title: Mobility-Enhancing Coatings for Vitreoretinal Surgical Devices: Hydrophilic and Enzymatic Coatings Investigated by Microrheology.
abstract: Ophthalmic wireless microrobots are proposed for minimally invasive vitreoretinal surgery. Devices in the vitreous experience nonlinear mobility as a result of the complex mechanical properties of the vitreous and its interaction with the devices. A microdevice that will minimize its interaction with the macromolecules of the vitreous (i.e., mainly hyaluronan (HA) and collagen) can be utilized for ophthalmic surgeries. Although a few studies on the interactions between the vitreous and microdevices exist, there is no literature on the influence of coatings on these interactions. This paper presents how coatings on devices affect mobility in the vitreous. Surgical catheters in the vasculature use hydrophilic polymer coatings that reduce biomolecular absorption and enhance mobility. In this work such polymers, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and HA coatings were utilized, and their effects on mobility in the vitreous were characterized. Hydrophilic titanium dioxide (TiO2) coating was also developed and characterized. Collagenase and hyaluronidase enzymes were coated on probes' surfaces with a view to enhancing their mobility by enzymatic digestion of the collagen and HA of the vitreous, respectively. To model the human vitreous, ex vivo porcine vitreous and collagen were used. For studying the effects of hyaluronidase, the vitreous and HA were used. The hydrophilic and enzymatic coatings were characterized by oscillatory magnetic microrheology. The statistical significance of the mean relative displacements (i.e., mobility) of the coated probes with respect to control probes was assessed. All studied hydrophilic coatings improve mobility, except for HA which decreases mobility potentially due to bonding with vitreal macromolecules. TiO2 coating improves mobility in collagen by 28.3% and in the vitreous by 15.4%. PEG and PVP coatings improve mobility in collagen by 19.4 and by 39.6%, respectively, but their improvement in the vitreous is insignificant at a 95% confidence level (CL). HA coating affects mobility by reducing it in collagen by 35.6% (statistically significant) and in the vitreous by 16.8% (insignificant change at 95% CL). The coatings cause similar effects in collagen and in the vitreous. However, the effects are lower in the vitreous, which can be due to a lower concentration of collagen in the vitreous than in the prepared collagen samples. The coatings based on enzymatic activity increase mobility (i.e., >40% after 15 min experiments in the vitreous models) more than the hydrophilic coatings based on physicochemical interactions. However, the enzymes have time-dependent effects, and they dissolve from the probe surface with time. The presented results are useful for researchers and companies developing ophthalmic devices. They also pave the way to understanding how to adjust mobility of a microdevice in a complex fluid by choice of an appropriate coating.
authors.affiliation: Institute of Robotics and Intelligent Systems, ETH Zurich , Zurich, Switzerland.
authors.forename: Juho
authors.initials: J
authors.lastname: Pokki
authors.affiliation: Institute of Robotics and Intelligent Systems, ETH Zurich , Zurich, Switzerland.
authors.forename: Jemish
authors.initials: J
authors.lastname: Parmar
authors.affiliation: Institute of Robotics and Intelligent Systems, ETH Zurich , Zurich, Switzerland.
authors.forename: Olgaç
authors.initials: O
authors.lastname: Ergeneman
authors.affiliation: Department of Electrical and Electronics Engineering, Boğaziçi University , Istanbul, Turkey.|Center for Life Sciences and Technologies, Boğaziçi University , Istanbul, Turkey.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Torun
authors.affiliation: Departament de Física, Universitat Autònoma de Barcelona , Bellaterra, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Guerrero
authors.affiliation: Departament de Física, Universitat Autònoma de Barcelona , Bellaterra, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Pellicer
authors.affiliation: Departament de Física, Universitat Autònoma de Barcelona , Bellaterra, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA) , Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sort
authors.affiliation: Institute of Robotics and Intelligent Systems, ETH Zurich , Zurich, Switzerland.
authors.forename: Salvador
authors.initials: S
authors.lastname: Pané
authors.affiliation: Institute of Robotics and Intelligent Systems, ETH Zurich , Zurich, Switzerland.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Nelson
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D017364:Collagenases / Q000737:chemistry*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing / Q000379:methods*; D008866:Microsurgery; D012212:Rheology / Q000379:methods*; D065287:Robotic Surgical Procedures; D013552:Swine; D057586:Vitreoretinal Surgery / Q000295:instrumentation*
chemical_list: D020099:Coated Materials, Biocompatible; D006821:Hyaluronoglucosaminidase; D017364:Collagenases
keywords: and enzymes; coatings; microrheology; microrobots; ophthalmic instruments