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Nuno M Oliveira, Rui L Reis, João F Mano
Biological tissues are recurrently exposed to several dynamic mechanical forces that influence cell behavior. On this work, the focus is on the shear stress forces induced by fluid flow. The study of flow-induced effects on cells leads to important advances in cardiovascular, cancer, stem cell, and bone biology understanding. These studies are performed using cell culture flow (CCF) systems, mainly parallel plate flow chambers (PPFC), and microfluidic systems. Here, it is proposed an original CCF system based on the open fluidics concept...
October 16, 2017: Advanced Healthcare Materials
Seong-Hee Moon, Ikyon Kim, Seong Hwan Kim
Bone morphogenetic protein 2 (BMP-2) has been used clinically to encourage bone regeneration; although, there can be major side effects with larger doses. Therefore, there is a need to identify new small molecules to potentiate the osteogenic action of BMP-2. In this study, we investigated the effect of mollugin on bone formation in murine bi-potential mesenchymal progenitor C2C12 cells by combination with BMP-2. We found mollugin could enhance the BMP-2-mediated osteoblast differentiation of C2C12 cells. This was accompanied by the induction of other osteogenic BMPs...
October 12, 2017: Archives of Pharmacal Research
Rosanne M Raftery, Irene Mencía Castaño, Gang Chen, Brenton Cavanagh, Brian Quinn, Caroline M Curtin, Sally Ann Cryan, Fergal J O'Brien
The clinical translation of bioactive scaffolds for the treatment of large segmental bone defects has remained a challenge due to safety and efficacy concerns as well as prohibitive costs. The design of an implantable, biocompatible and resorbable device, which can fill the defect space, allow for cell infiltration, differentiation and neovascularisation, while also recapitulating the natural repair process and inducing cells to lay down new bone tissue, would alleviate the problems with existing treatments...
October 4, 2017: Biomaterials
Zhaohui Pan, Pingping Jiang, Shan Xue, Tao Wang, Hongfei Li, Jianli Wang
Various synthetic bone substitutes are not suitable for reconstructing critical-size bone defects. This study tested whether a bioglass-β-tricalcium phosphate (β-TCP) monoblock is effective for repairing critical-size segmental bone defects if combined with a vascularized periosteal flap and bone morphogenetic protein (BMP)-2. A femoral osteotomy with a gap size of 20 mm was created and stabilized using a plate in 40 rabbits.The defect was left untreated (group A) or repaired using a monoblock (group B), a monoblock with a vascularized periosteal flap (group C), or a monoblock with a vascularized periosteal flap and BMP-2 (group D)...
October 11, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Sadaaki Kanayama, Takashi Kaito, Kazuma Kitaguchi, Hiroyuki Ishiguro, Kunihiko Hashimoto, Ryota Chijimatsu, Satoru Otsuru, Shota Takenaka, Takahiro Makino, Yusuke Sakai, Akira Myoui, Hideki Yoshikawa
STUDY DESIGN: In vitro and in vivo assessment of osteogenic effect by prostacyclin agonist (ONO-1301) OBJECTIVE.: To investigate the effects of ONO-1301 on in vitro osteoblastic differentiation and in vivo bone formation induced by bone morphogenetic protein (BMP). SUMMARY OF BACKGROUND DATA: Among prostaglandins (PGs), PGE2 is the most abundant in bone tissue and its effects on bone formation have been well studied. PGI2 (prostacyclin) is the second most abundant PG in bone tissue and plays important roles in hemodynamics...
October 9, 2017: Spine
Lijia Guo, Seiko Min, Yingying Su, Jianxia Tang, Juan Du, Bee Tin Goh, Leonardo Saigo, Songlin Wang, Sahar Ansari, Alireza Moshaverinia, Homayoun H Zadeh, Yi Liu
Recombinant human bone morphogenetic protein (BMP)-2 is an FDA-approved therapy for nonunion tibia fracture, though it has a number of biological and practical disadvantages. Our research group has developed a novel tissue engineering strategy termed antibody-mediated osseous regeneration. This entails application of anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMP's to mediate in vivo bone formation. This has been documented in a number of animal models. The present exploratory study sought to investigate the application of antibody-mediated osseous regeneration for repair of nonunion tibia defect in a nonhuman primate model...
October 2017: Journal of Biomaterials Applications
Xin-Sheng Deng, Xianzhong Meng, Neil Venardos, Rui Song, Katsuhiro Yamanaka, David Fullerton, James Jaggers
BACKGROUND: Autophagy is a physiological process that plays an important role in maintaining cellular functions. When aortic valve interstitial cells (AVICs) are stimulated with inflammatory or mechanical stress, one response is elevated pro-osteogenic activity. We hypothesized that autophagy is important in the prevention or regulation of this pro-osteogenic activity in AVICs. MATERIALS AND METHODS: AVICs were isolated. Autophagy activity was examined and its role in AVIC's pro-osteogenic activity was determined using chemical inhibitors and genetic techniques...
October 2017: Journal of Surgical Research
Fangying Cao, Shaoping Wang, Xiangrong Cao, Xiaoxiao Liu, Kun Fu, Peng Hao, Jinghua Liu
OBJECTIVES: Vascular calcification is a dysfunction of the vasculature. Recent findings indicate that fibroblast growth factor21 (FGF21), a protector of the cardiovascular system, is related to the mineral deposition of bone and enhances the osteogenic activity of bone morphogenic protein (BMP)-2. In this study, we explored whether FGF21 suppresses vascular calcification. METHODS: A calcifying model was established by culturing primary rat vascular aortic smooth muscle cells (VSMCs) in a beta-glycerophosphate (BGP)-containing calcifying medium for 14 days...
October 4, 2017: Journal of Pharmacy and Pharmacology
Rasmus Cleemann, Mette Sørensen, Joan E Bechtold, Kjeld Søballe, Jørgen Baas
The bone-implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone-implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone Morphogenetic Protein 2 (BMP-2) stimulates osteoblast formation to increase new bone formation but indirectly stimulates osteoclast activity. In this experiment we investigate the hypothesis that osseointegration, defined as mechanical push-out and histomorphometry, depends on the dose of BMP-2 when delivered as an anabolic agent with systemic administration of the anti-resorptive agent zoledronate to curb an increase in osteoclast activity...
October 4, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
O G Davies, S C Cox, R L Williams, D Tsaroucha, R M Dorrepaal, M P Lewis, L M Grover
The application of extracellular vesicles (EVs) as natural delivery vehicles capable of enhancing tissue regeneration could represent an exciting new phase in medicine. We sought to define the capacity of EVs derived from mineralising osteoblasts (MO-EVs) to induce mineralisation in mesenchymal stem cell (MSC) cultures and delineate the underlying biochemical mechanisms involved. Strikingly, we show that the addition of MO-EVs to MSC cultures significantly (P < 0.05) enhanced the expression of alkaline phosphatase, as well as the rate and volume of mineralisation beyond the current gold-standard, BMP-2...
October 3, 2017: Scientific Reports
Robert N Bearden, Shannon S Huggins, Kevin J Cummings, Roger Smith, Carl A Gregory, William B Saunders
BACKGROUND: The dog represents an excellent large animal model for translational cell-based studies. Importantly, the properties of canine multipotent stromal cells (cMSCs) and the ideal tissue source for specific translational studies have yet to be established. The aim of this study was to characterize cMSCs derived from synovium, bone marrow, and adipose tissue using a donor-matched study design and a comprehensive series of in-vitro characterization, differentiation, and immunomodulation assays...
October 3, 2017: Stem Cell Research & Therapy
Chuandong Wang, Weien Yuan, Fei Xiao, Yaokai Gan, Xiaotian Zhao, Zhanjing Zhai, Xiaoying Zhao, Chen Zhao, Penglei Cui, Tuo Jin, Xiaodong Chen, Xiaoling Zhang
Small-interfering RNA (siRNA) provides a rapid solution for drug design and provides new methods to develop customizable medicines. Polyethyleneimine 25 kDa (PEI25kDa) is an effective transfection agent used in siRNA delivery. However, the lack of degradable linkage causes undesirable toxicity, hindering its clinical application. We designed a low-molecular-weight cross-linked polyethylenimine named PEI-Et (Mn:1220, Mw:2895) by using degradable ethylene biscarbamate linkage with lower cytotoxicity and higher knockdown efficiency than PEI25kDa in delivery Chordin siRNA to human bone mesenchymal stem cells (hBMSCs)...
2017: Frontiers in Pharmacology
Chuan Fu, Xiaoyu Yang, Shulian Tan, Liangsong Song
Lack of bioactivity has seriously restricted the development of biodegradable implants for bone tissue engineering. Therefore, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. Bone morphogenetic protein-2 (BMP-2), a key factor in inducing osteogenesis and promoting bone regeneration, has been widely used in various clinical therapeutic trials. In this study, BMP-2 was successfully immobilized on graphene oxide-incorporated PLGA/HA (GO-PLGA/HA) biodegradable microcarriers...
October 2, 2017: Scientific Reports
Zhao Tian, Haizhen Zhou, Yuben Xu, Jie Bai
BACKGROUND MicroRNAs play critical roles in post-translational gene expression. In this study, we explored the role of miR-495 in new bone regeneration. MATERIAL AND METHODS Murine calvarial osteoblasts were isolated and cultured. Microarray was performed to identify differential miRNAs in medicarpin-induced osteoblasts differentiation. Luciferase reporter assay was performed to identify the target gene of miRNA. Murine osteoblast cells were transfected with miC, miR-495, or anti-miR-495. CCK-8 and flow cytometry were performed to detect osteoblasts proliferation and apoptosis...
September 30, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yang Lv, Chen-Wei Gao, Bo Liu, Hao-Yu Wang, Hai-Ping Wang
The present study tested the hypotheses that bone morphogenetic protein 2(BMP-2) combined with salvianolic acid B(Sal-B) enhance the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) towards cardiomyocytes in vitro. BMSCs were treated with BMP-2 and Sal-B, alone or in combination, for 72 h, then added new media (excluding inductive substance) and cultured for 4 weeks. The morphologic characteristics, surface antigens and mRNA expression of several transcription factors were also assessed. We found that they could all be identified by the positive staining for cardiomyocyte-specific proteins, desmin and cardiac troponin T, in these cells...
October 2017: Kaohsiung Journal of Medical Sciences
Shen-Peng Liu, Guo-Dong Wang, Xue-Jun Du, Guang Wan, Jun-Tao Wu, Lian-Bao Miao, Qiu-Dong Liang
Chronic inflammation often delays fracture healing or leads to bone nonunion. Effectively suppressing pathological inflammation is crucial for fracture healing or bone remodeling. Triptolide, which is a diterpenoid epoxide, is the major active component of the Thunder God Vine, Tripterygium wilfordii. The aim of the present study was to investigate the role of triptolide in osteoblast differentiation and explore the molecular mechanisms of triptolide in fracture healing. Alkaline phosphatase (ALP) activity was used to evaluate osteoblast differentiation...
September 2017: Experimental and Therapeutic Medicine
William S Pietrzak, Saba N Ali
Bone morphogenetic proteins (BMPs) are associated with bone extracellular matrix and impart osteoinductive properties to demineralized bone matrix (DBM) grafts. The first step of the osteoinductive process is BMP release from DBM in situ; however, this has not been characterized for human DBM. The authors investigated the release of BMPs 2, 4, and 7 from a clinical human DBM putty (Bonus II DBM, Biomet Inc, Warsaw, IN). The DBM was placed in Sorensen buffer and the BMP concentrations in the Sorensen buffer and guanidine extracts of the DBM were measured concurrently by enzymelinked immunosorbant assay for up to 7 days...
September 25, 2017: Journal of Craniofacial Surgery
Yufu Wang, Changcheng You, Rongzhi Wei, Jianing Zu, Chengchao Song, Jing Li, Jinglong Yan
With the emerging role of umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) for bone regeneration and delivery of therapeutic proteins, there is an increasing need for effective gene delivery systems to modify such cells. mTAT, a TAT peptide sequence bearing histidine and cysteine residues, has been successfully used for intracellular gene delivery. Using a gWiz-GFP plasmid, we demonstrated that polyethylenimine combined with mTAT (mTAT/PEI) displayed good transfection efficacy in hUCB-MSC. hUCB-MSC transfected with mTAT/PEI were shown to express more BMP-2 protein and mRNA, indicating the feasibility of using the cells as a BMP-2 delivery system...
2017: BioMed Research International
Gloria Gronowicz, Emily Jacobs, Tao Peng, Li Zhu, Marja Hurley, Liisa T Kuhn
A drug delivery coating for synthetic bone grafts has been developed to provide sequential delivery of multiple osteoinductive factors to better mimic aspects of the natural regenerative process. The coating is composed of a biomimetic calcium phosphate (bCaP) layer that is applied to a synthetic bone graft and then covered with a poly-L-Lysine/poly-L-Glutamic acid polyelectrolyte multilayer (PEM) film. Bone morphogenetic protein-2 (BMP-2) was applied prior to the coating process directly on the synthetic bone graft and then bCaP-PEM was deposited followed by adsorption of fibroblast growth factor-2 (FGF-2) into the PEM layer...
September 25, 2017: Tissue Engineering. Part A
Hong Liu, Xun Zheng, Liang Chen, Chao Jian, Xiang Hu, Yong Zhao, Zonghuan Li, Aixi Yu
Negative pressure wound therapy (NPWT) has been revealed to be effective in the treatment of open fractures, although the underlying mechanism is not clear. This article aimed to investigate the effects of NPWT on muscle-derived stem cell (MDSC) osteoblastic differentiation and the related potential mechanism. The cell proliferation rate was substantially increased in NPWT-treated MDSCs in comparison with a static group for 3 days. There was no observable effect on the apoptosis of MDSC treated with NPWT compared with the control group for 3 days...
September 25, 2017: Journal of Cellular and Molecular Medicine
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