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.


2020 ◽  
Vol 15 (5) ◽  
pp. 055038
Author(s):  
Sirirat T. Rattanachan ◽  
Nuan La-ong Srakaew ◽  
Paritat Thaitalay ◽  
Oranich Thongsri ◽  
Rawee Dangviriyakul ◽  
...  

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).


2012 ◽  
Vol 23 (7) ◽  
pp. 1785-1796 ◽  
Author(s):  
A. Gala-García ◽  
M. B. H. Carneiro ◽  
G. A. B. Silva ◽  
L. S. Ferreira ◽  
L. Q. Vieira ◽  
...  

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

2020 ◽  
Vol 21 (15) ◽  
pp. 5550
Author(s):  
Chih-Chien Hu ◽  
Chih-Hsiang Chang ◽  
Yi-min Hsiao ◽  
Yuhan Chang ◽  
Ying-Yu Wu ◽  
...  

Lipoteichoic acid (LTA) is a cell wall component of Gram-positive bacteria. Limited data suggest that LTA is beneficial for bone regeneration in vitro. Thus, we used a mouse model of femoral defects to explore the effects of LTA on bone healing in vivo. Micro-computed tomography analysis and double-fluorochrome labeling were utilized to examine whether LTA can accelerate dynamic bone formation in vivo. The effects of LTA on osteoblastogenesis and osteoclastogenesis were also studied in vitro. LTA treatment induced prompt bone bridge formation, rapid endochondral ossification, and accelerated healing of fractures in mice with femoral bone defects. In vitro, LTA directly enhanced indicators of osteogenic factor-induced MC3T3-E1 cell differentiation, including alkaline phosphatase activity, calcium deposition and osteopontin expression. LTA also inhibited osteoclast activation induced by receptor activator of nuclear factor-kappa B ligand. We identified six molecules that may be associated with LTA-accelerated bone healing: monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 1, cystatin C, growth/differentiation factor 15, endostatin and neutrophil gelatinase-associated lipocalin. Finally, double-fluorochrome, dynamic-labeling data indicated that LTA significantly enhanced bone-formation rates in vivo. In conclusion, our findings suggest that LTA has promising bone-regeneration properties.


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