| 1. |
- Aulin, Cecilia, et al.
(author)
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Extracellular matrix-polymer hybrid materials produced in a pulsed-flow bioreactor system
- 2009
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In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons, Ltd. - 1932-6254 .- 1932-7005. ; 3:3, s. 188-195
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Journal article (peer-reviewed)abstract
- Cell adhesion, interaction with material, cell proliferation and the production of an extracellular matrix (ECM) are all important factors determining the successful performance of an engineered scaffold. Scaffold design should aim at creating structures which can guide cells into forming new, functional tissue. In this study, the concept of in situ deposition of ECM by human dermal fibroblasts onto a compliant, knitted poly (ethyleneterephtalate) support is demonstrated, creating in vitro produced ECM polymer hybrid materials for tissue engineering. Comparison of cells cultured under static and dynamic conditions were examined, and the structure and morphology of the materials so formed were evaluated, along with the amount collagen deposited by the seeded cells. In vitro produced ECM polymer hybrid scaffolds could be created in this way, with the dynamic culture conditions increasing ECM deposition. Histological analysis indicated a homogenous distribution of cells in the 1 mm thick scaffold, surrounded by a matrix-like structure. ECM deposition was observed throughout the materials wigh 81.6 µg/cm2 of collagen deposited after 6 weeks. Cell produced bundles of ECM fibres bridged the polymer filaments and anchored cells to the support. These findings open hereto unknown possibilities of producing materials with structure designed by engineering together with biochemical composition given by cells.
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| 2. |
- Aulin, Cecilia, et al.
(author)
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In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis
- 2011
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 5:8, s. E188-E196
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Journal article (peer-reviewed)abstract
- The present work describes the feasibility of a cross-linkable injectable hyaluronan hydrogel for cartilage repair. The hydrogel used is a two-component system based on aldehyde-modified hyaluronan and hydrazide-modified polyvinyl alcohol, which are rapidly cross-linked in situ upon mixing. The in vitro study showed that chondrocytes and mesenchymal cells cultured in the gel form cartilage-like tissue, rich in glycosaminoglycans, collagen type II and aggrecan. In a rabbit animal model the injection of the hydrogel improved the healing of a full-thickness cartilage defect created in the knee as compared to non-treated controls. This rabbit study showed that the regenerated cartilage defects stained more intensely for type II collagen upon treatment with the hydrogel. The hyaluronan-based hydrogel may be used as a delivery vehicle for both growth factors and/or cells for cartilage repair. The in vivo study also indicated that the hydrogel alone has a beneficial effect on cartilage regeneration.
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| 3. |
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| 4. |
- Barreto Henriksson, Helena, et al.
(author)
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Investigation of different cell types and gel carriers for cell-based intervertebral disc therapy, in vitro and in vivo studies.
- 2012
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 6:9, s. 738-747
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Journal article (peer-reviewed)abstract
- Biological treatment options for the repair of intervertebral disc damage have been suggested for patients with chronic low back pain. The aim of this study was to investigate possible cell types and gel carriers for use in the regenerative treatment of degenerative intervertebral discs (IVD). In vitro: human mesenchymal cells (hMSCs), IVD cells (hDCs), and chondrocytes (hCs) were cultivated in three gel types: hyaluronan gel (Durolane®), hydrogel (Puramatrix®), and tissue-glue gel (TISSEEL®) in chondrogenic differentiation media for 9days. Cell proliferation and proteoglycan accumulation were evaluated with microscopy and histology. In vivo: hMSCs or hCs and hyaluronan gel were co-injected into injured IVDs of six minipigs. Animals were sacrificed at 3 or 6months. Transplanted cells were traced with anti-human antibodies. IVD appearance was visualized by MRI, immunohistochemistry, and histology. Hyaluronan gel induced the highest cell proliferation in vitro for all cell types. Xenotransplanted hMSCs and hCs survived in porcine IVDs for 6months and produced collagen II in all six animals. Six months after transplantation of cell/gel, pronounced endplate changes indicating severe IVD degeneration were observed at MRI in 1/3 hC/gel, 1/3 hMSCs/gel and 1/3 gel only injected IVDs at MRI and 1/3hMSC/gel, 3/3hC/gel, 2/3 gel and 1/3 injured IVDs showed positive staining for bone mineralization. In 1 of 3 discs receiving hC/gel, in 1 of 3 receiving hMSCs/gel, and in 1 of 3 discs receiving gel alone. Injected IVDs on MRI results in 1 of 3 hMSC/gel, in 3 of 3 hC/gel, in 2 of 3 gel, and in 1 of 3 injured IVDs animals showed positive staining for bone mineralization. The investigated hyaluronan gel carrier is not suitable for use in cell therapy of injured/degenerated IVDs. The high cell proliferation observed in vitro in the hyaluronan could have been a negative factor in vivo, since most cell/gel transplanted IVDs showed degenerative changes at MRI and positive bone mineralization staining. However, this xenotransplantation model is valuable for evaluating possible cell therapy strategies for human degenerated IVDs. Copyright © 2011 John Wiley & Sons, Ltd.
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| 5. |
- Bodin, Aase Katarina, 1977, et al.
(author)
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Bacterial cellulose as a potential meniscus implant
- 2007
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 1:5, s. 406-8
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Journal article (peer-reviewed)abstract
- Traumatic or degenerative meniscal lesions are a frequent problem. The meniscus cannot regenerate after resection. These lesions often progress and lead to osteoarthritis. Collagen meniscal implants have been used in clinical practice to regenerate meniscal tissue after partial meniscectomy. The mechanical properties of bacterial cellulose (BC) gel were compared with a collagen material and the pig meniscus. BC was grown statically in corn steep liquid medium, as described elsewhere. Pig meniscus was harvested from pigs. The collagen implant was packed in sterile conditions until use. The different materials were evaluated under tensile and compression load, using an Instron 5542 with a 500 N load cell. The feasibility for implantation was explored using a pig model. The Young's modulus of bacterial cellulose was measured to be 1 MPa, 100 times less for the collagen material, 0.01 MPa in tensile load. The Young's modulus of bacterial cellulose and meniscus are similar in magnitude under a compression load of 2 kPa and with five times better mechanical properties than the collagen material. At higher compression strain, however, the pig meniscus is clearly stronger. These differences are clearly due to a more ordered and arranged structure of the collagen fibrils in the meniscus. The combination of the facts that BC is inexpensive, can be produced in a meniscus shape, and promotes cell migration makes it an attractive material for consideration as a meniscus implant. Copyright (c) 2007 John Wiley & Sons, Ltd.
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| 6. |
- Bäckdahl, Henrik, 1977, et al.
(author)
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Engineering microporosity in bacterial cellulose scaffolds
- 2008
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 2:6, s. 320-330
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Journal article (peer-reviewed)abstract
- The scaffold is an essential component in tissue engineering. A novel method to prepare threedimensional (3D) nanofibril network scaffolds with controlled microporosity has been developed. By placing paraffin wax and starch particles of various sizes in a growing culture of Acetobacter xylinum, bacterial cellulose scaffolds of different morphologies and interconnectivity were prepared. Paraffin particles were incorporated throughout the scaffold, while starch particles were found only in the outermost area of the resulting scaffold. The porogens were successfully removed after culture with bacteria and no residues were detected with electron spectroscopy for chemical analysis (ESCA) or Fourier transform infra-red spectroscopy (FT-IR). Resulting scaffolds were seeded with smooth muscle cells (SMCs) and investigated using histology and organ bath techniques. SMC were selected as the cell type since the main purpose of the resulting scaffolds is for tissue engineered blood vessels. SMCs attached to and proliferated on and partly into the scaffolds. Copyright © 2008 John Wiley & Sons, Ltd.
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| 7. |
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| 8. |
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| 9. |
- Concaro, Sebastian, et al.
(author)
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Effect of cell seeding concentration on the quality of tissue engineered constructs loaded with adult human articular chondrocytes.
- 2008
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 2:1, s. 14-21
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Journal article (peer-reviewed)abstract
- Many aspects of the process of in vitro differentiation of chondrocytes in three-dimensional (3D) scaffolds need to be further investigated. Chitosan scaffolds were produced by freeze-drying 3% w/v 90% DDA chitosan gels. The effect of the cell seeding concentration was evaluated by culturing human adult chondrocytes in chitosan scaffolds After the first passage, cells were seeded into chitosan scaffolds with a diameter of 8 mm. The final cell seeding concentration per cm3 of chitosan scaffold was: Group A, 3 x 10(6); Group B, 6 x 10(6); Group C, 12 x 10(6); and Group D, 25 x 10(6) cells. After 14 and 28 days in 3D culture, the constructs were assesed for collagen, glucosaminoglycans and DNA content. The mechanical properties of the constructs were determined using a dynamic oscillatory shear test. The histological aspect of the constructs was evaluated using the Bern score. The collagen and GAG concentration increased, varying the cell seeding concentration. There was a significant increase in proteoglycan and hydroxyproline production between groups C and D. The sulphated GAG content increased significantly in the group D as compared to the other groups. The mechanical properties of the different constructs increased over time, from 9.6 G'/kPa at 14 days of 3D culture to 14.6 G'/kPa at 28 days under the same culture conditions. In this study we were able to determine that concentrations of 12-25 million cells/cm2 are needed to increase the matrix production and mechanical properties of human adult chondrocytes under static conditions.
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| 10. |
- Diez-Escudero, Anna, et al.
(author)
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Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells
- 2019
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In: Journal of Tissue Engineering and Regenerative Medicine. - : WILEY. - 1932-6254 .- 1932-7005. ; 13:7, s. 1217-1229
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Journal article (peer-reviewed)abstract
- The immobilization of natural molecules on synthetic bone grafts stands as a strategy to enhance their biological interactions. During the early stages of healing, immune cells and osteoclasts (OC) modulate the inflammatory response and resorb the biomaterial, respectively. In this study, heparin, a naturally occurring molecule in the bone extracellular matrix, was covalently immobilized on biomimetic calcium-deficient hydroxyapatite (CDHA). The effect of heparin-functionalized CDHA on inflammation and osteoclastogenesis was investigated using primary human cells and compared with pristine CDHA and beta-tricalcium phosphate (beta-TCP). Biomimetic substrates led to lower oxidative stresses by neutrophils and monocytes than sintered beta-TCP, even though no further reduction was induced by the presence of heparin. In contrast, heparinized CDHA fostered osteoclastogenesis. Optical images of stained TRAP positive cells showed an earlier and higher presence of multinucleated cells, compatible with OC at 14 days, while pristine CDHA and beta-TCP present OC at 21-28 days. Although no statistically significant differences were found in the OC activity, microscopy images evidenced early stages of degradation on heparinized CDHA, compatible with osteoclastic resorption. Overall, the results suggest that the functionalization with heparin fostered the formation and activity of OC, thus offering a promising strategy to integrate biomaterials in the bone remodelling cycle by increasing their OC-mediated resorption.
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| 11. |
- Dravida, Subhadra, et al.
(author)
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A biomimetic scaffold for culturing limbal stem cells: a promising alternative for clinical transplantation
- 2008
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In: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE. - : John Wiley and Sons. - 1932-6254 .- 1932-7005. ; 2:5, s. 263-271
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Journal article (peer-reviewed)abstract
- Limbal tissues can be cultured on various types of scaffolds to create a sheet of limbal-corneal epithelium for research as well as clinical transplantation. An optically clear, biocompatible, biomimetic scaffold would be an ideal replacement graft for transplanting limbal stem cells. in this study, we evaluated the physical and culture characteristics of the recombinant human cross-linked collagen scaffold (RHC-III scaffold) and compared it with denuded human amniotic membrane (HAM). Optical/mechanical properties and microbial susceptibility were measured for the scaffolds. With the approval of the institutional review board, 2 mm. fresh human limbal tissues were cultured on 2.5 x 2.5 cm(2) scaffolds in a medium containing autologous serum in a feeder cell-free submerged system. The cultured cell systems were characterized by morphology and immunohistochemistry for putative stem cells and differentiated cell markers. The refractive index (RI) and tensile strength of the RHC-III scaffold were comparable to human cornea, with delayed in vitro degradation compared to HAM. RHC-III scaffolds were 10-fold less susceptible to microbial growth. Cultures were initiated on day 1, expanded to form a monolayer by day 3 and covered the entire growth surface in 10 days. Stratified epithelium on the scaffolds was visualized by transmission electron microscopy. The cultured cells showed p63 and ABCG2 positivity in the basal layer and were immunoreactive for cytokeratin K3 and K12 in the suprabasal layers. RHC-III scaffold supports and retains the growth and stemness of limbal stem cells, in addition to resembling human cornea; thus, it could be a good replacement scaffold for growing cells for clinical transplantation.
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| 12. |
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| 13. |
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| 14. |
- Fink, Helen, 1978, et al.
(author)
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Bacterial cellulose modified with xyloglucan bearing the adhesion peptide RGD promotes endothelial cell adhesion and metabolism--a promising modification for vascular grafts.
- 2011
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 5:6, s. 454-63
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Journal article (peer-reviewed)abstract
- Today, biomaterials such as polytetrafluorethylene (ePTFE) are used clinically as prosthetic grafts for vascular surgery of large vessels (>5 mm). In small diameter vessels, however, their performance is poor due to early thrombosis. Bacterial-derived cellulose (BC) is a new promising material as a replacement for blood vessels. This material is highly biocompatible in vivo but shows poor cell adhesion. In the native blood vessel, the endothelium creates a smooth non-thrombogenic surface. In order to sustain cell adhesion, BC has to be modified. With a novel xyloglucan (XG) glycoconjugate method, it is possible to introduce the cell adhesion peptide RGD (Arg-Gly-Asp) onto bacterial cellulose. The advantage of the XG-technique is that it is an easy one-step procedure carried out in water and it does not weaken or alter the fiber structure of the hydrogel. In this study, BC was modified with XG and XGRGD to asses primary human vascular endothelial cell adhesion, proliferation, and metabolism as compared with unmodified BC. This XG-RGD-modification significantly increased cell adhesion and the metabolism of seeded primary endothelial cells as compared with unmodified BC whereas the proliferation rate was affected only to some extent. The introduction of an RGD-peptide to the BC surface further resulted in enhanced cell spreading with more pronounced stress fiber formation and mature phenotype. This makes BC together with the XG-method a promising material for synthetic grafts in vascular surgery and cardiovascular research.
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| 15. |
- Foroughi, Farhad, et al.
(author)
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Bulk collagen incorporation rates into knitted stiff fibre polymer in tissue-engineered scaffolds : the rate-limiting step
- 2008
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In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons, Ltd.. - 1932-6254 .- 1932-7005. ; 2:8, s. 507-514
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Journal article (peer-reviewed)abstract
- Fabrication of tissue-engineered constructs in vitro relies on sufficient synthesis of extracellular matrix (ECM) by cells to form a material suitable for normal function in vivo. Collagen synthesis by human dermal fibroblasts grown in vitro on two polymers, polyethylene terephthalate (PET) and polyglycolic acid (PGA), was measured by high-performance liquid chromatography (HPLC). Cells were either cultured in a dynamic environment, where meshes were loaded onto a pulsing tube in a bioreactor, or in a static environment without pulsing. Collagen synthesis by cells cultured on a static mesh increased by six-fold compared to monolayer culture, and increased by up to a further 5.4-fold in a pulsed bioreactor. However, little of the collagen synthesized was deposited onto the meshes, almost all being lost to the medium. The amount of collagen deposited onto meshes was highest when cells were cultured dynamically on PET meshes (17.6 µg), but deposition still represented only 1.4% of the total synthesized. Although total collagen synthesis was increased by the use of 3D culture and the introduction of pulsing, the results suggest that the limiting factor for fabrication of a tissue-engineered construct within practical timescales is not the amount of collagen synthesized but the quantity retained (i.e. deposited) within the construct during culture. This may be enhanced by systems which promote or assemble true 3D multi-layers of cells.
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| 16. |
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| 17. |
- Greuel, Selina, et al.
(author)
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Online measurement of oxygen enables continuous noninvasive evaluation of human-induced pluripotent stem cell (hiPSC) culture in a perfused 3D hollow-fiber bioreactor
- 2019
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In: Journal of Tissue Engineering and Regenerative Medicine. - : WILEY. - 1932-6254 .- 1932-7005. ; 13:7, s. 1203-1216
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Journal article (peer-reviewed)abstract
- For clinical and/or pharmaceutical use of human-induced pluripotent stem cells (hiPSCs), large cell quantities of high quality are demanded. Therefore, we combined the expansion of hiPSCs in closed, perfusion-based 3D bioreactors with noninvasive online monitoring of oxygen as culture control mechanism. Bioreactors with a cell compartment volume of 3 or 17 ml were inoculated with either 10 x 10(6) or 50 x 10(6) cells, and cells were expanded over 15 days with online oxygen and offline glucose and lactate measurements being performed. The CellTiter-Blue (R) Assay was performed at the end of the bioreactor experiments for indirect cell quantification. Model simulations enabled an estimation of cell numbers based on kinetic equations and experimental data during the 15-day bioreactor cultures. Calculated oxygen uptake rates (OUR), glucose consumption rates (GCR), and lactate production rates (LPR) revealed a highly significant correlation (p amp;lt; 0.0001). Oxygen consumption, which was measured at the beginning and the end of the experiment, showed a strong culture growth in line with the OUR and GCR data. Furthermore, the yield coefficient of lactate from glucose and the OUR to GCR ratio revealed a shift from nonoxidative to oxidative metabolism. The presented results indicate that oxygen is equally as applicable as parameter for hiPSC expansion as glucose while providing an accurate real-time impression of hiPSC culture development. Additionally, oxygen measurements inform about the metabolic state of the cells. Thus, the use of oxygen online monitoring for culture control facilitates the translation of hiPSC use to the clinical setting.
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| 18. |
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| 19. |
- Hilborn, Jöns, et al.
(author)
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A new and evolving paradigm for biocompatibitity
- 2007
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 1:2, s. 110-119
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Journal article (peer-reviewed)abstract
- We propose that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response and the performance of the device. The interfacial mechanics depends on several different factors related to the physical shape of the device and its surface as well as properties of the host tissue and the loading conditions of the device and surrounding tissue. It seems plausible that the growth of the fibrotic tissue to support mechanical loads is governed by the same priniciples as depicted by Wolfs' Law for bone. Of course, biocompatibility will have different implications depending on which vantage point we look at the host-material interface. Another implication is that only limited aspects of biocompatibility is measurable with current in vitro tests and that the elicited host response in vivo models remains crucial for evaluation of medical devices and tissue engineering constructs.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Hulsart-Billstrom, Gry, 1982-, et al.
(author)
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Guiding bone formation using semi‐onlay calcium phosphate implants in an ovine calvarial model
- 2022
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 16:5, s. 435-447
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Journal article (peer-reviewed)abstract
- The restoration of cranio-maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof-of-concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium-reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro-computed tomography (μCT) and comprehensive histological analysis. Histology showed that the space between implant and the recipient bone was filled with a higher percentage of newly formed bone (NFB) versus soft tissue with a median of 53% and 47%, respectively. Similar results were obtained from the μ-CT analysis, with a median of 56% NFB and 44% soft tissue filling the void. Noteworthy, significantly higher bone-implant contact was found for the CaP (78%, range 14%–94%) versus the Titanium (29%, range 0%–75%) portion of the implant exposed to the surrounding bone. The histological analysis indicates that the CaP replacement by bone is driven by macrophages over time, emphasized by material-filled macrophages found in close vicinity to the CaP with only a small number of single osteoclasts found actively remodeling the NFB. This study shows that CaP based implants can be assembled with the help of additive manufacturing to guide vertical bone formation without decortification or administration of growth factors. Furthermore, it highlights the potential disadvantage of a seamless fit between the implant and the recipient's bone.
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| 24. |
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| 25. |
- Hulsart-Billström, Gry, et al.
(author)
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A uni-cortical femoral defect model in the rat : evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-2
- 2015
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 9:7, s. 799-807
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Journal article (peer-reviewed)abstract
- The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.
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| 26. |
- Håkansson, Joakim, 1975, et al.
(author)
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Individualized tissue-engineered veins as vascular grafts: A proof of concept study in pig
- 2021
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 15:10, s. 818-830
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Journal article (peer-reviewed)abstract
- Personalized tissue engineered vascular grafts are a promising advanced therapy medicinal product alternative to autologous or synthetic vascular grafts utilized in blood vessel bypass or replacement surgery. We hypothesized that an individualized tissue engineered vein (P-TEV) would make the body recognize the transplanted blood vessel as autologous, decrease the risk of rejection and thereby avoid lifelong treatment with immune suppressant medication as is standard with allogenic organ transplantation. To individualize blood vessels, we decellularized vena cava from six deceased donor pigs and tested them for cellular removal and histological integrity. A solution with peripheral blood from the recipient pigs was used for individualized reconditioning in a perfusion bioreactor for seven days prior to transplantation. To evaluate safety and functionality of the individualized vascular graft in vivo, we transplanted reconditioned porcine vena cava into six pigs and analyzed histology and patency of the graft at different time points, with three pigs at the final endpoint 4-5 weeks after surgery. Our results showed that the P-TEV was fully patent in all animals, did not induce any occlusion or stenosis formation and we did not find any signs of rejection. The P-TEV showed rapid recellularization in vivo with the luminal surface covered with endothelial cells. In summary, the results indicate that P-TEV is functional and have potential for use as clinical transplant grafts.
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| 27. |
- Johannesson, S., et al.
(author)
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Bacterial nanocellulose scaffolds; a novel three-dimensional in vitro model for neuronal cell culture
- 2012
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In: Journal of Tissue Engineering and Regenerative Medicine. - 1932-6254 .- 1932-7005. ; 6:Suppl. 1
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Journal article (other academic/artistic)abstract
- Neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are characterized by loss of synapses and neurons. To be able to achieve a deeper understanding of the mechanisms behind neurodegenerative diseases, advanced and reliable in vitro models, preferable based on human cells, are needed. This project focuses on the development of an in vitro artificial 3D neuronal network model based on neuronal cells seeded on nano-cellulose scaffold. The viability and maturity of the neuronal cells grown on the scaffolds have been evaluated using electron microscopy, immunohistochemical- and electrophysiological methods. We have investigated the possibility to use bacterial nanocellulose (BNC) as an extracellular matrix mimic for neural cell culture. To further enhance cell attachment on the BNC we used different chemical surface modifications (THMAP and CDAP-treatment) and protein coatings such as Collagen type 1. The human neuroblastoma cell line SH-SY5Y, was used as a neuronal cell model due to its ability to be differentiated into mature neurons. With electron microscopy the cells were visualized on the material, showing that the cells were well integrated with the BNC and showed good proliferation and viability. Whole cell patch clamp recordings showed that it is possible to differentiate the SH-SY5Y cells to mature neuronal cells on the BNC, as demonstrated with an ability of the cells to produce mature action potentials.
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| 28. |
- Jones, Iwan, et al.
(author)
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Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury
- 2018
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 12:4, s. E2099-E2109
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Journal article (peer-reviewed)abstract
- Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair.
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| 29. |
- Kettenberger, Ulrike, et al.
(author)
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In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation
- 2017
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 11:7, s. 1974-1985
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Journal article (peer-reviewed)abstract
- Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation.
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| 30. |
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| 31. |
- König, Niclas, et al.
(author)
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Murine neural crest stem cells and embryonic stem cell derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion
- 2017
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In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons. - 1932-6254 .- 1932-7005. ; 11:1, s. 129-137
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Journal article (peer-reviewed)abstract
- Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second order neurons in the dorsal horn. The ultimate objective with the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we explore if stem cells transplanted on the surface of avulsed spinal cord can survive, differentiate and migrate into the damaged spinal cord during the first few weeks after this intervention. Murine boundary cap neural crest stem cells (bNCSCs) or embryonic stem cell (ESC)-derived, pre-differentiated neuron precursors were implanted acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of differentiation. Thus, bNCSCs migrated into the spinal cord, expressed glial markers, and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone(DRTZ) area. In contrast, the ESC-transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survive implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion.
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| 32. |
- Lauvrud, Anne Therese, et al.
(author)
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Characterization of human adipose tissue-derived stem cells with enhanced angiogenic and adipogenic properties
- 2017
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons. - 1932-6254 .- 1932-7005. ; 11:9, s. 2490-2502
-
Journal article (peer-reviewed)abstract
- Autologous fat grafting is a popular method for soft tissue reconstructions but graft survival remains highly unpredictable. Supplementation of the graft with the stromal vascular fraction (SVF) or cultured adipose tissue-derived stem cells (ASCs) can enhance graft viability. In this study we have examined the phenotypic properties of a selected population of cells isolated from ASCs, with a view to determining their suitability for transplantation into grafts. ASCs were isolated from the SVF of human abdominal fat (n = 8 female patients) and CD146(+) cells were selected using immunomagnetic beads. The angiogenic and adipogenic properties of the positively selected cells were compared with the negative fraction. CD146(+) cells expressed the immunophenotypic characteristics of pericytes. With prolonged in vitro expansion, CD146(-) cells exhibited increased population doubling times and morphological signs of senescence, whereas CD146(+) cells did not. CD146(+) cells expressed higher levels of the angiogenic molecules VEGF-A, angiopoietin-1 and FGF-1. Conditioned medium taken from CD146(+) cells significantly increased formation of in vitro endothelial cell tube networks, whereas CD146(-) cells did not. CD146(+) cells could be differentiated into adipocytes in greater numbers than CD146(-) cells. Consistent with this, differentiated CD146(+) cells expressed higher levels of the adipocyte markers adiponectin and leptin. These results suggest that CD146(+) cells selected from a heterogeneous mix of ASCs have more favourable angiogenic and adipogenic properties, which might provide significant benefits for reconstructive and tissue-engineering applications. Copyright © 2016 John Wiley & Sons, Ltd.
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| 33. |
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| 34. |
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| 35. |
- Moelzer, Christine, et al.
(author)
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Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition
- 2019
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In: Journal of Tissue Engineering and Regenerative Medicine. - : WILEY. - 1932-6254 .- 1932-7005. ; 13:9, s. 1528-1543
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Journal article (peer-reviewed)abstract
- Activated T cells are known to promote fibrosis, a major complication limiting the range of polymeric hydrogels as artificial corneal implants. As T cells are activated by dendritic cells (DC), minimally activating hydrogels would be optimal. In this study, we evaluated the ability of a series of engineered (manufactured/fabricated) and natural collagen matrices to either activate DC or conversely induce DC apoptosis in vitro. Bone marrow DC were cultured on a series of singly and doubly crosslinked hydrogels (made from recombinant human collagen III [RHCIII] or collagen mimetic peptide [CMP]) or on natural collagen-containing matrices, Matrigel(TM) and de-cellularised mouse corneal stroma. DC surface expression of major histocompatibility complex Class II and CD86 as well as apoptosis markers were examined. Natural matrices induced low levels of DC activation and maintained a "tolerogenic" phenotype. The same applied to singly crosslinked CMP-PEG gels. RHCIII gels singly crosslinked using either N-(3-dimethylaminopropyl)-N -ethylcarbodiimide with the coinitiator N-hydroxy succinimide (EDC-NHS) or N-cyclohexyl-N-(2-morpholinoethyl)carbodiimide metho-p-toulenesulfonate with NHS (CMC-NHS) induced varying levels of DC activation. In contrast, however, RHCIII hydrogels incorporating an additional polymeric network of 2-methacryloyloxyethyl phosphorylcholine did not activate DC but instead induced DC apoptosis, a phenomenon observed in natural matrices. This correlated with increased DC expression of leukocyte-associated immunoglobulin-like receptor-1. Despite low immunogenic potential, viable tolerogenic DC migrated into and through both natural and manufactured RHCIII gels. These data show that the immunogenic potential of RHCIII gels varies with the nature and composition of the gel. Preclinical evaluation of hydrogel immunogenic/fibrogenic potential is recommended.
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| 36. |
- Molzer, Christine, et al.
(author)
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TGF-beta 1-activated type 2 dendritic cells promote wound healing and induce fibroblasts to express tenascin c following corneal full-thickness hydrogel transplantation
- 2019
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : WILEY. - 1932-6254 .- 1932-7005. ; 13:9, s. 1507-1517
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Journal article (peer-reviewed)abstract
- We showed previously that 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide hydrochloride (EDC) cross-linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4 years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers-bulky, aromatic N-cyclohexyl-N0-(2-morpholinoethyl)-carbodiimide (CMC), and nonbulky EDC-in a mouse corneal graft model. Murine corneas undergoing full-thickness implantation with these gels became opaque due to dense retro-corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c(+) dendritic cells (DC) were found, suggesting a hydrogel-specific innate immune response. More DC infiltrated the stroma surrounding EDC-N-hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis-associated tenascin c expression. The opposite was true for CMC-NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor beta 1 (TGF-beta 1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF-beta 1 neutralisation. Furthermore, tenascin c staining was found in 40- to 50 mu m long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF-beta 1 alternatively activated (tolerising) DC regulate fibroblast-mediated tenascin c secretion, possibly via local production of TGF-beta 1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries.
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| 37. |
- Motalleb, Reza, 1985, et al.
(author)
-
In vivo migration of endogenous brain progenitor cells guided by an injectable peptide amphiphile biomaterial
- 2018
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 12:4
-
Journal article (peer-reviewed)abstract
- Biomaterials hold great promise in helping the adult brain regenerate and rebuild after trauma. Peptide amphiphiles (PAs) are highly versatile biomaterials, gelling and forming macromolecular structures when exposed to physiological levels of electrolytes. We are here reporting on the first ever in vivo use of self-assembling PA carrying a Tenascin-C signal (E(2)Ten-C PA) for the redirection of endogenous neuroblasts in the rodent brain. The PA forms highly aligned nanofibers, displaying the migratory sequence of Tenascin-C glycoprotein as epitope. In this in vivo work, we have formed in situ a gel of aligned PA nanofibers presenting a migratory Tenascin-C signal sequence in the ventral horn of the rostral migratory stream, creating a track reaching the neocortex. Seven days posttransplant, doublecortin positive cells were observed migrating inside and alongside the injected biomaterial, reaching the cortex. We observed a 24-fold increase in number of redirected neuroblasts for the E(2)Ten-C PA-injected animals compared to control. We also found injecting the E(2)Ten-C PA to cause minimal neuroinflammatory response. Analysing GFAP(+) astrocytes and Iba1(+) microglia activation, the PA does not elicit a stronger neuroinflammatory response than would be expected from a small needle stab wound. Redirecting endogenous neuroblasts and increasing the number of cells reaching a site of injury using PAs may open up new avenues for utilizing the pool of neuroblasts and neural stem cells within the adult brain for regenerating damaged brain tissue and replacing neurons lost to injury.
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| 38. |
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| 39. |
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| 40. |
- Padma, Arvind M., et al.
(author)
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Decellularization protocol-dependent damage-associated molecular patterns in rat uterus scaffolds differentially affect the immune response after transplantation.
- 2021
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 15:7, s. 674-685
-
Journal article (peer-reviewed)abstract
- Scaffolds derived from decellularized tissue possess many advantages for bioengineering applications, including for novel infertility treatments. However, the decellularization process results in allogenic-independent damage-associated molecular patterns (DAMPs). This field is poorly studied, in particular for uterus bioengineering applications. An increased knowledge concerning the immune system activation after transplantation of decellularized tissue will enable safer construct development and thereby accelerate translation from research to clinic. We therefore transplanted rat uterus scaffolds produced by three different decellularization protocols based on Triton X-100 (P1 and P2) or sodium deoxycholate (P3) in a syngeneic animal model and assessed the immune response towards DAMPs exposed by the decellularization process. Biopsies were retrieved on day 5, 15, and 30 post transplantation and immunohistochemistry-stained CD45+ (leucocytes), CD4+ (T-cells), CD8a+ (cytotoxic T-cells), CD22+ (B-cells), NCR1+ (NK-cells), CD68+ (pan-macrophages), and CD163+ (M2 macrophages) cells within the grafts were quantified. The gene expression for interferon γ, interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF) eotaxin-2, RANTES, MCP-1, MIP-1α, MIP-3α, IL-8 were also measured. Scaffolds from P1 induced a rapid cell infiltration after transplantation, presumably induced by DNA-based DAMPs. However, this response was only transient. Protocol 3 derived scaffolds induced an early pro-inflammatory cytokine response at the transcript level which remained high throughout the study. This response may be caused by the stronger decellularization detergent that could expose more extracellular matrix-related DAMPs. However, earlier proteomics analysis also identified significantly more abundant heat shook proteins-related DAMPs in this scaffold type. Protocol 2 caused the least immunogenic scaffolds and should thus be the future focus for in vivo uterus bioengineering applications.
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| 41. |
- Pettersson, Sofia, et al.
(author)
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Human articular chondrocytes on macroporous gelatin microcarriers form structurally stable constructs with blood-derived biological glues in vitro.
- 2009
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 3:6, s. 450-60
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Journal article (peer-reviewed)abstract
- Biodegradable macroporous gelatin microcarriers fixed with blood-derived biodegradable glue are proposed as a delivery system for human autologous chondrocytes. Cell-seeded microcarriers were embedded in four biological glues-recalcified citrated whole blood, recalcified citrated plasma with or without platelets, and a commercially available fibrin glue-and cultured in an in vitro model under static conditions for 16 weeks. No differences could be verified between the commercial fibrin glue and the blood-derived alternatives. Five further experiments were conducted with recalcified citrated platelet-rich plasma alone as microcarrier sealant, using two different in vitro culture models and chondrocytes from three additional donors. The microcarriers supported chondrocyte adhesion and expansion as well as extracellular matrix (ECM) synthesis. Matrix formation occurred predominantly at sample surfaces under the static conditions. The presence of microcarriers proved essential for the glues to support the structural takeover of ECM proteins produced by the embedded chondrocytes, as exclusion of the microcarriers resulted in unstable structures that dissolved before matrix formation could occur. Immunohistochemical analysis revealed the presence of SOX-9- and S-100-positive chondrocytes as well as the production of aggrecan and collagen type I, but not of the cartilage-specific collagen type II. These results imply that blood-derived glues are indeed potentially applicable for encapsulation of chondrocyte-seeded microcarriers. However, the static in vitro models used in this study proved incapable of supporting cartilage formation throughout the engineered constructs.
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| 42. |
- Piskounova, Sonya, et al.
(author)
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Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of I-125-radiolabelling
- 2014
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 8:10, s. 821-830
-
Journal article (peer-reviewed)abstract
- This study presents a thorough in vitro and in vivo characterization of the delivery of bone morphogenetic protein 2 (BMP-2) from a hyaluronan-based hydrogel system. The in vitro release of BMP-2 from similar hydrogels has previously been studied by enzyme-linked immunosorbent assay (ELISA), by which only a fraction of the loaded protein is detected. In the current study, I-125 radiolabelling was used instead to monitor BMP-2 in vitro and in vivo. To minimize protein loss during handling, I-125-BMP-2 adsorption to different tubes was studied at different times and temperatures. The data showed that Protein LoBind tubes exhibited the lowest protein affinity. Furthermore, a biphasic release profile of biologically active BMP-2 was observed both in vitro and in vivo, with the initial fast phase during the first week, followed by a slower release during the remaining 3 weeks. The initial fast-release phase corresponded to the early bone formation observed after 8 days in an ectopic model in rats. Bone volume and mineral content increased until day 14, after which a decrease in bone volume was observed, possibly due to resorption in response to decreased amounts of released BMP-2. Overall, the results suggested that cautious protein handling and a reliable quantification technique are essential factors for successful design of a BMP-2 delivery system.
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| 43. |
- Ramani-Mohan, R. -K, et al.
(author)
-
Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation
- 2018
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley and Sons Ltd. - 1932-6254 .- 1932-7005. ; 12:3, s. e1474-e1479
-
Journal article (peer-reviewed)abstract
- Mesenchymal stem cells play a major role during bone remodelling and are thus of high interest for tissue engineering and regenerative medicine applications. Mechanical stimuli, that is, deformation strain and interstitial fluid-flow-induced shear stress, promote osteogenic lineage commitment. However, the predominant physical stimulus that drives early osteogenic cell maturation is not clearly identified. The evaluation of each stimulus is challenging, as deformation and fluid-flow-induced shear stress interdepend. In this study, we developed a bioreactor that was used to culture mesenchymal stem cells harbouring a strain-responsive AP-1 luciferase reporter construct, on porous scaffolds. In addition to the reporter, mineralization and vitality of the cells was investigated by alizarin red staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Quantification of the expression of genes associated to bone regeneration and bone remodelling was used to confirm alizarin red measurements. Controlled perfusion and deformation of the 3-dimensional scaffold facilitated the alteration of the expression of osteogenic markers, luciferase activity, and calcification. To isolate the specific impact of scaffold deformation, a computational model was developed to derive a perfusion flow profile that results in dynamic shear stress conditions present in periodically loaded scaffolds. In comparison to actually deformed scaffolds, a lower expression of all measured readout parameters indicated that deformation strain is the predominant stimulus for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation.
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| 44. |
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| 45. |
- Schaakxs, Dominique, et al.
(author)
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Poly-3-hydroxybutyrate strips seeded with regenerative cells are effective promoters of peripheral nerve repair
- 2017
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 11:3, s. 812-821
-
Journal article (peer-reviewed)abstract
- Peripheral nerve injuries are often associated with loss of nerve tissue and require a graft to bridge the gap. Autologous nerve grafts are still the 'gold standard' in reconstructive surgery but have several disadvantages, such as sacrifice of a functional nerve, neuroma formation and loss of sensation at the donor site. Bioengineered grafts represent a promising approach to address this problem. In this study, poly-3-hydroxybutyrate (PHB) strips were used to bridge a 10 mm rat sciatic nerve gap and their effects on long-term (12 weeks) nerve regeneration were compared. PHB strips were seeded with different cell types, either primary Schwann cells (SCs) or SC-like differentiated adipose-derived stem cells (dASCs) suspended in a fibrin glue matrix. The control group was PHB and fibrin matrix without cells. Functional and morphological properties of the regenerated nerve were assessed using walking track analysis, EMGs, muscle weight ratios and muscle and nerve histology. The animals treated with PHB strips seeded with SCs or dASCs showed significantly better functional ability than the control group. This correlated with less muscle atrophy and greater axon myelination in the cell groups. These findings suggest that the PHB strip seeded with cells provides a beneficial environment for nerve regeneration. Furthermore, dASCs, which are abundant and easily accessible, constitute an attractive cell source for future applications of cell therapy for the clinical repair of traumatic nerve injuries.
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| 46. |
- Shanbhag, Siddharth, et al.
(author)
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Alveolar bone tissue engineering in critical-size defects of experimental animal models : a systematic review and meta-analysis
- 2017
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons. - 1932-6254 .- 1932-7005. ; 11:10, s. 2935-2949
-
Journal article (peer-reviewed)abstract
- Regeneration of large, 'critical-size' bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous, allogeneic and biomaterial-based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell-based BTE strategies enhance regeneration in alveolar bone critical-size defects (CSDs), compared with grafting with only biomaterial scaffolds or autogenous bone? Following PRISMA guidelines, electronic databases were searched for controlled animal studies reporting maxillary or mandibular CSD and implantation of mesenchymal stem cells (MSCs) or osteoblasts (OBs) seeded on biomaterial scaffolds. A random effects meta-analysis was performed for the outcome histomorphometric new bone formation (%NBF). Thirty-six studies were included that reported on large- (monkeys, dogs, sheep, minipigs) and small-animal (rabbits, rats) models. On average, studies presented with an unclear-to-high risk of bias and short observation times. In most studies, MSCs or OBs were used in combination with alloplastic mineral-phase scaffolds. In five studies, cells were modified by ex vivo gene transfer of bone morphogenetic proteins (BMPs). The meta-analysis indicated statistically significant benefits in favour of: (1) cell-loaded vs. cell-free scaffolds [weighted mean difference (WMD) 15.59-49.15% and 8.60-13.85% NBF in large- and small-animal models, respectively]; and (2) BMP-gene-modified vs. unmodified cells (WMD 10.06-20.83% NBF in small-animal models). Results of cell-loaded scaffolds vs. autogenous bone were inconclusive. Overall, heterogeneity in the meta-analysis was high (I2 > 90%). In summary, alveolar bone regeneration is enhanced by addition of osteogenic cells to biomaterial scaffolds. The direction and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of BTE.
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| 47. |
- Shanbhag, Siddharth, et al.
(author)
-
Bone tissue engineering in oral peri-implant defects in preclinical in vivo research : A systematic review and meta-analysis.
- 2018
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons. - 1932-6254 .- 1932-7005. ; 12:1, s. e336-e349
-
Journal article (peer-reviewed)abstract
- The regeneration and establishment of osseointegration within oral peri-implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial-based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell-based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri-implant defects, compared with grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri-implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Random effects meta-analyses were performed for the outcomes histomorphometric bone area fraction (BA) and bone-to-implant contact (BIC). Nineteen studies reporting on large animal models (dogs and sheep) were included. Experimental defects were created surgically (16 studies) or via ligature-induced peri-implantitis (LIPI, three studies). In general, studies presented with an unclear to high risk of bias. In most studies, MSC were used in combination with alloplastic mineral phase or polymer scaffolds; no study directly compared cell-loaded scaffolds vs. autogenous bone. In three studies, cells were also modified by ex vivo gene transfer of osteoinductive factors. The meta-analyses indicated statistically significant benefits in favour of: (a) cell-loaded vs. cell-free scaffolds [weighted mean differences (WMD) of 10.73-12.30% BA and 11.77-15.15% BIC] in canine surgical defect and LIPI models; and (b) gene-modified vs. unmodified cells (WMD of 29.44% BA and 16.50% BIC) in canine LIPI models. Overall, heterogeneity in the meta-analyses was high (I2 70-88%); considerable variation was observed among studies regarding the nature of cells and scaffolds used. In summary, bone regeneration and osseointegration in peri-implant defects are enhanced by the addition of osteogenic cells to biomaterial scaffolds. Although the direction of treatment outcome is clearly in favour of BTE strategies, due to the limited magnitude of treatment effect observed, no conclusive statements regarding the clinical benefit of such procedures for oral indications can yet be made. Copyright (c) 2017 John Wiley & Sons, Ltd.
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| 48. |
- Sladkova, Martina, et al.
(author)
-
Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds
- 2018
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 12:3, s. 715-726
-
Journal article (peer-reviewed)abstract
- Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials, but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps and demonstrated long-term biocompatibility in vitro. However, there is no knowledge on the potential use of these scaffolds for bone engineering and whether the porosity of the scaffolds affects osteogenic differentiation and tissue formation in vitro. In this study, we explored the bone engineering potential of CPC scaffolds with two different macroporosities using human mesenchymal progenitors derived from induced pluripotent stem cells (iPSC-MP) or isolated from bone marrow (BMSC). Biomimetic decellularized bone scaffolds were used as reference material in all experiments. The results demonstrate that, irrespective of their macroporosity, the CPC scaffolds tested in this study support attachment, viability, and growth of iPSC-MP and BMSC cells similarly to decellularized bone. Importantly, the tested materials sustained differentiation of the cells as evidenced by increased expression of osteogenic markers and formation of a mineralized tissue. In conclusion, the results of this study suggest that the CPC scaffolds fabricated using our method are suitable to engineer bone grafts from different cell sources and could lead to the development of safe and more affordable tissue grafts for reconstructive dentistry and orthopaedics and in vitro models for basic and applied research.
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| 49. |
- Stenhamre, Hanna, et al.
(author)
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Influence of pore size on the redifferentiation potential of human articular chondrocytes in poly(urethane urea) scaffolds
- 2011
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In: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 5:7, s. 578-588
-
Journal article (peer-reviewed)abstract
- The chemical and physical properties of scaffolds affect cellular behaviour, which ultimately determines the performance and outcome of tissue-engineered cartilage constructs. The objective of this study was to assess whether a degradable porous poly(urethane urea) scaffold could be a suitable material for cartilage tissue engineering. We also investigated whether the post-expansion redifferentiation and cartilage tissue formation of in vitro expanded adult human chondrocytes could be regulated by controlled modifications of the scaffold architecture. Scaffolds with different pore sizes, < 150 µm, 150-300 µm and 300-500 µm, were seeded with chondrocytes and subjected to chondrogenic and osteogenic induction in vitro. The poly(urethane urea) scaffold with the smaller pore size enhanced the hyaline-like extracellular matrix and thus neocartilage formation. Conversely, the chondrocytes differentiated to a greater extent into the osteogenic pathway in the scaffold with the larger pore size. In conclusion, our results demonstrate that poly(urethane urea) may be useful as a scaffold material in cartilage tissue engineering. Furthermore, the chondrogenic and the osteogenic differentiation capacity of in vitro expanded human articular chondrocytes can be influenced by the scaffold architecture. By tailoring the pore sizes, the performance of the tissue-engineered cartilage constructs might be influenced and thus also the clinical outcome in the long run.
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| 50. |
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