Titanium to enhance biointegration of the Boston Keratoprosthesis with corneal tissue: a study in rabbits

Abstract

Purpose: To test the feasibility of using titanium (Ti) and titanium oxide coatings to improve the biointegration of Boston Keratoprosthesis (B-KPro), and ultimately decrease the risk of various implant-associated complications, such as endophthalmitis.

Methods: Cylindrical rods of poly(methyl methacrylate) (PMMA) (15 mm in length, 3.5 mm in diameter) were coated with titanium dioxide (TiO2) over a layer of polydopamine. Medical grade titanium rods with two different surface roughnesses (smooth and sandblasted) were also prepared. Some of the Ti rods were treated by oxygen plasma for 5 min in order to increase the surface titanium oxide layer. The surface of each rod was imaged by scanning electron microscopy (SEM), and its surface roughness was estimated by atomic force microscopy (AFM). Surface chemistry was analyzed by X-ray photoelectron spectroscopy (XPS). The rods were fitted into holes punched into the center of porcine corneas ex vivo (1 cm in diameter) and the whole constructs were cultured in modified Chen’s media. The adhesion force between the rod and the cornea was measured at days 0 and 14 of incubation to assess the degree of biointegration. In vitro viability of corneal fibroblasts on each surface was measured using alamarBlue. The material with the best adhesion ex vivo was used for in vivo implantation in rabbits. Therefore, a Ti_ox sleeve was placed around the stem of the B-KPro, and tissue response was assessed after 2 months.

Results: XPS and AFM showed successful deposition of TiO2 on polydopamine-coated PMMA, with a resulting increase in surface roughness. Cell viability was not affected adversely by any of the samples. After 14 days of incubation in porcine corneas, TiO2-coated PMMA rods and smooth titanium rods treated with oxygen plasma (Ti_ox) had significantly higher adhesion forces (0.331N and 0.357N) compared to bare PMMA (0.0947N) and untreated Ti rods (0.132N). Tissue reaction around the Ti_ox sleeve around the stem after 2 months was benign.

Conclusions: TiO2-polydopamine coating of PMMA and Ti_ox showed a significant increase in adherence to corneal tissue ex vivo. Because Ti_ox showed higher adhesion values than TiO2, it was used in vivo as a sleeve around the stem of the B-KPro, and showed benign tissue reaction after 2 months. Therefore, Ti_ox may be the preferable choice in patients.

Keywords: 575 keratoprostheses • 480 cornea: basic science • 607 nanotechnology