title: Synthesis, characterization, and in vitro evaluation of a hydrogel-based corneal onlay.
abstract: Blindness due to opacity of the cornea is treated by corneal transplantation with donor tissue. Due to the limited supply of suitable donor corneas, the need for synthetic corneal equivalents is clear. Herein we report the design and in vitro characterization of a hydrogel-based implant; this implant will serve as a permanent, transparent, space-filling onlay with a two-layer design that mimics the native corneal stratification to support surface epithelialization and foster integration with the surrounding tissue. The top layer of the implant was composed of a 2-hydroxyethylmethacrylate hydrogel containing methacrylic acid as the co-monomer (HEMA-co-MAA) with tunable dimensions and compressive modulus ranging from 700-1000 kPa. The bottom layer, which constitutes the bulk of the implant and is designed to provide integration with the corneal stroma, is a dendrimer hydrogel with high water content and compressive modulus ranging from 500-1200 kPa. Both hydrogels were found to possess optical and diffusion properties similar to those of the human cornea. In addition, composite implants with uniform and structurally sound interfaces were formed when the gels were sequentially injected and cross-linked in the same mold. HEMA-co-MAA hydrogels were covalently modified with type I collagen to enable corneal epithelial cell adhesion and spreading that was dependent upon the collagen coating density but independent of hydrogel stiffness. Similarly, dendrimer hydrogels supported the adhesion and spreading of corneal fibroblasts upon modification with the adhesion ligand arginine-glycine-aspartic acid (RGD). Fibroblast adhesion was not dependent upon dendrimer hydrogel stiffness for the formulations studied and, after in vitro culture for 4 weeks, fibroblasts remained able to adhere to and conformally coat the hydrogel surface. In conclusion, the tunable physical properties and structural integrity of the laminated interface suggests that this design is suitable for further study. The judicious tuning of material properties and inclusion of bioactive moieties is a promising strategy for promotion of implant epithelialization and tissue integration.
authors: Chemistry Department, Boston University, Boston, MA 02215, USA. aoelker@mit.edu
authors: Abigail M
authors: AM
authors: Oelker
authors: Mark W
authors: MW
authors: Grinstaff
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry; D004847:Epithelial Cells / Q000166:cytology; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D008689:Methacrylates / Q000737:chemistry; D008856:Microscopy, Fluorescence; D019736:Prostheses and Implants; D011817:Rabbits
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D050091:Dendrimers; D020100:Hydrogels; D008689:Methacrylates; C008384:methacrylic acid; C005044:hydroxyethyl methacrylate