BioAdhere: Tailor-made bioadhesives for epiretinal visual prostheses

18/10/2022
 

Kai-Wolfgang Hintzen, Christian Simons, Kim Schaffrath, Gernot Roessler, Sandra Johnen, Felix Jakob, Peter Walter, Ulrich Schwaneberg, Tibor Lohmann, Biomaterials Science, https://doi.org/10.1039/D1BM01946E

Design and application of biadhesive peptide (peptesive) for fixation of intraocular implants.

Visual prostheses, i.e. epiretinal stimulating arrays, are a promising therapy in treating retinal dystrophies and degenerations. In the wake of a new generation of devices, an innovative method for epiretinal fixation of stimulator arrays is required. We present the development of tailor-made bioadhesive peptides (peptesives) for fixating epiretinal stimulating arrays omitting the use of traumatic retinal tacks. Binding motifs on the stimulating array (poly[chloro-p-xylylene] (Parylene C)) and in the extracellular matrix of the retinal surface (collagens I and IV, laminin, fibronectin) were identified. The anchor peptides cecropin A (CecA), KH1, KH2 (author's initials) and osteopontin (OPN) were genetically fused to reporter proteins to assess their binding behavior to coated microtiter plates via fluorescence-based assays. Domain Z (DZ) of staphylococcal protein A was used as a separator to generate a bioadhesive peptide. Direct and non-direct cytotoxicity testing was performed. Lastly, the fixating capabilities of the peptesives were tested in proof-of-principle experiments. The generation of the bioadhesive peptide required the evaluation of the N- and C-terminal located anchor peptide. The YmPh–CecA construct (N-terminal fusion) showed the highest activity on Parylene C in comparison with the wildtype phytase without the anchor peptide. The C-terminal anchor peptide fusion (eGFP–OPN) was binding to all four investigated ECM proteins. The strongest binding to collagen I was observed for eGFP–KH1, while the strongest binding to fibronectin was observed for eGFP–KH2. The selectivity of binding was checked by incubating eGFP–CecA and eGFP–OPN on ECM proteins and on Parylene C, respectively. Direct and non-direct cytotoxicity testing of the final biadhesive peptide cecropin-A–DZ–OPN showed good biocompatibility properties. Proof-of-concept experiments in post-mortem rabbit eyes suggested an increased adhesion of CecA–DZ–OPN–coated stimulating arrays. This is the first study to prove the applicability and biocompatibility of peptesives for the fixation of macroscopic objects.

The RWTH Aachen University ERS Seed Fund (OPSF473) supported this work.

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Kai-Wolfgang Hintzen, Christian Simons, Kim Schaffrath, Gernot Roessler, Sandra Johnen, Felix Jakob, Peter Walter, Ulrich Schwaneberg, Tibor Lohmann, Biomaterials Science, https://doi.org/10.1039/D1BM01946E

 
  Concept of the BioAdhere study: A biadhesive peptide (peptesive) CecA-DomainZ-OPN for fixation of an epiretinal stimulator on the retinal surface. Copyright: © biotec Concept of the BioAdhere study: A biadhesive peptide (peptesive) CecA-DomainZ-OPN for fixation of an epiretinal stimulator on the retinal surface.