scholarly journals In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Beom Su Kim ◽  
Feride Shkembi ◽  
Jun Lee
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Release Kinetics ◽  
Human Mesenchymal Stem Cells ◽  
Calvarial Defect ◽  
Defect Model ◽  
Fibrin Gel ◽  
In Vivo Evaluation

Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young’s modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.

scholarly journals Temporal induction of Lhx8 by optogenetic control system for efficient bone regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Delan Huang ◽  
Runze Li ◽  
Jianhan Ren ◽  
Haotian Luo ◽  
Weicai Wang ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Control System ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Blue Light ◽  
Calvarial Defect ◽  
Defect Model ◽  
Alizarin Red ◽  
Optogenetic Control

Abstract Background The spatiotemporal regulation of essential genes is crucial for controlling the growth and differentiation of cells in a precise manner during regeneration. Recently, optogenetics was considered as a potent technology for sophisticated regulation of target genes, which might be a promising tool for regenerative medicine. In this study, we used an optogenetic control system to precisely regulate the expression of Lhx8 to promote efficient bone regeneration. Methods Quantitative real-time PCR and western blotting were used to detect the expression of Lhx8 and osteogenic marker genes. Alkaline phosphatase staining and alizarin red staining were used to detect alkaline phosphatase activity and calcium nodules. A customized optogenetic expression system was constructed to regulate Lhx8, of which the expression was activated in blue light but not in dark. We also used a critical calvarial defect model for the analysis of bone regeneration in vivo. Moreover, micro-computed tomography (micro-CT), three-dimensional reconstruction, quantitative bone measurement, and histological and immunohistochemistry analysis were performed to investigate the formation of new bone in vivo. Results During the osteogenic differentiation of BMSCs, the expression levels of Lhx8 increased initially but then decreased thereafter. Lhx8 promoted the early proliferation of BMSCs but inhibited subsequent osteogenic differentiation. The optogenetic activation of Lhx8 in BMSCs in the early stages of differentiation by blue light stimulation led to a significant increase in cell proliferation, thus allowing a sufficient number of differentiating BMSCs to enter the later osteogenic differentiation stage. Analysis of the critical calvarial defect model revealed that the pulsed optogenetic activation of Lhx8 in transplanted BMSCs over a 5-day period led to a significant increase in the generation of bone in vivo. Conclusions Lhx8 plays a critical role in balancing proliferation and osteogenic differentiation in BMSCs. The optogenetic activation of Lhx8 expression at early stage of BMSCs differentiation led to better osteogenesis, which would be a promising strategy for precise bone regeneration.

scholarly journals Cathelicidin LL37 Promotes Osteogenic Differentiation in vitro and Bone Regeneration in vivo

2021 ◽  
Vol 9 ◽  
Author(s):  
Lunhao Li ◽  
Yiyu Peng ◽  
Qingyue Yuan ◽  
Jing Sun ◽  
Ai Zhuang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Antibacterial Properties ◽  
Bone Defects ◽  
Optimum Concentration ◽  
Calvarial Defect ◽  
Defect Model ◽  
Calvarial Bone ◽  
Rat Calvarial Defect

Different types of biomaterials have been used to repair the defect of bony orbit. However, exposure and infections are still critical risks in clinical application. Biomaterials with characteristics of osteogenesis and antibiosis are needed for bone regeneration. In this study, we aimed to characterize the antimicrobial effects of cathelicidin-LL37 and to assess any impacts on osteogenic activity. Furthermore, we attempted to demonstrate the feasibility of LL37 as a potential strategy in the reconstruction of clinical bone defects. Human adipose-derived mesenchyme stem cells (hADSCs) were cultured with different concentrations of LL37 and the optimum concentration for osteogenesis was selected for further in vitro studies. We then evaluated the antibiotic properties of LL37 at the optimum osteogenic concentration. Finally, we estimated the efficiency of a PSeD/hADSCs/LL37 combined scaffold on reconstructing bone defects in the rat calvarial defect model. The osteogenic ability on hADSCs in vitro was shown to be dependent on the concentration of LL37 and reached a peak at 4 μg/ml. The optimum concentration of LL37 showed good antimicrobial properties against Escherichia coli and Staphylococcus anurans. The combination scaffold of PSeD/hADSCs/LL37 showed superior osteogenic properties compared to the PSeD/hADSCs, PSeD, and control groups scaffolds, indicating a strong bone reconstruction effect in the rat calvarial bone defect model. In Conclusion, LL37 was shown to promote osteogenic differentiation in vitro as well as antibacterial properties. The combination of PSeD/hADSCs/LL37 was advantageous in the rat calvarial defect reconstruction model, showing high potential in clinical bone regeneration.

In vitro and in vivo evaluation of novel Tadalafil/β-TCP/Collagen scaffold for bone regeneration: A rabbit critical-size calvarial defect study

2019 ◽  
Vol 39 (3) ◽  
pp. 789-796 ◽  
Author(s):  
Reza Sayyad Soufdoost ◽  
Mohsen Yazdanian ◽  
Elaheh Tahmasebi ◽  
Alireza Yazdanian ◽  
Hamid Tebyanian ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Critical Size ◽  
Collagen Scaffold ◽  
Calvarial Defect ◽  
In Vivo Evaluation

scholarly journals Canine Mesenchymal Stromal Cell-Mediated Bone Regeneration is Enhanced in the Presence of Sub-Therapeutic Concentrations of BMP-2 in a Murine Calvarial Defect Model

2021 ◽  
Vol 9 ◽  
Author(s):  
Lauren K. Dobson ◽  
Suzanne Zeitouni ◽  
Eoin P. McNeill ◽  
Robert N. Bearden ◽  
Carl A. Gregory ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Healing ◽  
Human Mscs ◽  
Calvarial Defect ◽  
Defect Model ◽  
Alp Activity ◽  
Calvarial Defects ◽  
Species Specific

Novel bone regeneration strategies often show promise in rodent models yet are unable to successfully translate to clinical therapy. Sheep, goats, and dogs are used as translational models in preparation for human clinical trials. While human MSCs (hMSCs) undergo osteogenesis in response to well-defined protocols, canine MSCs (cMSCs) are more incompletely characterized. Prior work suggests that cMSCs require additional agonists such as IGF-1, NELL-1, or BMP-2 to undergo robust osteogenic differentiation in vitro. When compared directly to hMSCs, cMSCs perform poorly in vivo. Thus, from both mechanistic and clinical perspectives, cMSC and hMSC-mediated bone regeneration may differ. The objectives of this study were twofold. The first was to determine if previous in vitro findings regarding cMSC osteogenesis were substantiated in vivo using an established murine calvarial defect model. The second was to assess in vitro ALP activity and endogenous BMP-2 gene expression in both canine and human MSCs. Calvarial defects (4 mm) were treated with cMSCs, sub-therapeutic BMP-2, or the combination of cMSCs and sub-therapeutic BMP-2. At 28 days, while there was increased healing in defects treated with cMSCs, defects treated with cMSCs and BMP-2 exhibited the greatest degree of bone healing as determined by quantitative μCT and histology. Using species-specific qPCR, cMSCs were not detected in relevant numbers 10 days after implantation, suggesting that bone healing was mediated by anabolic cMSC or ECM-driven cues and not via engraftment of cMSCs. In support of this finding, defects treated with cMSC + BMP-2 exhibited robust deposition of Collagens I, III, and VI using immunofluorescence. Importantly, cMSCs exhibited minimal ALP activity unless cultured in the presence of BMP-2 and did not express endogenous canine BMP-2 under any condition. In contrast, human MSCs exhibited robust ALP activity in all conditions and expressed human BMP-2 when cultured in control and osteoinduction media. This is the first in vivo study in support of previous in vitro findings regarding cMSC osteogenesis, namely that cMSCs require additional agonists to initiate robust osteogenesis. These findings are highly relevant to translational cell-based bone healing studies and represent an important finding for the field of canine MSC-mediated bone regeneration.

Melatonin decorated 3D-printed beta-tricalcium phosphate scaffolds promoting bone regeneration in a rat calvarial defect model

2019 ◽  
Vol 7 (20) ◽  
pp. 3250-3259 ◽  
Author(s):  
Yali Miao ◽  
Yunhua Chen ◽  
Xiao Liu ◽  
Jingjing Diao ◽  
Naru Zhao ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Tricalcium Phosphate ◽  
Calvarial Defect ◽  
Defect Model ◽  
Beta Tricalcium Phosphate ◽  
3D Printed ◽  
Rat Calvarial Defect

3D-printed β-TCP scaffolds decorated with melatonin via dopamine mussel-inspired chemistry enhance the osteogenesis and in vivo bone regeneration.

scholarly journals DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Release Profile ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Release Mechanism ◽  
In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

scholarly journals In Vitro and In Vivo Evaluation of a Three-Dimensional Porous Multi-Walled Carbon Nanotube Scaffold for Bone Regeneration

Nanomaterials ◽  
2017 ◽  
Vol 7 (2) ◽  
pp. 46 ◽  
Author(s):  
Manabu Tanaka ◽  
Yoshinori Sato ◽  
Mei Zhang ◽  
Hisao Haniu ◽  
Masanori Okamoto ◽  
...  
Keyword(s):  
Carbon Nanotube ◽  
Bone Regeneration ◽  
Three Dimensional ◽  
In Vivo Evaluation ◽  
Multi Walled Carbon Nanotube

In Vitro and In Vivo Evaluation of a nHA/PA66 Composite Membrane for Guided Bone Regeneration

2011 ◽  
Vol 22 (1-3) ◽  
pp. 263-275 ◽  
Author(s):  
Jidong Li ◽  
Yi Man ◽  
Yi Zuo ◽  
Li Zhang ◽  
Cui Huang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Composite Membrane ◽  
Guided Bone Regeneration ◽  
In Vivo Evaluation
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