| 1. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Free-form-fabricated commercially-pure Ti and Ti6Al4V porous scaffolds support the growth of human embryonic stem cell-derived medsodermal progenitors
- 2012
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Ingår i: The Scientific World Journal. - : Hindawi Limited. - 2356-6140 .- 1537-744X. ; 2012
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Tidskriftsartikel (refereegranskat)abstract
- Commercially-pure titanium (cp-Ti) and the titanium-aluminum-vanadium alloy (Ti6Al4V) are widely used as reconstructive implants for skeletal engineering applications, due to their good mechanical properties, biocompatibility and ability to integrate with the surrounding bone. Electron beam melting technology (EBM) allows the fabrication of customized implants with tailored mechanical properties and high potential in the clinical practice. In order to augment the interaction with the biological tissue, stem cells have recently been combined with metallic scaffolds for skeletal engineering applications. We previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold a great potential to provide a homogeneous and unlimited supply of cells for bone engineering applications. This study demonstrates the effect of EBM-fabricated cp-Ti and Ti6Al4V porous scaffolds on hES-MPs behavior, in terms of cell attachment, growth and osteogenic differentiation. Displaying different chemical composition but similar surface properties, EBM-fabricated cp-Ti and Ti6Al4V scaffolds supported cell attachment and growth, and did not seem to alter the expression of genes involved in osteogenic differentiation and affect the alkaline phosphatase activity. In conclusion, interfacing hES-MPs to EBM-fabricated scaffolds may represent an interesting strategy for design of third-generation biomaterials, with the potential to promote implant integration in clinical conditions characterized by poor bone quality. Copyright 2012 G. M. de Peppo et al.
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| 2. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Human Embryonic Stem Cell-Derived Mesodermal Progenitors Display Substantially Increased Tissue Formation Compared to Human Mesenchymal Stem Cells Under Dynamic Culture Conditions in a Packed Bed/Column Bioreactor.
- 2013
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Ingår i: Tissue engineering. Part A. - 1937-335X. ; 19:1-2, s. 175-87
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Tidskriftsartikel (refereegranskat)abstract
- Bone tissue engineering represents a promising strategy to obviate bone deficiencies, allowing the ex vivo construction of bone substitutes with unprecedented potential in the clinical practice. Considering that in the human body cells are constantly stimulated by chemical and mechanical stimuli, the use of bioreactor is emerging as an essential factor for providing the proper environment for the reproducible and large-scale production of the engineered substitutes. Human mesenchymal stem cells (hMSCs) are experimentally relevant cells but, regardless the encouraging results reported after culture under dynamic conditions in bioreactors, show important limitations for tissue engineering applications, especially considering their limited proliferative potential, loss of functionality following protracted expansion, and decline in cellular fitness associated with aging. On the other hand, we previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold great potential to provide a homogenous and unlimited source of cells for bone engineering applications. Based on prior scientific evidence using different types of stem cells, in the present study we hypothesized that dynamic culture of hES-MPs in a packed bed/column bioreactor had the potential to affect proliferation, expression of genes involved in osteogenic differentiation, and matrix mineralization, therefore resulting in increased bone-like tissue formation. The reported findings suggest that hES-MPs constitute a suitable alternative cell source to hMSCs and hold great potential for the construction of bone substitutes for tissue engineering applications in clinical settings.
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| 3. |
- Hulander, Mats, et al.
(författare)
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Gradients in surface nanotopography used to study platelet adhesion and activation
- 2013
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Ingår i: Colloids and Surfaces B-Biointerfaces. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 110, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- Gradients in surface nanotopography were prepared by adsorbing gold nanoparticles on smooth gold substrates using diffusion technique. Following a sintering procedure the particle binding chemistry was removed, and integration of the particles into the underlying gold substrate was achieved, leaving a nanostructured surface with uniform surface chemistry. After pre-adsorption of human fibrinogen, the effect of surface nanotopography on platelets was studied. The use of a gradient in nanotopography allowed for platelet adhesion and activation to be studied as a function of nanoparticle coverage on one single substrate. A peak in platelet adhesion was found at 23% nanoparticle surface coverage. The highest number of activated platelets was found on the smooth control part of the surface, and did not coincide with the number of adhered platelets. Activation correlated inversely with particle coverage, hence the lowest fraction of activated platelets was found at high particle coverage. Hydrophobization of the gradient surface lowered the total number of adhering cells, but not the ratio of activated cells. Little or no effect was seen on gradients with 36 nm particles, suggesting the existence of a lower limit for sensing of surface nano-roughness in platelets. These results demonstrate that parameters such as ratio between size and inter-particle distance can be more relevant for cell response than wettability on nanostructured surfaces. The minor effect of hydrophobicity, the generally reduced activation on nanostructured surfaces and the presence of a cut-off in activation of human platelets as a function of nanoparticle size could have implications for the design of future blood-contacting biomaterials.
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| 4. |
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| 5. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 136, s. 279-290
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Tidskriftsartikel (refereegranskat)abstract
- The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of Significance: The role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo.
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| 6. |
- Shah, Furqan A., et al.
(författare)
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3D printed Ti6Al4V implant surface promotes bone maturation and retains a higher density of less aged osteocytes at the bone-implant interface.
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 30, s. 357-367
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Tidskriftsartikel (refereegranskat)abstract
- For load-bearing orthopaedic applications, metal implants having an interconnected pore structure exhibit the potential to facilitate bone ingrowth and the possibility for reducing the stiffness mismatch between the implant and bone, thus eliminating stress-shielding effects. 3D printed solid and macro-porous Ti6Al4V implants were evaluated after six-months healing in adult sheep femora. The ultrastructural composition of the bone-implant interface was investigated using Raman spectroscopy and electron microscopy, in a correlative manner. The mineral crystallinity and the mineral-to-matrix ratios of the interfacial tissue and the native bone were found to be similar. However, lower Ca/P ratios, lower carbonate content, but higher proline, phenylalanine and tyrosine levels indicated that the interfacial tissue remained less mature. Bone healing was more advanced at the porous implant surface (vs. the solid implant surface) based on the interfacial tissue ν1 CO3(2-)/ν2 PO4(3-) ratio, phenylalanine and tyrosine levels approaching those of the native bone. The mechanosensing infrastructure in bone, the osteocyte lacuno-canalicular network, retained ∼40% more canaliculi per osteocyte lacuna, i.e., a 'less aged' morphology at the interface. The osteocyte density per mineralised surface area was ∼36-71% higher at the interface after extended healing periods.
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| 7. |
- Shah, Furqan A., et al.
(författare)
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Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting.
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 36:May, s. 296-309
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Tidskriftsartikel (refereegranskat)abstract
- In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39±4%) than CoCr (27±4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications.
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| 8. |
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| 9. |
- Thorfve, Anna, 1982, et al.
(författare)
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Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo
- 2014
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 10:3, s. 1451-1462
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Tidskriftsartikel (refereegranskat)abstract
- Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li+). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction. HA-coated implants showed, irrespective of Li+ content, bone-implant contact (BIC) and removal torque significantly higher than those of reference Ti. Further, the expressions of OCN, CTSK, COL1A1, LRP5/6 and WISP1 were significantly higher in implant-adherent cells of HA-coated implants, with or without Li+. Significantly higher β-catenin expression and significantly lower COL2A1 expression were observed in peri-implant bone cells from HA with 14ngcm-2 released Li+. Interestingly, Ti implants showed a significantly larger bone area in the threads than HA with 39ngcm-2 released Li+, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li+ is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.
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| 10. |
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