| 1. |
- Dietrich-Zagonel, Franciele, et al.
(författare)
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Stimulation of Tendon Healing With Delayed Dexamethasone Treatment Is Modified by the Microbiome
- 2018
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Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 46:13, s. 3281-3287
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Tidskriftsartikel (refereegranskat)abstract
- Background:The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment.Hypothesis:A change in microbiome would influence the response to dexamethasone on regenerate remodeling, specifically tendon material properties (peak stress).Study Design:Controlled laboratory study.Methods:Specific opportunist and pathogen-free female rats were housed separately (n = 41) or together with specific pathogen-free rats carrying opportunistic microbes such as Staphylococcus aureus (n = 41). After 6 weeks, all co-housed rats appeared healthy but now carried S aureus. Changes in the gut bacterial flora were tested by API and RapID biochemical tests. All rats (clean and contaminated) underwent Achilles tendon transection under aseptic conditions. Flow cytometry was performed 8 days postoperatively on tendon tissue. Sixty rats received subcutaneous dexamethasone or saline injections on days 5 through 9 after transection. The tendons were tested mechanically on day 12. The predetermined primary outcome was the interaction between contamination and dexamethasone regarding peak stress, tested by 2-way analysis of variance.Results:Dexamethasone increased peak stress in all groups but more in contaminated rats (105%) than in clean rats (53%) (interaction, P = .018). A similar interaction was found for an estimate of elastic modulus (P = .021). Furthermore, dexamethasone treatment reduced transverse area but had small effects on peak force and stiffness. In rats treated with saline only, contamination reduced peak stress by 16% (P = .04) and elastic modulus by 35% (P = .004). Contamination led to changes in the gut bacterial flora and higher levels of T cells (CD3+CD4+) in the healing tendon (P < .05).Conclusion:Changes in the microbiome influence tendon healing and enhance the positive effects of dexamethasone treatment during the early remodeling phase of tendon healing.Clinical Relevance:The positive effect of dexamethasone on early tendon remodeling in rats is strikingly strong. If similar effects could be shown in humans, immune modulation by a few days of systemic corticosteroids, or more specific compounds, could open new approaches to rehabilitation after tendon injury.
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| 2. |
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| 3. |
- Gelmi, Amy, et al.
(författare)
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Influence of conductive polymer doping on the viability of cardiac progenitor cells
- 2014
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 2:24, s. 3860-3867
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac tissue engineering via the use of stem cells is the future for repairing impaired heart function that results from a myocardial infarction. Developing an optimised platform to support the stem cells is vital to realising this, and through utilising new smart materials such as conductive polymers we can provide a multi-pronged approach to supporting and stimulating the stem cells via engineered surface properties, electrical, and electromechanical stimulation. Here we present a fundamental study on the viability of cardiac progenitor cells on conductive polymer surfaces, focusing on the impact of surface properties such as roughness, surface energy, and surface chemistry with variation of the polymer dopant molecules. The conductive polymer materials were shown to provide a viable support for both endothelial and cardiac progenitor cells, while the surface energy and roughness were observed to influence viability for both progenitor cell types. Characterising the interaction between the cardiac progenitor cells and the conductive polymer surface is a critical step towards optimising these materials for cardiac tissue regeneration, and this study will advance the limited knowledge on biomaterial surface interactions with cardiac cells.
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| 4. |
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| 5. |
- Haagdorens, Michel, et al.
(författare)
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Plant Recombinant Human Collagen Type I Hydrogels for Corneal Regeneration
- 2022
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Ingår i: REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE. - : Springer Berlin/Heidelberg. - 2364-4133 .- 2364-4141. ; 8:2, s. 269-283
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To determine feasibility of plant-derived recombinant human collagen type I (RHCI) for use in corneal regenerative implantsMethods RHCI was crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to form hydrogels. Application of shear force to liquid crystalline RHCI aligned the collagen fibrils. Both aligned and random hydrogels were evaluated for mechanical and optical properties, as well as in vitro biocompatibility. Further evaluation was performed in vivo by subcutaneous implantation in rats and corneal implantation in Gottingen minipigs.Results Spontaneous crosslinking of randomly aligned RHCI (rRHCI) formed robust, transparent hydrogels that were sufficient for implantation. Aligning the RHCI (aRHCI) resulted in thicker collagen fibrils forming an opaque hydrogel with insufficient transverse mechanical strength for surgical manipulation. rRHCI showed minimal inflammation when implanted subcutaneously in rats. The corneal implants in minipigs showed that rRHCI hydrogels promoted regeneration of corneal epithelium, stroma, and nerves; some myofibroblasts were seen in the regenerated neo-corneas.Conclusion Plant-derived RHCI was used to fabricate a hydrogel that is transparent, mechanically stable, and biocompatible when grafted as corneal implants in minipigs. Plant-derived collagen is determined to be a safe alternative to allografts, animal collagens, or yeast-derived recombinant human collagen for tissue engineering applications. The main advantage is that unlike donor corneas or yeast-produced collagen, the RHCI supply is potentially unlimited due to the high yields of this production method. Lay Summary A severe shortage of human-donor corneas for transplantation has led scientists to develop synthetic alternatives. Here, recombinant human collagen type I made of tobacco plants through genetic engineering was tested for use in making corneal implants. We made strong, transparent hydrogels that were tested by implanting subcutaneously in rats and in the corneas of minipigs. We showed that the plant collagen was biocompatible and was able to stably regenerate the corneas of minipigs comparable to yeast-produced recombinant collagen that we previously tested in clinical trials. The advantage of the plant collagen is that the supply is potentially limitless.
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| 6. |
- Henningsson, Anna, et al.
(författare)
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Low risk of seroconversion or clinical disease in humans after a bite by an Anaplasma phagocytophilum-infected tick
- 2015
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Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 6:6, s. 787-792
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Tidskriftsartikel (refereegranskat)abstract
- The risk of contracting human granulocytic anaplasmosis (HGA) after a tick bite is mainly unknown. In this study we investigated the clinical and serological response in 30 humans bitten by ticks positive for Anaplasma phagocytophilum (Group A), 30 humans bitten by Borrelia burgdorferi sensu lato (s.l.)-positive ticks (Group B), and 30 humans bitten by ticks negative for both A. phagocytophilum and B. burgdorferi s.l. (Group C). Ticks, blood samples and questionnaires were collected from tick-bitten humans at 34 primary healthcare centres in Sweden and in the Åland Islands, Finland, at the time of the tick bite and after three months. A total of 2553 ticks detached from humans in 2007-2009 were analyzed by polymerase chain reaction, and 31 (1.2%) were positive for A. phagocytophilum, 556 (21.8%) were positive for B. burgdorferi s.l., and eight (0.3%) were co-infected by A. phagocytophilum and B. burgdorferi s.l. The overall prevalence of Anaplasma IgG antibodies in the included participants (n=90) was 17%, and there was no significant difference between the groups A-C. Only one of the participants (in Group C) showed a four-fold increase of IgG antibodies against A. phagocytophilum at the three-month follow-up, but reported no symptoms. The frequency of reported symptoms did not differ between groups A-C, and was unrelated to the findings of A. phagocytophilum and B. burgdorferi s.l. in the detached ticks. We conclude that the risk for HGA or asymptomatic seroconversion after a tick bite in Sweden or in the Åland Islands is low, even if the tick is infected by A. phagocytophilum.
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| 7. |
- Islam, Mohammad Mirazul, et al.
(författare)
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Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation
- 2016
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Ingår i: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 6:61, s. 55745-55749
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potentially ideal substitutes. Self-assembling collagen-like-peptides conjugated with PEG-maleimide were assembled into hydrogels. When tested pre-clinically as corneal implants in mini-pigs, they promoted cell and nerve regeneration, forming neo-corneas structurally and functionally similar to natural corneas.
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| 8. |
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| 9. |
- Jangamreddy, Jaganmohan, et al.
(författare)
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Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 69, s. 120-130
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Tidskriftsartikel (refereegranskat)abstract
- Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a preclinical mini-pig model. We also show that these peptide analogs exerted their pro-regeneration effects through stimulating extracellular vesicle production by host cells. Our results support future use of CLP-PEG implants for corneal regeneration, suggesting the feasibility of these or similar peptide analogs in clinical application in the eye and other tissues.
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| 10. |
- Kesik-Brodacka, Malgorzata, et al.
(författare)
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Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae
- 2017
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Ingår i: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica ( CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli. In this study, we explore oral vaccination, which may be the desired method of delivery and is potentially capable of preventing infections at the site of helminth entry. To provide antigen encapsulation and to protect the vaccine antigen from degradation in the intestinal tract, transgenic plant-based systems are used. Methodology Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%)was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly-rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responsesIn the present study, we aimed to evaluate the protective ability of mucosal vaccinations of 12-week- old rats with CPFhW produced in a transgenic-plant-based system. To avoid inducing tolerance and to maximise the immune response induced by oral immunisation, we used the hepatitis B virus (HBV) core protein ( HBcAg) as a carrier. Animals were immunised with two doses of the antigen and challenged with 25 or 30 metacercariae of F. hepatica. Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%) was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly- rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responses to CPFhW for 4 consecutive weeks after the challenge.
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| 11. |
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| 12. |
- Kozak Ljunggren, Monika, et al.
(författare)
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Effect of Surgical Technique on Corneal Implant Performance.
- 2014
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Ingår i: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology (ARVO). - 2164-2591. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Our aim was to determine the effect of a surgical technique on biomaterial implant performance, specifically graft retention.METHODS: Twelve mini pigs were implanted with cell-free, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked recombinant human collagen type III (RHCIII) hydrogels as substitutes for donor corneal allografts using overlying sutures with or without human amniotic membrane (HAM) versus interrupted sutures with HAM. The effects of the retention method were compared as well as the effects of collagen concentration (13.7% to 15% RHCIII).RESULTS: All implanted corneas showed initial haze that cleared with time, resulting in corneas with optical clarity matching those of untreated controls. Biochemical analysis showed that by 12 months post operation, the initial RHCIII implants had been completely remodeled, as type I collagen, was the major collagenous protein detected, whereas no RHCIII could be detected. Histological analysis showed all implanted corneas exhibited regeneration of epithelial and stromal layers as well as nerves, along with touch sensitivity and tear production. Most neovascularization was seen in corneas stabilized by interrupted sutures.CONCLUSIONS: This showed that the surgical technique used does have a significant effect on the overall performance of corneal implants, overlying sutures caused less vascularization than interrupted sutures.TRANSLATIONAL RELEVANCE: Understanding the significance of the suturing technique can aid the selection of the most appropriate procedure when implanting artificial corneal substitutes. The same degree of regeneration, despite a higher collagen content indicates that future material development can progress toward stronger, more resistant implants.
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| 13. |
- McTiernan, Christopher D., et al.
(författare)
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LiQD Cornea: Pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation
- 2020
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Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 6:25
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation with donor corneas is the mainstay for treating corneal blindness, but a severe worldwide shortage necessitates the development of other treatment options. Corneal perforation from infection or inflammation is sealed with cyanoacrylate glue. However, the resulting cytotoxicity requires transplantation. LiQD Cornea is an alternative to conventional corneal transplantation and sealants. It is a cell-free, liquid hydrogel matrix for corneal regeneration, comprising short collagen-like peptides conjugated with polyethylene glycol and mixed with fibrinogen to promote adhesion within tissue defects. Gelation occurs spontaneously at body temperature within 5 min. Light exposure is not required-particularly advantageous because patients with corneal inflammation are typically photophobic. The self-assembling, fully defined, synthetic collagen analog is much less costly than human recombinant collagen and reduces the risk of immune rejection associated with xenogeneic materials. In situ gelation potentially allows for clinical application in outpatient clinics instead of operating theaters, maximizing practicality, and minimizing health care costs.
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| 14. |
- Merrett, Kimberly, et al.
(författare)
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Collagen Type I : A Promising Scaffold Material for Tissue Engineering and Regenerative Medicine
- 2012
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Ingår i: Type I collagen. - : Nova Science Publishers, Inc.. - 9781622576265 ; , s. 1-43
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- It is now recognized that biological macromolecules such as components of the extracellular matrix (ECM) are important as instructive templates in Regenerative Medicine applications. They are now increasingly used in the development of a new generation of bio-mimetic materials that allow for restoration of function when the self-renewal capacity of a tissue or organ cannot overcome degeneration caused by disease, injury or age-related wear. For example, macromolecules derived from connective tissue have been isolated, chemically modified, and used in medical applications ranging from tissue repair and reconstruction to drug and cell delivery systems. Common ECM macromolecules of vertebrates include collagen, proteoglycans, elastin, and other cell-interactive proteins such as fibronectin and laminin. Of these, type I collagen is the most abundant ECM macromolecule and is the primary scaffolding material that maintains the 3-dimensional structure of tissues and organs within the body. It also provides the micro-environmental milieu for cellular attachment, migration, and proliferation.Animal-derived collagen is frequently used in tissue engineering applications due to its biocompatibility, but there are significant concerns about the immunogenicity of xenogeneic material as well as the possibility of pathogen transmission. Most recently, synthetic collagens and recombinant human collagens have been produced for medical application. Regardless of the source, however, macromolecules require processing and chemical treatment in order to improve their stability both in vitro and in vivo. This is most commonly achieved by cross-linking using a variety of agents. Cross-linking also allows for the development of “tailor-made” collagen-based biomaterials that possess specific properties for tissue engineering. Chemical cross-linkers such as glutaraldehyde and epoxy compounds are frequently used but their cytotoxicities have limited their clinical application. This has led to the use of zero-length cross-linkers such as carbodiimides and naturally derived agents such as genipin. Enzymatic cross-linking is becoming an attractive method to induce in situ biomaterial formation due to the mildness of the reaction. Naturally occurring enzymes such as transglutaminase are now commonly used. Photosensitizers used in combination with ultra-violet light irradiation can be used as exogenous cross-linkers. For example, riboflavin in combination with ultra-violet light is used clinically to augment the properties of collagen-based tissues such as the sclera and the cornea.Collagen type I is a good candidate for tissue engineering and in vivo delivery systems for cells, proteins, and drugs. Important to its versatile and functional nature are its chemotactic properties, which promote cellular proliferation and differentiation, richness in cross-linking sites, and biodegradability. Collagen based delivery matrices have been reported to improve the results of cell delivery by improving cell viability.
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| 15. |
- Puckert, C., et al.
(författare)
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Optimisation of conductive polymer biomaterials for cardiac progenitor cells
- 2016
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Ingår i: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 6:67, s. 62270-62277
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Tidskriftsartikel (refereegranskat)abstract
- The characterisation of biomaterials for cardiac tissue engineering applications is vital for the development of effective treatments for the repair of cardiac function. New smart materials developed from conductive polymers can provide dynamic benefits in supporting and stimulating stem cells via controlled surface properties, electrical and electromechanical stimulation. In this study we investigate the control of surface properties of conductive polymers through a systematic approach to variable synthesis parameters, and how the resulting surface properties influence the viability of cardiac progenitor cells. A thorough analysis investigating the effect of electropolymerisation parameters, such as current density and growth, and reagent variation on physical properties provides a fundamental understanding of how to optimise conductive polymer biomaterials for cardiac progenitor cells.
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| 16. |
- Simpson, Fiona, et al.
(författare)
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Electron-Beam Irradiated Recombinant Human Collagen-Phosphorylcholine Corneal Implants Retain Pro-Regeneration Capacity
- 2022
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB) irradiation is a terminal sterilization method that has been used for biologically-derived implants. Here, recombinant human collagen type III-phosphorylcholine (RHCIII-MPC) hydrogels were irradiated with EB doses of 17, 19, or 21 kGy and their subsequent biocompatibility and ability to promote regeneration in rabbit corneas was evaluated. Unirradiated hydrogels stored in 1% chloroform in phosphate-buffered saline (C-PBS) were the controls. There were no significant differences between irradiated and non-irradiated samples in optical or physical properties (tensile strength, modulus, elasticity), or the ability to support cell growth. However, irradiated implants were more sensitive to high levels of collagenase than unirradiated controls and the C-PBS implants had increased cell growth compared to EB and controls at 72 h. Corneal implants e-beamed at 17 kGy or e-beamed and subsequently frozen (EB-F) to increase shelf-life showed no adverse biological effects of the irradiation. EB, EB-F, and C-PBS implanted corneas all rapidly re-epithelialized but showed mild neovascularization that resolved over 6 months. The regenerated neo-corneas were transparent at 6 months post-operation. In vivo confocal microscopy confirmed normal morphology for the epithelium, stroma, sub-basal nerves and unoperated endothelium. Histology showed that all the regenerated corneas were morphologically similar to the normal. Immunohistochemistry indicated the presence of a differentiated corneal epithelium and functional tear film. In conclusion, the e-beamed corneal implants performed as well as non-irradiated control implants, resulting in fully regenerated neo-corneas with new nerves and without blood vessels or inflammation that may impede vision or corneal function. Therefore, a complete validation study to establish EB irradiation as an effective means for corneal implant sterilization prior to clinical application is necessary as a next step.
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| 17. |
- Wesolowska, Agnieszka, et al.
(författare)
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A Preliminary Study of a Lettuce-Based Edible Vaccine Expressing the Cysteine Proteinase of Fasciola hepatica for Fasciolosis Control in Livestock
- 2018
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Oral vaccination with edible vaccines is one of the most promising approaches in modern vaccinology. Edible vaccines are an alternative to conventional vaccines, which are typically delivered by injection. Here, freeze-dried transgenic lettuce expressing the cysteine proteinase of the trematode Fasciola hepatica (CPFhVV) was used to orally vaccinate cattle and sheep against fasciolosis, which is the most important trematode disease due to the parasites global distribution, wide spectrum of host species and significant economic losses of farmers. In the study, goals such as reducing the intensity of infection, liver damage and F. hepatica fecundity were achieved. Moreover, we demonstrated that the host sex influenced the outcome of infection following vaccination, with female calves and male lambs showing better protection than their counterparts. Since differences occurred following vaccination and infection, different immunization strategies should be considered for different sexes and host species when developing new control methods. The results of the present study highlight the potential of oral vaccination with plant-made and plant-delivered vaccines for F. hepatica infection control.
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| 18. |
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