Publications by authors named "Dunstan C"

Article Synopsis
  • Bone can regenerate itself for minor defects, but this ability is reduced in large defects, leading to increased interest in synthetic materials like bioceramic implants.
  • The effectiveness of bioceramics in clinics relies on both their material properties and internal porous structures, prompting a study on how different channel sizes and shapes affect bone regeneration in rabbits.
  • Results indicated that a circular channel size of about 0.9 mm significantly improved bone formation, while the shape didn't affect new bone volume, and concave surfaces enhanced tissue growth, highlighting the importance of scaffold design for better bone healing.
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-Nitroaniline (ONA) is a model for the insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) that shares strong hydrogen bonding character between adjacent nitro and amino groups. This work reports femtosecond time-resolved mass spectrometry (FTRMS) measurements and theoretical calculations that explain the high stability of the ONA cation compared with related nitroaromatic molecules. Ab initio calculations found that the lowest-lying electronic excited state of the ONA cation, D, lies more than 2 eV above the ground state, and the energetic barriers to rearrangement and dissociation reactions exceed this D energy.

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The exposome, reflecting the range of environmental exposures individuals encounter throughout their life, can influence a variety of health outcomes and can play a role in how the environment impacts our genes. Telomeres, genetic structures regulating cell growth and senescence, are one pathway through which the exposome may impact health. Greenspace exposure, representing the amount of green areas in one's neighborhood, is one component of the exposome and has been associated with multiple health benefits.

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Here we report the first atom probe study to reveal the atomic-scale composition of in vivo bone formed in a bioceramic scaffold (strontium-hardystonite-gahnite) after 12-month implantation in a large bone defect in sheep tibia. The composition of the newly formed bone tissue differs to that of mature cortical bone tissue, and elements from the degrading bioceramic implant, particularly aluminium (Al), are present in both the newly formed bone and in the original mature cortical bone tissue at the perimeter of the bioceramic implant. Atom probe tomography confirmed that the trace elements are released from the bioceramic and are actively transported into the newly formed bone.

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Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells by increasing the production of reactive oxygen species (ROS), activating endoplasmic reticulum (ER)-stress and promoting apoptosis. However, prolonged treatment with high doses of CTU were required for in vivo anti-tumor activity.

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Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing.

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The selection of biomaterials as biomedical implants is a significant challenge. Ultra-high molecular weight polyethylene (UHMWPE) and composites of such kind have been extensively used in medical implants, notably in the bearings of the hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the Anterior Cruciate Ligament (ACL) graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and extremely high tensile strength.

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There is an unmet clinical need for a spinal fusion implant material that recapitulates the biological and mechanical performance of natural bone. We have developed a bioceramic, Sr-HT-Gahnite, which has been identified as a potential fusion device material. This material has the capacity to transform the future of the global interbody devices market, with follow on social, economic, and environmental benefits, rooted in its remarkable combination of mechanical properties and bioactivity.

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The cancer cell mitochondrion is functionally different from that in normal cells and could be targeted to develop novel experimental therapeutics. The aryl-ureido fatty acid CTU (16({[4-chloro-3-(trifluoromethyl)phenyl]-carbamoyl}amino)hexadecanoic acid) is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells. Here we show that CTU rapidly depolarized the inner mitochondrial membrane, selectively inhibited complex III of the electron transport chain and increased reactive oxygen species (ROS) production.

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Migration and invasion promote tumor cell metastasis, which is the leading cause of cancer death. At present there are no effective treatments. Epidemiological studies have suggested that ω-3 polyunsaturated fatty acids (PUFA) may decrease cancer aggressiveness.

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Article Synopsis
  • Researchers in orthopedics are seeking effective synthetic ceramic scaffolds for treating large bone defects that don't heal on their own, using a bioactive ceramic called baghdadite.
  • A new stereolithography printing technique was developed to create custom-shaped scaffolds that can co-deliver bone morphogenetic protein-2 (BMP2) and zoledronic acid (ZA) to enhance bone formation in a rat model.
  • The study found that increasing doses of BMP2 and ZA significantly improved bone growth within the scaffolds, making them much stronger and more flexible, and laid the groundwork for future personalized implants in clinical settings.
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The development of suitable synthetic scaffolds for use as human tendon grafts to repair tendon ruptures remains a significant engineering challenge. Previous synthetic tendon grafts have demonstrated suboptimal tissue ingrowth and synovitis due to wear particles from fiber-to-fiber abrasion. In this study, we present a novel fiber-reinforced hydrogel (FRH) that mimics the hierarchical structure of the native human tendon for synthetic tendon graft material.

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Bone fractures and critical-sized bone defects present significant health threats for the elderly who have limited capacity for regeneration due to the presence of functionally compromised senescent cells. A wide range of synthetic materials has been developed to promote the regeneration of critical-sized bone defects, but it is largely unknown if a synthetic biomaterial (scaffold) can modulate cellular senescence and improve bone regeneration in aged scenarios. The current study investigates the interaction of Baghdadite (CaZrSiO) ceramic scaffolds with senescent human primary osteoblast-like cells (HOBs) and its bone regeneration capacity in aged rats.

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The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans-differentiation approach employing natural factors may allow better control over reprogramming and improved safety.

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Achieving adequate healing in large or load-bearing bone defects is highly challenging even with surgical intervention. The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium-hardystonite-gahnite or "Sr-HT-Gahnite" (a multi-component, calcium silicate-based ceramic) is developed, which when 3D-printed combines high strength with outstanding bone regeneration ability.

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The successful regeneration of functional bone tissue in critical-size defects remains a significant clinical challenge. To address this challenge, synthetic bone scaffolds are widely developed, but remarkably few are translated to the clinic due to poor performance in vivo. Here, it is demonstrated how architectural design of 3D printed scaffolds can improve in vivo outcomes.

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Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathways linked to their proliferation and invasiveness. In particular, ω-3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study, 16-(4'-chloro-3'-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω-3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI < 0.

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Objective: The aim of this study was to assess the potential of improving orthodontic miniscrews' (MSs) primary stability in vivo by evaluating the dispersion capacity of an injectable bone graft substitute (iBGS) through a newly designed hollow MS [The Sydney Mini Screw (SMS)] and its integration with the cortical and trabecular bone by using the femur and tibia in a New Zealand rabbit animal model.

Methods: In total, 24 MSs were randomly placed in each proximal tibia and femur of 6 New Zealand rabbits with an open surgery process. Aarhus MSs were used as controls and the effect of injection of iBGS was studied by implanting SMSs with and without iBGS injection.

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Extensive bone loss due to trauma or disease leads to impaired healing. Current bone grafts and substitutes have major drawbacks that limit their effectiveness for treating large bone defects. A number of bone substitutes in development are undergoing preclinical testing, but few studies specifically investigate the in vivo material-tissue interactions that provide an important indicator to long-term implant safety and efficacy.

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Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25(OH)D] are mediated through binding to the vitamin D receptor (VDR). Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation Implantation of these VDR knockdown cells into the mammary fat pad (MDA-MB-231), subcutaneously (PC3) or intra-tibially (both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls.

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Cancer cell mitochondria are promising anticancer drug targets because they control cell death and are structurally and functionally different from normal cell mitochondria. We synthesized arylurea fatty acids and found that the analogue 16-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid (13b) decreased proliferation and activated apoptosis in MDA-MB-231 breast cancer cells in vitro and in vivo. In mechanistic studies 13b emerged as the prototype of a novel class of mitochondrion-targeted agents that deplete cardiolipin and promote cancer cell death.

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Vitamin D has pleiotropic effects on multiple tissues, including malignant tumors. Vitamin D inhibits breast cancer growth through activation of the vitamin D receptor (VDR) and via classical nuclear signaling pathways. Here, we demonstrate that the VDR can also function in the absence of its ligand to control behaviour of human breast cancer cells both outside and within the bone microenvironment.

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Mesenchymal stem cells (MSCs) have been widely used for tissue repair and regeneration. However, the inherent drawbacks, including limited cell survival after cell transplantation, have hindered direct MSC transplantation for tissue repair and regeneration. The aim of this study was to investigate if exosomes isolated from MSCs can promote the proliferation and differentiation of human primary osteoblastic cells (HOBs) and be potentially used for bone tissue regeneration.

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Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken.

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