| 1. |
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| 2. |
- Asif, Sana, et al.
(författare)
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Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 35, s. 194-205
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Tidskriftsartikel (refereegranskat)abstract
- Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 3. |
- Atefyekta, Saba, 1987, et al.
(författare)
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Antibiofilm elastin-like polypeptide coatings: functionality, stability, and selectivity
- 2019
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 83, s. 245-256
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Tidskriftsartikel (refereegranskat)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 strategy to increase the long-term stability and minimize the toxicity. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was used to modify elastin-like polypeptide (ELP) surface coatings containing cell-adhesive peptide domains (RGD) using covalent chemistry. The AMP retained its antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa when covalently bonded to ELP surfaces. Simultaneously, the AMP functionalization had insignificant effect on the viability, function, and differentiation of human osteosarcoma MG63 cells and human mesenchymal stem cells (hMSCs). Furthermore, stability of the immobilized AMP in human blood serum was investigated, and the results suggested that the AMP preserved its antibacterial activity up to 24 h. Combined, the results show that covalently attached AMPs onto RGD-containing ELP are an excellent candidate as an antimicrobial coating for medical devices.
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| 4. |
- Barba, Albert, et al.
(författare)
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Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 79, s. 135-147
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need of synthetic bone grafts with enhanced osteogenic capacity. This can be achieved by combining biomaterials with exogenous growth factors, which however can have numerous undesired side effects, but also by tuning the intrinsic biomaterial properties. In a previous study, we showed the synergistic effect of nanostructure and pore architecture of biomimetic calcium deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e. fostering the differentiation of mesenchymal stem cells to bone forming cells. This was demonstrated by assessing bone formation after implanting the scaffolds intramuscularly. The present study goes one step forward, since it analyzes the effect of the geometrical features of the same CDHA scaffolds, obtained either by 3D-printing or by foaming, on the osteogenic potential and resorption behaviour in a bony environment. After 6 and 12 weeks of intraosseous implantation, both bone formation and material degradation had been drastically affected by the macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to be highly osteoconductive both in the robocast and foamed scaffolds, a superior osteogenic capacity was observed in the foamed scaffolds, which was associated with their higher intrinsic osteoinductive potential. Moreover, they showed a significantly higher cell-mediated degradation than the robocast constructs, with a simultaneous and progressive replacement of the scaffold by new bone. In conclusion, these results demonstrate that the control of macropore architecture is a crucial parameter in the design of synthetic bone grafts, which allows fostering both material degradation and new bone formation. Statement of Significance 3D-printing technologies open new perspectives for the design of patient-specific bone grafts, since they allow customizing the external shape together with the internal architecture of implants. In this respect, it is important to design the appropriate pore geometry to maximize the bone healing capacity of these implants. The present study analyses the effect of pore architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D-printing or foaming, on the osteogenic potential and scaffold resorption in an in vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive properties irrespective of pore geometry, we demonstrated that the spherical, concave macropores of foamed scaffolds significantly promoted both material resorption and bone regeneration compared to the 3D-printed scaffolds with orthogonal-patterned struts and therefore prismatic, convex macropores.
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| 5. |
- Brash, John L., et al.
(författare)
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The blood compatibility challenge. Part 2: Protein adsorption phenomena governing blood reactivity
- 2019
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 94, s. 11-24
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Acta Materialia Inc. The adsorption of proteins is the initiating event in the processes occurring when blood contacts a “foreign” surface in a medical device, leading inevitably to thrombus formation. Knowledge of protein adsorption in this context has accumulated over many years but remains fragmentary and incomplete. Moreover, the significance and relevance of the information for blood compatibility are not entirely agreed upon in the biomaterials research community. In this review, protein adsorption from blood is discussed under the headings “agreed upon” and “not agreed upon or not known” with respect to: protein layer composition, effects on coagulation and complement activation, effects on platelet adhesion and activation, protein conformational change and denaturation, prevention of nonspecific protein adsorption, and controlling/tailoring the protein layer composition. Statement of Significance: This paper is part 2 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.
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| 6. |
- Cai, Yixiao, et al.
(författare)
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Strategy towards independent electrical stimulation from cochlear implants : Guided auditory neuron growth on topographically modified nanocrystalline diamond
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 31, s. 211-220
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Tidskriftsartikel (refereegranskat)abstract
- Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.
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| 7. |
- Elgali, Ibrahim, et al.
(författare)
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Guided bone regeneration using resorbable membrane and different bone substitutes : Early histological and molecular events
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 29, s. 409-423
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Tidskriftsartikel (refereegranskat)abstract
- Bone insufficiency remains a major challenge for bone-anchored implants. The combination of guided bone regeneration (GBR) and bone augmentation is an established procedure to restore the bone. However, a proper understanding of the interactions between the bone substitute and GBR membrane materials and the bone-healing environment is lacking. This study aimed to investigate the early events of bone healing and the cellular activities in response to a combination of GBR membrane and different calcium phosphate (CaP) materials. Defects were created in the trabecular region of rat femurs, and filled with deproteinized bovine bone (DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All the defects were covered with an extracellular matrix membrane. Defects were harvested after 12 h, 3 d and 6 d for histology/histomorphometry, immunohistochemistry and gene expression analyses. Histology revealed new bone, at 6 d, in all the defects. Larger amount of bone was observed in the SrHA-filled defect. This was in parallel with the reduced expression of osteoclastic genes (CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects. The observations of CD68 and periostin-expressing cells in the membrane per se indicated that the membrane may contribute to the healing process in the defect. It is concluded that the bone-promoting effects of Sr in vivo are mediated by a reduction in catabolic and osteoblast-osteoclast coupling processes. The combination of a bioactive membrane and CaP bone substitute material doped with Sr may produce early synergistic effects during GBR. Statement of significance The study provides novel molecular, cellular and structural evidence on the promotion of early bone regeneration in response to synthetic strontium-containing hydroxyapatite (SrHA) substitute, in combination with a resorbable, guided bone regeneration (GBR) membrane. The prevailing view, based mainly upon in vitro data, is that the beneficial effects of Sr are exerted by the stimulation of bone-forming cells (osteoblasts) and the inhibition of bone-resorbing cells (osteoclasts). In contrast, the present study demonstrates that the local effect of Sr in vivo is predominantly via the inhibition of osteoclast number and activity and the reduction of osteoblast-osteoclast coupling. This experimental data will form the basis for clinical studies, using this material as an interesting bone substitute for guided bone regeneration.
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| 8. |
- Guex, Anne Geraldine, et al.
(författare)
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Highly porous scaffolds of PEDOT:PSS for bone tissue engineering
- 2017
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Ingår i: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 62, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6 +/- 5.9 mu m and a total pore surface area of 7.72 +/- 1.7 m(2).g(-1). The electrical conductivity, based on I-V curves, was measured to be 140 mu S.cm(-1) with a reduced, but stable conductivity of 6.1 mu S.cm(-1) after 28 days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4 weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Statement of Significance Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd.
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| 9. |
- Hayes, Sally, et al.
(författare)
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The structural and optical properties of type III human collagen biosynthetic corneal substitutes
- 2015
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Ingår i: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 25, s. 121-130
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Tidskriftsartikel (refereegranskat)abstract
- The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2-9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd.
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| 10. |
- Islam, Mohammad Mirazul, et al.
(författare)
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Effects of gamma radiation sterilization on the structural and biological properties of decellularized corneal xenografts
- 2019
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 96, s. 330-344
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Tidskriftsartikel (refereegranskat)abstract
- To address the shortcomings associated with corneal transplants, substantial efforts have been focused on developing new modalities such as xenotransplantion. Xenogeneic corneas are anatomically and biomechanically similar to the human cornea, yet their applications require prior decellularization to remove the antigenic components to avoid rejection. In the context of bringing decellularized corneas into clinical use, sterilization is a crucial step that determines the success of the transplantation. Well-standardized sterilization methods, such as gamma irradiation (GI), have been applied to decellularized porcine corneas (DPC) to avoid graft-associated infections in human recipients. However, little is known about the effect of GI on decellularized corneal xenografts. Here, we evaluated the radiation effect on the ultrastructure, optical, mechanical and biological properties of DPC. Transmission electron microscopy revealed that gamma irradiated decellularized porcine cornea (G-DPC) preserved its structural integrity. Moreover, the radiation did not reduce the optical properties of the tissue. Neither DPC nor G-DPC led to further activation of complement system compared to native porcine cornea when exposed to plasma. Although, DPC were mechanically comparable to the native tissue, GI increased the mechanical strength, tissue hydrophobicity and resistance to enzymatic degradation. Despite these changes, human corneal epithelial, stromal, endothelial and hybrid neuroblastoma cells grew and differentiated on DPC and G-DPC. Thus, GI may achieve effective tissue sterilization without affecting critical properties that are essential for corneal transplant survival. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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