Recreating the Trabecular Outflow Tissue on Implantable, Micropatterned, Ultrathin, Porous Polycaprolactone Scaffolds

Area of Science:

• Biomaterials Science
• Ophthalmology
• Tissue Engineering

Background:

• Glaucoma, a leading cause of irreversible blindness, involves optic nerve damage due to elevated intraocular pressure (IOP).
• Primary open-angle glaucoma is linked to impaired aqueous humor outflow caused by malfunctioning human trabecular meshwork (HTM) cells.
• Tissue engineering offers a potential solution by replacing damaged HTM cells to restore proper ocular fluid dynamics.

Purpose of the Study:

• To develop and evaluate novel polycaprolactone (PCL) scaffolds for tissue engineering of ocular outflow pathways.
• To assess the biocompatibility and efficacy of micropatterned PCL scaffolds in supporting HTM cell function.

Main Methods:

• Lithographic fabrication of submicron-thick, porous PCL scaffolds with defined micropatterns (grid, hexagonal).
• Coating scaffolds with gelatin to enhance cell adhesion.
• Evaluating HTM cell growth, metabolic activity, and cytoskeletal organization using SEM, MTS assays, and F-actin staining.
• Assessing HTM-specific marker expression and extracellular matrix (ECM) deposition via immunocytochemistry and qPCR.

Main Results:

• Gelatin-coated PCL scaffolds with a grid micropattern supported robust HTM cell growth and organization.
• Scaffolds facilitated proper HTM cell cytoskeleton development and expression of key HTM markers.
• Evidence of significant ECM deposition was observed on the PCL scaffolds.
• The results demonstrate the suitability of these scaffolds for creating functional ocular tissue.

Conclusions:

• Micropatterned, gelatin-coated, ultrathin PCL scaffolds are effective for supporting HTM cell growth and function.
• These PCL scaffolds show feasibility for tissue-engineering implantable ocular outflow tissue.
• This approach holds potential for developing new treatments for glaucoma by restoring fluid regulation in the eye.