New thin-film adhesive for sealing full-thickness corneal incisions in rabbits.

PURPOSE: To compare the repair of penetrating corneal incisions in an in vivo rabbit model using a laser-activated thin-film adhesive, sutures, or self-seal. SETTING: The University of Sydney, Camperdown, Australia. DESIGN: Animal studies. METHODS: Under an operating microscope, 2.0 mm penetrating incisions were created in 162 right eyes. Incisions in one group were repaired with the adhesive, the second group received a single 10-0 nylon suture, and the third group was left to self-seal. Rabbits were killed humanely at predetermined timepoints over 2 weeks, and wound healing was assessed using burst pressure and immunohistological studies. A modified McDonald-Shadduck scoring was used to assess eyes. RESULTS: The mean burst pressure of the adhesive group was significantly higher than the sutured or self-sealed groups at all timepoints within the first 72 hours. At 0 hour, the burst pressure was 98.0 (±17.0) mm Hg, 30.6 (±2.1) mm Hg, and 3.8 (±0.6) mm Hg (P < .00001) for adhesive-treated (n = 5), sutured (n = 5), and self-sealed wounds (n = 5), respectively. These increased to 229.0 (±53.7) mm Hg, 12.4 (±2.9) mm Hg, and 27.3 (±4.0) mm Hg (P = .0011) at 72 hours. The modified McDonald-Shadduck score was significantly higher for eyes repaired using the adhesive than those sutured or left to self-seal for the first 72 hours. On histology and immunofluorescence, adhesive treatment demonstrated better wound approximation and higher myofibroblastic activation than the other groups. CONCLUSIONS: The adhesive was efficacious in sealing penetrating corneal incisions and tolerated higher burst pressures than sutures or self-seal. The adhesive was biocompatible in rabbits, and incisions demonstrated a rapid gain in wound strength that sustained over the study period.

Laser-Activated Corneal Adhesive: Retinal Safety in Rabbit Model.

Purpose: The purpose of this study was to investigate whether laser irradiation, used to activate an adhesive for sealing penetrating corneal incisions, causes any ophthalmoscopically or histologically visible retinal changes. Methods: Baseline fundus assessment was conducted prior to laser irradiation of eyes of pigmented Dutch Belted rabbits. Treatment group was 18 eyes with the corneal adhesive activated in situ by a near infrared laser (125 mW for 45 seconds). The positive control group was 18 eyes, each irradiated for 60 seconds at 375, 500, 625, and 750 mW at different retinal locations. Unexposed regions of the retina were used as negative internal control. Ophthalmoscopic assessment was conducted immediately after laser exposure and prior to euthanasia. Retinas were histologically assessed at 0, 3, 72, and 168 hours after treatment. Results: No ophthalmoscopically or histologically visible retinal changes were observed in the treatment group immediately, nor up to 168 hours after laser irradiation. In the positive control group, the incidences of ophthalmoscopically visible retinal lesions increased with irradiation power: 5.6% at 375 mW, 16.7% at 500 mW, 44.4% at 625 mW, and 50% at 750 mW. Histologically, retinal damage was observed as coagulative necrosis to all layers of the neural retina, including the retinal pigment epithelium. Conclusions: The laser irradiation process used in the corneal adhesive technology did not cause any ophthalmoscopically or histologically visible retinal changes in the in vivo pigmented rabbit model. Prolonged exposure with this laser and at higher power can cause coagulative necrosis to the retina. Translational Relevance: The corneal adhesive can be applied in humans without causing laser retinal damage.

Corneal Sealants in Clinical Use: A Systematic Review.

AIM: To review the use of clinical corneal sealants for the closure of full thickness corneal wounds. METHODS: A systematic review was conducted across CENTRAL, Medline, PubMed, Embase, Scopus, mRCT and ICTRP for the keywords of 'cornea', 'full-thickness wound', 'sealant' and their synonyms. Only evidence level 2 of higher as graded by Oxford Centre of Evidence-based Medicine were included for this review. RESULTS: Seven studies were included; three randomized controlled trials investigated ReSure® sealant, 2 OcuSeal®, 1 human fibrin glue vs cyanoacrylate and 1 human fibrin glue as an adjunct to sutures vs sutures alone in penetrating keratoplasty. ReSure® was superior to suture for sealing leaking corneal incisions after cataract surgery despite provocation. ReSure® sealant has not been tested on complex full thickness corneal wounds, perforated ulcers or penetrating keratoplasty. OcuSeal® was also able to seal full thickness cornea wound post-cataract surgery to prevent ingress of Trypan blue dye. Human fibrin glue and cyanoacrylate were similarly effective in treating corneal perforations <3 mm of mixed etiologies. CONCLUSION: There are limited high-level evidence for corneal sealants. The currently available sealants with human data are ReSure®, OcuSeal®, human fibrin glue and cyanoacrylates. While ReSure® and OcuSeal® are effective post-cataract surgery, there are no data for perforations from other etiologies. Post-approval data from ReSure® registry report good tolerability and no apparent safety concerns.

Chitosan as a Biomaterial: Influence of Degree of Deacetylation on Its Physiochemical, Material and Biological Properties.

Chitosan is a biomaterial with a range of current and potential biomedical applications. Manipulation of chitosan degree of deacetylation (DDA) to achieve specific properties appears feasible, but studies investigating its influence on properties are often contradictory. With a view to the potential of chitosan in the regeneration of nerve tissue, the influence of DDA on the growth and health of olfactory ensheathing cells (OECs) was investigated. There was a linear increase in OEC proliferation as the DDA increased from 72 to 85%. This correlated with linear increases in average surface roughness (0.62 to 0.78 µm) and crystallinity (4.3 to 10.1%) of the chitosan films. Mitochondrial activity and membrane integrity of OECs was significantly different for OECs cultivated on chitosan with DDAs below 75%, while those on films with DDAs up to 85% were similar to cells in asynchronous growth. Apoptotic indices and cell cycle analysis also suggested that chitosan films with DDAs below 75% were cytocompatible but induced cellular stress, while OECs grown on films fabricated from chitosan with DDAs above 75% showed no significant differences compared to those in asynchronous growth. Tensile strength and elongation to break varied with DDA from 32.3 to 45.3 MPa and 3.6 to 7.1% respectively. DDA had no significant influence on abiotic and biotic degradation profiles of the chitosan films which showed approximately 8 and 20% weight loss respectively. Finally, perceived patterns in property changes are subject to change based on potential variations in DDA analysis. NMR examination of the chitosan samples here revealed significant differences depending upon which peaks were selected for integration; 6 to 13% in DDA values within individual samples. Furthermore, differences between DDA values determined here and those reported by the commercial suppliers were significant and this may also be a source of concern when selecting commercial chitosans for biomaterial research.

Towards scarless wound healing: a comparison of protein expression between human, adult and foetal fibroblasts.

Proteins from human adult and foetal fibroblast cell lines were compared, focusing on those involved in wound healing. Proteins were separated through two-dimensional gel electrophoresis (2DE). Differences in protein spot intensity between the lineages were quantified through 3D gel scanning densitometry. Selected protein spots were excised, subjected to tryptic digests, prior to separation using HPLC with a linear ion trap mass spectrometer, and identified. Protein maps representing the proteomes from adult and foetal fibroblasts showed similar distributions but revealed differences in expression levels. Heat shock cognate 71 kDA protein, Tubulin alpha-1A chain, actin cytoplasmic-1, and neuron cytoplasmic protein were all expressed in significantly higher concentrations by foetal fibroblasts, nearly double those observed for their adult counterparts. Fructose bisphosphate aldolase A, Cofilin-1, Peroxiredoxin-1, Lactotransferrin Galectin-1, Profilin-1, and Calreticulin were expressed at comparatively higher concentrations by the adult fibroblasts. Significant differences in the expression levels of some proteins in human adult and foetal fibroblasts correlated with known differences in wound healing behaviour. This data may assist in the development of technologies to promote scarless wound healing and better functional tissue repair and regeneration.

A tuneable switch for controlling environmental degradation of bioplastics: addition of isothiazolinone to polyhydroxyalkanoates.

Controlling the environmental degradation of polyhydroxybutyrate (PHB) and polyhydroxyvalerate (P(HB-co-HV)) bioplastics would expand the range of their potential applications. Combining PHB and P(HB-co-HV) films with the anti-fouling agent 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOI, <10% w/w) restricted microbial colonisation in soil, but did not significantly affect melting temperature or the tensile strength of films. DCOI films showed reduced biofouling and postponed the onset of weight loss by up to 100 days, a 10-fold increase compared to unmodified films where the microbial coverage was significant. In addition, the rate of PHA-DCOI weight loss, post-onset, reduced by about 150%; in contrast a recorded weight loss of only 0.05% per day for P(HB-co-HV) with a 10% DCOI loading was observed. This is in stark contrast to the unmodified PHB film, where a recorded weight loss of only 0.75% per day was made. The 'switch' that initiates film weight loss, and its subsequent reduced rate, depended on the DCOI loading to control biofouling. The control of biofouling and environmental degradation for these DCOI modified bioplastics increases their potential use in biodegradable applications.

Diversity of microbial species implicated in keratitis: a review.

BACKGROUND: Microbial keratitis is an infectious disease of the cornea characterised by inflammation and is considered an ophthalmic emergency requiring immediate attention. While a variety of pathogenic microbes associated with microbial keratitis have been identified, a comprehensive review identifying the diversity of species has not been completed. METHODS: A search of peer-reviewed publications including case reports and research articles reporting microorganims implicated in keratitis was conducted. Search engines including PubMed, Scopus and Web of Science with years ranging from 1950-2012 were used. RESULTS: 232 different species from 142 genera, representing 80 families were found to be implicated in microbial keratitis. Fungi exhibited the largest diversity with 144 species from 92 genera. In comparison, 77 species of bacteria from 42 genera, 12 species of protozoa from 4 genera and 4 types of virus were identified as the infectious agents. A comparison of their aetiologies shows reports of similarities between genera. CONCLUSIONS: The diversity of microbial species implicated in keratitis has not previously been reported and is considerably greater than suggested by incidence studies. Effective treatment is heavily reliant upon correct identification of the responsible microorganisms. Species identification, the risk factors associated with, and pathogenesis of microbial keratitis will allow the development of improved therapies. This review provides a resource for clinicians and researchers to assist in identification and readily source treatment information.