Engineering copolymeric artificial cornea with salt porogen

Abstract

Artificial corneas or keratoprostheses (KPros) are designed to replace diseased or damaged cornea. Although many synthetic KPros have been developed, current products are often inappropriate or inadequate for long term use due to ineffective host integration. This study presents an alternative approach of engineering a KPro that comprises a combination of poly (2-hydroxyethyl methacrylate) (PHEMA), poly (methyl methacrylate) (PMMA), and sodium chloride (NaCl) as porogen. Based on the core-skirt model for KPro, the porous outer portion of artificial cornea (skirt) was engineered by combining NaCl with HEMA and MMA monomers to promote tissue ingrowth from the host. The central optic (core) was designed to provide >85% light transmission in the visible wavelength range and securely attached to the skirt. Mechanical tensile data indicated that our KPro (referred to as salt porogen KPro) is mechanically stable to maintain its structure in the ocular environment and during implantation. Using human corneal fibroblasts (HCFs), we demonstrate that the cells grew into the pores of the skirt and proliferated, suggesting biointegration is adequately achieved. This novel PHEMA-PMMA copolymeric salt porogen KPro may offer a cornea replacement option that leads to minimal risk of corneal melting by permitting sufficient tissue ingrowth and mass transport.

Poly (Ethylene Glycol)‐Based Hydrogels as Self‐Inflating Tissue Expanders with Tunable Mechanical and Swelling Properties

“…Previous studies have reported the effects of PEGDA polymer chains length on mechanical properties of the resulting hydrogels. For example, Zellander et al showed that combinations of short and long PEGDA chains created polymer structures with increased strength and stiffness compared to structures composed of a given longer PEGDA chain . Lin et al also demonstrated that varying the molecular weight of PEGDA precursors exhibited a significant effect on the structural and mechanical properties of the hydrogels .…”

Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications

“…Another important difference from prior composite keratoprosthesis designs is that biologically inert materials require surface modifications or coating with collagen or other growth factors to support cell adhesion, and special steps to maintain permeability for nutrient diffusion for cell survival [7,[9][10][11][12]. Construction of inert prostheses with regenerative capacity therefore includes many technically demanding steps [9,11,12].…”

“…Composite core-and-skirt designs have been used to improve integration of biologically inert synthetic prostheses with the surrounding host tissue [4,[7][8][9][10][11][12]. The composite developed here is fundamentally different from an inert prosthetic material, because it is biodegradable and designed to interact with surrounding host tissue and stimulate endogenous corneal regeneration, with eventual replacement by natural stroma through population by host keratocytes and fibroblasts which remodel the extracellular matrix [14].…”

“…Construction of inert prostheses with regenerative capacity therefore includes many technically demanding steps [9,11,12]. Alternatively, composites presented here are composed of a safe and well-characterized medical-grade porcine collagen not requiring surface modification.…”

“…Transplantation with human cadaveric tissue is presently the only treatment option in most cases, but severe tissue shortage has led to an urgent need to develop bioengineered alternatives to donor corneal tissue [2][3][4][5][6][7][8][9][10][11][12]. Natural collagen-derived corneal scaffolds are the most mature of these [13][14][15][16][17][18][19], and we recently reported results from collagen-based scaffolds four years after implantation into diseased human corneas [13].…”