Abstract:
:The quest for predictive tumor markers for osteosarcoma (OS) has not well progressed over the last two decades due to a lack of preclinical models. The aim of this study was to investigate if microenvironmental modifications in an original humanized in vivo model alter the expression of OS tumor markers. Human bone micro-chips and bone marrow, harvested during hip arthroplasty, were implanted at the flanks of NOD/scid mice. We administered recombinant human bone morphogenetic protein 7 (rhBMP-7) in human bone micro-chips/bone marrow group I in order to modulate bone matrix and bone marrow humanization. Ten weeks post-implantation, human Luc-SAOS-2 OS cells were injected into the humanized tissue-engineered bone organs (hTEBOs). Tumors were harvested 5 weeks post-implantation to determine the expression of the previously described OS markers ezrin, periostin, VEGF, HIF1α and HIF2α. Representation of these proteins was analyzed in two different OS patient cohorts. Ezrin was downregulated in OS in hTEBOs with rhBMP-7, whereas HIF2α was significantly upregulated in comparison to hTEBOs without rhBMP-7. The expression of periostin, VEGF and HIF1α did not differ significantly between both groups. HIF2α was consistently present in OS patients and dependent on tumor site and clinical stage. OS patients post-chemotherapy had suppressed levels of HIF2α. In conclusion, we demonstrated the overall expression of OS-related factors in a preclinical model, which is based on a humanized bone organ. Our preclinical research results and analysis of two comprehensive patient cohorts imply that HIF2α is a potential prognostic marker and/or therapeutic target. STATEMENT OF SIGNIFICANCE: This study demonstrates the clinical relevance of the humanized organ bone microenvironment in osteosarcoma research and validates the expression of tumor markers, especially HIF2α. The convergence of clinically proven bone engineering concepts for the development of humanized mice models is a new starting point for investigations of OS-related marker expression. The validation and first data set in such a model let one conclude that further clinical studies on the role of HIF2α as a prognostic marker and its potential as therapeutic target is a condition sine qua non.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Wagner F,Holzapfel BM,Martine LC,McGovern J,Lahr CA,Boxberg M,Prodinger PM,Grässel S,Loessner D,Hutmacher DWdoi
10.1016/j.actbio.2019.02.051subject
Has Abstractpub_date
2019-04-15 00:00:00pages
372-381eissn
1742-7061issn
1878-7568pii
S1742-7061(19)30164-3journal_volume
89pub_type
杂志文章abstract::Conjunctival reconstruction is an integral component of ocular surface restoration. Decellularised tissues are frequently used clinically for tissue engineering. This study identifies porcine decellularised conjunctiva (PDC) and human decellularised conjunctiva (HDC) as promising substitutes for conjunctival reconstru...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.11.054
更新日期:2018-02-01 00:00:00
abstract::A dual targeting delivery system was developed to completely conquer the two barriers that glioma treatment faces: the blood-brain barrier (BBB) and the brain-glioma barrier. Recently, a system comprising AS1411 aptamer (for glioma targeting) and TGN peptide (for BBB targeting) modified nanoparticles (AsTNPs) was deve...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.11.003
更新日期:2014-02-01 00:00:00
abstract:UNLABELLED:Given the wide spread clinical use of ceramic-based bone void fillers, we sought to determine the efficacy of an FDA-approved β-tricalcium phosphate bone graft substitute (JAX™) in combination with a carboxymethyl cellulose (CMC) handling agent that included a particular heparan glycosaminoglycan (GAG) varia...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.09.008
更新日期:2015-12-01 00:00:00
abstract::Antimicrobial peptides (AMPs) are currently receiving interest as an alternative to conventional antibiotics to treat biomaterial-associated infection. However, the inherent instability of such peptides often limits their efficacy in intended clinical applications. Covalent immobilization of AMPs to surfaces is one st...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.10.039
更新日期:2019-01-01 00:00:00
abstract::Abnormal wound healing caused by the over-expression of collagen and fibronectin leads to fibrosis, the major complication of all treatment modalities. A three-layer nanofiber scaffold was designed, optimized, and fabricated. This scaffold comprised two supportive polycaprolactone (PCL)-chitosan layers on the sides an...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.06.031
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Avascular necrosis of bone (AVN) leads to sclerosis and collapse of bone and joints. The standard of care, vascularized bone grafts, is limited by donor site morbidity and restricted availability. The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.09.003
更新日期:2017-11-01 00:00:00
abstract::A series of six unique Ca-based bulk metallic glasses were synthesized and characterized. The glasses were designed to consist solely of the biocompatible elements Ca, Mg and Zn, with the view to their potential use as bioresorbable metals for orthopaedic applications. The alloys had a critical casting thickness of up...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.03.009
更新日期:2012-07-01 00:00:00
abstract::A biphasic layer with a Zn-containing beta-tricalcium phosphate (ZnTCP) phase and a fluoridated hydroxyapatite (FHA) phase on titanium alloy substrate was prepared by the sol-gel technique. Scanning electron microscopy and energy-dispersive X-ray analysis results showed the ZnTCP/FHA layer to have a heterogeneous surf...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2007.08.013
更新日期:2008-03-01 00:00:00
abstract::Patterned surfaces direct cell spatial dynamics, yielding cells oriented along the surface geometry, in a process known as contact guidance. The Rho family of GTPases controls the assembly of focal adhesions and cytoskeleton dynamics, but its role in modulating bone-cell alignment on patterned surfaces remains unknown...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.11.035
更新日期:2011-04-01 00:00:00
abstract::We report injectable nanoengineered hemostats for enhanced wound healing and tissue regeneration. The nanoengineered system consists of the natural polysaccharide, κ-carrageenan (κCA), loaded with synthetic two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be in...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.01.045
更新日期:2018-04-01 00:00:00
abstract::The effect of calcium phosphate-based microchannels on the growth and orientation of human osteoblast cells is investigated in this study. As substrates, hydroxyapatite-based microchannels with high contouring accuracy were fabricated by a novel micro-moulding technique. Microchannels obtained by this method featured ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.07.031
更新日期:2012-01-01 00:00:00
abstract::Our objective was to compare the polymerization stress (sigma(pol)) of a series of composites obtained using poly(methyl methacrylate) (PMMA) or glass as bonding substrates, and to compare the results with those from in vitro microleakage of composite restorations. The tested hypothesis was that stress values obtained...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.07.003
更新日期:2010-02-01 00:00:00
abstract::The sequence of steps of a chemical treatment having as its goal the induce of nucleation and the growth of hydroxyl carbonated apatite (HCA) at the surface of titanium implants was studied by scanning and transmission electron microscopy in cross-section. In the first step, an acid etching forms a rough titanium hydr...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.05.001
更新日期:2008-11-01 00:00:00
abstract::This work demonstrates the effects of both surface preparation and surface post-treatment by exposure to electron beam on the surface texture, contact angle and the interaction with bone-forming cells of electrochemically deposited hydroxyapatite (HAp) coating. Both the surface texture and the contact angle of the gro...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.04.005
更新日期:2009-10-01 00:00:00
abstract::Wounds sustained under battlefield conditions are considered to be contaminated and their initial treatment should focus on decreasing this contamination and thus reducing the possibility of infection. The early and aggressive administration of antimicrobial treatment starting with intervention on the battlefield has ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.04.003
更新日期:2011-07-01 00:00:00
abstract::Beta-tricalcium phosphate (beta-TCP) is a suitable biomaterial in oral and maxillofacial surgery since it can induce a rapid proliferation of woven bone. Granules, prepared by the polyurethane foam method, were implanted in critical size defects performed in the femoral condyles of New Zealand rabbits. Animals were st...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.01.042
更新日期:2010-08-01 00:00:00
abstract::The calcareous spicules from sponges, e.g. from Sycon raphanus, are composed of almost pure calcium carbonate. In order to elucidate the formation of those structural skeletal elements, the function of the enzyme carbonic anhydrase (CA), isolated from this species, during the in vitro calcium carbonate-based spicule f...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.08.025
更新日期:2014-01-01 00:00:00
abstract::Tilapia fish-scale type I atelocollagen hydrogels with aligned fibril structures were fabricated under a strong magnetic field of 6 or 12 T using two different methods. In the first method, a solution of acid-soluble collagen was neutralized with phosphate buffer saline and maintained in the magnetic field at 28°C for...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.09.014
更新日期:2011-02-01 00:00:00
abstract::Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the abili...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2017.07.028
更新日期:2017-10-15 00:00:00
abstract::In this work, plasma-sprayed nanostructured zirconia coatings stabilized with 3mol.% yttria (3Y-TZP) were deposited on Ti substrates. The microstructure and phase composition of coatings were characterized using scanning electron microscopy and X-ray diffraction. The in vitro bioactivity of coatings was evaluated by e...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.01.023
更新日期:2009-07-01 00:00:00
abstract::Human enamel has been found to be a coating with excellent mechanical performance, and has undergone extensive investigation and discussion. However, most of the reported studies consider the enamel as a homogeneous anisotropic biocomposite. The current study illustrated the graded properties of the biocomposite from ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.12.029
更新日期:2013-05-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.01.032
更新日期:2014-06-01 00:00:00
abstract::The tooth enamel of vertebrates comprises a hyper-mineralized bioceramic, but is distinguished by an exceptional durability to resist impact and wear throughout the lifetime of organisms; however, enamels exhibit a low resistance to the initiation of large-scale cracks comparable to that of geological minerals based o...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.09.053
更新日期:2018-11-01 00:00:00
abstract::Synthetic three-dimensional scaffolds for cell and tissue engineering routinely utilize peptide ligands to provide sites for cell adhesion and to promote cellular activity. Given the fact that recent studies have dedicated great attention to the mechanisms by which cell behavior is influenced by various ligands and sc...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.03.040
更新日期:2010-09-01 00:00:00
abstract::Nanocrystalline hydroxyapatite (HAp) and silicon-containing hydroxyapatite (SiHAp) particles were synthesized by a wet-chemical procedure and their heterogeneous structures involving a disordered phase were analyzed in detail by X-ray diffractometry (XRD), transmission electron microscopy (TEM), Fourier transform infr...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.08.024
更新日期:2013-01-01 00:00:00
abstract::Synthetic polymer microarray technology holds remarkable promise to rapidly identify suitable biomaterials for stem cell and tissue engineering applications. However, most of previous microarrayed synthetic polymers do not possess biological ligands (e.g., peptides) to directly engage cell surface receptors. Here, we ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.09.006
更新日期:2016-11-01 00:00:00
abstract::The rationale for the use of polymer-ceramic composites for bone regeneration stems from the natural composition of bone, with collagen type I and biological apatite as the main organic and inorganic constituents, respectively. In the present study composite materials of PolyActive™ (PA), a poly(ethylene oxide terepht...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.10.044
更新日期:2013-03-01 00:00:00
abstract::Tissue-derived extracellular matrix (ECM) biomaterials to regenerate the meniscus have gained increasing attention in treating meniscus injuries and diseases, particularly for aged persons and athletes. However, ECM scaffold has poor cell infiltration and can only be implanted using surgical procedures. To overcome th...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.01.027
更新日期:2015-04-01 00:00:00
abstract::A novel bactericidal material comprising rod-shaped core-shell-shell Au-Ag-Au nanorods is constructed as a nanoheater in the near-infrared (NIR) region. The outer Au shell melts under laser irradiation and results in exposure of the inner Ag shell, facilitating the controlled release of the antibacterial Ag shell/laye...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.09.005
更新日期:2015-01-01 00:00:00
abstract::Inkjet printing of antibiotic- and calcium-eluting micropatterns was explored as a novel means of preventing the formation of biofilm colonies and facilitating osteogenic cell development on orthopedic implant surfaces. The micropatterns consisted of a periodic array of ∼50 μm circular dots separated by ∼150 μm. The c...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.08.006
更新日期:2012-01-01 00:00:00