| 1. |
- Åberg, Jonas, 1982-, et al.
(författare)
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Biocompatibility and resorption of a radiopaque premixed calcium phosphate cement
- 2012
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 100A:5, s. 1269-1278
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate cements (CPC) are used as bone void filler in various orthopedic indications; however, there are some major drawbacks regarding mixing, transfer, and injection of traditional CPC. By using glycerol as mixing liquid, a premixed calcium phosphate cement (pCPC), some of these difficulties can be overcome. In the treatment of vertebral fractures the handling characteristics need to be excellent including a high radio-opacity for optimal control during injection. The aim of this study is to evaluate a radiopaque pCPC regarding its resorption behavior and biocompatibility in vivo. pCPC and a water-based CPC were injected into a circle divide 4-mm drilled femur defect in rabbits. The rabbits were sacrificed after 2 and 12 weeks. Cross sections of the defects were evaluated using histology, electron microscopy, and immunohistochemical analysis. Signs of inflammation were evaluated both locally and systemically. The results showed a higher bone formation in the pCPC compared to the water-based CPC after 2 weeks by expression of RUNX-2. After 12 weeks most of the cement had been resorbed in both groups. Both materials were considered to have a high biocompatibility since no marked immunological response was induced and extensive bone ingrowth was observed. The conclusion from the study was that pCPC with ZrO2 radiopacifier is a promising alternative regarding bone replacement material and may be suggested for treatment of, for example, vertebral fractures based on its high biocompatibility, fast bone ingrowth, and good handling properties.
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| 2. |
- Apelgren, Peter, et al.
(författare)
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Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.
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| 3. |
- Thorfve, Anna, 1982, et al.
(författare)
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Madindoline A Affects the Osteogenic Potential and the Wnt Signaling
- 2014
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Ingår i: Journal of Bone Marrow Research. - : OMICS Publishing Group. - 2329-8820. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human mesenchymal stem cells (hMSCs) have the potential to differentiate at least into adipocytes, chondrocytes and osteoblasts. The differentiation capacity can be modulated by drugs, or chemical substances that affect diverse mechanisms essential for e.g. bone formation. The aim of this study was to investigate the osteoinductive capacity of the interleukin-6 (IL-6) inhibitor Madindoline A (MadA) and its relation to the bone-inducing Wnt signaling pathways. Methods: After stimulation with MadA of hMSC from 4 donors (aged 13-33 years) in an in vitro culture, alkaline phosphatase (ALP) activity and extracellular matrix (ECM) mineralization of hMSCs were quantified and calcification visualized by von Kossa staining. The expression of bone- and Wnt related markers was further studied at gene and protein levels. In addition, stimulation with the non-canonical Wnt5a ligand was added as a positive control, and the effect of MadA on IL-6 gene expression and STAT3 phosphorylation was evaluated. Results: Stimulation with MadA induced increased ECM mineralization and upregulated the expression of the bone related genes RUNX2, COL1A1 and Osteocalcin, although large donor-to-donor differences were observed. Further, MadA affected both the canonical and non-canonical Wnt signaling pathways and displayed a superior osteoinducing property compared to Wnt5a in some cases. Conclusion: In summary, all donors displayed higher gene expression of IL-6 and reduced STAT3 phosphorylation after MadA stimulation. The present results provide for the first time indications of an in vitro osteoinduction potential of the IL-6 inhibitor MadA.
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| 4. |
- Lindahl, Anders, 1954, et al.
(författare)
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Cartilage and Bone Regeneration
- 2014
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Ingår i: Tissue Engineering: Second Edition. - Amsterdam : Elsevier, Inc.. ; , s. 529-582
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Bokkapitel (refereegranskat)abstract
- This chapter deals with the tissue engineering aspects of one of the mesenchymal tissues-cartilage. It includes a brief description of the different cartilage types and their embryonal origin. Tissue structures including chondrocyte and extracellular matrix components are described in detail. The disease aspect of hyaline cartilage with emphasis on cartilage injuries and the tissue engineering approach to cartilage regeneration with the autologous chondrocyte implantation technique is described in depth. The future aspects of cartilage regeneration techniques with potential cell types other than autologous chondrocytes as well as new promising scaffold techniques are described. © 2015 Elsevier Inc. All rights reserved.
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| 5. |
- Stenhamre, Hanna, et al.
(författare)
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Nanosized fibers' effect on adult human articular chondrocytes behavior.
- 2013
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Ingår i: Materials science & engineering. C, Materials for biological applications. - : Elsevier BV. - 1873-0191 .- 0928-4931. ; 33:3, s. 1539-1545
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Tidskriftsartikel (refereegranskat)abstract
- Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior.
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| 6. |
- Apelgren, Peter, et al.
(författare)
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Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation
- 2021
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276
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Tidskriftsartikel (refereegranskat)abstract
- Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
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| 7. |
- Thorfve, Anna, 1982, et al.
(författare)
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Gene Expression Profiling of Peri-Implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway In Vivo
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of beta-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors' knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.
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| 8. |
- Zhao, C. H., et al.
(författare)
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Combination of positive charges and honeycomb pores to promote MC3T3-E1 cell behaviour
- 2015
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Ingår i: Rsc Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:53, s. 42276-42286
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Tidskriftsartikel (refereegranskat)abstract
- A facile chemistry route to prepare symmetric poly(L-lactide) (PLLA)-based dendritic L-lysine copolymer (PLLA-d), with a PLLA block as the core and lysine dendrons in the two ends to provide certain density of positive charges, through a divergent method is reported. The polymers were characterized by H-1 NMR, GPC and MALDI-TOF to confirm the well-defined chemical architecture. The study on crystallization behaviour demonstrated that the introduction of the lysine dendron favoured the formation of banded spherulites when compared with the PLLA polymer. The differential scanning calorimetry (DSC) results showed that the lysine dendron disrupted PLLA crystalline region and lowered the melting point and crystallinity of PLLA. The PLLA-d was fabricated into honeycomb films (H-PLLA-d) through the breath-figure method for water contact angle test and in vitro study, with flat PLLA, honeycomb PLLA, and flat PLLA-d films (PLLA, H-PLLA, and F-PLLA-d, respectively) as the controls. The water contact angle test indicated that the hydrophilicity of the PLLA-d film was strongly improved after the incorporation of the lysine dendron into PLLA. The incorporation of the lysine dendron increased the surface zeta potential and decreased the mechanical properties of PLLA. Mouse osteoblastic cell (MC3T3-E1) functions including cell attachment, adhesion, proliferation, and differentiation were investigated on PLLA, H-PLLA, F-PLLA-d and H-PLLA-d films. The results indicated that MC3T3-E1 cell functions were significantly enhanced on F-PLLA-d or H-PLLA films and especially H-PLLA-d ones. This study not only demonstrates a facile approach to fabricate a novel copolymer film (H-PLLA-d), which combines positive charges with honeycomb pores, but also provides a potential biomaterial for bone repair by improving osteoblastic cell functions.
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