Biocompatible, Biodegradable and Porous Liquid Crystal Elastomer Scaffolds for Spatial Cell Cultures

Abstract

Here we report on the modular synthesis and characterization of biodegradable, controlled porous, liquid crystal elastomers (LCE) and their use as three-dimensional cell culture scaffolds. The elastomers were prepared by cross-linking of star block-co-polymers with pendant cholesterol units resulting in the formation of smectic-A LCEs as determined by polarized optical microscopy, DSC, and X-ray diffraction. Scanning electron microscopy revealed the porosity of the as-prepared biocompatible LCEs, making them suitable as 3D cell culture scaffolds. Biodegradability studies in physiological buffers at varying pH show that these scaffolds are intact for about 11 weeks after which degradation sets in at an exponential rate. Initial results from cell culture studies indicate that these smectic LCEs are compatible with growth, survival, and expansion of cultured neuroblastomas and myoblasts when grown on the LCEs for extended time periods (about a month). These preliminary cell studies focused on characterizing the elastomer-based scaffolds' biocompatibility and the successful 3D incorporation as well as growth of cells in 60 to 150-μm thick elastomer sheets.

Advances in Cell Scaffolds for Tissue Engineering: The Value of Liquid Crystalline Elastomers

“…[29] Av ery different mesogen structure used for LCEi s based on cholesterol derivatives obtained by esterification of the hydroxyl group to introduce the desired spacer. [30] The first LCE preparation was performed by Finkelmann et al with the use of silicone chemistry.E xploiting the platinum-catalysed addition of terminal C=Cd ouble bonds to SiÀH bonds,i ti sp ossible to attach mesogensand to crosslinkd ifferent chainst oapolyhydrosiloxane backbone( Figure 5a). [23] The silicone precursor was mixed with monovinyl functionalized mesogens, divinylc ompounds and an appropriate catalyst.…”

“…An efficient strategy to obtain biodegradable LCE has been developed by Hegmann and co-workers by means of coupling between ab iodegradable polyester chain and biocompatible cholesterol derivatives (Figure 5f). [30] First, as tar block copolymer was synthesized by ring opening polymerization employing am ixture of two lactone based monomers, (d,l)-lactide and am ultifunctional central node (such as glycerol, pentaerythritolo rd ipentaerythritol) affording a3 -, 4-or 6-arm star copolymer,r espectively.T hen, the mesogenic cholesteryl derivatives were attached to the backbone exploitingafunctional group present on one of the caprolactone block (halogen atom subsequentially substituted by an azide and employed in ac lick reaction) imparting liquid crystalline properties to the system.A tt he end, crosslinking of the copolymers was obtained by reaction of the terminal hydroxyl groups of the lactides with ab iscaprolactone or by hexamethylene diisocyanate (Figure 5f).…”

“…In particular,3 -arm howing the "Swiss-cheese" internal morphology of LCE-g,(cross-sectional views;5mm average pore size);adapted with permission from ref. [30].Middle:Primary human dermal fibroblast (hDF) cultures grownf or 5d ays on 4L CE-a elastomer films. Right:D irectionality analysis of primary hDF cells grownonp etri dishes;a dapted with permission from ref.…”

“…[57] SeedingC 2C12 on such scaffolds results in an improved cell proliferation capability in comparison to conventional porous films. [30] Very recently the same authors improved the 3D porous scaffold preparation by using as alt leaching method (Figure 8d), overcoming the residual alloyedc arbon (used in fabrication on the Ni templates) on the scaffold (responsible of the black colour), and gaining ab etter control over pore size and pore size distribution within the LCE bulk. The method is quite simple and consists of mixing the salt crystals( chosen on the basis of the desired pore dimensions), the LC-polymer and the crosslinker in as olvent, pouring the obtained mixture into a mold (mechanicalc ompressiona ssures the integrity of the foam and increases the pore interconnectivity) and crosslinking it.…”

Role of Surfactant during Microemulsion Photopolymerization for the Creation of Three-Dimensional Liquid Crystal Elastomer Microsphere Spatial Cell Scaffolds

“…We have previously reported the use of biocompatible smectic LCEs where their anisotropic nature and different internal morphology promoted not only cell adhesion and permeation within the bulk of LCEs (Sharma et al, 2014;Gao et al, 2016) but also a suitable substrate to support three-dimensional (3D) cell growth. We also reported (Bera et al, 2015) the use of microemulsion photopolymerization in a proof-of-concept study on the utilization of nematic LCEs as 3D connected microsphere scaffolds for muscle cells.…”