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Pterygium excision with conjunctival autograft attached with fibrin glue. (A) Before operation; (B) 1 day after operation; (C) 1 week after operation; (D) 3 months after operation.
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Tissue adhesive sealants have been used as substitutes for sutures in ophthalmic surgery in recent years since the latter may cause irritation, inflammation and infection. Tissue adhesives were developed as suture adjuncts and alternatives for sealing wounded tissues. They are gaining popularity for their ease of use and postoperative comfort. Two...
Citations
... The development of safe and efficient tissue adhesives to replace suturing is urgently needed in modern ophthalmic surgery [1][2][3]. Suturing, particularly in keratoplasty, is not only time-consuming but also traumatic, often leading to complications such as corneal infections and vascularization. These issues can result in surgical failure and reduce the longterm survival rate of the cornea [4]. ...
A traumatic tissue adhesive technology is highly sought after in ophthalmic surgery; however, many polymeric adhesives face significant limitations in clinical ophthalmology, particularly in corneal transplantation. A major challenge is achieving rapid adhesion without introducing polymer barriers or chemical toxicity from cross-linking. To address this, we developed a novel cornea-specific nanoadhesive constructed through protein-DNA co-assembly and applied it to corneal transplantation. In this system, a rigid tetrahedral DNA framework was employed to guide the spatial distribution of polycationic recombinant proteins (K72) and serve as the core of the nanoadhesive, facilitating energy conversion during tissue connection. The adhesive demonstrated a strength of 2.3 kPa between corneal lenticules. After modification with RGD peptides, the adhesive system significantly enhanced corneal epithelialization, reduced inflammation and neovascularization, and ultimately promoted corneal repair. This study represents the first application of a nanoadhesive in ophthalmic surgery, providing a novel solution for developing ophthalmic-specific adhesives for clinical use.
... Uses of cyanoacrylate glue 1. Corneal perforation/melt: [7,9,10] It can be used in cases of small corneal perforation (<3 mm in size), impending corneal perforation due to microbial keratitis, neurotrophic keratitis, chemical keratitis, trauma, or noninfectious corneal melts 2. Conjunctiva and ocular surface: It has been used for sealing the leaking blebs and sealing the buttonholing of conjunctiva during glaucoma surgeries [5] 3. Cyanoacrylate adhesives have been used for healing limbal ulceration as an adjunct to tenonplasty, [11] securing hard/rigid contact lenses in severe ocular surface disease (e.g, chemical burns), as well as in the treatment of amblyopia (as a method of occlusion therapy), removal of nonmagnetic deep corneal foreign bodies. [7] Methods of application After obtaining the informed consent, the procedure can be carried out in the outpatient department in sitting position or in minor operation theater (OT)/OT under sterile conditions in the supine position. ...
... 1. Conjunctival surgery: Fibrin glue has been shown to be as effective as sutures for conjunctival wound closure and transplantation with the advantages of reduced operative time, postoperative discomfort, and inflammation [5] 2. Pterygium surgery: Fibrin glue has often been used for attaching conjunctival autografts in pterygium surgery. Its use is associated with lower recurrence rates than those associated with suturing [5] [ Figure 6] 3. Corneal perforation/melt: Fibrin glue is mainly used for plugging ulcer-induced perforations. ...
... 1. Conjunctival surgery: Fibrin glue has been shown to be as effective as sutures for conjunctival wound closure and transplantation with the advantages of reduced operative time, postoperative discomfort, and inflammation [5] 2. Pterygium surgery: Fibrin glue has often been used for attaching conjunctival autografts in pterygium surgery. Its use is associated with lower recurrence rates than those associated with suturing [5] [ Figure 6] 3. Corneal perforation/melt: Fibrin glue is mainly used for plugging ulcer-induced perforations. Fibrin glue-assisted corneal patch, AM grafting (AMG), or tenon's patch graft [ Figure 7] have been shown to be effective for treating corneal defects ≥3 mm in size [5,28,29] 4. AM transplantation: In simple limbal epithelial transplant surgery, AMG is secured over the recipient cornea and limbus and pieces of limbal biopsies to the AMG with the help of fibrin glue [ Figure 8] [30] 5. Keratoplasty: Fibrin glue use has been reported in lamellar keratoplasty, deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty. ...
... Uses of cyanoacrylate glue 1. Corneal perforation/melt: [7,9,10] It can be used in cases of small corneal perforation (<3 mm in size), impending corneal perforation due to microbial keratitis, neurotrophic keratitis, chemical keratitis, trauma, or noninfectious corneal melts 2. Conjunctiva and ocular surface: It has been used for sealing the leaking blebs and sealing the buttonholing of conjunctiva during glaucoma surgeries [5] 3. Cyanoacrylate adhesives have been used for healing limbal ulceration as an adjunct to tenonplasty, [11] securing hard/rigid contact lenses in severe ocular surface disease (e.g, chemical burns), as well as in the treatment of amblyopia (as a method of occlusion therapy), removal of nonmagnetic deep corneal foreign bodies. [7] Methods of application After obtaining the informed consent, the procedure can be carried out in the outpatient department in sitting position or in minor operation theater (OT)/OT under sterile conditions in the supine position. ...
... 1. Conjunctival surgery: Fibrin glue has been shown to be as effective as sutures for conjunctival wound closure and transplantation with the advantages of reduced operative time, postoperative discomfort, and inflammation [5] 2. Pterygium surgery: Fibrin glue has often been used for attaching conjunctival autografts in pterygium surgery. Its use is associated with lower recurrence rates than those associated with suturing [5] [ Figure 6] 3. Corneal perforation/melt: Fibrin glue is mainly used for plugging ulcer-induced perforations. ...
... 1. Conjunctival surgery: Fibrin glue has been shown to be as effective as sutures for conjunctival wound closure and transplantation with the advantages of reduced operative time, postoperative discomfort, and inflammation [5] 2. Pterygium surgery: Fibrin glue has often been used for attaching conjunctival autografts in pterygium surgery. Its use is associated with lower recurrence rates than those associated with suturing [5] [ Figure 6] 3. Corneal perforation/melt: Fibrin glue is mainly used for plugging ulcer-induced perforations. Fibrin glue-assisted corneal patch, AM grafting (AMG), or tenon's patch graft [ Figure 7] have been shown to be effective for treating corneal defects ≥3 mm in size [5,28,29] 4. AM transplantation: In simple limbal epithelial transplant surgery, AMG is secured over the recipient cornea and limbus and pieces of limbal biopsies to the AMG with the help of fibrin glue [ Figure 8] [30] 5. Keratoplasty: Fibrin glue use has been reported in lamellar keratoplasty, deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty. ...
... Both ReSure® and OcuSeal®, the commercially available sealants have only been clinically used to seal the leaky corneal incisions after cataract surgeries. The application of these sealants to repair traumatic corneal wounds has not been reported [12][13][14][15][16]. Cyanoacrylates (a synthetic material) and fibrin glue (a natural material) are commonly used clinically but are mainly intended to manage perforations and prevent aqueous humor leakage and not for corneal regeneration [17] . ...
... The application of these sealants to repair traumatic corneal wounds has not been reported [12][13][14][15][16]. Cyanoacrylates (a synthetic material) and fibrin glue (a natural material) are commonly used clinically but are mainly intended to manage perforations and prevent aqueous humor leakage and not for corneal regeneration [17] . Other synthetic and naturally derived hydrogels are not yet in clinical use [13] . Synthetic polymers allow customization, however, they exhibit inferior tissue regeneration and poor integration with the host stroma and also require chemical crosslinkers [18] . ...
... However, the addition of chemical crosslinkers or synthetic materials for stability and or poor adhesion at the applied site are the reported problems [18] . Moreover, many of them failed to integrate with native cornea stroma and replicate optical properties such as transparency and curvature [13] . Apart from all the above limitations, a native microenvironment includes ECM components and soluble bioactive factors, an ideal condition for the cells to migrate, proliferate and differentiate, support cell-cell and cell-matrix interactions, and tissue remodeling are absent in the above-discussed materials to replicate the tissue functions [28] . ...
Corneal scarring and opacification are a significant cause of blindness affecting millions worldwide. The current standard of care for corneal blindness is corneal transplantation, which suffers from several drawbacks. One alternative approach that has shown promise is the use of xenogeneic corneal extracellular matrix (ECM), but its clinical applicability is challenging due to safety concerns. This study reports the innovative use of human cornea-derived ECM to prevent post-traumatic corneal scarring. About 30 - 40% of corneas donated to the eye banks do not meet the standards defined for clinical use and are generally discarded, although they are completely screened for their safety. In this study, human decellularized cornea matrix hydrogel was prepared from the non-transplantation grade human cadaveric corneas obtained from an accredited eye-bank. The prepared hydrogel was screened for its efficacy against corneal opacification following an injury in an animal model. Our in vivo study revealed that, the control collagen-treated group developed corneal opacification, while the prophylactic application of human cornea-derived hydrogel effectively prevented corneal scarring and opacification. The human hydrogel-treated corneas were indistinguishable from healthy corneas and comparable to those treated with the xenogeneic bovine corneal hydrogel. We also demonstrated that the application of the hydrogel retained the biological milieu including cell behavior, protein components, optical properties, curvature, and nerve regeneration by remodeling the corneal wound after injury. The hydrogel application is also sutureless, resulting in faster corneal healing. We envision that this human cornea-derived ECM-based hydrogel has potential clinical application in preventing scarring from corneal wounding. STATEMENT OF SIGNIFICANCE: There are significant challenges around corneal regeneration after injury due to extensive scarring. Although there is substantial research on corneal regeneration, much of it uses synthetic materials with chemical cross-linking methods or xenogeneic tissue-based material devices which have to undergo exhaustive safety analysis before clinical trials. Herein, we demonstrate the potential application of a human corneal extracellular matrix hydrogel without any additional materials for scarless corneal tissue regeneration, and a method to reduce the wasting of donated allogenic corneal tissue from eye banks. We found no difference in efficacy between the usage of human tissues compared to xenogeneic sources. This may help ease clinical translation and can be used topically without sutures as an outpatient procedure.
... However, one of the major shortcomings of this adhesive is the fast gelation time (≤30s), which leaves approximately 14−17 s after mixing the components, leading to very little freedom for handling during surgery. Moreover, ReSure adhesive cannot be used to seal actively leaking perforations, cannot fill in stromal defects where parts of corneal stromal tissue are missing, and is stable only up to three days, 14 or falls off too quickly if not covered by a tissue. 14 Similar cross-linking chemistry was also used to form a hydrogel between PEG and collagen, which were used for corneal defect filling. ...
Injectable hydrogels show great promise in developing novel regenerative medicine solutions and present advantages for minimally invasive applications. Hydrogels based on extracellular matrix components, such as collagen, have the benefits of cell adhesiveness, biocompatibility, and degradability by enzymes. However, to date, reported collagen hydrogels possess severe shortcomings, such as nonbiocompatible cross-linking chemistry, significant swelling, limited range of mechanical properties, or gelation kinetics unsuitable for in vivo injection. To solve these issues, we report the design and characterization of an injectable collagen hydrogel based on covalently modified acetyl thiol collagen cross-linked using thiol-maleimide click chemistry. The hydrogel is injectable for up to 72 h after preparation, shows no noticeable swelling, is transparent, can be molded in situ, and retains its shape in solution for at least one year. Notably, the hydrogel mechanical properties can be fine-tuned by simply adjusting the reactant stoichiometries, which to date was only reported for synthetic polymer hydrogels. The biocompatibility of the hydrogel is demonstrated in vitro using human corneal epithelial cells, which maintain viability and proliferation on the hydrogels for at least seven days. Furthermore, the developed hydrogel showed an adhesion strength on soft tissues similar to fibrin glue. Additionally, the developed hydrogel can be used as a sealant for repairing corneal perforations and can potentially alleviate the off-label use of cyanoacrylate tissue adhesive for repairing corneal perforations. Taken together, these characteristics show the potential of the thiol collagen hydrogel for future use as a prefabricated implant, injectable filler, or as sealant for corneal repair and regeneration.
... They also may be a more economic option than suturing. 4,5 An ideal tissue adhesive is cost-effective, transparent, easy to apply, biodegradable, and biocompatible. It should set rapidly, have high tensile strength (by creating a strong bridge between wound margins), and offer postoperative comfort. ...
... Currently, two main classes of tissue adhesives are in use: synthetic (eg, cyanoacrylate and acrylic-based polymers) and biological (eg, fibrin glue, bio-dendrimers, and riboflavin-fibrinogen compounds). 5 In this review, we will discuss the properties and applications of these two classes of tissue adhesives and review the available literature on their use. ...
... Cyanoacrylates are esters of cyanoacrylic acid, and are produced by the condensation of cyanoacetate with formaldehyde in the presence of a chemical catalyst. 5 This type of synthetic glue polymerizes rapidly on coming in contact with a wet surface. 4 ...
Corneal perforations are ophthalmological emergencies which can have serious and detrimental consequences, if not managed timely and appropriately. These are a significant cause of ocular morbidity and can result in decreased vision, blindness, and even loss of the eye. Corneal perforations can be managed using a range of treatment approaches, including temporary solutions such as the application of corneal glue and bandage contact lens, as well as definitive treatment such as corneal transplantation. Tissue glues/adhesives were developed as substitutes for sutures in ophthalmic surgery. Unlike sutures, these glues are associated with shorter overall surgical times and reduced inflammation, thus improving postoperative comfort without compromising wound strength. The available tissue adhesives can be broadly classified into two types: synthetic (eg, cyanoacrylate derivatives) and biological (eg, fibrin glue). Cyanoacrylate glue is chiefly used as a corneal patch to manage acute corneal perforations and improve visual outcomes. Fibrin glue can be used instead of cyanoacrylate glue in many conditions with the benefits of reduced conjunctival and corneal inflammation and reaction. Apart from this, each type of adhesive is distinct in terms of its benefits as well as limitations and is accordingly used for different indications. The present review focuses on the two main types of tissue adhesives, their applications in the management of corneal perforations, the associated complications, safety and efficacy data related to their use available in the literature and the need for newer adhesives in this field.
... They also may be a more economic option than suturing. 4,5 An ideal tissue adhesive is cost-effective, transparent, easy to apply, biodegradable, and biocompatible. It should set rapidly, have high tensile strength (by creating a strong bridge between wound margins), and offer postoperative comfort. ...
... Currently, two main classes of tissue adhesives are in use: synthetic (eg, cyanoacrylate and acrylic-based polymers) and biological (eg, fibrin glue, bio-dendrimers, and riboflavin-fibrinogen compounds). 5 In this review, we will discuss the properties and applications of these two classes of tissue adhesives and review the available literature on their use. ...
... Cyanoacrylates are esters of cyanoacrylic acid, and are produced by the condensation of cyanoacetate with formaldehyde in the presence of a chemical catalyst. 5 This type of synthetic glue polymerizes rapidly on coming in contact with a wet surface. 4 ...
Corneal perforations are ophthalmological emergencies which can have serious and detrimental consequences, if not managed timely and appropriately. These are a significant cause of ocular morbidity and can result in decreased vision, blindness, and even loss of the eye. Corneal perforations can be managed using a range of treatment approaches, including temporary solutions such as the application of corneal glue and bandage contact lens, as well as definitive treatment such as corneal transplantation. Tissue glues/adhesives were developed as substitutes for sutures in ophthalmic surgery. Unlike sutures, these glues are associated with shorter overall surgical times and reduced inflammation, thus improving postoperative comfort without compromising wound strength. The available tissue adhesives can be broadly classified into two types: synthetic (eg, cyanoacrylate derivatives) and biological (eg, fibrin glue). Cyanoacrylate glue is chiefly used as a corneal patch to manage acute corneal perforations and improve visual outcomes. Fibrin glue can be used instead of cyanoacrylate glue in many conditions with the benefits of reduced conjunctival and corneal inflammation and reaction. Apart from this, each type of adhesive is distinct in terms of its benefits as well as limitations and is accordingly used for different indications. The present review focuses on the two main types of tissue adhesives, their applications in the management of corneal perforations, the associated complications, safety and efficacy data related to their use available in the literature and the need for newer adhesives in this field.
... The currently available biomaterials used as corneal adhesives cannot be used as stromal substitutes. For instance, the PEG-based materials ReSure (Ocular Therapeutix Inc., MA, USA) or OcuSeal (Beaver-Visitec International, MA, USA) cannot be used as filling biomaterials due to fast and uncontrollable polymerization, low adhesiveness, and lack of the mechanical properties required for regeneration 20,21 . Preclinical pilot study was demonstrated using human cadaveric donor cornea from ECM microparticles have been used; however, immunologic reactions may be problematic 22 . ...
The available treatment options include corneal transplantation for significant corneal defects and opacity. However, shortage of donor corneas and safety issues in performing corneal transplantation are the main limitations. Accordingly, we adopted the injectable in situ-forming hydrogels of collagen type I crosslinked via multifunctional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) for treatment and evaluated in vivo biocompatibility. The New Zealand White rabbits (N = 20) were randomly grouped into the keratectomy-only and keratectomy with PEG-collagen hydrogel-treated groups. Samples were processed for immunohistochemical evaluation. In both clinical and histologic observations, epithelial cells were able to migrate and form multilayers over the PEG-collagen hydrogels at the site of the corneal stromal defect. There was no evidence of inflammatory or immunological reactions or increased IOP for PEG-collagen hydrogel-treated corneas during the four weeks of observation. Immunohistochemistry revealed the presence of α-smooth muscle actin (α-SMA) in the superior corneal stroma of the keratectomy-only group (indicative of fibrotic healing), whereas low stromal α-SMA expression was detected in the keratectomy with PEG-collagen hydrogel-treated group. Taken together, we suggest that PEG-collagen may be used as a safe and effective alternative in treating corneal defect in clinical setting.
... Also, if suturing is applied, the process not only requires high skill levels from the surgery team and a relatively long time for operation, but can also cause multiple complications including inflammation, astigmatism, suture breakage, secondary neovascularization, microbial infection, as well as the lack of control of disease recurrence (Chan and Boisjoly, 2004;Bhatia, 2006;Grinstaff, 2007;Romano et al., 2016;Santiago et al., 2019). Ocular adhesives used as an alternative for the above treatments typically consist of synthetic materials, such as cyanoacrylatebased, PEG-based, and dendrimer-based adhesives, and naturally derived materials, such as protein-based and polysaccharidebased adhesives (Park et al., 2011;Koivusalo et al., 2019;Santiago et al., 2019). In particular, cyanoacrylate-based glues, PEG-based adhesives, and fibrin glues have been most commonly used in treatments for various ocular conditions (Santiago et al., 2019). ...
... Cyanoacrylates are one of the earliest ocular adhesive solutions used. However, their cytotoxicity, rough texture, poor biodegradability and bioabsorbability, inflexibility after solidification, and lack of transparency impose major limitations on their application in clinical treatments (Ciapetti et al., 1994;Kaufman et al., 2003;Chan and Boisjoly, 2004;Bhatia, 2006;Chen et al., 2007;Park et al., 2011). An FDA-approved PEGbased adhesive for ocular repair, ReSure R , has already been used in cataract surgery and laser-assisted in situ keratomileusis (LASIK) surgery (Masket et al., 2014;Ramsook and Hersh, 2015;Tong et al., 2018). ...
... An FDA-approved PEGbased adhesive for ocular repair, ReSure R , has already been used in cataract surgery and laser-assisted in situ keratomileusis (LASIK) surgery (Masket et al., 2014;Ramsook and Hersh, 2015;Tong et al., 2018). But this hydrogel adhesive requires rapid operation, has limited stability, cannot seal large leaky incisions, or fill in stromal defects (Park et al., 2011). The drawbacks of fibrin glue mainly lie in its poor adhesion ability to wet surfaces, difficulty to control product quality, and potential risks of viral contamination and immunological problems (Shirzaei Sani et al., 2019). ...
A variety of suture and bioglue techniques are conventionally used to secure engineered scaffold systems onto the target tissues. These techniques, however, confront several obstacles including secondary damages, cytotoxicity, insufficient adhesion strength, improper degradation rate, and possible allergic reactions. Adhesive tissue engineering scaffolds (ATESs) can circumvent these limitations by introducing their intrinsic tissue adhesion ability. This article highlights the significance of ATESs, reviews their key characteristics and requirements, and explores various mechanisms of action to secure the scaffold onto the tissue. We discuss the current applications of advanced ATES products in various fields of tissue engineering, together with some of the key challenges for each specific field. Strategies for qualitative and quantitative assessment of adhesive properties of scaffolds are presented. Furthermore, we highlight the future prospective in the development of advanced ATES systems for regenerative medicine therapies.
... Główną zaletą stosowania klejów fibrynowych jest skrócenie czasu gojenia ran pooperacyjnych, w porównaniu z klejami cyjanoakrylanowymi (około jednego tygodnia szybciej) oraz mniej intensywny proces neowaskularyzacji rogówki [125]. Jednakże ich wadami są: niska siła adhezji do mokrych powierzchni, długi czas przygotowania, podatność na degradację proteolityczną oraz ryzyko przeniesienia czynnika zakaźnego [127]. Kleje tkankowe w okulistyce są używane w wielu rodzajach operacji. ...
