| 1. |
- Liu, Lei, et al.
(author)
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Immunological responses in mice to full-thickness corneal grafts engineered from porcine collagen
- 2007
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In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 28:26, s. 3807-3814
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Journal article (peer-reviewed)abstract
- Tissue-engineered (TE) corneas were fabricated from porcine collagen cross-linked with 1-ethyl-3-(3-dimethyl aminoproplyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS), and were transplanted into BALB/c mice orthotopically using a full-thickness penetrating keratoplasty (PKP) procedure. The biocompatibility was evaluated by assessing both local and systemic immune responses. Myeloid cells including granulocytes and macrophages were the main infiltrating cells in recipient cornea and in retro-TE corneal membrane which developed 7-10 days post surgery. Sodium citrate was found to be effective in reducing fibrin accumulation in anterior chamber post grafting at early time points, but it did not prevent formation of the retro-TE corneal membrane. No significant T cell activation was observed in the submandibular draining lymph nodes (SMDLN) by flow cytometry. Anti-porcine type I collagen IgG antibodies were detected in the serum of grafted mice from 2 weeks post grafting and the concentration of antibodies increased with time. Overall, porcine collagen-EDC/NHS TE corneas were tolerated well in murine recipients, causing mainly a self-limiting local innate immune response and a low-grade humoral response with little evidence of sustained T cell activation. Retro-TE corneal membrane formation was the main complication and barrier to clarity.
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| 2. |
- Merrett, Kimberley, et al.
(author)
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Synthetic neoglycopolymer-recombinant human collagen hybrids as biomimetic crosslinking agents in corneal tissue engineering
- 2009
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In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 30:29, s. 5403-5408
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Journal article (peer-reviewed)abstract
- Saturated neoglycopolymers, prepared via tandem ROMP-hydrogenation (ROMP = ring-opening metathesis polymerization) of carbohydrate-functionalized norbornenes, are investigated as novel collagen crosslinking agents in corneal tissue engineering. The neoglycopolymers were incorporated into recombinant human collagen type III (RHC III) as collagen crosslinking agents and glycosaminoglycan (GAG) mimics. The purely synthetic nature of these composites is designed to reduce susceptibility to immunological and allergic reactions, and to circumvent the transmission of animal infectious diseases. The collagen-neoglycopolymer biomaterials exhibit higher stability to collagenase-induced biodegradation than the control materials, composites of RHC III crosslinked using EDC/NHS (EDC = 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide; NHS = N-hydroxysuccinimide). Even at this proof of concept stage, the thermal stability, enzymatic resistance, and permeability of the neoglycopolymer hydrogels are comparable or superior to those of these fully optimized control materials, which have successfully been tested clinically. Tensile strength is adequate for transplantation, but lower than that of the optimized control materials.
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| 3. |
- Fagerholm, Per, et al.
(author)
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A biosynthetic alternative to human donor tissue for inducing corneal regeneration : 24-month follow-up of a phase 1 clinical study
- 2010
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In: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 2:46, s. 46-61
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Journal article (peer-reviewed)abstract
- Corneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage.
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| 4. |
- Fagerholm, Per, et al.
(author)
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Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold
- 2014
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In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 35:8, s. 2420-2427
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Journal article (peer-reviewed)abstract
- We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.
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| 5. |
- Griffith, May, et al.
(author)
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Vision Enhancing Ophthalmic Devices and Related Methods and Compositions
- 2005
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Patent (pop. science, debate, etc.)abstract
- Devices, methods, and compositions for improving vision or treating diseases, disorders or injury of the eye are described. Ophthalmic devices, such as corneal onlays, corneal inlays, and full-thickness corneal implants, are made of a material that is effective in facilitating nerve growth through or over the device. The material may include an amount of collagen greater than 1% (w/w), such as between about 10% (w/w) and about 30% (w/w). The material may include collagen polymers and/or a second biopolymer or water-soluble synthetic polymer cross-linked using EDC/NHS chemistry. The material may additionally comprise a synthetic polymer. The devices are placed into an eye to correct or improve the vision of an individual or to treat a disease, disorder or injury of an eye of an individual.
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| 6. |
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| 7. |
- Hobein, Matthias, et al.
(author)
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Evaporative Cooling and Coherent Axial Oscillations of Highly Charged Ions in a Penning Trap
- 2011
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:1, s. 013002-
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Journal article (peer-reviewed)abstract
- Externally, in an electron beam ion trap, generated Ar16+ ions were retrapped in a Penning trap and evaporatively cooled in their axial motion. The cooling was observed by a novel extraction technique based on the excitation of a coherent axial oscillation which yields short ion bunches of well-defined energies. The initial temperature of the ion cloud was decreased by a factor of more than 140 within 1 s, while the phase-space density of the coldest extracted ion pulses was increased by a factor of up to about 9.
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| 8. |
- Hobein, Matthias, et al.
(author)
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Re-trapping and cooling of highly-charged
- 2009
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In: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 163, s. 012109-
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Journal article (peer-reviewed)abstract
- Presently, a trapping system for cooling highly-charged ions (HCI) is being set up at AlbaNova at Stockholm University. The experiment aims at production of low temperature (emittance) HCI at very low energy. HCI are extracted from the new Stockholm EBIT (S-EBIT) before evaporative cooling is applied in a Penning trap. In the future the cooled ions will be injected into the precision trap of the high-precision mass spectrometer SMILETRAP II. In first tests the emittance of trapped ions was measured and it was shown that highly and low-charged ions could be simultaneously stored
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| 9. |
- Hobein, Matthias, 1981-, et al.
(author)
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SMILETRAP II
- 2011
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In: Hyperfine Interactions. - : Springer Netherlands. - 0304-3843 .- 1572-9540. ; 199:1-3, s. 141-150
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Journal article (peer-reviewed)abstract
- The new Penning trap mass spectrometer SMILETRAP II has been set up at the AlbaNova Research Center, Stockholm. Based on the former spectrometer SMILETRAP I, it uses the merits of highly-charged ions to achieve high precision in the mass measurements. Various improvements over the SMILETRAP I setup will allow to routinely perform mass measurements with relative uncertainties of 10−10 and below. In this paper we will discuss the limitations of SMILETRAP I and present the corresponding improvements of SMILETRAP II. An overview on the SMILETRAP II setup is given.
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| 10. |
- Liu, Yuwen, et al.
(author)
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A simple, cross-linked collagen tissue substitute for corneal implantation
- 2006
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In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 47:5, s. 1869-1875
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Journal article (peer-reviewed)abstract
- PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%, pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations. Copyright © Association for Research in Vision and Ophthalmology.
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