| 1. |
- Griffith, May, et al.
(författare)
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Artificial human corneas - Scaffolds for transplantation and host regeneration
- 2002
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Ingår i: Cornea. - : Lippincott, Williams andamp; Wilkins. - 0277-3740 .- 1536-4798. ; 21:7, s. S54-S61
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To review the development of artificial corneas (prostheses and tissue equivalents) for transplantation, and to provide recent updates on our tissue-engineered replacement corneas. Methods. Modified natural polymers and synthetic polymers were screened for their potential to replace damaged portions of the human cornea or the entire corneal thickness. These polymers, combined with cells derived from each of the three main corneal layers or stem cells, were used to develop artificial corneas. Functional testing was performed in vitro. Trials of biocompatibility and immune and inflammatory reactions were performed by implanting the most promising polymers into rabbit corneas. Results. Collagen-based biopolymers, combined with synthetic crosslinkers or copolymers, formed effective scaffolds for developing prototype artificial corneas that could be used as tissue replacements in the future. We have previously developed an artificial cornea that mimicked key morphologic and functional properties of the human cornea. The addition of synthetic polymers increased its toughness as it retained transparency and low light scattering, making the matrix scaffold more suitable for transplantation. These new composites were implanted into rabbits without causing any acute inflammation or immune response. We have also fabricated full-thickness composites that can be fully sutured. However, the long-term effects of these artificial corneas need to be evaluated. Conclusions. Novel tissue-engineered corneas that comprise composites of natural and synthetic biopolymers together with corneal cell lines or stem cells will, in the future, replace portions of the cornea that are damaged. Our results provide a basis for the development of both implantable temporary and permanent corneal replacements.
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| 2. |
- Liu, Wenguang, et al.
(författare)
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Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes
- 2009
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Ingår i: BIOMATERIALS. - : Elsevier BV. - 0142-9612. ; 30:8, s. 1551-1559
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Tidskriftsartikel (refereegranskat)abstract
- A biointeractive collagen-phospholipid corneal Substitute was fabricated from interpenetrating polymeric networks comprising 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide and N-hydroxysuccinimide crosslinked porcine atelocollagen, and poly(ethylene glycol) diacrylate crosslinked 2-methacryloyloxyethyl phosphorylcholine (MPC). The resulting hydrogels showed ail overall increase in mechanical strength beyond that of either original component and enhanced stability against enzymatic digestion (by collagenase) or UV degradation. More strikingly, these hydrogels retained the full biointeractive, cell friendly properties of collagen in promoting corneal cell and nerve in-growth and, regeneration (despite MPCs known anti-adhesive properties). Measurements of refractive indices, white light transmission and backscatter showed the optical properties of collagen-MPC are comparable or superior to those of the human cornea.In addition, the glucose and albumin permeability were comparable to those Of human corneas. Twelve-month post-implantation results of collagen-MPC hydrogels into mini-pigs showed regeneration of corneal tissue (epithelium, stroma) as well as the tear film and sensory nerves. We also show that porcine collagen can be Substituted with recombinant human collagen, resulting in a fully-synthetic implant that is free from the potential risks of disease transmission (e.g. prions) present in animal Source materials.
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| 3. |
- Liu, Wenguang, et al.
(författare)
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Recombinant human collagen for tissue engineered corneal substitutes
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:9, s. 1147-1158
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Tidskriftsartikel (refereegranskat)abstract
- We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens. © 2007 Elsevier Ltd. All rights reserved.
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| 4. |
- McLaughlin, Christopher, et al.
(författare)
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Regeneration of Corneal Cells and Nerves in an Implanted Collagen Corneal Substitute
- 2008
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Ingår i: Cornea. - 0277-3740 .- 1536-4798. ; 27:5, s. 580-589
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Our objective was to evaluate promotion of tissue regeneration by extracellular matrix (ECM) mimics, by using corneal implantation as a model system.METHODS: Carbodiimide cross-linked porcine type I collagen was molded into appropriate corneal dimensions to serve as substitutes for natural corneal ECM. These were implanted into corneas of mini-pigs after removal of the host tissue, and tracked over 12 months, by clinical examination, slit-lamp biomicroscopy, in vivo confocal microscopy, topography, and esthesiometry. Histopathology and tensile strength testing were performed at the end of 12 months. Other samples were biotin labeled and implanted into mice to evaluate matrix remodeling.RESULTS: The implants promoted regeneration of corneal cells, nerves, and the tear film while retaining optical clarity. Mechanical testing data were consistent with stable, seamless host-graft integration in regenerated corneas, which were as robust as the untreated fellow corneas. Biotin conjugation is an effective method for tracking the implant within the host tissue.CONCLUSIONS: We show that a simple ECM mimetic can promote regeneration of corneal cells and nerves. Gradual turnover of matrix material as part of the natural remodeling process allowed for stable integration with host tissue and restoration of mechanical properties of the organ. The simplicity in fabrication and shown functionality shows potential for ECM
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| 5. |
- Merrett, Kimberley, et al.
(författare)
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Tissue-engineered recombinant human collagen-based corneal substitutes for implantation : Performance of type I versus type III collagen
- 2008
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 49:9, s. 3887-3894
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.
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| 6. |
- Shimmura, Shigeto, et al.
(författare)
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Collagen-poly(N-isopropylacrylamide)-based membranes for corneal stroma scaffolds
- 2003
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Ingår i: Cornea. - : Lippincott, Williams andamp; Wilkins. - 0277-3740 .- 1536-4798. ; 22:7, s. S81-S88
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the feasibility of using the biocompatibility of collagen-based blended biomaterials as cell-delivery systems in ocular surface reconstruction in vivo. Methods: Collagen-based composites that were blended with synthetic acrylamide-based polymers [poly(N-isopropylacrylamide), pNIPAAm] were transplanted into corneal pockets of white rabbits, with a 3-mm epithelial window. Epithelial cells were allowed to migrate onto the polymer. Transplanted eyes were examined daily for up to 30 days, after which animals; were killed for histologic examination. lm- munohistochemistry was performed for vimentin, a-smooth muscle actin (alpha-SMA), CD4, and CD8. Gold-chloride staining was performed to observe neuronal regrowth. Human amniotic membranes (AMs) and sham-operated corneas served as controls. All animals received topical antibiotics (levofloxacin) without the use of steroids or other immunosuppressive agents. Results: The pNIPAAm polymer allowed smooth epitheliatization of the cornea, which was similar to the epithelialization observed in sham controls and AM-transplanted eyes. Histology revealed that epithelium overlying the polymer was bundled into several layers, without the orientation observed with AM and sham controls. The polymer gradually thinned and was gradually replaced by host tissue. Vimentin- and alpha-SMA-positive cells were found in stromal pockets up to 1 month following polymer transplantation. These cells were responsible for slight subepithelial haze near the wound edge. CD4- and CD8-positive lymphocytes were also observed in the vicinity of the polymer. Gold-chloride staining showed nerve regrowth in the wound edge after 1 month and subepithelial branches after 3 months. Conclusion: Collagen-pNIPAAm blended polymers may he effective as biomaterials to be used in the early stages of lamellar stromal replacement.
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| 7. |
- Suuronen, Erik J., et al.
(författare)
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Innervated human corneal equivalents as in vitro models for nerve-target cell interactions
- 2003
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Ingår i: The FASEB Journal. - : Federation of American Society of Experimental Biology (FASEB). - 0892-6638 .- 1530-6860. ; 17, s. 170-
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Tidskriftsartikel (refereegranskat)abstract
- A sensory nerve supply is crucial for optimal tissue function. However, the mechanisms for successful innervation and the signaling pathways between nerves and their target tissue are not fully understood. Engineered tissue substitutes can provide controllable environments in which to study tissue innervation. We have therefore engineered human corneal substitutes that promote nerve in-growth in a pattern similar to in vivo re-innervation. We demonstrate that these nerves (a) are morphologically equivalent to natural corneal nerves; (b) make appropriate contact with target cells; (c) can generate action potentials; (d) respond to chemical and physical stimuli; and (e) play an important role in the overall functioning of the bioengineered tissue. This model can be used for studying the more general topics of nerve ingrowth or regeneration and the interaction between nerves and their target cells and, more specifically, the role of nerves in corneal function. This model could also be used as an in vitro alternative to animals for safety and efficacy testing of chemicals and drugs.
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