1. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Micah, Angela E., et al.
(author)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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6. |
- Rashad, Ahmad, et al.
(author)
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Inflammatory responses and tissue reactions to wood-Based nanocellulose scaffolds
- 2019
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In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 97, s. 208-221
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Journal article (peer-reviewed)abstract
- Two wood-derived cellulose nanofibril (CNF) porous scaffolds were prepared by TEMPO-oxidation and carboxymethylation. The effects of these scaffolds on the production of inflammatory cytokines by human macrophage-like cells (U937) was profiled in vitro after 1 and 3 days and in subcutaneous tissues of rats after 4 and 30 days, using PCR and Multiplex arrays. Tissue culture plates (TCP) and gelatin scaffolds served as controls in vitro and in vivo respectively. After 3 days in vitro, there was no significant difference between the effects of CNF scaffolds and TCP on the production of chemokines/growth factors and pro-inflammatory cytokines. At day 4 in vivo there was significantly higher gene expression of the anti-inflammatory IL-1Ra in the CNF scaffolds than the gelatin scaffold. Production of IL-1β, IL-6, MCP-1, MIP-1α CXCL-1 and M-CSF was significantly less than in the gelatin, demonstrating an early mild inflammatory response. At day 30, both CNF scaffolds significantly stimulated the production of the anti-inflammatory cytokine IL-10. Unlike gelatin, neither CNF scaffold had degraded 180 days post-implantation. The slow degradation of CNF scaffolds resulted in a foreign body reaction, with high production of IL-1β, IL-2, TNF-α, IFN-Ï, MCP-1, MIP-1α, M-CSF, VEGF cytokines and expression of MMP-9 gene. The surface chemistry of the CNF scaffolds elicited a modest effect on cytokine production and did not shift the inflammatory profile in vitro or in vivo. The decisive role in development of the foreign body reaction was the slow degradation of the CNF scaffolds.
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7. |
- Ahlinder, Astrid, et al.
(author)
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Nondegradative additive manufacturing of medical grade copolyesters of high molecular weight and with varied elastic response
- 2020
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In: Journal of Applied Polymer Science. - : WILEY. - 0021-8995 .- 1097-4628. ; 137:15
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Journal article (peer-reviewed)abstract
- Although additive manufacturing through melt extrusion has become increasingly popular as a route to design scaffolds with complex geometries the technique if often limited by the reduction in molecular weight and the viscoelastic response when degradable aliphatic polyesters of high molecular weight are used. Here we use a melt extruder and fused filament fabrication printer to produce a reliable nondegradative route for scaffold fabrication of medical grade copolymers of L-lactide, poly(epsilon-caprolactone-co-L-lactide), and poly(L-lactide-co-trimethylene carbonate). We show that degradation is avoided using filament extrusion and fused filament fabrication if the process parameters are deliberately chosen based upon the rheological behavior, mechanical properties, and polymer composition. Structural, mechanical, and thermal properties were assessed throughout the process to obtain comprehension of the relationship between the rheological properties and the behavior of the medical grade copolymers in the extruder and printer. Scaffolds with a controlled architecture were achieved using high-molecular-weight polyesters exhibiting a large range in the elastic response causing negligible degradation of the polymers.
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8. |
- Bartaula-Brevik, Sushma, et al.
(author)
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Angiogenic and Immunomodulatory Properties of Endothelial and Mesenchymal Stem Cells
- 2016
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In: Tissue Engineering. Part A. - : Mary Ann Liebert. - 1937-3341 .- 1937-335X. ; 22:3-4, s. 244-252
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Journal article (peer-reviewed)abstract
- It has been suggested that the effect of implanted cells on the local environment is important when selecting the appropriate cell type for tissue regeneration. Our aim was to compare the local tissue response to implanted human mesenchymal stem cells (MSC) and human umbilical vein endothelial cells (EC). MSC and EC were cultured in poly(l-lactide-co-1,5-dioxepan-2-one) scaffolds for 1 week in a bioreactor system, after which they were implanted subcutaneously in NOD/SCID mice. After 3 weeks, scaffolds were retrieved, and the mRNA expression of selected genes involved in hypoxia and inflammation was examined by real-time reverse transcription polymerase chain reaction and correlated with immunofluorescent staining for corresponding proteins. The Toll-like receptor signaling pathway was examined by superarray hybridization. The expression of 53 angiogenesis-related proteins was investigated by a proteome profiler angiogenesis antibody array kit. Vascularization was quantified using immunohistochemistry for CD31. The expression of hypoxia-inducible factors and biomarkers for angiogenesis was more strongly upregulated in response to implanted EC than to MSC, suggesting a higher sensitivity to low oxygen tension among EC. Hypoxic signaling was increased after implantation of EC compared with MSC, leading to a prolonged acute inflammatory phase that promoted ingrowth of vascular cells and establishment of the circulation. Inflammatory cytokines were also differently expressed at the gene and protein levels in the two experimental groups, resulting in altered recruitment of acute and chronic inflammatory cells. The end result of these differences was increased vessel formation within the constructs in the EC group.
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9. |
- Bartaula-Brevik, Sushma, et al.
(author)
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Leukocyte transmigration into tissue-engineered constructs is influenced by endothelial cells through Toll-like receptor signaling
- 2014
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In: Stem Cell Research & Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 5, s. 143-
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Journal article (peer-reviewed)abstract
- Introduction: Inflammation plays a crucial role in tissue regeneration, wound healing, and the success of tissue-engineered constructs. The aim of this study was to investigate the influence of human umbilical vein endothelial cells (ECs) on leukocyte transmigration when co-cultured with primary human bone marrow-derived multipotent stromal cells (MSCs). Methods: MSCs with and without ECs were cultured in poly (L-lactide-co-1, 5-dioxepan-2-one) (poly (LLA-co-DXO)) scaffolds for 1 week in vitro in a bioreactor system, after which they were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. After 1 and 3 weeks, scaffolds were retrieved, and the mRNA expression of interleukin 1-beta (IL-1 beta), IL-6, IL-10, hypoxia-inducible factor 1-alpha (HIF-1 alpha), HIF-1 beta, and mammalian target of rapamycin was examined by real-time reverse transcription-polymerase chain reaction. Furthermore, immunofluorescent staining was performed for IL-1 beta, IL-6, neutrophils, and CD11b. In addition, Western blotting was done for IL-1 beta and IL-6. Leukocyte transmigration genes and genes in Toll-like receptor pathways, expressed by MSCs cultured in vitro with or without ECs, were further investigated with a microarray dataset. Results: In vitro, genes involved in leukocyte transmigration and Toll-like receptor pathways were clearly influenced by the addition of ECs. Platelet/endothelial cell adhesion molecule-1 (PECAM-1) and cadherin-5 (CDH5), both genes involved in leukocyte transmigration, were expressed significantly higher in the MSC/EC group. In vivo, the MSC/EC group showed higher mRNA expression of hypoxia-inducible factors HIF-1 alpha and HIF-1 beta. The mRNA expression of anti-inflammatory cytokine IL-10 showed no significant difference, whereas the mRNA and protein expression of pro-inflammatory cytokines IL-1 beta and IL-6 were lower in the MSC/EC group. The quantitative analysis of immunofluorescent staining revealed a significant difference in the number of neutrophils migrating into constructs, with the highest density found in the MSC/EC group. The number of macrophages positive for IL-6 and CD11b was significantly reduced in the MSC/EC group. Conclusions: The recruitment of leukocytes into tissue-engineered constructs with MSCs is strongly influenced by the addition of ECs via activation of leukocyte transmigration and Toll-like receptor pathways.
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10. |
- Bougas, Kostas, et al.
(author)
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Novel implant coating agent promotes gene expression of osteogenic markers in rats during early osseointegration
- 2012
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In: International Journal of Biomaterials. - : Hindawi Publishing Corporation. - 1687-8787 .- 1687-8795. ; 2012
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate the early bone response around laminin-1-coated titanium implants. Forty-five rats distributed in three equally sized groups were provided with one control (turned) and one test (laminin-1-coated) implant and were sacrificed after 3, 7, and 21 days. Real-time reverse-transcriptase polymerase chain reaction was performed for osteoblast markers (alkaline phosphatase, runt-related transcription factor 2, osteocalcin, type I collagen, and bone morphogenic protein 2), osteoclast markers (cathepsin K and tartrate-resistant acid phosphatase), inflammation markers (tumor necrosis factor α, interleukin 1β and interleukin 10), and integrin β1. Bone implant contact (BIC) and bone area (BA) were assessed and compared to the gene expression. After 3 days, the expression of bone markers was higher for the control group. After 7 days, the expression of integrin β1 and osteogenic markers was enhanced for the test group, while cathepsin K and inflammation markers were downregulated. No significant differences in BIC or BA were detected between test and control at any time point. As a conclusion, implant coating with laminin-1 altered gene expression in the bone-implant interface. However, traditional evaluation methods, as histomorphometry, were not adequately sensitive to detect such changes due to the short follow-up time.
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11. |
- Campodoni, Elisabetta, et al.
(author)
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Polymeric 3D scaffolds for tissue regeneration : Evaluation of biopolymer nanocomposite reinforced with cellulose nanofibrils
- 2019
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In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier Ltd. - 0928-4931 .- 1873-0191. ; 94, s. 867-878
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Journal article (peer-reviewed)abstract
- Biopolymers such as gelatin (Gel) and cellulose nanofibrils (CNF) have many of the essential requirements for being used as scaffolding materials in tissue regeneration; biocompatibility, surface chemistry, ability to generate homogeneous hydrogels and 3D structures with suitable pore size and interconnection, which allows cell colonization and proliferation. The purpose of this study was to investigate whether the mechanical behaviour of the Gel matrix can be improved by means of functionalization with cellulose nanofibrils and proper cross-linking treatments. Blending processes were developed to achieve a polymer nanocomposite incorporating the best features of both biopolymers: biomimicry of the Gel and structural reinforcement by the CNF. The designed 3D structures underline interconnected porosity achieved by freeze-drying process, improved mechanical properties and chemical stability that are tailored by CNF addition and different cross-linking approaches. In vitro evaluations reveal the preservation of the biocompatibility of Gel and its good interaction with cells by promoting cell colonization and proliferation. The results support the addition of cellulose nanofibrils to improve the mechanical behaviour of 3D porous structures suitable as scaffolding for tissue regeneration.
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12. |
- Carlström, Ingeborg, et al.
(author)
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Cross-linked gelatin-nanocellulose scaffolds for bone tissue engineering
- 2020
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In: Materials letters (General ed.). - : Elsevier B.V.. - 0167-577X .- 1873-4979. ; 264
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Journal article (peer-reviewed)abstract
- Wood-based cellulose nanofibrils (CNFs) have, in addition to high specific surface area and high surface reactivity, ability to mimic nanostructured collagen in bone extracellular matrix. These properties make CNFs promising materials for bone tissue engineering (BTE). The CNFs degrade slowly in vivo. By blending and cross-linking gelatin (Gel) with CNFs, scaffolds were produced with tuned degradation rate and enhanced mechanical properties, more suitable for BTE applications. This in vitro study aimed to examine initial biological responses of human bone marrow mesenchymal stem cells to cross-linked Gel-CNF scaffolds. The scaffolds were fabricated from 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized CNF blended with Gel and cross-linked either by dehydrothermal treatment (DHT) or by a combination of hexamethylenediamine, genipin, and DHT. CNF scaffolds without cross-linking served as control. The produced scaffolds supported cell attachment, spreading, and osteogenic differentiation. However, the early cell attachment after 1 day and the expression of RUNX2 and SPP1 genes after 7 days were highest in the CNF scaffolds. The results suggest that cross-linked Gel-CNF are cytocompatible and holds potential for BTE applications.
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13. |
- Danmark, Staffan, et al.
(author)
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Osteogenic Differentiation by Rat Bone Marrow Stromal Cells on Customized Biodegradable Polymer Scaffolds
- 2010
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In: Journal of bioactive and compatible polymers (Print). - : SAGE Publications. - 0883-9115 .- 1530-8030. ; 25:2, s. 207-223
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Journal article (peer-reviewed)abstract
- In this report, poly(L-lactide-co-epsilon-caprolactone), poly(LLA-co-CL) and poly(L-lactide-co-1,5-dioxepan-2-one), poly(LLA-co-DXO) were evaluated and compared for potential use in bone tissue engineering constructs together with bone marrow stromal cells (BMSC). The copolymers were tailored to reduce the level of harmful tin residuals in the scaffolding. BMSC isolated from Sprague-Dawley rats were seeded onto the scaffolds and cultured in vitro for up to 21 days. Cell spreading and proliferation was analyzed after 72 h by scanning electron microscopy and thiazolyl blue tetrazolium bromide (MTT) conversion assay. Osteogenic differentiation of BMSC was evaluated by real-time PCR after 14 and 21 days of culture. Hydrophilicity was significantly different between poly(LLA-co-CL) and poly(LLA-co-DXO) with the latter being more hydrophilic. After 72 h, both scaffolds supported increased cell proliferation and the mRNA expression of osteocalcin and osteopontin was significantly increased after 21 days. Further investigation of these constructs, with lower levels of tin residuals, are being pursued.
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14. |
- Dånmark, Staffan, et al.
(author)
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Development of a novel microfluidic device for long-term in situ monitoring of live cells in 3-dimensional matrices
- 2012
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In: Biomedical microdevices (Print). - : Springer Science and Business Media LLC. - 1387-2176 .- 1572-8781. ; 14:5, s. 885-893
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Journal article (peer-reviewed)abstract
- Using the latest innovations in microfabrication technology, 3-dimensional microfluidic cell culture systems have been developed as an attractive alternative to traditional 2-dimensional culturing systems as a model for long-term microscale cell-based research. Most microfluidic systems are based on the embedding of cells in hydrogels. However, physiologically realistic conditions based on hydrogels are difficult to obtain and the systems are often too complicated. We have developed a microfluidic cell culture device that incorporates a biodegradable rigid 3D polymer scaffold using standard soft lithography methods. The device permits repeated high-resolution fluorescent imaging of live cell populations within the matrix over a 4 week period. It was also possible to track cell development at the same spatial location throughout this time. In addition, human primary periodontal ligament cells were induced to produce quantifiable calcium deposits within the system. This simple and versatile device should be readily applicable for cell-based studies that require long-term culture and high-resolution bioimaging.
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17. |
- Dånmark, Staffan, et al.
(author)
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Integrin-mediated adhesion of human mesenchymal stem cells to extracellular matrix proteins adsorbed to polymer surfaces
- 2012
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In: Biomedical Materials. - : IOP Publishing. - 1748-6041 .- 1748-605X. ; 7:3, s. 035011-
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Journal article (peer-reviewed)abstract
- In vitro, degradable aliphatic polyesters are widely used as cell carriers for bone tissue engineering, despite their lack of biological cues. Their biological active surface is rather determined by an adsorbed layer of proteins from the surrounding media. Initial cell fate, including adhesion and proliferation, which are key properties for efficient cell carriers, is determined by the adsorbed layer of proteins. Herein we have investigated the ability of human bone marrow derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins, including fibronectin and vitronectin which are present in plasma and serum. hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin. Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the corresponding integrins. Although purified fibronectin and vitronectin adsorbed to aliphatic polyesters to a lower extent than to cell culture polystyrene, these low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma- and serum-coated polystyrene adsorbed significant levels of both fibronectin and vitronectin, and fibronectin was identified as the major adhesive component of plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of fibronectin under similar conditions resulting in impaired cell adhesion. Altogether, the results suggest that the efficiency of aliphatic polyesters cell carriers could be improved by increasing their ability to adsorb fibronectin.
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18. |
- Dånmark, Staffan
(author)
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Polyester scaffold: Material design and cell-protein-material interaction
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Tissue engineering has emerged as a valid approach for the regeneration and restoration of bone defects. The concept of bone tissue engineering includes degradable scaffolds, osteogenic cells and osteoinductive growth factors either alone or in any combination of these three. The scaffold bulk material and its design, in particular, are essential for reaching clinically relevant treatments. It is essential that the scaffold is biocompatible and acts as a temporary extra-cellular matrix with a porous 3-dimensional structure, supporting adhesion, proliferation and differentiation of osteogenic cells. Yet another criterion of the scaffold is that is must have sufficient mechanical stability to maintain structural integrity and protect the cells with a gradual transfer of mechanical load to the developing tissue. At the same time, the scaffolds needs to be bioresorbable with a controllable degradation rate depending on its application and the rate of tissue regrowth. In this thesis, aliphatic polyester scaffolds have been modified and shown to be suitable for bone tissue engineering applications. In addition, a new microfluidic device for live imaging of cell behavior within porous 3-dimensional scaffolds has been developed. Highly porous and degradable aliphatic polyester scaffolds with varying pore sizes and interconnected pores were fabricated. The polyesters assayed were random co-polyesters poly(L-lactide-co-ε-caprolactone) [poly(LLA-co-CL)] and poly(L-lactide-co-1,5-dioxepan-2-one) [poly(LLA-co-DXO] and the homopolymer poly(L-lactide) [poly(LLA)]. The inherently different polymers yielded scaffolds with a wide range of properties with respect to surface chemistry, thermal properties, mechanical stability and degradation rate. The polyester scaffolds were shown to support the increased proliferation of bone marrow-derived stromal cells (BMSC) as well as enhanced osteogenic differentiation, with increased levels of osteocalcin gene expression, which emphasized their potential to act as cells carriers in bone tissue engineering. The potential of poly(LLA-co-CL) scaffolds and common biomedical polyesters in bone tissue engineering was further enhanced by surface functionalization. This involved two different methods of immobilization of bone morphogenetic protein-2 (BMP-2), a potent bone-growth-inducing factor, to the assayed polyesters. The first method used BMP-2 immobilized to heparin functionalized polyesters, while the second method covalently bonded BMP-2 to grafted linker groups on polyesters. Both immobilization techniques retain the bioactivity of BMP-2, and growth-factor-modified polyesters showed an increasing expression of osteogenic genes and production of osteocalcin in osteoblasts-like cells as well as increased proliferation in the mouse cell line, C3H10T1/2. The rate of degradation of electron-beam-sterilized polyester scaffolds and the subsequent loss of mechanical stability were strongly dependent on the chemical, physical and macroscopic architecture of the samples. The degradation rate and loss of mechanical integrity were much greater in porous scaffolds with hydrophilic co-monomers. By incorporating hydrophobic co-monomers with a limited ability to crystalize instead of hydrophilic co-monomers, the mechanical stability was retained for a longer time during the degradation process. The polyester supported spreading and flattened the morphology of both BMSC and osteoblast-like cells. The early cell adhesion to synthetic surfaces is mainly governed by the proteins adsorbed from its surrounding fluids. Early adhesion of BMSC to blood-plasma-coated polyesters was limited, despite the ability of the polyesters to adsorb adhesive proteins and expression of appropriate integrins on BMSC. However, adhesion to a purified adhesive matrix protein on the polyesters did occur, suggesting that pretreatment of polyester scaffolds with adhesive proteins or peptides is a feasible way to enhance the efficiency of cell loading into polyester scaffolds. Polyester scaffolds were combined with microfluidics and soft lithography to develop a new method for high-resolution imaging of live cells within porous scaffolds. The microfluidic device was used to frequently follow live cell proliferation and differentiation on the same spatial location within 3-dimansional porous scaffolds over a period of more than four weeks. This device is attractive for the evaluation of cells and materials intended for tissue engineering. We conclude that degradable aliphatic co-polyester scaffolds carefully designed with respect to macroscopic structure, bulk material and surface chemistry are able to meet the specific requirements of various bone tissue engineering applications. In addition, microfluidic devices permit reoccurring high resolution imaging of live cells within porous scaffolds and have a potential as a method of evaluating tissue engineering constructs.
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19. |
- Ferati, Mexhid, et al.
(author)
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Gender Stereotypes and Women Participation in STEM Fields in the Western Balkans : A Scoping Review
- 2023
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In: Academic Journal of Interdisciplinary Studies. - : Richtmann Publishing. - 2281-3993 .- 2281-4612. ; 12:2, s. 228-239
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Research review (peer-reviewed)abstract
- The prevalence of gender stereotypes in STEM fields is evidenced by a large body of literature across the world, however, this area of research is still understudied in the Western Balkan region. To get a better knowledge of the extent of studies addressing this topic, we conducted a scoping review investigating existing gender stereotypes and educational choices in STEM in that region. As expected, the number of studies discovered was very limited, despite our generous inclusion criteria. In these limited studies, however, we found ample evidence of existing gender stereotypes in STEM and their impact on career aspirations. As this scoping review focused only on high-school university students, we conclude the paper with thoughts on future work ideas to expand the target group as well as to use systems thinking as an overarching perspective to conduct a holistic examination. This could be achieved by including relevant actors within and outside the immediate context, such as parents, schools, policymakers, businesses, and organizations. Finally, the paper also discusses the impact and opportunities that come with digitalization efforts, which could be leveraged to increase women participation in STEM.
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20. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(author)
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Poly(epsilon-caprolactone-co-p-dioxanone) : a Degradable and Printable Copolymer for Pliable 3D Scaffolds Fabrication toward Adipose Tissue Regeneration
- 2020
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In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 21:1, s. 188-198
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Journal article (peer-reviewed)abstract
- The advancement of 3D printing technologies in the fabrication of degradable scaffolds for tissue engineering includes, from the standpoint of the polymer chemists, an urgent need to develop new materials that can be used as ink and are suitable for medical applications. Here, we demonstrate that a copolymer of epsilon-caprolactone (CL) with low amounts of p-dioxanone (DX) (15 mol %) is a degradable and printable material that suits the requirements of melt extrusion 3D printing technologies, including negligible degradation during thermal processing. It is therefore a potential candidate for soft tissue regeneration. The semicrystalline CL/DX copolymer is processed at a lower temperature than a commercial polycaprolactone (PCL), shaped as a filament for melt extrusion 3D printing and as porous and pliable scaffolds with a gradient design. Scaffolds have Young's modulus in the range of 60-80 MPa, values suitable for provision of structural support for damaged soft tissue such as breast tissue. SEM and confocal microscope indicate that the CL/DX copolymer scaffolds support adipose stem cell attachment, spreading, and proliferation.
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21. |
- Galli, Silvia, et al.
(author)
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Local release of magnesium from mesoporous TiO2 coatings stimulates the peri-implant expression of osteogenic markers and improves osteoconductivity in vivo
- 2014
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In: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 10:12, s. 5193-5201
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Journal article (peer-reviewed)abstract
- Local release of Mg ions from titanium implant surfaces has been shown to enhance implant retention and integration. To clarify the biological events that lead to this positive outcome, threaded implants coated with mesoporous TiO2 thin films were loaded with Mg-ions and placed in the tibia of rabbits for 3 weeks, after surface characterization. Non-loaded mesoporous coated implants were used as controls. Peri-implant gene expression of a set of osteogenic and inflammatory assays was quantified by means of real-time quantitative polymerase chain reaction. The expression of three osteogenic markers (OC, RUNX-2 and IGF-1) was significantly more pronounced in the test specimens, suggesting that the release of Mg ions directly at the implant sites may stimulate an osteogenic environment. Furthermore, bone healing around implants was evaluated on histological slides and by diffraction-enhanced imaging (DEI), using synchrotron radiation. The histological analysis demonstrated new bone formation around all implants, without negative responses, with a significant increase in the number of threads filled with new bone for test surfaces. DEI analysis attested the high mineral content of the newly formed bone. Improved surface osteoconductivity and increased expression of genes involved in the bone regeneration were found for magnesium-incorporation of mesoporous TiO2 coatings.
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22. |
- Galli, Silvia, et al.
(author)
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Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone.
- 2017
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In: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 105:7, s. 2118-2125
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The release of magnesium ions (Mg2+ ) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing.METHODS: Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR.RESULTS: Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups.SIGNIFICANCE: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2118-2125, 2017.
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24. |
- Gjerde, Cecilie, et al.
(author)
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Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial
- 2018
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In: Stem Cell Research & Therapy. - : BMC. - 1757-6512. ; 9
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Journal article (peer-reviewed)abstract
- Background: Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption. Methods: The study included 11 subjects aged 52-79 years with severe mandibular ridge resorption. Bone marrow cells were aspirated from the posterior iliac crest and plastic adherent cells were expanded in culture medium containing human platelet lysate. The MSCs and biphasic calcium phosphate granules as scaffolds were inserted subperiosteally onto the resorbed alveolar ridge. After 4-6 months of healing, new bone formation was assessed clinically and radiographically, as were safety and feasibility. Bone at the implant site was biopsied for micro computed topography and histological analyses and dental implants were placed in the newly regenerated bone. Functional outcomes and patient satisfaction were assessed after 12 months. Results: The bone marrow cells, expanded in vitro and inserted into the defect together with biphasic calcium phosphate granules, induced significant new bone formation. The regenerated bone volume was adequate for dental implant installation. Healing was uneventful, without adverse events. The patients were satisfied with the esthetic and functional outcomes. No side effects were observed. Conclusions: The results of this comprehensive clinical trial in human subjects confirm that MSCs can successfully induce significant formation of new bone, with no untoward sequelae. Hence, this novel augmentation procedure warrants further investigation and may form the basis of a valid treatment protocol, challenging the current gold standard.
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25. |
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26. |
- Guo, Baolin, et al.
(author)
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Electroactive porous tubular scaffolds with degradability and non-cytotoxicity for neural tissue regeneration
- 2011
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In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 8:1, s. 144-153
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Journal article (peer-reviewed)abstract
- Electroactive degradable porous tubular scaffolds were fabricated from the blends of polycaprolactone and a hyperbranched degradable conducting copolymer at different feed ratios by a solution-casting/salt-leaching method. Scaning electron microscopy (SEM) and microcomputed tomography tests indicated that these scaffolds had homogeneously distributed interconnected pores on the cross-section and surface. The electrical conductivity of films with the same composition as the scaffolds was between 3.4×10(-6) and 3.1×10(-7)Scm(-1), depending on the ratio of hyperbranched degradable conducting copolymer to polycaprolactone. A hydrophilic surface with a contact angle of water about 30° was achieved by doping the films with (±)-10-camphorsulfonic acid. The mechanical properties of the films were investigated by tensile tests, and the morphology of the films was studied by SEM. The scaffolds were subjected to the WST test (a cell proliferation and cytotoxicity assay using water-soluble tetrazolium salts) with HaCaT keratinocyte cells, and the results show that these scaffolds are non-cytotoxic. These degradable electroactive tubular scaffolds are good candidates for neural tissue engineering application.
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27. |
- Gurzawska-Comis, Katarzyna, et al.
(author)
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GUIDED BONE REGENERATION IN OSTEOPOROSIS BY PLANT-DERIVED NANOPARTICLES
- 2023
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In: Tissue Engineering. Part A. - : MARY ANN LIEBERT, INC. - 1937-3341 .- 1937-335X. ; 29:11-12, s. 576-577
-
Journal article (other academic/artistic)abstract
- Background: The repair and treatment of large bone defects in patients with compromised bone metabolism due to ageing and medical conditions such as osteoporosis present often a clinical challenge. Therefore, adjunctive methods to enhance bone healing are needed.Bone tissue engineering with application of nanotechnology allows to construct biomaterials with desired properties being osteoconductive, osteoinductive and osteogenic.Aim / Hypothesis: The aim of our study was to promote bone regeneration using functionalised scaffold with Rhamnogalacturonan-I pectins (RG-I) in vitro and in vivo using aging and osteoporotic rodent models.Material and Methods: The biomaterials were poly(l-lactide-co-ε-caprolactone) scaffolds and the RG-I was from potato. The chemical and physical properties of functionalised biomaterials with RG-I nanoparticles were characterised using confocal and atomic force microscopy. Functionalised scaffolds with RG-I (tested sample) were evaluated in vitro with human osteoblasts from osteoporotic patients and their response was tested using real-time PCR. In vivo evaluation was performed using critical-size calvaria bone defect model in ageing and osteoporotic rat models. Scaffolds were implanted randomly in the calvaria defects of aged female Wistar rats (11-12 months old) and osteoporotic female Wistar rats induced by ovariectomy. The control was scaffold without RG-I. After 2 and 8 weeks, animals were euthanised. Harvested samples were analysed for osteogenic and inflammatory markers using real-time PCR. Bone formation was evaluated radiographically and histologically. The data was analysed using one-way ANOVA.Results: The chemical and physical properties results indicated success of the functionalisation of scaffolds with RG-I. Osteoblasts response suggested osteogenic (upregulation osteopontin, osteocalcin, collagen1, bone sialoprotein) and anti-inflammatory properties (downregulation IL-1, IL-8, TNF-alpha) on the scaffold functionalised with RG-I. The in vivo results in aged and osteoporotic rat calvaria model of early (2 weeks) bone regeneration showed increase of osteogenic markers and decrease of proinflammatory markers and RANKL, compared to control. In osteoporotic rat model at week 2 and 8 and in aged rat model at week 8, the mean percentage of BV / TV (bone volume / tissue volume) in the defect with RG-I scaffold was significantly greater than the defect with control. The histological evaluation in both rat models revealed larger areas of new bone formation in RG-I scaffolds than in control.Conclusion and Clinical implications: In conclusion, the plant-derived nanoparticles significantly increased osteogenic and decreased pro-inflammatory response in vitro and in vivo. These finding may have a crucial impact on bone repair process especially in elderly and osteoporotic patients.
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28. |
- Idris, Shaza B., et al.
(author)
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Biocompatibility of Polyester Scaffolds with Fibroblasts and Osteoblast-like Cells for Bone Tissue Engineering
- 2010
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In: Journal of bioactive and compatible polymers (Print). - : SAGE Publications. - 0883-9115 .- 1530-8030. ; 25:6, s. 567-583
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate the in vitro cytotoxicity and cytocompatibility of the developed aliphatic polyester co-polymer scaffolds: poly(L-lactide-co-epsilon-caprolactone) and poly(L-lactide-co-1,5-dioxepan-2-one). The scaffolds were produced by solvent casting and particulate leaching, and tested by direct and indirect contact cytotoxicity assays on human osteoblast-like cells and mouse fibroblasts. Cell morphology was documented by light and scanning electron microscopy. Viability was assessed by the MTT, neutral red uptake, lactic dehydrogenase and apoptosis assays. Extraction tests confirmed that the scaffolds did not have a cytotoxic effect on the cells. The cells grew and spread well on the test scaffolds with good cellular attachment and viability. The scaffolds are noncytotoxic and biocompatible with the two cell types and warrant continued investigation as potential constructs for bone tissue engineering.
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29. |
- Idris, Shaza B., et al.
(author)
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Global Gene Expression Profile of Osteoblast-Like Cells Grown on Polyester Copolymer Scaffolds
- 2011
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In: Tissue Engineering. Part A. - NEW ROCHELLE, NY : Mary Ann Liebert. - 1937-3341 .- 1937-335X. ; 17:21-22, s. 2817-2831
-
Journal article (peer-reviewed)abstract
- One of the principal goals in tissue engineering is to produce scaffold materials that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. Poly(l-lactide-co-1,5-dioxepan-2-one) [Poly(LLA-co-DXO)], a potential scaffolding material for bone tissue engineering, has high hydrophilicity. Previous in vitro studies using human osteoblast-like cells (HOBs) demonstrated greater cytocompatibility and enhanced osteogenic differentiation when HOBs were seeded onto Poly(LLA-co-DXO) compared to Poly(llactide) [P(LLA)] scaffolds. The aim of the study was to identify the gene expression profiles of HOBs obtained from alveolar bone and grown on Poly(LLA-co-DXO) biodegradable polymer scaffolds compared to P(LLA) one. Illumina HumanWG-6 v3.0 Expression BeadChips were used for the gene expression analysis. Several genes were found as differentially expressed at 24 h and at 21 days. Expression of genes related to cell adhesion, cytoskeleton, antiapoptosis, proliferation, and bone mineralization was influenced by adding the monomer 1,5-dioxepan-2-one to the l-lactide. Genes related to three biological pathways involving Integrin, Notch, and Ras were found to be upregulated. For selected genes, results were confirmed by quantitative reverse transcriptase– polymerase chain reaction. Further, calcium content analysis revealed a significant enhancement of calcium deposition on both tested scaffolds. This observation was confirmed by Von Kossa and Alizarin Red S staining. Findings of this study are relevant to a better understanding of the molecular mechanisms underlying the behavior of HOBs in bone regenerative procedure.
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30. |
- Jain, Shubham, 1990-
(author)
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Engineering 3D degradable pliable scaffolds for adipose tissue regeneration : Advancing cell-material interactions by understanding the influence from thermal, chemical, mechanical properties and scaffold design
- 2021
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Doctoral thesis (other academic/artistic)abstract
- In soft tissue defects that arise due to trauma, tumor resections and complex burns, a significant loss in adipose tissue remains a considerable challenge due to the insufficient regenerative capacity of the tissue. This thesis focuses on assessing cell-material interactions between degradable 3D polymer scaffolds with different designs and adipose tissue-derived stem cells. This knowledge can be used to engineer 3D scaffolds with adequate physio-chemical and mechanical properties along with an appropriate design that augments adipose tissue regeneration.Salt-leaching 3D scaffolds were fabricated from various medical-grade polyesters, and cellular behavior was evaluated by correlating the physical, chemical, and mechanical properties of the scaffolds. The results showed that the glass transition temperature modulated the mechanical properties of the scaffolds, affecting stem cell proliferation and adipogenic differentiation. The same sets of polymers were further used in melt extrusion-based 3D printer and printability was established for the fabrication of customized 3D scaffolds. Based on printability and cell-scaffolds interaction results, poly (L-lactide-co-trimethylene carbonate) was used to print 3D scaffolds in different soft and pliable designs that promoted adipogenic differentiation. To fabricate even softer, and more hydrophilic 3D scaffolds, poly (ɛ-caprolactone-co-p-dioxanone) and a unique scaffold design were utilized within the research group. The copolymer 3D scaffolds were further combined with knitted mesh and electrospun nanofibers to develop scaffolds with multilayer architecture, modular scaffolds. The in vitro results asserted that the modular scaffold enhanced cell-material interactions by almost five times of those observed for the scaffold alone. Therefore, it can be concluded that softness and pliability are crucial and an appropriate scaffold design with adequate mechanical support is required for enhancing cell-material interaction. The in vitro results asserted that the modular scaffold enhanced cell-material interactions by almost five times of those observed for the scaffold alone. Therefore, it can be concluded that softness and pliability are crucial and an appropriate scaffold design with adequate mechanical support is required for enhancing cell-material interaction. The in vitro results asserted that the modular scaffold enhanced cell-material interactions by almost five times of those observed for the scaffold alone. Therefore, it can be concluded that softness and pliability are crucial and an appropriate scaffold design with adequate mechanical support is required for enhancing cell-material interaction.
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31. |
- Jain, Shubham, et al.
(author)
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Engineering 3D degradable, pliable scaffolds toward adipose tissue regeneration; optimized printability, simulations and surface modification
- 2020
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In: Journal of Tissue Engineering. - : SAGE Publications. - 2041-7314. ; 11
-
Journal article (peer-reviewed)abstract
- We present a solution to regenerate adipose tissue using degradable, soft, pliable 3D-printed scaffolds made of a medical-grade copolymer coated with polydopamine. The problem today is that while printing, the medical grade copolyesters degrade and the scaffolds become very stiff and brittle, being not optimal for adipose tissue defects. Herein, we have used high molar mass poly(L-lactide-co-trimethylene carbonate) (PLATMC) to engineer scaffolds using a direct extrusion-based 3D printer, the 3D Bioplotter (R). Our approach was first focused on how the printing influences the polymer and scaffold's mechanical properties, then on exploring different printing designs and, in the end, on assessing surface functionalization. Finite element analysis revealed that scaffold's mechanical properties vary according to the gradual degradation of the polymer as a consequence of the molar mass decrease during printing. Considering this, we defined optimal printing parameters to minimize material's degradation and printed scaffolds with different designs. We subsequently functionalized one scaffold design with polydopamine coating and conducted in vitro cell studies. Results showed that polydopamine augmented stem cell proliferation and adipogenic differentiation owing to increased surface hydrophilicity. Thus, the present research show that the medical grade PLATMC based scaffolds are a potential candidate towards the development of implantable, resorbable, medical devices for adipose tissue regeneration.
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32. |
- Jain, Shubham, et al.
(author)
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Printability and Critical Insight into Polymer Properties during Direct-Extrusion Based 3D Printing of Medical Grade Polylactide and Copolyesters
- 2020
-
In: Biomacromolecules. - : AMER CHEMICAL SOC. - 1525-7797 .- 1526-4602. ; 21:2, s. 388-396
-
Research review (peer-reviewed)abstract
- Various 3D printing techniques currently use degradable polymers such as aliphatic polyesters to create well-defined scaffolds. Even though degradable polymers are influenced by the printing process, and this subsequently affects the mechanical properties and degradation profile, degradation of the polymer during the process is not often considered. Degradable scaffolds are today printed and cell-material interactions evaluated without considering the fact that the polymer change while printing the scaffold. Our methodology herein was to vary the printing parameters such as temperature, pressure, and speed to define the relationship between printability, polymer microstructure, composition, degradation profile during the process, and rheological behavior. We used high molecular weight medical-grade (co)polymers, poly(L-lactide-co-epsilon-caprolactone) (PCLA), poly(L-lactide-co-glycolide) (PLGA), and poly(D,L-lactide-co-glycolide) (PDLGA), with L-lactide content ranging from 25 to 100 mol %, for printing in an extrusion-based printer (3D Bioplotter). Optical microscopy confirmed that the polymers were printable at high resolution and good speed, until a certain degree of degradation. The results show also that printability can not be claimed just by optimizing printing parameters and highlight the importance of a careful analysis of how the polymer's structure and properties vary during printing. The polymers thermally decomposed from the first processing minute and caused a decrease in the average block length of the lactide blocks in the copolymers and generated lower crystallinity. Poly(L-lactide) (PLLA) and PCLA are printable at a higher molecular weight, less degradation before printing was possible, compared to PLGA and PDLGA, a result explained by the higher complex viscosity and more elastic polymeric melt of the copolymer containing glycolide (GA) and lactide (LA). In more detail, copolymers comprised of LA and epsilon-caprolactone (CL) formed lower molecular weight compounds over the course of printing, while the PLGA copolymer was more susceptible to intermolecular transesterification reactions, which do not affect the overall molecular weight, but cause changes in the copolymer microstructure. This results in a longer printing time for PLGA than PLLA and PCLA.
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33. |
- Jain, Shubham, et al.
(author)
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Understanding of how the properties of medical grade lactide based copolymer scaffolds influence adipose tissue regeneration : Sterilization and a systematic in vitro assessment
- 2021
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In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 124
-
Journal article (peer-reviewed)abstract
- Aliphatic polyesters are the synthetic polymers most commonly used in the development of resorbable medical implants / devices. Various three-dimensional (3D) scaffolds have been fabricated from these polymers and used in adipose tissue engineering. However, their systematic evaluation altogether lacks, which makes it difficult to select a suitable degradable polymer to design 3D resorbable implants and / or devices able to effectively mimic the properties of adipose tissue. Additionally, the impact of sterilization methods on the medical devices, if any, must be taken into account. We evaluate and compare five different medical-grade resorbable polyesters with l-lactide content ranging from 50 to 100 mol% and exhibiting different physiochemical properties depending on the comonomer (d-lactide, ε-caprolactone, glycolide, and trimethylene carbonate). The salt-leaching technique was used to prepare 3D microporous scaffolds. A comprehensive assessment of the physical, chemical, and mechanical properties of the scaffolds was carried out in PBS at 37 ° C. The cell-material interactions and the ability of the scaffolds to promote adipogenesis of human adipose tissue-derived stem cells were assessed in vitro. The diverse physical and mechanical properties of the scaffolds, due to the different composition of the copolymers, influenced human adipose tissue-derived stem cells proliferation and differentiation. Scaffolds made from polymers which were above their glass transition temperature and with low degree of crystallinity showed better proliferation and adipogenic differentiation of stem cells. The effect of sterilization techniques (electron beam and ethylene oxide) on the polymer properties was also evaluated. Results showed that scaffolds sterilized with the ethylene oxide method better retained their physical and chemical properties. Overall, the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices / implants; (ii) directions to prefer a sterilization method that does not change polymer properties. the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices / implants; (ii) directions to prefer a sterilization method that does not change polymer properties. the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices / implants; (ii) directions to prefer a sterilization method that does not change polymer properties.
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34. |
- Kamal, M. Mustafa, et al.
(author)
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Proper Orthogonal Decomposition Analysis of Non-Swirling Turbulent Stratified and Premixed Methane/Air Flames
- 2014
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In: Proceedings of the ASME Turbo Expo: Turbine Technical Conference and Exposition, 2014. ; 4B
-
Conference paper (peer-reviewed)abstract
- This paper reports proper orthogonal decomposition (POD) analyses for the velocity fields measured in a test burner. The Cambridge/Sandia Stratified Swirl Burner has been used in various studies as a benchmark for high resolution scalar and velocity measurements, for comparison with numerical model prediction. Flow field data was collected for a series of bluff-body stabilized premixed and stratified methane/air flames at turbulent, globally lean conditions (phi = 0.75) using high speed stereoscopic particle image velocimetry (HS-SPIV). In this paper, a modal analysis was performed to identify the large scale flow structures and their impact on the flame dynamics. The high speed PIV system was operated at 3 kHz to acquire a series of 4096 sequential flow field images both for reactive and non-reactive cases, sufficient to follow the large-scale spatial and temporal evolution of flame and flow dynamics. The POD analysis allows identification of vortical structures, created by the bluff body, and in the shear layers surrounding the stabilization point. In addition, the analysis reveals that dominant structures are a strong function of the mixture stratification in the flow field. The dominant energetic modes of reactive and non-reactive flows are very different, as the expansion of gases and the high temperatures alter the unstable modes and their survival in the flow.
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35. |
- Kassebaum, Nicholas J., et al.
(author)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
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Journal article (peer-reviewed)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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36. |
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37. |
- Korkeamäki, Jannika T., et al.
(author)
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Biomimetic highly porous nanocellulose–nanohydroxyapatite scaffolds for bone tissue engineering
- 2024
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In: Cellulose. - : Springer Science and Business Media B.V.. - 0969-0239 .- 1572-882X. ; 31:4, s. 2503-2521
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Journal article (peer-reviewed)abstract
- Wood-derived TEMPO-oxidized cellulose nanofibrils (CNFs) have potential as scaffolding for bone tissue engineering. Although biocompatible, the material lacks osteoconductive and appropriate mechanical properties. Incorporation of nano-hydroxyapatite (nHA) and modification of scaffold preparation methods could improve applicability. In this study, freeze-dried porous scaffolds were prepared using a range of nHA (0, 20, 33, 50%) and CNF compositions. Not only the microarchitecture but also the chemical composition of the scaffolds was studied. Osteoblast-like osteosarcoma derived cells (Saos-2) were cultured on the scaffolds and their responses (viability, attachment, proliferation, and osteogenic phenotype) to the different scaffolds were documented. The results show that incorporation of nHA influenced the microarchitecture, mechanical stiffness and surface properties of the scaffolds. Moreover, biological characterization demonstrated good cell viability in all the groups. However, the increase of nHA concentration beyond 20% does not offer further advantages. It is concluded that the incorporation of 20% nHA resulted in the widest and most biomimetic pore size distribution, increased surface roughness and improved protein adsorption. These changes in material properties enhanced cell spreading and the osteogenic gene expression of osteoblast-like cells seeded on the scaffolds. Moreover, 20% nHA warrants further investigation as a potential scaffolding material for bone tissue engineering. Graphical abstract: (Figure presented.).
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38. |
- Lindgren, Christer, et al.
(author)
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Surface modified biphasic calcium phosphate-particles enhance expression of bone markers in osteoblast-like cells
-
Other publication (other academic/artistic)abstract
- Objectives: The aim of the present in vitro study was to evaluate the response of human osteoblast-like cells (HOB) to nano-crystalline-diamond-particle-modified (nDP-modified) and un-modified (control) deproteinized bovine bone (DBB) and biphasic calcium phosphate (BCP) scaffolds. Materials and methods: nDP-modification of DBB and BCP- particles was carried out through different steps of preparation including grinding and ultrasonic technique. In each experiment, 100 mg materials from each of the 4 groups (nDP-modified DBB, nDP-modified BCP, un-modified DBB and un-modified BCP) were plated into a 48 well cell culture plate and 200.000 cells/well were seeded onto the materials. Scanning electron microscopy (SEM) was carried out after 24 hours and 3 days. Real time-polymerase chain reaction (PCR) was carried out after 3 days, 1 week and 2 weeks of incubation. The following markers were analyzed; alkaline phosphatase (ALP), osteocalcin (OC), bone morphogenetic protein type 2 (BMP-2) and integrin alpha 10 (ITGA 10). The general tendency of DBB and BCP was compared. Results: Cellular responses were evaluated in terms of attachment and differentiation. SEM after 24 hours and 3 days of incubation disclosed similar cell attachment and spreading for nDP-modified and non-modified DBB and BCP particles. Real-time PCR revealed significant up-regulation of mRNA expression of ALP and OC by HOB grown on nDP-modified DBB and BCP-particles after 1 and 2 weeks compared to non-modified particles. A significant down-regulation of BMP-2 on nDP-modified DBB and a significant up-regulation of BMP-2 on nDP-modified BCP were disclosed for HOB in relation to un-modified particles. Cell adhesion marker ITGA 10 showed significant down-regulated in the mRNA level for both nDP-modified groups after 2 weeks of incubation (nDP-BCP (p<.01) and nDP-DBB (p<.05) compared to the non-modified materials. Conclusion: nDP-modified BCP-particles seem to enhance the expression of osteogenic markers in HOB in vitro. The results indicate that nDP-modified BCP enhance the osteoblast phenotype and suggest that these scaffolds might be appropriate cell carriers, superior to nonmodified BCP-particles. The osteogenic markers of OC and ALP were increased for nDPmodified DBB particles but BMP-2 was down regulated in relation to non-modified DBB particles.
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39. |
- Munir, Arooj, et al.
(author)
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Efficacy of copolymer scaffolds delivering human demineralised dentine matrix for bone regeneration
- 2019
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In: Journal of Tissue Engineering. - : SAGE PUBLICATIONS INC. - 2041-7314. ; 10
-
Journal article (peer-reviewed)abstract
- Poly(L-lactide-co-epsilon-caprolactone) scaffolds were functionalised by 10 or 20 mu g/mL of human demineralised dentine matrix. Release kinetics up to 21 days and their osteogenic potential on human bone marrow stromal cells after 7 and 21 days were studied. A total of 390 proteins were identified by mass spectrometry. Bone regeneration proteins showed initial burst of release. Human bone marrow stromal cells were cultured on scaffolds physisorbed with 20 mu g/mL and cultured in basal medium (DDM group) or physisorbed and cultured in osteogenic medium or cultured on non-functionalised scaffolds in osteogenic medium. The human bone marrow stromal cells proliferated less in demineralised dentine matrix group and activated ERK/1/2 after both time points. Cells on DDM group showed highest expression of IL-6 and IL-8 at 7 days and expressed higher collagen type 1 alpha 2, SPP1 and bone morphogenetic protein-2 until 21 days. Extracellular protein revealed higher collagen type 1 and bone morphogenetic protein-2 at 21 days in demineralised dentine matrix group. Cells on DDM group showed signs of mineralisation. The functionalised scaffolds were able to stimulate osteogenic differentiation of human bone marrow stromal cells.
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40. |
- Mustafa, Arwa, et al.
(author)
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Effect of extraction pH on acrylamide content in fresh and stored rye crisp bread
- 2008
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In: Journal of Food Composition and Analysis. - : Elsevier BV. - 0889-1575 .- 1096-0481. ; 21:4, s. 351-355
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Journal article (peer-reviewed)abstract
- Acrylamide (AA) is a heat-generated food toxicant and from a food safety point of view, it is important that its intake to be reduced as much as possible, and that the quantitative analyses provide reliable and relevant levels. In an experiment designed with added AA precursors (asparagine and fructose), it was found that the yield of alkali-extractable AA in rye crisp bread 2 was on average 37% higher than the yield of water-extractable AA. A strong correlation between water and alkaline extractable AA (R-2 = 0.99) indicated that they were formed from a common precursor(s). The storage of samples for 20 months lead to a decrease in the AA content but did not change the correlation between the AA yield from neutral and alkaline extraction. An experiment with labeled AA, added to the dough, ruled out the possibility that AA released by alkali extraction was bound to or entrapped in the matrix.
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41. |
- Mustafa, Arwa, et al.
(author)
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Interaction effects of fermentation time and added asparagine and glycine on acrylamide content in yeast-leavened bread
- 2009
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In: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 112, s. 767-774
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Journal article (peer-reviewed)abstract
- The interaction effects of fermentation time and added asparagine and glycine on acrylamide precursors (asparagine and reducing sugars) in dough and content of acrylamide in yeast-leavened wheat bread were Studied. Two experiments, with low and high levels of added asparagine (0-0.044 and 0.071-0.476 g/100 g flour, respectively), were performed. Glycine was added (0.042-0.380 g/100 g flour) only in the high asparagine addition experiment. The fermentation time, which was varied between 13 and 164 min, showed a reducing effect on acrylamide precursors in the dough ill both experiments (p < 0.001). These effects of fermentation were more pronounced in the experiment with low asparagine levels, which resembled levels in ingredients. In contrast, fermentation time did not affect the content of glycine in the dough. Added asparagine increased the levels of asparagine in dough and of acrylamide in bread (p < 0,001). A strong correlation was found between the contents of asparagine in the fermented dough and acrylamide in breads at all levels of asparagine, Glycine significantly increased the colour intensity and reduced the acrylamide in bread (p < 0.001) with the latter effect being dependent on the level of asparagine. (c) 2008 Elsevier Ltd. All rights reserved.
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42. |
- Mustafa, Kamal
(author)
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Cellular responses to titanium surfaces blasted with TiO2 particles
- 2001
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Doctoral thesis (other academic/artistic)abstract
- A major determinant of successful osseointegration of endosseous implants is the surface topography of the implant, which influences the cellular response of the surrounding tissues. This series of experimental studies investigated cellular responses to surface modifications of titanium implant material. With machined (turned) surfaces as controls, the topography was altered by blasting with Ti02 particles of varying size. Surface roughness increased with increasing particle size, up to 106- 180 µm. Further increasing particle size to 300 gm did not significantly increase surface roughness. Cellular response was studied in two cell types: primary cultures of human gingival fibroblasts and osteoblast-like cells. The following responses were investigated: attachment, proliferation, differentiation and production of transforming growth factor beta1 (TGF-beta1) and prostaglandin E2 (PGE2). In study I, turned surfaces favored fibroblast attachment, least attachment occurring on the surfaces blasted with 63-90 µm particles, whereas in study II, turned surfaces and those blasted with 63-90 gm particles provided the most favorable attachment for osteoblast-like cells. This strongly suggests that in contact with implant surfaces, bonederived cells behave differently from fibroblasts. Hence the results highlight the importance of using the relevant cell system for evaluation of dental implant material. Blasting with larger particles (300 gm) did not further enhance the initial attachment of osteoblast-like cells compared to the turned surfaces (study III). Studies III & IV concerned the effect of surface roughness on attachment, proliferation and differentiation of human osteoblast-like cells, as well as the production of two factors known to have potent effects on tissues surrounding an implant: TGF-beta1, and PGE2. Incorporation of [3H]-thymidine and osteocalcin synthesis were significantly increased on all blasted surfaces compared to the turned surfaces. The production of TGFbeta1, and PGE2 was also higher on the blasted surfaces. In study V, the different surfaces subjected to cell culture tests were characterized by electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy. Compared to the turned surfaces, the effective surface area is several times larger on the blasted surfaces, with less carbon contamination. Corrosion resistance was unaffected by blasting the normal machined titanium surfaces with titanium dioxide particles or exposing the samples to the culture conditions for 28 days. Osteoblast-like cells enhance ion incorporation and precipitation processes, whereas the amount of calcium absorption is independent of surface roughness. In summary, the results show that the technique used for isolation of human osteoblast-like cells from mandibular bone is useful for investigating the biocompatibility of dental implant materials in vitro. Attachment of fibroblasts may be enhanced on turned surfaces and inhibited on surfaces roughened by blasting. Surface roughness, achieved by blasting titanium surfaces with various sizes of Ti02 particles significantly favored proliferation, differentiation and production of TGFbeta1 and PGE2. Increasing surface roughness to this range may modulate the activity of cells interacting with an implant, thereby enhancing tissue healing and implant success.
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43. |
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44. |
- Mustafa, Kamal, et al.
(author)
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The influence of surface topography of ceramic abutments on the attachment and proliferation of human oral fibroblasts.
- 2005
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In: Biomaterials. - : Elsevier BV. - 0142-9612. ; 26:4, s. 373-81
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Journal article (peer-reviewed)abstract
- As different implant abutments are introduced to obtain a sufficient soft tissue barrier, the aim of this study was to determine the effect of three different surface modifications of densely sintered high-purity aluminium oxide on morphology, attachment and proliferation of human gingival fibroblasts. Fibroblasts were cultured on pressed aluminium oxide, milled, and then sintered to full density (1), on pressed, densely sintered (2), and on pressed, densely sintered and then polished surfaces (3). The different surfaces were analyzed using a confocal laser scanner, an atomic force microscope and a scanning electron microscope. The cell profile areas were measured using a semiautomatic interactive image analyzer and the figures were expressed as percent of attachment. The polished specimens had the smoothest surfaces and the roughest were the milled surfaces in terms of height deviation. No difference was found in the spacing between the peaks on the polished surfaces compared to the milled surfaces. Fibroblasts on the milled ceramic appeared to follow the direction of the fine irregularities on the surface. The analyses showed the polished surfaces had significantly higher percentages of initial cell attachment than the other surfaces (P < 0.05). After 3 days of cell culture, significantly more cells were attached to the milled and sintered surfaces than to the polished one, possibly indicating higher proliferation capacity on those types of surfaces.
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45. |
- Ojansivu, Miina, et al.
(author)
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Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells
- 2019
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In: Biofabrication. - : Institute of Physics Publishing (IOPP). - 1758-5082 .- 1758-5090. ; 11:3
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Journal article (peer-reviewed)abstract
- A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological and physicochemical properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils (CNF) and bioactive glass (BaG) on the rheological properties of gelatin-alginate bioinks and the initial responses ofbone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDX and ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells (Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels and crosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP) were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a constant increase in the ALP activity in all the hydrogels. Further bioprinting experiments were conducted using human bone marrow-derived mesenchymal stem cells (hBMSCs), a clinically relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG to gelatin-alginate bioinks holds great potential for bone tissue engineering applications.
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46. |
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47. |
- Pedersen, Torbjorn O., et al.
(author)
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Endothelial microvascular networks affect gene-expression profiles and osteogenic potential of tissue-engineered constructs
- 2013
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In: STEM CELL RES THER. - : Springer Science and Business Media LLC. - 1757-6512. ; 4, s. 52-
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Journal article (peer-reviewed)abstract
- Introduction: A major determinant of the potential size of cell/scaffold constructs in tissue engineering is vascularization. The aims of this study were twofold: first to determine the in vitro angiogenic and osteogenic geneexpression profiles of endothelial cells (ECs) and mesenchymal stem cells (MSCs) cocultured in a dynamic 3D environment; and second, to assess differentiation and the potential for osteogenesis after in vivo implantation. Methods: MSCs and ECs were grown in dynamic culture in poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) copolymer scaffolds for 1 week, to generate three-dimensional endothelial microvascular networks. The constructs were then implanted in vivo, in a murine model for ectopic bone formation. Expression of selected genes for angiogenesis and osteogenesis was studied after a 1-week culture in vitro. Human cell proliferation was assessed as expression of ki67, whereas a-smooth muscle actin was used to determine the perivascular differentiation of MSCs. Osteogenesis was evaluated in vivo through detection of selected markers, by using real-time RT-PCR, alkaline phosphatase (ALP), Alizarin Red, hematoxylin/eosin (HE), and Masson trichrome staining. Results: The results show that endothelial microvascular networks could be generated in a poly(LLA-co-DXO) scaffold in vitro and sustained after in vivo implantation. The addition of ECs to MSCs influenced both angiogenic and osteogenic gene-expression profiles. Furthermore, human ki67 was upregulated before and after implantation. MSCs could support functional blood vessels as perivascular cells independent of implanted ECs. In addition, the expression of ALP was upregulated in the presence of endothelial microvascular networks. Conclusions: This study demonstrates that copolymer poly(LLA-co-DXO) scaffolds can be prevascularized with ECs and MSCs. Although a local osteoinductive environment is required to achieve ectopic bone formation, seeding of MSCs with or without ECs increases the osteogenic potential of tissue-engineered constructs.
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48. |
- Pedersen, Torbjorn O., et al.
(author)
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Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation
- 2014
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In: Stem Cell Research & Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 5, s. 23-
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Journal article (peer-reviewed)abstract
- Introduction: Rapid establishment of functional blood vessels is a prerequisite for successful tissue engineering. During vascular development, endothelial cells (ECs) and perivascular cells assemble into a complex regulating proliferation of ECs, vessel diameter and production of extracellular matrix proteins. The aim of this study was to evaluate the ability of mesenchymal stem cells (MSCs) to establish an endothelial-perivascular complex in tissue-engineered constructs comprising ECs and MSCs. Methods: Primary human ECs and MSCs were seeded onto poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) scaffolds and grown in dynamic culture before subcutaneous implantation in immunocompromised mice for 1 and 3 weeks. Cellular activity, angiogenic stimulation and vascular assembly in cell/scaffold constructs seeded with ECs or ECs/MSCs in a 5:1 ratio was monitored with real-time RT-PCR, ELISA and immunohistochemical microscopy analysis. Results: A quiescent phenotype of ECs was generated, by adding MSCs to the culture system. Decreased proliferation of ECs, in addition to up-regulation of selected markers for vascular maturation was demonstrated. Baseline expression of VEGFa was higher for MSCs compared with EC (P < 0.001), with subsequent up-regulated VEGFa-expression for EC/MSC constructs before (P < 0.05) and after implantation (P < 0.01). Furthermore, an inflammatory response with CD11b + cells was generated from implantation of human cells. At the end of the 3 week experimental period, a higher vascular density was shown for both cellular constructs compared with empty control scaffolds (P < 0.01), with the highest density of capillaries being generated in constructs comprising both ECs and MSCs. Conclusions: Induction of a quiescent phenotype of ECs associated with vascular maturation can be achieved by co-seeding with MSCs. Hence, MSCs can be appropriate perivascular cells for tissue-engineered constructs.
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49. |
- Rashad, Ahmad, et al.
(author)
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Coating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem Cells
- 2018
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 19:11, s. 4307-4319
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Journal article (peer-reviewed)abstract
- 3D printed polycaprolactone (PCL) has potential as a scaffold for bone tissue engineering, but the hydrophobic surface may hinder optimal cell responses. The surface properties can be improved by coating the scaffold with cellulose nanofibrils material (CNF), a multiscale hydrophilic biocompatible biomaterial derived from wood. In this study, human bone marrow-derived mesenchymal stem cells were cultured on tissue culture plates (TCP) and 3D printed PCL scaffolds coated with CNF. Cellular responses to the surfaces (viability, attachment, proliferation, and osteogenic differentiation) were documented. CNF significantly enhanced the hydrophilic properties of PCL scaffolds and promoted protein adsorption. Live/dead staining and lactate dehydrogenase release assays confirmed that CNF did not inhibit cellular viability. The CNF between the 3D printed PCL strands and pores acted as a hydrophilic barrier, enhancing cell seeding efficiency, and proliferation. CNF supported the formation of a well-organized actin cytoskeleton and cellular production of vinculin protein on the surfaces of TCP and PCL scaffolds. Moreover, CNF-coated surfaces enhanced not only alkaline phosphatase activity, but also collagen Type-I and mineral formation. It is concluded that CNF coating enhances cell attachment, proliferation, and osteogenic differentiation and has the potential to improve the performance of 3D printed PCL scaffolds for bone tissue engineering.
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50. |
- Rashad, Amad, et al.
(author)
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Cytocompatibility of Wood-Derived Cellulose Nanofibril Hydrogels with Different Surface Chemistry
- 2017
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 18:4, s. 1238-1248
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Journal article (peer-reviewed)abstract
- The current study aims to demonstrate the influence of the surface chemistry of wood-derived cellulose nanofibril (CNF) hydrogels on fibroblasts for tissue engineering applications. TEMPO-mediated oxidation or carboxymethylation pretreatments were employed to produce hydrogels with different surface chemistry. This study demonstrates the following: first, the gelation of CNF with cell culture medium and formation of stable hydrogels with improved rheological properties; second, the response of mouse fibroblasts cultured on the surface of the hydrogels or sandwiched within the materials with respect to cytotoxicity, cell attachment, proliferation, morphology, and migration. Indirect cytotoxicity tests showed no toxic effect of either hydrogel. The direct contact with the carboxymethylated hydrogel adversely influenced the morphology of the cells and limited their spreading, while typical morphology and spreading of cells were observed with the TEMPO-oxidized hydrogel. The porous fibrous structure may be a key to cell proliferation and migration in the hydrogels.
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