Molecular layer deposition builds biocompatible substrates for epithelial cells

Abstract

The demand for novel biocompatible materials as surface coating in the field of regenerative medicine is high. We explored molecular layer deposition (MLD) technique for building surface coatings and introduced a new group of substrates consisting of amino acids, or nucleobases, and the biocompatible metal titanium. The substrates were built from titanium tetraisopropoxide (TTIP) with l-lysine, glycine, l-aspartic acid, l-arginine, thymine, uracil, and adenine. Substrates based on zirconium chloride and terephthalic acid were also included. Titanium oxide (TiO ) substrates made by atomic layer deposition and uncoated cover slips served as controls. Rat conjunctival epithelial goblet cells were grown in RPMI 1640 and RT-PCR, immunofluorescence, cell attachment, proliferation, and viability were analyzed. Cells cultured on MLD and uncoated substrates were proliferating (positive for Ki67). Cell attachment after 3 h of culture on MLD substrates was similar to uncoated coverslips (p > 0.05). Compared to uncoated coverslips, cell proliferation assayed with alamarBlue® after 4 days was significantly higher on all MLD substrates (p < 0.05), whereas terephthalic acid-containing MLD substrates reduced proliferation (p < 0.01). Viability assessed by LIVE/DEAD® was high (>85%) for all substrates after 5 days. The novel MLD technique is promising for building biocompatible substrates that direct epithelial cell growth. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3090-3098, 2018.

In situ analysis of growth rate evolution during molecular layer deposition of ultra-thin polyurea films using aliphatic and aromatic precursors

“…Molecular layer deposition (MLD) has drawn increasing interest for its potential to precisely tune the structure and functionality of organic or hybrid organic/inorganic thin films for applications in microelectronics, 1,2 battery electrodes, 3 catalysts, 4 solar cells, 5 capacitors, 6,7 and biomedical devices. 8 Analogous to atomic layer deposition (ALD), MLD is a low temperature (typically < 200 °C) processing technique that utilizes sequential, self-limiting vapor-solid surface reactions to build up conformal organic polymer, oligomer, or metal coordination (i.e. metal-organic or organic/inorganic) thin films on receptive surfaces.…”

Biocompatible organic–inorganic hybrid materials based on nucleobases and titanium developed by molecular layer deposition

“…The thickness of the same samples was measured after each period of water treatment. The three hour and four day time periods are the durations in which cells were cultured on these substrates for cell attachment and cell proliferation assays, respectively, in our previous study [23]. Unlike for the Ti-amino acids films that were virtually unchanged by water treatment, the thickness of the films decreases significantly after 15 minutes of water treatment for all systems but thereafter remains almost constant at ≈30 nm, where the data is shown in Table 2.…”

“…This is verified by our characterization of density and index of refraction of the films, even after leaching. We have recently compared the bioactivity of these films by growth of goblet cells showing comparable cell adhesion, viability and proliferation as anatase TiO 2 , however, all being significantly better than uncoated cover slips [23].…”

“…Moreover, ALD can provide specialized surface functionalities useful for biological applications [19]. Such biocompatible surfaces have not been widely adapted within use of ALD, although recent attempts have been reported for deposition of biocompatible hydroxyapatite thin films [20] and hydrophilic ALD-deposited alumina thin films [21], in addition to our prior work on titaminates [22], and our recent investigation of biocompatibility of a selection of ALD materials, including the films developed here [23]. Despite these attempts, the design of biocompatible and bioactive surfaces is a huge field where ALD/MLD has only just begun to provide solutions.…”

“…1). We have recently reported a significant increase in the proliferation rate of rat conjunctival goblet cells cultured on substrates coated with these hybrid materials based on amino acids, and also the currently presented nucleobases, compared to uncoated glass coverslips using alamarBlue ® proliferation assay [23]. The current contribution describes the growth of the films based on nucleobases in more detail.…”