title: Subretinal delivery of ultrathin rigid-elastic cell carriers using a metallic shooter instrument and biodegradable hydrogel encapsulation.
abstract: OBJECTIVE
  To develop a surgical technique for the subretinal implantation of cell carriers suitable for the transplantation of cultured retinal pigment epithelium (RPE) in a preclinical animal model.
  
  
  METHODS
  Cell carriers were porous 10-μm-thick polyester membranes. A custom-made shooter instrument consisted of a 20-gauge metallic nozzle with a nonstick plunger. Fetal human RPE cultures were used for vitality assessment during instrument handling. Transvitreal subretinal implantation of carriers without RPE was performed in 31 rabbits after vitrectomy. Fourteen of 31 implants were encapsulated in gelatin. Fluid turbulence over the implantation site was minimized using a novel infusion cannula. Six rabbits had intravitreal plasmin injections before surgery. SD-OCT in vivo images were obtained after 3, 7, and 14 days, followed by perfusion-fixed histology.
  
  
  RESULTS
  Gelatin encapsulation of RPE/polyester implants made cell loss during handling reproducible, compared with 40% of controls showing random, large damage zones. Gelatin implants were ejected smoothly in 12 of 14 surgeries (86%), whereas "naked" implants frequently became trapped with the instrument, which reduced success to 9 of 17 cases (53%). Vitreous remnants after vitrectomy alone complicated subretinal placement of encapsulated and naked implants in 7 of 25 cases (28%). Plasmin-assisted vitrectomy resulted in implant ejection unperturbed by vitreous adhesions in six experiments. SD-OCT and histology demonstrated atraumatic subretinal implant delivery after uncomplicated surgery.
  
  
  CONCLUSIONS
  A novel shooter instrument design allows for safe and atraumatic transvitreal delivery of hydrogel-encapsulated, ultrathin, rigid-elastic carriers into the subretinal space. The procedure may be used in the future to deliver cultured RPE.
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany. stanzel@uni-bonn.de
authors.forename: Boris V
authors.initials: BV
authors.lastname: Stanzel
authors.forename: Zengping
authors.initials: Z
authors.lastname: Liu
authors.forename: Ralf
authors.initials: R
authors.lastname: Brinken
authors.forename: Norbert
authors.initials: N
authors.lastname: Braun
authors.forename: Frank G
authors.initials: FG
authors.lastname: Holz
authors.forename: Nicole
authors.initials: N
authors.lastname: Eter
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002214:Capsules; D017690:Cell Transplantation / Q000295:instrumentation*; D002478:Cells, Cultured / Q000637:transplantation; D004195:Disease Models, Animal; D004337:Drug Carriers; D004867:Equipment Design; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007267:Injections / Q000295:instrumentation; D008904:Miniaturization; D011091:Polyesters; D011817:Rabbits; D012160:Retina / Q000473:pathology / Q000601:surgery*; D012162:Retinal Degeneration / Q000601:surgery; D055213:Retinal Pigment Epithelium / Q000637:transplantation*; D041623:Tomography, Optical Coherence
chemical_list: D002214:Capsules; D004337:Drug Carriers; D011091:Polyesters; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate