| 1. |
- Ajalloueian, Fatemeh, et al.
(författare)
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A bedside collagen-PLGA nanofibrous construct for autologous transplantation of minced bladder mucosal
- 2012
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254. ; 6:suppl 1, s. 128-128
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Bladder regeneration using minced bladder mucosa is an alternative to costly and time-consuming conventional in vitro culturing of urothelial cells. In this method, the uroepithelium expands in vivo and the patient body appears as an incubator. With our preliminary successes, designing an appropriate scaffold that supports in vivo cell expansion and surgical handling in a clinical setting was our aim. This study, investigates cell expansion in a hybrid construct of collagen/poly (lactic-co-glycolide)(PLGA).Materials and methods: An electrospun PLGA mat was placed on a semi-gel collagen inside a mold and covered with a second collagen layer. After gel formation, minced particles of pig bladder mucosa were seeded on the hybrid construct and then processed by plastic compression (PC). The scaffolds were incubated for 2, 4 and 6 weeks in vitro for further studies.Results: Tensile tests show an increase in tensile strength of 0.6 ± 0.1 MPa in PC collagen to 3.6 ± 1.1 MPa in hybrid construct. Morphological studies, histological staining and SEM show that the construct has kept its integrity during the time and proliferated urothelial cells have reached confluence after 4 weeks and a multi-layered urothelium after 6 weeks.Conclusion: We have designed a mechanically robust scaffold that permits surgical handling and tissue expansion in vivo. The construct is easy-to-use for clinical application in an ordinary surgical operating theater for bladder regeneration.
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| 2. |
- Ajalloueian, Fatemeh, et al.
(författare)
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Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder
- 2018
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Ingår i: Nature reviews. Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 15:3, s. 155-174
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Forskningsöversikt (refereegranskat)abstract
- The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.
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| 3. |
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| 4. |
- Ajalloueian, Fatemeh, et al.
(författare)
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Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion
- 2014
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 35:22, s. 5741-5748
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Tidskriftsartikel (refereegranskat)abstract
- Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.
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| 5. |
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| 6. |
- Ajalloueian, Fatemeh, et al.
(författare)
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Investigation of Human Mesenchymal Stromal Cells Cultured on PLGA orPLGA/Chitosan Electrospun Nanofibers
- 2015
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Ingår i: Journal of Bioprocessing & Biotechniques. - : OMICS Publishing Group. - 2155-9821. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- We compared the viability, proliferation, and differentiation of human Mesenchymal Stromal Cells (MSC)after culture on poly(lactic-co-glycolic acid) (PLGA) and PLGA/chitosan (PLGA/CH) hybrid scaffolds. We appliedconventional and emulsion electrospinning techniques, respectively, for the fabrication of the PLGA and PLGA/CH scaffolds. Electrospinning under optimum conditions resulted in an average fiber diameter of 166 ± 33 nmfor the PLGA/CH and 680 ± 175 nm for the PLGA scaffold. The difference between the tensile strength of thePLGA and PLGA/CH nanofibers was not significant, but PLGA/CH showed a significantly lower tensile modulusand elongation at break. However, it should be noted that the extensibility of the PLGA/CH was higher than thatof the nanofibrous scaffolds of pure chitosan. As expected, a higher degree of hydrophilicity was seen with PLGA/CH, as compared to PLGA alone. The biocompatibility of the PLGA and PLGA/CH scaffolds was compared usingMTS assay as well as analysis by scanning electron microscopy and confocal microscopy. The results showed thatboth scaffold types supported the viability and proliferation of human MSC, with significantly higher rates on PLGA/CH nanofibers. Nonetheless, an analysis of gene expression of MSC grown on either PLGA or PLGA/CH showed asimilar differentiation pattern towards bone, nerve and adipose tissues.
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| 7. |
- Ajalloueian, Fatemeh, et al.
(författare)
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One-Stage Tissue Engineering of Bladder Wall Patches for an Easy-To-Use Approach at the Surgical Table
- 2013
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Ingår i: Tissue Engineering. Part C, Methods. - : Mary Ann Liebert Inc. - 1937-3384 .- 1937-3392. ; 19:9, s. 688-696
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Tidskriftsartikel (refereegranskat)abstract
- We present a method for producing a cell-scaffold hybrid construct at the bedside. The construct is composed of plastic-compressed collagen together with a poly(e-caprolactone) (PCL)-knitted mesh that yields an integrated, natural-synthetic scaffold. This construct was evaluated by seeding of minced bladder mucosa, followed by proliferation in vitro. High mechanical strength in combination with a biological environment suitable for tissue growth was achieved through the creation of a hybrid construct that showed an increased tensile strength (17.9 +/- 2.6 MPa) when compared to plastic-compressed collagen (0.6 +/- 0.12 MPa). Intimate contact between the collagen and the PCL fabric was required to ensure integrity without delamination of the construct. This contact was achieved by surface alkaline hydrolysis of the PCL, followed by adsorption of poly(vinyl) alcohol. The improvement in hydrophilicity of the PCL-knitted mesh was confirmed through water contact angle measurements, and penetration of the collagen into the mesh was evaluated by scanning electron microscopy (SEM). Particles of minced bladder mucosa tissue were seeded onto this scaffold, and the proliferation was followed for 6 weeks in vitro. Results obtained from phase contrast microscopy, SEM, and histological staining indicated that cells migrated from the minced tissue particles and reorganized on the scaffold. Cells were viable and proliferative, with morphological features characteristic of urothelial cells. Proliferation reached the point at which a multilayer with a resemblance to stratified urothelium was achieved. This successful method could potentially be used for in vivo applications in reconstructive urology as an engineered autologous tissue transplant without the requirement for in vitro culture before transplantation.
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| 8. |
- Akhtar, Sultan
(författare)
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Transmission Electron Microscopy of Graphene and Hydrated Biomaterial Nanostructures : Novel Techniques and Analysis
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transmission Electron Microscopy (TEM) on light element materials and soft matters is problematic due to electron irradiation damage and low contrast. In this doctoral thesis techniques were developed to address some of those issues and successfully characterize these materials at high resolution. These techniques were demonstrated on graphene flakes, DNA/magnetic beads and a number of water containing biomaterials. The details of these studies are given below.A TEM based method was presented for thickness characterization of graphene flakes. For the thickness characterization, the dynamical theory of electron diffraction is used to obtain an analytical expression for the intensity of the transmitted electron beam as a function of thickness. From JEMS simulations (experiments) the absorption constant λ in a low symmetry orientation was found to be ~ 208 nm (225 ± 9 nm). When compared to standard techniques for thickness determination of graphene/graphite, the method has the advantage of being relatively simple, fast and requiring only the acquisition of bright-field (BF) images. Using the proposed method, it is possible to measure the thickness change due to one monolayer of graphene if the flake has uniform thickness over a larger area.A real-space TEM study on magnetic bead-DNA coil interaction was conducted and a statistical analysis of the number of beads attached to the DNA-coils was performed. The average number of beads per DNA coil was calculated around 6 and slightly above 2 for samples with 40 nm and 130 nm beads, respectively. These results are in good agreement with magnetic measurements. In addition, the TEM analysis supported an earlier hypothesis that 40 nm beads are preferably attached interior of the DNA-coils while 130 nm beads closer to the exterior of the coils.A focused ion-beam in-situ lift-out technique for hydrated biological specimens was developed for cryo-TEM. The technique was demonstrated on frozen Aspergillus niger spores which were frozen with liquid nitrogen to preserve their cellular structures. A thin lamella was prepared, lifted out and welded to a TEM grid. Once the lamella was thinned to electron transparency, the grid was cryogenically transferred to the TEM using a cryo-transfer bath. The structure of the cells was revealed by BF imaging. Also, a series of energy filtered images was acquired and C, N and Mn elemental maps were produced. Furthermore, 3 Å lattice fringes of the underlying Al support were successfully resolved by high resolution imaging, confirming that the technique has the potential to extract structural information down to the atomic scale. The experimental protocol is ready now to be employed on a large variety of samples e.g. soft/hard matter interfaces.
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| 9. |
- Ananta, M., et al.
(författare)
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A Novel Poly(L-Lactide-co-e-Caprolactone)-Collagen Hybrid Construct for Application in Tissue Engineering
- 2007
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Ingår i: Termis-EU Meeting Abstracts, London, UK September 4-7 2007. - : Mary Ann Liebert Inc.. ; , s. 1637-1637
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A biodegradable hybrid construct consisting of a slow degrading poly(L-lactide-co-e-caprolactone) (PLA-e-CL) knitted mesh, plastically compressed (1) between two collagen gels was fabricated and tested in vitro for tissue engineering applications. The polymer mesh was incorporated to give greater mechanical stability to the compressed collagen scaffolds. The hybrid construct was characterized for fluid (weight) loss and cell viability during compression and mechanical properties. Hybrid constructs embedded and surface layered with human dermal fibroblasts (2, Eþ5 per 5 ml) were cultured for up to one week in static culture. Quantitative and qualitative data on cell viability and proliferation were obtained. It was found that the fluid (weight) loss in plastic compression of the hybrid construct was time dependent and not weight dependent at an applied load of 240 grams. No significant cell death was observed during the plastic compression process and a homogenous cell distribution was achieved. One week of static culture showed that the cultivated hybrid construct retained its mechanical properties with no evidence of degradation, and cells inside the constructs as well as layered on top of the constructs proliferated. We found the PLA-e-CL-Collagen hybrid construct a useful three-dimensional scaffold for tissue engineering of stratified tissues and potential applications in bladder wall, blood vessels and skin are currently being explored.
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| 10. |
- Ananta, M, et al.
(författare)
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A Poly(Lactic Acid-Co-Caprolactone)–Collagen Hybrid for Tissue Engineering Applications
- 2009
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Ingår i: Tissue engineering Part A. - : Mary Ann Liebert, Inc.. - 1937-3341 .- 1937-335X. ; 15:7, s. 1667-1675
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Tidskriftsartikel (refereegranskat)abstract
- A biodegradable hybrid scaffold consisting of a synthetic polymer, poly(lactic acid-co-caprolactone) (PLACL), and a naturally derived polymer, collagen, was constructed by plastic compressing hyperhydrated collagen gels onto a flat warp-knitted PLACL mesh. The collagen compaction process was characterized, and it was found that the duration, rather than the applied load under the test conditions in the plastic compression, was the determining factor of the collagen and cell density in the cell-carrying component. Cells were spatially distributed in three different setups and statically cultured for a period of 7 days. Short-term biocompatibility of the hybrid construct was quantitatively assessed with AlamarBlue and qualitatively with fluorescence staining and confocal microscopy. No significant cell death was observed after the plastic compression of the interstitial equivalents, confirming previous reports of good cell viability retention. The interstitial, epithelial, and composite tissue equivalents showed no macroscopic signs of contraction and good cell proliferation with a two- to threefold increase in cell number over 7 days. Quantitative analysis showed a homogenous cell distribution and good biocompatibility. The results indicate that viable and proliferating multilayered tissue equivalents can be engineered using the PLACL-collagen hybrid construct in the space of several hours.
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| 11. |
- Arnander, Claes, et al.
(författare)
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Three-Dimensional Technology and Bone Morphogenetic Protein in Frontal Bone Reconstruction
- 2006
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Ingår i: Journal of Craniofacial Surgery. ; 17:2, s. 275-279
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Tidskriftsartikel (refereegranskat)abstract
- Osteoinductive bone morphogenetic proteins (BMPs) may be used in humans to facilitate healing of bony defects. The effect of different BMPs is, as with many other growth factors, highly dependent on the delivery vehicle. Bovine type I collagen is currently used in the clinical setting as a carrier and has been approved in several countries for human use. Here, we report the reconstruction of a frontal bone defect using heparin together with bovine type I collagen, hyaluronic acid, and fibrin as vehicles for BMP-2. A bony structure was created on the back of the patient by treating the latissimus dorsi muscle with the growth factor. A polyamide mold was used as a template to achieve the desired shape. The bone structure was transplanted into the defect site via microsurgical techniques. Although the prefabricated bone was not large enough tocover the entire frontal defect, the reconstruction was completed by using an additional cranial implant.
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| 12. |
- Asem, Heba, 1987-
(författare)
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Synthesis of Polymeric Nanocomposites for Drug Delivery and Bioimaging
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nanomaterials have gained great attention for biomedical applications due to their extraordinary physico-chemical and biological properties. The current dissertation presents the design and development of multifunctional nanoparticles for molecular imaging and controlled drug delivery applications which include biodegradable polymeric nanoparticles, superparamagnetic iron oxide nanoparticles (SPION)/polymeric nanocomposite for magnetic resonance imaging (MRI) and drug delivery, manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs)/ SPION/ polymeric nanocomposites for fluorescence imaging, MRI and drug delivery.Bioimaging is an important function of multifunctional nanoparticles in this thesis. Imaging probes were made of SPION and Mn:ZnS QDs for in vitro and in vivo imaging. The SPION have been prepared through a high temperature decomposition method to be used as MRI contrast agent. SPION and Mn:ZnS were encapsulated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles during the particles formation. The hydrophobic model drug, busulphan, was loaded in the PLGA vesicles in the composite particles. T2*-weighted MRI of SPION-Mn:ZnS-PLGA phantoms exhibited enhanced negative contrast with r2* relaxivity of 523 mM-1 s-1. SPION-Mn:ZnS-PLGA-NPs have been successfully applied to enhance the contrast of liver in rat model.The biodegradable and biocompatible poly (ethylene glycol)-co-poly (caprolactone) (PEG-PCL) was used as matrix materials for polymeric nanoparticles -based drug delivery system. The PEG-PCL nanoparticles have been constructed to encapsulate SPION and therapeutic agent. The encapsulation efficiency of busulphan was found to be ~ 83 %. PEG-PCL nanoparticles showed a sustained release of the loaded busulphan over a period of 10 h. The SPION-PEG-PCL phantoms showed contrast enhancement in T2*-weighted MRI. Fluorescein-labeled PEG-PCL nanoparticles have been observed in the cytoplasm of the murine macrophage cells (J774A) by fluorescence microscopy. Around 100 % cell viability were noticed for PEG-PCL nanoparticles when incubated with HL60 cell line. The in vivo biodistribution of fluorescent tagged PEG-PCL nanoparticles demonstrated accumulation of PEG-PCL nanoparticles in different tissues including lungs, spleen, liver and kidneys after intravenous administration.
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| 13. |
- Asplund, Basse, 1974-
(författare)
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Biodegradable Thermoplastic Elastomers
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A novel strategy for synthesising segmented poly(urethane urea) (PUU) without using a chain extender but nevertheless with the opportunity to vary the hard segment content has been developed. The strategy is based on amine formation from isocyanate upon reaction with water. By adding a dissolved soft segment to an excess of diisocyanate followed by the addition of water in the gas phase, amines are formed in situ. Urea linkages are then formed when these amines react with the excess of isocyanate groups. The gas phase addition facilitates addition in a slow and continuous manner. The hard segment content can easily altered by varying the diisocyanate/soft segment ratio. Even though the strategy is shown to be applicable to different diisocyanates, the focus has been on the potentially biodegradable methyl-2,6-diisocyanatehexanoate (LDI) and 1.4-butanediisocyanate (BDI) and various well known biodegradable polyesters and polycarbonates. All the synthesised materials exhibited pronounced phase separation and hydrogen bonding within the hard domains. However, a major increase in hydrogen bonding strength was seen when a symmetric diisocyanate was used instead of an asymmetric. Based on FTIR measurements, PUUs with BDI and a polydisperse hard segment can exhibit the same degree of phase separation and hydrogen bonding as the monodisperse product.The elastic properties of this new group of PUUs were exceptional with an elongation at break from 1600% to almost 5000% and the elastic modulus could be varied from a few MPa up to a couple of hundreds. Hydrolytic degradation was greater in the polyester-based than in the polycarbonate-based PUUs due to the more reactive ester bonds. Low mass loss but a considerable loss in molecular weight was seen in the polyester PUUs. The tensile strength decreased dramatically due to the loss of strain hardening.An MTT seeding assay using human fibroblasts and an in vivo biocompatibility study were performed and no signs of cytotoxicity were seen and the inflammatory response was comparable to other inert polymers.A biodegradable PUU with properties that can be tailored through an easy synthesis is here presented.
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| 14. |
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| 15. |
- Asplund, Basse, et al.
(författare)
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In vitro degradation and in vivo biocompatibility study of a new linear poly(urethane urea)
- 2008
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Ingår i: Journal of biomedical materials research. Part B: Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 86B:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Segmented poly(urethane urea)s (PUUs) with hard segments derived only from methyl 2,6-diisocyantohexanoate (LDI) without the use of a chain extender have previously been described. These materials, which contain hard segments with multiple urea linkages, show exceptionally high strain capability (1600-4700%). In the study reported here, the rate and effect of hydrolysis of these materials were determined for gamma-sterilized and nonsterilized samples. Materials investigated contained PCL, PTMC, P(TMC-co-CL), P(CL-co-DLLA), or P(TMC-co-DLLA) as soft segments and, as well as their mechanical properties, changes in mass, inherent viscosity (IN.), and thermal properties were studied over 20 weeks. Results showed that the degradation rate was dependant on the soft segment structure, with a higher rate of degradation for the polyester-dominating PUUs exhibiting a substantial loss in IN. A tendency of reduction of tensile strength and strain hardening was seen for all samples. Also, loss in elongation at break was detected, for PUU-P(CL-DLLA) it went from 1600% to 830% in 10 weeks. Gamma radiation caused an initial loss in I.V. and induced more rapid hydrolysis compared with nonsterilized samples, except for PUU-PTMC. A cytotoxicity test using human fibroblasts demonstrated that the material supports cell viability. In addition, an in vivo biocompatibility study showed a typical foreign body reaction after I and 6 weeks.
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| 16. |
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| 17. |
- Asplund, Basse, et al.
(författare)
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Variable Hard Segment Length in Poly(urethane urea) through Excess of Diisocyanate and Vapor Phase Addition of Water
- 2006
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 39, s. 4380-4385
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Tidskriftsartikel (refereegranskat)abstract
- Poly(urethane urea)s with hard segments derived only from diisocyanate linked via urea linkages were synthesized using a new and simple one-pot method. The creation of urea linkages were done via creating the amine in situ by adding water in vapor phase slowly and continuously. This synthesis method eliminates the tedious control to approach stoichiometry, is less sensitive to impurities, involves no intermediate isolation steps, and does not involve any chain extender. A study using a two-armed poly(-caprolactone) as soft segment and methyl 2,6-diisocyantohexanoate (LDI) as the hard segment was performed. The length of the hard segment was varied from 4.8 to 11.6 LDI units. Stress-strain measurements showed an increase in elastic modulus, 146 to 235 MPa, when increasing the hard segment length, while the elongation at break decreased, 980 to 548%. IR spectroscopy showed an increase in hydrogen bonding when increasing the hard segment length. The synthesis was also shown to be applicable to common diisocyanates such as HDI, TDI, and MDI.
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| 18. |
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| 19. |
- Asplund, J. O. Basse, et al.
(författare)
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Synthesis of highly elastic biodegradable poly(urethane urea)
- 2007
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 8:3, s. 905-911
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Tidskriftsartikel (refereegranskat)abstract
- Linear poly(urethane urea) containing a biodegradable soft segment and a hard segment built solely from methyl-2,6-diisocyanatehexanoate (LDI) is presented, using a procedure where no chain extender is required. By having LDI in excess, together with a soft segment, and adding water in the vapor phase continuously creates amines in situ resulting in hard segments containing multiple LDI units linked via urea linkages. As soft segments, polymers of trimethylene carbonate (TMC) and copolymers of TMC, ε-caprolactone, and d,l-lactic acid (DLLA) were used. High inherent viscosity, 0.95−1.65 dL/g, was afforded even when DLLA-containing soft segments were used, which usually undergo aminolysis. With a hard segment content between 12% and 18%, all of the materials showed very high elongation at breakage, ranging from 1600% to 4700%, and an elastic modulus from 2.1 to 140 MPa. This one-pot synthesis is simple and has now been shown to be applicable to a large number of systems.
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| 20. |
- Atthoff, Björn, et al.
(författare)
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Biodegradable Ionomers
- 2006
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 39:11, s. 3907-3913
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Tidskriftsartikel (refereegranskat)abstract
- Several telechelic anionic or cationic ionomers were synthesized starting from poly(trimethylene carbonate) diols (PTMC) of different molecular weight, ranging from 1000 to 12 000 g/mol. In the synthesis of the anionomer, addition of sulfur trioxide trimethylene complex to the PTMC end-group hydroxyls and subsequent ion exchange afforded a disulfate monoester sodium salt. The cationomer was synthesized in two steps. Acylation of the PTMC diol using 4-chlorobuturyl chloride was followed by displacement of the alkyl chloride with trimethylamine to give a quaternary ammonium salt. These ionomers showed excellent swelling properties, up to around 500% in H2O, while the unfunctionlized PTMC did not swell at all. The lowest molecular weight ionomers were soluble in both water and chloroform. The physical properties of the ionomers were analyzed with oscillating rheological experiments. Interestingly, the ionomers displayed "rubbery plateau". The mechanical and swelling properties may be linked to phase separation resulting in ionic aggregates within the bulk, which may function as physical cross-links. At ambient temperatures, the PTMC starting material behaved like a highly viscous fluid, while the ionomers behaved as elastomers. In a hydrophilic environment, the ionomers displayed a surface rearrangement making the surface of the ionomer hydrophilic by allowing the ionic end groups to appear at the water ionomer interface. In air or vacuum all the ionic groups were found in the bulk of the material as analyzed by XPS or contact angle measurements. Finally, we showed that with the specific ionic groups it was possible to complex specific molecules to the ionomers.
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| 21. |
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| 22. |
- Atthoff, Björn, et al.
(författare)
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Polarized protein membrane for high cell seeding efficiency
- 2007
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Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 83:2, s. 472-480
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Tidskriftsartikel (refereegranskat)abstract
- A new type of scaffold for tissue engineering was developed to give enhanced cell seeding in three dimensions. A gradient of either collagen or fibrin protein was prepared, supported by a knitted poly(ethylene terephtalate) PET fabric. The membranes were, after hydrolysis and acetic acid wash, submerged in a protein solution for adsorption followed by immersion into a gelling agent. The immediate contact between the protein solution held by the fabric and the gelling agent resulted in a dense, fibrous protein network with pore sizes around 0.5 μm at the surface, and larger pores of 10-50 μm size throughout the interior of the fabric as observed by scanning electron microscopy. By separating the fabric double layers holding this network, a gradient porosity membrane was produced. To evaluate the fractions of cells trapped in the matrix upon seeding, i.e. the seeding efficiency, 500 μl 3T3 fibroblasts cell suspension containing one million cells was seeded by filtering through the gradient protein membrane. For both the collagen and fibrin membranes, the seeding efficiency was ∼93%, which was significantly higher than that of 28% from the corresponding PET fabric without protein immobilization. Attempt to seed cells from the dense side of the protein networks resulted in no cell penetration into the scaffold. Histology on subsequent culture of the cells in the scaffold demonstrated viability and proliferation in three dimensions throughout the scaffold. This new and simple way of producing scaffolds play an important role when the cells are precious or scarce and cell seeding in three dimensions is important.
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| 23. |
- Atthoff, Björn, et al.
(författare)
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Protein adsorption onto polyester surfaces : Is there a need for surface activation?
- 2007
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Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 80:1, s. 121-130
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Tidskriftsartikel (refereegranskat)abstract
- Surface hydrolysis of polyester scaffolds is a convenient technique suggested to promote protein adsorption for improving cell attachment. We have, therefore, investigated the effect of hydrolysis of polyester surfaces for protein adsorption to clarify the conditions needed. Three polyesters, poly(ethylene terephthalate) (PET), poly(lactic acid) (PLA), and poly(glycolic acid) (PGA), were selected. Adsorption was investigated by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and quartz crystal microbalance (QCM). Hydrolyzed PET adsorbed significantly more proteins than nonhydrolyzed. Degradable polymers adsorbed at higher rates when the polymers were hydrolyzed prior to adsorption, but the same amount as noehydrolyzed, suggesting spontaneous hydrolysis during the adsorption. XPS shows that hydrolysis prior to absorption for PET results in a surface nitrogen composition of ∼14%, similar to pure protein (16%). Nonhydrolyzed PET surfaces showed only ∼7% nitrogen, indicating protein layers thinner than ∼10 nm. Adsorption to PLA and PGA shows nitrogen contents of 14-15% in both cases. SEM revealed striking differences in morphology of the protein coating. Hydrolyzed or spontaneously hydrolyzable surfaces display a pronounced fibrous structure while nonhydrolyzed surfaces give smooth structures. In combination, the results show that surface hydrolysis increase adsorption rate, but not the amount of proteins on polyesters that degrades in vivo. Surface treatment of nondegradable polyester increases the total amount of proteins and induces the formation of fibrous protein structures. Post hydrolysis treatment by acetic acid, replacing the counter-ion to a proton, further enhances protein attachment. Finally, cell attachment experiments verifies that protein adsorption increase the cell attachment to polyester surfaces.
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| 24. |
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| 25. |
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| 26. |
- Atthoff, Björn, et al.
(författare)
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Synthetic Biodegradable Ionomers that Engulf, Store, and Deliver Intact Proteins
- 2006
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 7:8, s. 2401-2406
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Tidskriftsartikel (refereegranskat)abstract
- Telechelic anionic and cationic biodegradable ionomers capable of loading, storing, and releasing proteins are presented. Two different ionomers have been synthesized with either anionic or cationic end groups. The reaction was done quantitatively as shown by 1H NMR. The swelling properties of the hydrophobic poly(trimethylene carbonate) polymer are contributed to the ionic end groups that display hydrophilic properties. Depending on the molecular weight of the ionomer, and also on the ionic charge, the materials swell differently in water, from ~50% for Mw = 12 000 g/mol to ~500% when dealing with 2000 g/mol. The high swelling led us to believe that it would be possible to load and release proteins preferably in a still active form. As models, two different proteins were chosen: hemoglobin and cytochrome c. The swelling and release study shows that both ionomers possess the capability to adsorb and later release the proteins with retained structure. Release measurements from both the swollen and dried states have been evaluated with similar results, showing that the dried state seems to release a little bit less than the swollen one. These kinds of materials should be interesting for a wide variety of applications where drug and protein release is wanted, as well as in applications such as protein separation media.
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| 27. |
- Atthoff, Björn, 1973-
(författare)
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Tailoring of Biomaterials using Ionic Interactions : Synthesis, Characterization and Application
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interactions between polymers and components of biological systems are an important area of interest within the fields of tissue engineering, polymer chemistry, medicine and biomaterials. In order to create such a biomimetic material, it must show the inherent ability to reproduce or elicit a biological function. How do we design synthetic materials in order to direct their interactions with biological systems?This thesis contributes to this research with aspects of how polymers interact with biological materials with the help of ionic interactions. Polyesters, biodegradable or not, may after a hydrolytic cleavage interact ionically with protonated amines by the liberated carboxylate functions. Amines are found in proteins and this fact will help us to anchor proteins to polyester surfaces. Another type of interaction is to culture cells in polymeric materials, i.e. scaffolds. We have been working on compliant substrates, knitted structures, to allow cell culture in three dimensions. A problem that arises here is how to get a high cell seeding efficiency? By working on the interactions between polymers, proteins and finally cells, it is possible to create a polarized protein membrane that allows for very efficient cell seeding, and subsequent three dimensional cell cultures. Finally a synthetic route to taylor interaction was developed. Here a group of polymers known as ionomers were synthesized. In our case ionic end groups have been placed onto biodegradable polycarbonates, we have created amphiphilic telechelic ionomers. Functionalization, anionic or cationic, changes the properties of the material in many ways due to aggregation and surface enrichment of ionic groups. It is possible to add functional groups for a variety of different interactions, for example introducing ionic groups that interact and bind to the complementary charge of proteins or on the other hand one can chose groups to prevent protein interactions, like the phosphorylcholine zwitterionomers. Such interactions can be utilized to modulate the release of proteins from these materials when used in protein delivery applications. The swelling properties, Tg, degradation rate and mechanical properties are among other things that will easily be altered with the choice of functional groups or backbone polymer.
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| 28. |
- Aulin, C., et al.
(författare)
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Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits
- 2013
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Ingår i: Laboratory Animals. - : SAGE Publications. - 0023-6772 .- 1758-1117. ; 47:1, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint.
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| 29. |
- Aulin, Cecilia, et al.
(författare)
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Cell produced ECM on engineered polymer structures
- 2006
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Ingår i: Tissue Engineering and Regenerative Medicine International Society Conference, Rotterdam, 08 – 11 oktober 2006, oral presentation.
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Konferensbidrag (populärvet., debatt m.m.)
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| 30. |
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| 31. |
- Aulin, Cecilia, et al.
(författare)
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Designing Extracellular Matrix Scaffolds by Dynamic culture of fibroblasts
- 2007
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Ingår i: TERMIS-EU Meeting Abstracts London, UK September 4–7, 2007. - : Mary Ann Liebert. ; , s. 1667-1667
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Our bodies are constantly exposed to different sorts of mechanical forces, from muscle tension to wound healing. Connective tissue adapts its extracellular matrix (ECM) to changes in mechanical load and the influence of mechanical stimulation on fibroblasts has been studied for a long time [1, 2]. When exposed to forces, fibroblasts are known to respond with expression and remodeling of ECM proteins, in particular collagen type I [3]. In this study the effect of dynamic culture conditions on human dermal fibroblasts was evaluated in terms of deposition and remodeling of ECM, with the aim of producing an ECM based scaffold. The fibroblasts were grown on compliant polymer supports either in a bioreactor with a pulsating flow or under static conditions. By applying dynamic culture conditions, the collagen deposition on the polymer supports increased fivefold. Scanning electron microscopy showed that polymer fibers were well integrated with cells and ECM and alignment along the polymer fibers was observed. Scaffold design should aim at creating structures that can help guiding the cells to form new, functional tissue. The presented system may present a new way of producing designed extracellular matrix based scaffolds for tissue engineering.
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| 32. |
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| 33. |
- Aulin, Cecilia, 1979-
(författare)
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Extracellular Matrix Based Materials for Tissue Engineering
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
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| 34. |
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| 35. |
- Aulin, Cecilia, et al.
(författare)
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Extracellular matrix-polymer hybrid materials produced in a pulsed-flow bioreactor system
- 2009
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley & Sons, Ltd. - 1932-6254 .- 1932-7005. ; 3:3, s. 188-195
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Tidskriftsartikel (refereegranskat)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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| 36. |
- Aulin, Cecilia, et al.
(författare)
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In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis
- 2011
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Ingår i: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 5:8, s. E188-E196
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Tidskriftsartikel (refereegranskat)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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| 37. |
- Aulin, Cecilia, et al.
(författare)
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In vitro/ Produced Extracellular Matrix Scaffolds
- 2005
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Ingår i: European Tissue Engineering Society International Conference, München 8 Aug – 3 sept 2005, oral presentation.
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Konferensbidrag (populärvet., debatt m.m.)
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| 38. |
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| 39. |
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| 40. |
- Badali, Elham, et al.
(författare)
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Enzymatic Crosslinked Hydrogels for Biomedical Application
- 2021
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Ingår i: Polymer science. - : Springer. - 0965-545X. ; 63:SUPPL 1, s. S1-S22
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Forskningsöversikt (refereegranskat)abstract
- Self-assembled structures primarily arise through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of the main biological processes constructing supramolecular hydrogel networks required for biomedical applications. Such enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most cases, the structure and substrates of hydrogels are adjusted by enzyme catalysis due to enzymes' chemo-, regio- and stereo-selectivity. Such hydrogels processed using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules, and drugs in tissue engineering, drug delivery, and regenerative medicine. The enzyme-mediated crosslinking hydrogels mimic the extracellular matrices by displaying unique physicochemical properties and functionalities such as water-retention capacity, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, and shape memory ability. In recent years, many enzymatic systems investigated polymer crosslinking. Herein, we review efficient strategies for enzymatic hydrogelation, including hydrogel synthesis and chemistry, and demonstrate their applicability in biomedical systems. Furthermore, the advantages, challenges, and prospects of enzymatic-crosslinkable hydrogels are discussed. The results of biocompatible hydrogel products show that these crosslinking mechanisms can fulfill requirements for a variety of biomedical applications, including tissue engineering, wound healing, and drug delivery.
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| 41. |
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| 42. |
- Bergman, Kristoffer, 1975-
(författare)
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Hyaluronan Derivatives and Injectable Gels for Tissue Engineering
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present work describes the preparation of hyaluronan derivatives and hydrogels with potential use in tissue engineering applications. A potentially injectable hydrogel consisting of hyaluronan and collagen was successfully used to grow neurons in vitro by encapsulation of neural stem and progenitor cells. Attempts were further made to establish a suitable modification strategy which could be used for the preparation of in vivo cross-linkable hyaluronan derivatives. The synthesis of a model substance consisting of a D-glucuronate derivative which could simplify the development of such a modification technique is described, although a new method to prepare hyaluronan derivatives was found without its use. The modification strategy involves the use of a triazine-reagent which enables the covalent attachment of hydrophilic and hydrophobic amines to hyaluronan carboxyl groups in a controlled fashion under mild conditions. Using triazine-activated amidation we synthesized an aldehyde-derivative of hyaluronan which was used to prepare gels by cross-linking with hydrazide-modified polyvinyl-alcohol. Gels were formed in less than 1 minute by mixing equal volumes of the polymer derivatives and they were subsequently used as a carrier for bone morphogenetic protein-2. An in vitro release study showed that approximately 88% of the growth factor is retained in the gel over a 4 week period. The ability to form new bone in vivo was further evaluated in an ectopic rat model by the injection of gels containing 30 µg BMP-2. Radiographic and histological examination 4 and 10 weeks after injection showed the formation of new bone without any signs of inflammation or foreign body response. Hydroxyapatite particles were further added to improve the mechanical properties of the gel, and a comparative study was conducted. This time the induced tissue consisted not only of bone, but also of interconnected cartilage and tendon, as confirmed by histology and immunohistochemistry.
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| 43. |
- Bergman, Kristoffer, et al.
(författare)
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Hyaluronic acid cross-linking chemistry
- 2005
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Ingår i: 8th International Symposium of Polymers for Advanced Technologies, 13th-16th Sept. 2005, Budapest, Hungary.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 44. |
- Bergman, Kristoffer, et al.
(författare)
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Hyaluronic acid derivatives prepared in aqueous media by triazine-activated amidation
- 2007
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 8:7, s. 2190-2195
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Tidskriftsartikel (refereegranskat)abstract
- A method is presented for the preparation of hyaluronic acid derivatives obtained through triazine-activated amidation. A number of amines were successfully reacted with hyaluronic acid carboxyl groups using 2-chloro-4,6-dimethoxy-1,3,5-triazine as an activating species in a mixture of water and acetonitrile under neutral conditions. By varying the amount of triazine reagent, it was possible to control the degree of modification. Depending on the amine chosen, degrees of modification ranging from 3 to 20% were obtained when using 0.5 equiv of the triazine to hyaluronic acid carboxyl groups. The possibility to perform the reaction in a mixture of water and acetonitrile facilitates the introduction of a wide range of both hydrophilic and hydrophobic amines. Triazine-activated amidation appears to be a highly versatile, controllable, and relatively mild technique for modification of hyaluronic acid, and we predict that it will be useful in the design of novel hyaluronic acid based biomaterials.
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| 45. |
- Bergman, Kristoffer, et al.
(författare)
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Injectable cell-free template for bone-tissue formation
- 2009
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Ingår i: Journal of Biomedical Materials Research-Part A. - : Wiley Periodicals, Inc. - 1549-3296 .- 1552-4965. ; 91A:4, s. 1111-1118
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a novel injectable hydrogel which forms a template for de novo formation of bone tissue. Hydrogel formation takes place in situ in less than 1 min by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives. Endogenous cells are recruited in vivo by incorporating bone morphogenetic protein-2 (BMP-2), a powerful promoter for osteogenic differentiation. The hydrogel was evaluated in vitro by performing a cell viability test and a release study and in vivo by a rat ectopic model. Examination by X-ray, microcomputed tomography, and histology revealed a significant bone formation at the target site for gels containing BMP-2, and a complete degradation was observed for gels without BMP-2 four weeks after injection. There were no signs of inflammation or foreign body response in either group and we believe that this system has the potential as an off-the-shelf injectable to be used where bone tissue is needed.
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| 46. |
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| 47. |
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| 48. |
- Bergman, Kristoffer, et al.
(författare)
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Selective Michael-type addition of a D-glucuronic acid derivative in the synthesis of model substances for uronic acid containing polysaccharides
- 2008
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Ingår i: Express Polymer Letters. - : Department of Polymer Engineering, Scientific Society of Mechanical Engineering. - 1788-618X. ; 2:8, s. 553-559
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Tidskriftsartikel (refereegranskat)abstract
- A flexible protocol for the preparation of model substances for uronic acid containing polysaccharides is presented.We have synthesized a D-glucuronic acid derivative which is designed so that it easily can be conjugated with differentstructures and architectures by selective Michael-type addition. By successful coupling of the glucuronic acidderivative to polyethylene glycol with high degree of conversion, products were obtained that were easily characterized andwhich resembled polysaccharides in terms of solubility and purification methods that could be employed. The model substancecan potentially be used to facilitate optimization of low-degree modification reactions of high molecular weightD-glucuronic acid containing polysaccharides.
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| 49. |
- Bermejo, Daniel, 1985-, et al.
(författare)
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First Aldol-Crosslinked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Gel with Tissue Adhesive Properties
-
Ingår i: Chemical Sciences Journal. - 2150-3494.
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there are limited approaches to tailor 3D scaffolds crosslinked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-crosslinking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely; an enolizable HA-aldehyde (HA-Eal) and a non-enolizable HA-aldehyde (HA-Nal). Hydrogels formed using HA-Eal demonstrate inferior crosslinking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-Eal and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of crosslinking at different pH is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Mc). The novel HA cross-aldol hydrogels demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product leads to adhesion to tissue as demonstrated by bonding two bone tissues. The aldehyde functionality also permits facile post-synthetic modifications with nucleophilic reagents such as Alexa FluorTM 488. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3–6 days of study.
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| 50. |
- Bermejo-Velasco, Daniel, 1985-, et al.
(författare)
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First Aldol Cross-Linked Hyaluronic Acid Hydrogel : Fast and Hydrolytically Stable Hydrogel with Tissue Adhesive Properties
- 2019
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 11:41, s. 38232-38239
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there are limited approaches to tailor 3D scaffolds cross-linked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-cross-linking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely, an enolizable HA-aldehyde (HA-EaI) and a non-enolizable HA-aldehyde (HA-NaI). Hydrogels formed using HA-EaI demonstrate inferior cross linking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-EaI and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of cross-linking at different pH values is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Me). The novel HA cross-aldol hydrogel demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase-mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product rendered the tissue adhesive properties by bonding two bone tissues. The aldehyde functionality also facilitated facile post-synthetic modifications with nucleophilic reagents. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3-6 days of study.
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