scholarly journals Local controlled release of simvastatin and PDGF from core/shell microspheres promotes bone regeneration in vivo

RSC Advances ◽  
2017 ◽  
Vol 7 (32) ◽  
pp. 19621-19629 ◽  
Author(s):  
Mingming Yan ◽  
Jiangdong Ni ◽  
Hongwei Shen ◽  
Deye Song ◽  
Muliang Ding ◽  
...  
Keyword(s):  
Controlled Release ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Core Shell ◽  
Potent Stimulator

Simvastatin is demonstrated to be a potent stimulator for bone formation.

scholarly journals The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Growth Promotion ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Therapeutic Molecules ◽  
Positive Effect

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.

scholarly journals Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics

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 ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Recipient Cell ◽  
Organic Matrix ◽  
Matrix Vesicles ◽  
Matrix Mineralization

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.

scholarly journals Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Philipp S. Lienemann ◽  
Stéphanie Metzger ◽  
Anna-Sofia Kiveliö ◽  
Alain Blanc ◽  
Panagiota Papageorgiou ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defects ◽  
Histological Evaluation ◽  
Biological Processes ◽  
Micro Ct ◽  
Pinhole Spect

Abstract Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

Effect of Silicate Incorporation in Alpha-Tricalcium Phosphate on Behaviors of Osteoblast-Like Cells

2016 ◽  
Vol 720 ◽  
pp. 90-94
Author(s):  
Masanobu Kamitakahara ◽  
Takashi Shirato ◽  
Taishi Yokoi ◽  
Hideaki Matsubara ◽  
Yasuaki Shibata ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Tricalcium Phosphate ◽  
Proliferation And Differentiation ◽  
Porous Silicate

Silicate-containing alpha-tricalcium phosphate (α-TCP) ceramics are expected to be useful scaffolds for bone regeneration because α-TCP shows high biodegradability and silicate ions are expected to promote the bone formation. We previously revealed that the porous silicate-containing α-TCP granules provided earlier bone formation and showed lower biodegradability than the porous silicate-free α-TCP granules in vivo. In order to reveal the mechanism of the bone formation promoted by silicate incorporation, the proliferation and differentiation of osteoblast-like cells on the silicate-containing and silicate-free α-TCP ceramics were examined in vitro. The silicate incorporation in α-TCP promoted the differentiation of osteoblast-like cells, and it might be one of the factors to promote bone formation In Vivo.

scholarly journals Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Rasmus Hestehave Pedersen ◽  
Marina Rasmussen ◽  
Søren Overgaard ◽  
Ming Ding
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Volume Fraction ◽  
Structure Type ◽  
Osteoporotic Bone ◽  
Bone Volume Fraction ◽  
Defect Repair ◽  
Paired Design ◽  
Tibia Defect

This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15) on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of proximal tibial defects were evaluated at 4 time points. 21 days after surgery, tibias were harvested for histology and histomorphometry. Significantly increased bone volume fraction, surface density, and connectivity were seen in all groups at days 14 and 21 compared with day 0. Moreover, the structure type of ABM/P-15 group was changed toward typical plate-like structure. Microarchitectural properties of ABM/P-15 treated newly formed bones at 21 days were similar in normal and osteoporotic rats. Histologically, significant bone formation was seen in all groups. Interestingly, significantly increased bone formation was seen in osteoporotic rats treated with ABM/P-15 indicating optimized healing potential. Empty defects showed lower healing potential in osteoporotic bone. In conclusion, ABM/P-15 accelerated bone regeneration in osteoporotic rats but did not enhance bone regeneration in normal rats.

The potential of stromal cell-derived factor-1 delivery using a collagen membrane for bone regeneration

2017 ◽  
Vol 31 (7) ◽  
pp. 1049-1061 ◽  
Author(s):  
Tadahiro Takayama ◽  
Jisen Dai ◽  
Keita Tachi ◽  
Ryutaro Shohara ◽  
Hironori Kasai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Stromal Cell ◽  
In Vitro Studies ◽  
New Bone Formation ◽  
Stromal Cell Derived Factor

Stromal cell-derived factor-1 (SDF-1) is a cytokine that is important in stem and progenitor cell recruitment in tissue repair after injury. Regenerative procedures using collagen membranes (CMs) are presently well established in periodontal and implant dentistry. The objective of this study is to test the subsequent effects of the released SDF-1 from a CM on bone regeneration compared to platelet-derived growth factor (PDGF) in vitro and in vivo. For in vitro studies, cell proliferation, alkaline phosphatase activity, and osteoblastic differentiation marker genes were assessed after MC3T3-E1 mouse preosteoblasts were cultured with CMs containing factors. In vivo effects were investigated by placement of CMs containing SDF-1 or PDGF using a rat mandibular bone defect model. At 4 weeks after the surgery, the new bone formation was measured using micro-computed tomography (µCT) and histological analysis. The results of in vitro studies revealed that CM delivery of SDF-1 significantly induced cell proliferation, ALP activity, and gene expression of all osteogenic markers compared to the CM alone or control, similar to PDGF. Quantitative and qualitative µCT analysis for volume of new bone formation and the percentage of new bone area showed that SDF-1-treated groups significantly increased and accelerated bone regeneration compared to control and CM alone. The enhancement of bone formation in SDF-1-treated animals was dose-dependent and with levels similar to those measured with PDGF. These results suggest that a CM with SDF-1 may be a great candidate for growth factor delivery that could be a substitute for PDGF in clinical procedures where bone regeneration is necessary.

scholarly journals Increased BMSC Exosomal miR-140-3p Alleviates Bone Degradation and Promotes Bone Restoration by Targeting Plxnb1 in Diabetic Rats

2021 ◽  
Author(s):  
Ning Wang ◽  
Xuanchen Liu ◽  
Zhen Tang ◽  
Xinghui Wei ◽  
Hui Dong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Diabetic Rats ◽  
Osteogenic Potential ◽  
Bone Degradation ◽  
Defect Repair

Abstract Background: Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results: The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions: Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.

scholarly journals Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects

2020 ◽  
Vol 21 (15) ◽  
pp. 5550
Author(s):  
Chih-Chien Hu ◽  
Chih-Hsiang Chang ◽  
Yi-min Hsiao ◽  
Yuhan Chang ◽  
Ying-Yu Wu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Healing ◽  
Lipoteichoic Acid ◽  
Calcium Deposition ◽  
Micro Computed Tomography ◽  
Osteoclast Activation

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.

scholarly journals Porcine Collagen–Bone Composite Induced Osteoblast Differentiation and Bone Regeneration In Vitro and In Vivo

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 93 ◽  
Author(s):  
Eisner Salamanca ◽  
Chia Chen Hsu ◽  
Wan Ling Yao ◽  
Cheuk Sing Choy ◽  
Yu Hwa Pan ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Osteoblast Differentiation ◽  
Critical Size ◽  
Guided Bone Regeneration ◽  
Autogenous Bone ◽  
Critical Size Defects ◽  
Bone Formation Markers

Due to autogenous bone limitations, some substitute bone grafts were developed. Collagenated porcine graft (CPG) is able to regenerate new bone, although the number of studies is insufficient, highlighting the need for future studies to better understand the biomaterial. In order to understand better CPG′s possible dental guided bone regeneration indications, the aim of this work was to determine CPG′s biological capacity to induce osteoblast differentiation in vitro and guided bone regeneration in vivo, whilst being compared with commercial hydroxyapatite and beta tricalcium phosphate (HA/β-TCP) and porcine graft alone. Cell cytotoxicity (WST-1), alkaline phosphatase activity (ALP), and real-time polymerase chain reaction (qPCR) were assessed in vitro. Critical size defects of New Zealand white rabbits were used for the in vivo part, with critical size defect closures and histological analyses. WST-1 and ALP indicated that CPG directly stimulated a greater proliferation and confluency of cells with osteoblastic differentiation in vitro. Gene sequencing indicated stable bone formation markers, decreased resorption makers, and bone remodeling coupling factors, making the transition from osteoclast to osteoblast expression at the end of seven days. CPG resulted in the highest new bone regeneration by osteoconduction in critical size defects of rabbit calvaria at eight weeks. Nonetheless, all biomaterials achieved nearly complete calvaria defect closure. CPG was found to be osteoconductive, like porcine graft and HA/β-TCP, but with higher new bone formation in critical size defects of rabbit calvaria at eight weeks. CPG can be used for different dental guided bone regeneration procedures; however, further studies are necessary.

scholarly journals Apoptosis Repressor with Caspase Recruitment Domain (ARC) Promotes Bone Regeneration of Bone Marrow-Derived Mesenchymal Stem Cells by Activating Fgf-2/PI3K/Akt Signaling

2021 ◽  
Author(s):  
Longwei Hu ◽  
Yang Wang ◽  
Hongya Pan ◽  
Kathreena Kadir ◽  
Jin Wen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Cell Apoptosis ◽  
New Bone Formation ◽  
Caspase Recruitment Domain

Abstract Objectives: This study aims to investigate whether Apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow -derived mesenchymal stem cells (BMSCs). Materials and methods: The lentivirus transfection method was used to establish ARC -overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC -overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs. Results: ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway. Conclusions: The present study suggests that A RC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

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