Making microporous nanometre-scale fibrous PLA aerogels with clean and reliable supercritical CO₂ based approaches

Highlights

• Microporous nanoscale fibrous PLA aerogels are fabricated.

• A clean approach based on phase separation and supercritical CO₂ drying is proposed.

• PLA aerogels have porosity and surface area up to 95% and 95 m²/g.

• The fabrication of multi-scaled porous scaffolds for tissue engineering is discussed.

Abstract

Polylactic acid (PLA) aerogels, with a multiscale structure consisting of nanometre-scale fibres and interconnected micropores, were here fabricated by a novel thermal induced phase separation (TIPS) approach. The developed process is based on a biocompatible route combining ethyl lactate (EL) as a non-toxic solvent for PLA and supercritical CO₂ (scCO₂) as a clean drying agent. First, PLA was dissolved in EL to prepare homogeneous solutions with a polymer concentration ranging from 3 to 5.5 wt%. Subsequently, TIPS was generated by the controlled decrease of the temperature down to a temperature lower than the solution gelation point. Finally, solvent exchange, alcogel formation and scCO₂ drying allowed the manufacture of the desired nanometre-scale fibrous PLA aerogels. In particular, PLA aerogels with homogeneous morphology and constituted by an overall porosity in the range of 90–95% and a specific surface area in the range of 70–95 m²/g were manufactured by modulating polymer concentration in the starting EL solution, gelation temperature and EL extraction conditions. The obtained aerogels possessed a bimodal structure of fibres with a mean length of 100–200 nm coupled with nanopores of a mean diameter down to 2 nm. Finally, the combination of TIPS with gas foaming and porogen leaching techniques was explored as a suitable strategy to obtain multifunctional micro- and nano-sized fibrous PLA materials, suitable of providing biomimetic three-dimensional platforms for tissue engineering scaffolds.

Introduction

The pursuit of nanoscale porous aerogels characterised by a three dimensional fibre structure represents a new realm of matter of current research in functional materials design and fabrication. Porous aerogels with fibre diameter scales of the order of tens to few hundred nanometres possess unique transport, structural and biophysical properties for technological and biomedical applications [1], [2], [3]. Owning a high porosity and a large surface area, nanometre-scale fibrous materials offers outstanding properties in terms of the flexibility of surface functionalities and the control of transport properties [1]. Nanometre-scale fibres of various biocompatible materials have been deeply studied and are currently applied in tissue engineering as scaffolds for cell culture and tissue development [3], [4]. Indeed, nanometre-scale fibrous scaffolds are able to mimic the collagen structure of the extracellular matrix, enhancing cell/material cross-talking at the interface and promoting cell adhesion, proliferation and differentiation [4]. However, the true potential to create functional nanometre-scale fibrous materials depends on the control of the fibres structure.

In addition, for tissue engineering applications the materials should be prepared preferably by using non toxic large-scale manufacturing processes. Electrospinning, molecular self assembly and phase separation are common bottom-up nanofabrication techniques used to create three dimensional scaffolds composed of interwoven nanometre-scale fibres [4], [5], [6], [7], [8], [9]. Phase separation is one of the most versatile approach designed to large-scale fabrication of nanofibrous materials with controlled morphology and structure [8], [9]. Phase separation from a polymer–solvent solution is based on the thermodynamic de-mixing of the system into a polymer-rich and a polymer-poor phases, which can be caused by antisolvent addition, using either conventional liquids or supercritical fluids [10], [11], or by cooling down the solution below a binodal solubility curve [8], [9]. This last approach, named thermally induced phase separation (TIPS), allows for the large-scale formation of nanometre-scale fibrous structures with characteristic diameters in the 50–500 nm interval, controlled by selecting the appropriate polymer/solvent combination, the cooling temperature and the process kinetics [12]. Nanometre-scale fibrous polylactic acid (PLA) [12], polyhydroxyalkanoate (PHA) [13], chitosan [14] and gelatin [15] materials have been successfully manufactured by means of the TIPS technique. However, the solvent choice for polymers processing is still an opening question, as solvents are present not only in the production route, but also in the final product as a residue. In this work, the fabrication of nanometre-scale fibrous aerogels by using ethyl lactate (EL) to process PLA was investigated to overcome the limitations related to the use of toxic organic solvents, such as dioxane or tetrahydrofuran, for polymers processing. EL is a member of the lactate esters family. It does not show any potential health risk and it has been approved by FDA as additive in food products [16], [17], [18], [19], [20]. Therefore, the use of EL may allow for the green and sustainable large-scale fabrication of nanometre-scale fibrous PLA materials.

Another critical step when preparing nanometre-scale fibrous aerogels by phase separation is the drying of the gel. In general, a polymeric gel formed upon drying in air provides a white and dense collapsed xerogel, in which the fibre network does not retain the original three-dimensional structure [21]. Supercritical CO₂ (scCO₂) solvent extraction is a process that allows the drying of the gel through the formation of a supercritical mixture of the CO₂ and the liquid solvent, which is typically ethanol. The supercritical mixture shows no surface tension and can be easily eliminated in a single step by venting the vessel [21], [22]. Herein, we report a comprehensive study of a novel and clean approach, based on the combination of TIPS route for phase separation and scCO₂ for drying, for the design and fabrication of nanometre-scale fibrous PLA aerogels with controlled morphology and structural properties. The effect of important operating conditions, such as polymer concentration in the initial solution, gelation temperature and solvent choice for EL exchange, was investigated in terms of produced aerogels morphology, porosity, specific surface area, pore size distribution, mean fibre diameter and fibre diameter size distribution.