| 1. |
- Buznyk, Oleksiy, et al.
(författare)
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Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients
- 2015
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Ingår i: Clinical and Translational Science. - : WILEY-BLACKWELL. - 1752-8054 .- 1752-8062. ; 8:5, s. 558-562
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Tidskriftsartikel (refereegranskat)abstract
- Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial.
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| 2. |
- Ihnatko, Robert, et al.
(författare)
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Congenital Aniridia and the Ocular Surface
- 2016
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Ingår i: OCULAR SURFACE. - : ELSEVIER SCIENCE BV. - 1542-0124. ; 14:2, s. 196-206
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Tidskriftsartikel (refereegranskat)abstract
- Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye structures, including the cornea, iris, anterior chamber angle, lens, and fovea. The ocular surface, in particular, can be severely affected by a progressive pathology termed aniridia-associated keratopathy (AAK), markedly contributing to impaired vision. The purpose of this review is to provide an update of the current knowledge of the genetic, clinical, micro-morphological, and molecular aspects of AAK. We draw upon material presented in the literature and from our own observations in large aniridia cohorts. We summarize signs and symptoms of AAK, describe current options for management, and discuss the latest research findings that may lead to better diagnosis and new treatment or prevention strategies for this debilitating ocular surface condition.
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| 3. |
- Islam, Mohammad Mirazul, 1984-, et al.
(författare)
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Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation
- 2018
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Ingår i: NPJ Regenerative medicine. - : Springer Science and Business Media LLC. - 2057-3995. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1-2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to near normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal tissue and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients.
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| 4. |
- 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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| 5. |
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| 6. |
- 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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| 7. |
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| 8. |
- Koulikovska, Marina, et al.
(författare)
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Enhanced Regeneration of Corneal Tissue Via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique
- 2015
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Ingår i: Tissue Engineering. Part A. - : Mary Ann Liebert. - 1937-3341 .- 1937-335X. ; 21:5-6, s. 1116-1130
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Tidskriftsartikel (refereegranskat)abstract
- Severe shortage of donor corneas for transplantation, particularly in developing countries, has prompted the advancement of bioengineered tissue alternatives. Bioengineered corneas that can withstand transplantation while maintaining transparency and compatibility with host cells, and that are additionally amenable to standardized low-cost mass production are sought. In this study, a bioengineered porcine construct (BPC) was developed to function as a biodegradable scaffold to promote corneal stromal regeneration by host cells. Using high-purity medical-grade type I collagen, high 18% collagen content and optimized EDC-NHS cross-linker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and four-fold increase in strength and stiffness compared with previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated that BPC supported confluent human epithelial and stromal-derived mesenchymal stem cell populations. With a novel femtosecond laser-assisted corneal surgical model in rabbits, cell-free BPCs were implanted in vivo in the corneal stroma of 10 rabbits over an 8-week period. In vivo, transparency of implanted corneas was maintained throughout the postoperative period, while healing occurred rapidly without inflammation and without the use of postoperative steroids. BPC implants had a 100% retention rate at 8 weeks, when host stromal cells began to migrate into implants. Direct histochemical evidence of stromal tissue regeneration was observed by means of migrated host cells producing new collagen from within the implants. This study indicates that a cost-effective BPC extracellular matrix equivalent can incorporate cells passively to initiate regenerative healing of the corneal stroma, and is compatible with human stem or organ-specific cells for future therapeutic applications as a stromal replacement for treating blinding disorders of the cornea.
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| 9. |
- Koulikovska, Marina, 1970-, et al.
(författare)
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Platelet Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with Incisional Wound
- 2015
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 40:11, s. 1102-1110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to determine whether platelet rich plasma (PRP) has an effect on corneal stromal cells in a rat model of wound healing following corneal incision. Materials and Methods: The effect of PRP on corneal wound healing in vivo was investigated in a corneal incision wound model in rats. 40 rats were wounded by deep corneal incision, and treated with either topically administered PRP (20 rats) or sodium chloride (20 rats). At 4 hours and 1, 3, and 5 days after incision, α-smooth muscle actin (α SMA), SMAD2 and SMAD3 expression and apoptosis in stromal cells were evaluated by immunohistochemistry, and IL-1β mRNA expression was evaluated by real time PCR.Results: PRP treated corneas exhibited reduced stromal cell apoptosis at day 3 and day 5 (p = 0.038, and <0.001, respectively) relative to controls. Interleukin-1β mRNA expression, however, was unchanged in PRP treated corneas relative to controls. Topical PRP treatment resulted in a higher proportion of αSMA-positive myofibroblasts recruited to the wound site relative to control corneas. PRP did not affect activation of SMAD2 but activation of SMAD3 was significantly reduced at day 1 (p=0.001) and dramatically increased at day 5 (p=0.032).Conclusions: PRP treatment resulted in suppressed stromal cell apoptosis followed by SMAD3 activation and a greater proportion of myofibroblasts present at the wound site. Suppression of stromal cell apoptosis after corneal wounding by use of a growth factor rich formulation may lead to myofibroblast accumulation by modulation of the TGF-β pathway.
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| 10. |
- Koulikovska, Marina, 1970-, et al.
(författare)
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Topical Biglycan Modulates Stromal Cell Apoptosis in Corneal Incisional Wound Model
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The purpose of this study was to determine whether exogenous topicallyapplied biglycan has an effect on corneal stromal cells during wound healing.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to determine the effect of biglycan on cell survival in vitro following IL-1β induced cell death. In a corneal incisional wound model, 40 rats were wounded and treated with either topically administered biglycan or sodium chloride (sham control). At 4 hours and 1, 2, and 5 days after incision, α-smooth muscle actin (SMA) expression and apoptosis in stromal cells were evaluated by immunohistochemistry.Results: In vitro, biglycan significantly enhanced IL-1β-induced apoptosis of myofibroblasts (p = 0.038), but not corneal fibroblasts. Biglycan treated corneas exhibited reduced stromal cell apoptosis at 4 hours, day 1 and day 5 (p = 0.012, 0.040, and 0.048, respectively) and increased apoptosis at day 3 (p = 0.003) relative to controls. In wounded corneas, biglycan appeared to promote early accumulation of myofibroblasts and initiate an earlier subsequent apoptosis of these cells, relative to controls.Conclusion: Biglycan appears to accelerate corneal wound healing in vivo by modulating myofibroblast apoptosis, resulting in removal of myofibroblasts that may otherwise compromise corneal transparency.
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