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| 2. |
- Hoogenkamp, Henk R., et al.
(författare)
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Seamless Vascularized Large-Diameter Tubular Collagen Scaffolds Reinforced with Polymer Knittings for Esophageal Regenerative Medicine
- 2014
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Ingår i: Tissue Engineering. Part C, Methods. - : Mary Ann Liebert Inc. - 1937-3384 .- 1937-3392. ; 20:5, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- A clinical demand exists for alternatives to repair the esophagus in case of congenital defects, cancer, or trauma. A seamless biocompatible off-the-shelf large-diameter tubular scaffold, which is accessible for vascularization, could set the stage for regenerative medicine of the esophagus. The use of seamless scaffolds eliminates the error-prone tubularization step, which is necessary when emanating from flat scaffolds. In this study, we developed and characterized three different types of seamless tubular scaffolds, and evaluated in vivo tissue compatibility, including vascularization by omental wrapping. Scaffolds (luminal O approximate to 1.5cm) were constructed using freezing, lyophilizing, and cross-linking techniques and included (1) single-layered porous collagen scaffold, (2) dual-layered (porous+dense) collagen scaffold, and (3) hybrid scaffold (collagen+incorporated polycaprolacton knitting). The latter had an ultimate tensile strength comparable to a porcine esophagus. To induce rapid vascularization, scaffolds were implanted in the omentum of sheep using a wrapping technique. After 6 weeks of biocompatibility, vascularization, calcification, and hypoxia were evaluated using immunohistochemistry. Scaffolds were biocompatible, and cellular influx and ingrowth of blood vessels were observed throughout the whole scaffold. No calcification was observed, and slight hypoxic conditions were detected only in the direct vicinity of the polymer knitting. It is concluded that seamless large-diameter tubular collagen-based scaffolds can be constructed and vascularized in vivo. Such scaffolds provide novel tools for esophageal reconstruction.
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| 3. |
- Palacio-Castaneda, Valentina, et al.
(författare)
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Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform
- 2021
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 13:11, s. 1944-
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the delivery of next-generation macromolecular drugs, such as engineered proteins and mRNA-containing nanoparticles, there is an increasing push towards the use of physiologically relevant disease models that incorporate human cells and do not face ethical dilemmas associated with animal use. Here, we illustrate the versatility and ease of use of a microfluidic platform for studying drug delivery using high-resolution microscopy in 3D. Using this microfluidic platform, we successfully demonstrate the specific targeting of carbonic anhydrase IX (CAIX) on cells overexpressing the protein in a tumor-mimicking chip system using affibodies, with CAIX-negative cells and non-binding affibodies as controls. Furthermore, we demonstrate this system's feasibility for testing mRNA-containing biomaterials designed to regenerate bone defects. To this end, peptide-and lipid-based mRNA formulations were successfully mixed with colloidal gelatin in microfluidic devices, while translational activity was studied by the expression of a green fluorescent protein. This microfluidic platform enables the testing of mRNA delivery from colloidal biomaterials of relatively high densities, which represents a first important step towards a bone-on-a-chip platform. Collectively, by illustrating the ease of adaptation of our microfluidic platform towards use in distinct applications, we show that our microfluidic chip represents a powerful and flexible way to investigate drug delivery in 3D disease-mimicking culture systems that recapitulate key parameters associated with in vivo drug application.
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| 4. |
- Purdue, Mark P, et al.
(författare)
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Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:1, s. 60-65
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
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| 5. |
- Sun, Weilun, et al.
(författare)
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Improving the Cell Distribution in Collagen-Coated Poly-Caprolactone Knittings
- 2012
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Ingår i: TISSUE ENG PART C-ME. - : Mary Ann Liebert Inc. - 1937-3384. ; 18:10, s. 731-739
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Tidskriftsartikel (refereegranskat)abstract
- Adequate cellular in-growth into biomaterials is one of the fundamental requirements of scaffolds used in regenerative medicine. Type I collagen is the most commonly used material for soft tissue engineering, because it is nonimmunogenic and a highly porous network for cellular support can be produced. However, in general, adequate cell in-growth and cell seeding has been suboptimal. In this study we prepared collagen scaffolds of different collagen densities and investigated the cellular distribution. We also prepared a hybrid polymer-collagen scaffold to achieve an optimal cellular distribution as well as sufficient mechanical strength. Collagen scaffolds [ranging from 0.3% to 0.8% (w/v)] with and without a mechanically stable polymer knitting [polycaprolactone (PCL)] were prepared. The porous structure of collagen scaffolds was characterized using scanning electron microscopy and hematoxylin-eosin staining. The mechanical strength of hybrid scaffolds (collagen with or without PCL) was determined using tensile strength analysis. Cellular in-growth and interconnectivity were evaluated using fluorescent bead distribution and human bladder smooth muscle cells and human urothelium seeding. The lower density collagen scaffolds showed remarkably deeper cellular penetration and by combining it with PCL knitting the tensile strength was enhanced. This study indicated that a hybrid scaffold prepared from 0.4% collagen strengthened with knitting achieved the best cellular distribution.
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| 6. |
- Yuan, Hongbo, et al.
(författare)
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Synthetic fibrous hydrogels as a platform to decipher cell–matrix mechanical interactions
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 120:15
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Tidskriftsartikel (refereegranskat)abstract
- Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell–matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell–matrix interactions and to improve the design of materials for mechanobiology studies.
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