In Situ UNIversal Orthogonal Network (UNION) Bioink Deposition for Direct Delivery of Corneal Stromal Stem Cells to Corneal Wounds.

The scarcity of human donor corneal graft tissue worldwide available for corneal transplantation necessitates the development of alternative therapeutic strategies for treating patients with corneal blindness. Corneal stromal stem cells (CSSCs) have the potential to address this global shortage by allowing a single donor cornea to treat multiple patients. To directly deliver CSSCs to corneal defects within an engineered biomatrix, we developed a UNIversal Orthogonal Network (UNION) collagen bioink that crosslinks with a bioorthogonal, covalent chemistry.

Clinical outcomes of intravitreal treatment for ocular toxoplasmosis: systematic review and meta-analysis.

Background: Ocular toxoplasmosis is the leading cause of infectious posterior uveitis worldwide, accounting for 30-50% of all cases in immunocompetent patients. Conventional treatment is associated with adverse effects and does not prevent recurrence. Intravitreal drug administration can improve disease outcomes and reduce side effects.

Collagen Gels Crosslinked by Photoactivation of Riboflavin for the Repair and Regeneration of Corneal Defects.

Bioengineered corneal tissue is a promising therapeutic modality for the treatment of corneal blindness as a substitute for cadaveric graft tissue. In this study, we fabricated a collagen gel using ultraviolet-A (UV-A) light and riboflavin as a photosensitizer (PhotoCol-RB) as an -forming matrix to fill corneal wounds and create a cohesive interface between the crosslinked gel and adjacent collagen. The PhotoCol-RB gels supported corneal epithelialization and exhibited higher transparency compared to physically crosslinked collagen.

In Situ-Forming Collagen-Hyaluronate Semi-Interpenetrating Network Hydrogel Enhances Corneal Defect Repair.

Purpose: Millions worldwide suffer vision impairment or blindness from corneal injury, and there remains an urgent need for a more effective and accessible way to treat corneal defects. We have designed and characterized an in situ-forming semi-interpenetrating polymer network (SIPN) hydrogel using biomaterials widely used in ophthalmology and medicine.

Methods: The SIPN was formed by cross-linking collagen type I with bifunctional polyethylene glycol using N-hydroxysuccinimide ester chemistry in the presence of linear hyaluronic acid (HA).

In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects: 2-Month Follow-up In Vivo.

Purpose: We recently showed that in situ-forming collagen gels crosslinked through multifunctional polyethylene glycol (PEG) supported corneal epithelialization 7 days after treatment of lamellar keratectomy wounds. In this study, we aimed to evaluate the longer-term regenerative effects of this gel in animals.

Method: Corneal wound healing was assessed 60 days after lamellar keratectomy and gel treatment using slitlamp examination, optical coherence tomography (OCT), pachymetry, corneal topography, an ocular response analyzer, and tonometry.

Supramolecular host-guest hyaluronic acid hydrogels enhance corneal wound healing through dynamic spatiotemporal effects.

Severe corneal wounds can lead to ulceration and scarring if not promptly and adequately treated. Hyaluronic acid (HA) has been investigated for the treatment of corneal wounds due to its remarkable biocompatibility, transparency and mucoadhesive properties. However, linear HA has low retention time on the cornea while many chemical moieties used to crosslink HA can cause toxicity, which limits their clinical ocular applications.

Use of a slow-release intravitreal clindamycin implant for the management of ocular toxoplasmosis.

Purpose: To report the first patient with ocular toxoplasmosis treated with a slow-release biodegradable intravitreal clindamycin implant.

Observations: A 39-year-old human immunodeficiency virus (HIV)-positive woman with recurrent toxoplasmic retinochoroiditis and vitritis for whom oral medication was medically contraindicated was treated with an intravitreal slow-release clindamycin implant and three monthly intravitreal injections of clindamycin and dexamethasone. Serial ophthalmologic examinations demonstrated gradual, complete resolution of posterior uveitis and healing of the retinochoroidal lesion with cicatricial changes, as well as gradual improvement of cells in the anterior chamber.

Effect of mesenchymal stromal cells encapsulated within polyethylene glycol-collagen hydrogels formed in situ on alkali-burned corneas in an ex vivo organ culture model.

Background Aims: Corneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout.

In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects.

Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas.

Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo.

The therapeutic effects of secreted factors (secretome) produced by bone marrow-derived human mesenchymal stem cells (MSCs) were evaluated as a function of their growth in 2D culture conditions and on 3D electrospun fiber scaffolds. Electrospun fiber scaffolds composed of polycaprolactone and gelatin were fabricated to provide a 3D microenvironment for MSCs, and their mechanical properties were optimized to be similar to corneal tissue. The secretome produced by the MSCs cultured on 3D fiber matrices versus 2D culture dishes were analyzed using a Luminex immunoassay, and the secretome of MSCs cultured on the 3D versus 2D substrates showed substantial compositional differences.

Ocular biocompatibility of dexamethasone acetate loaded poly(ɛ-caprolactone) nanofibers.

Electrospinning technique has been explored to produce nanofibers incorporated with drugs as alternative drug delivery systems for therapeutic purposes in various organs and tissues. Before such systems could potentially be used, their biocompatibility must be evaluated. In this study, dexamethasone acetate-loaded poly(ɛ-caprolactone) nanofibers (DX PCL nanofibers) were developed for targeted delivery in the vitreous cavity in the treatment of retinal diseases.

Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier.

Severe corneal injuries often result in permanent vision loss and remain a clinical challenge. Human bone marrow-derived mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their antiscarring, anti-inflammatory, and antiangiogeneic properties. We aimed to deliver lyophilized MSC secretome (MSC-S) within a viscoelastic gel composed of hyaluronic acid (HA) and chondroitin sulfate (CS) as a way to enhance corneal re-epithelialization and reduce complications after mechanical and chemical injuries of the cornea.

Methotrexate Locally Released from Poly(e-Caprolactone) Implants: Inhibition of the Inflammatory Angiogenesis Response in a Murine Sponge Model and the Absence of Systemic Toxicity.

In this study, the methotrexate (MTX) was incorporated into the poly(e-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined.

Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats.

Purpose: Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug delivery system in the rat model of endotoxin-induced uveitis (EIU).

Methotrexate Locally Released from Poly(ε-Caprolactone) Implants: Inhibition of the Inflammatory Angiogenesis Response in a Murine Sponge Model and the Absence of Systemic Toxicity.

In this study, the methotrexate (MTX) was incorporated into the poly(ε-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined.

In vitro and in vivo ocular biocompatibility of electrospun poly(ɛ-caprolactone) nanofibers.

Biocompatibility is a requirement for the development of nanofibers for ophthalmic applications. In this study, nanofibers were elaborated using poly(ε-caprolactone) via electrospinning. The ocular biocompatibility of this material was investigated.