title: [Concept of a pressure-controlled microstent for glaucoma therapy].
abstract: A pressure-controlled microstent could permanently normalise the intraocular pressure (IOP) for open-angle glaucoma therapy by drainage into the suprachoroidal space. The complex requirements demand new technical solutions as well as an improved understanding of specific cell biological processes at the implant's surface to develop effective local drug delivery (LDD) concepts and surface modifications. Fluid mechanical requirements were derived from physiological data and the analysis of commercial glaucoma implants. The technological basics for the production of suitable structures are refined ultra-short pulse laser technology and 2-photon polymerisation (2PP). All known glaucoma implants induce unwanted cell proliferation resulting in a loss of function. It is assumed that the activity of fibroblasts is low in the suprachoroidal space. However, it was seen that LDD concepts are required to control cell proliferation. Fibroblasts from sclera and choroidea were isolated und cultured as the most relevant cell types for in vitro investigation. Potential materials and drugs were investigated by cell viability tests for biocompatibility or suppression of cell viability. The fluid mechanical analysis leads to smallest stent lumina (ID = 50 µm) at anatomically suitable implant lengths (7 - 10 mm). Only pressure control can manage the individual conditions with changing IOP. Finite element analysis of valves showed the need for highly flexible structures. This can be achieved by combining basic structures with micromechanically active valves added by 2PP. The potential materials show perfect in vitro and in vivo biocompatibility. Ormocers which are best suited for 2PP are also highly biocompatible. The selected drugs paclitaxel and triamcinolon acetonide open a wide therapeutic window to impair fibroblast growth. The surgical procedure was established by implantation of prototypes in rabbit eyes, connecting the anterior chamber with the suprachoroidal space. Highly flexible implants are required for correct placement within the eye. The new concept of the microstent combines biomechanical approaches, technologies for microfabrication and current LDD concepts and opens new perspectives for glaucoma therapy.
authors.affiliation: Institut für Biomedizinische Technik, Universität Rostock, Rostock. wolfram.schmidt@uni-rostock.de
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Schultze
authors.forename: O
authors.initials: O
authors.lastname: Stachs
authors.forename: R
authors.initials: R
authors.lastname: Allemann
authors.forename: M
authors.initials: M
authors.lastname: Löbler
authors.forename: K
authors.initials: K
authors.lastname: Sternberg
authors.forename: U
authors.initials: U
authors.lastname: Hinze
authors.forename: B N
authors.initials: BN
authors.lastname: Chichkov
authors.forename: R
authors.initials: R
authors.lastname: Guthoff
authors.forename: K-P
authors.initials: KP
authors.lastname: Schmitz
mesh_terms: D000818:Animals; D003198:Computer Simulation; D017076:Computer-Aided Design; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005901:Glaucoma / Q000503:physiopathology* / Q000601:surgery*; D006801:Humans; D007429:Intraocular Pressure; D008904:Miniaturization; D008954:Models, Biological; D011312:Pressure; D011817:Rabbits; D015607:Stents