Supramolecular Nested Microbeads as Building Blocks for Macroscopic Self‐Healing Scaffolds

Abstract The ability to construct self‐healing scaffolds that are injectable and capable of forming a designed morphology offers the possibility to engineer sustainable materials. Herein, we introduce supramolecular nested microbeads that can be used as building blocks to construct macroscopic self‐healing scaffolds. The core–shell microbeads remain in an “inert” state owing to the isolation of a pair of complementary polymers in a form that can be stored as an aqueous suspension. An annealing process after injection effectively induces the re‐construction of the microbead units, leading to supramolecular gelation in a preconfigured shape. The resulting macroscopic scaffold is dynamically stable, displaying self‐recovery in a self‐healing electronic conductor. This strategy of using the supramolecular assembled nested microbeads as building blocks represents an alternative to injectable hydrogel systems, and shows promise in the field of structural biomaterials and flexible electronics.


Materials and characterisation
All starting materials were purchased from Sigma-Aldrich and used as received, unless stated otherwise. CB [8] was prepared as documented previously. [1,2] Fluorous surfactant XL-01-171 was received a kind gift from Dr Xin Li, Sphere Fluidics Ltd. All aqueous solutions were made in deionized water treated with a Milli-Q TM reagent system (resistivity of 18.2 MΩ·cm at 25 °C). Images of droplet formation were obtained using a Phantom v7.2 camera attached to an Olympus IX71 inverted microscope. Microscopic images and fluorescence images were obtained using an Olympus IX81 inverted optical microscope coupled with a camera of Andor Technology EMCCD iXonEM+ DU 897. Scanning electron microscopy (SEM) observation of freeze-dried samples was carried out by using a Leo 1530 variable pressure SEM with an InLens detector. 1 H NMR spectra (500 MHz) were collected on a Bruker Avance QNP 500 MHz ultrashield spectrometer, equipped with a 5-mm BBO ATM probe with a z-gradient. Rheological characterisation was performed using a controlled stress Discovery Hybrid Rheometer (DHR-2) from TA Instruments, fitted with a 20-mm parallel plate and the results were analysed using TA Instruments' TRIOS software. The gap in the setup for rheological testing of the samples was set at 0.5 mm and experiments were conducted at 25 o C. Dynamic oscillatory strain amplitude sweep measurement was conducted at an angular frequency of 10 rad/s. Dynamic oscillatory frequency sweep measurement was conducted at 1% strain amplitude, between 0.01 to 100 rad/s. Step-strain measurement was performed at room temperature to investigate the recovery properties of macroscopic scaffolds upon destruction at high strains (γ = 1000%), followed by a low magnitude strain (γ = 0.1%) to monitor the recovery.

Synthesis of naphthyl-functionalised hydroxyethyl cellulose (HEC-Np)
To a solution of HEC (1.3 MDa, 1g) in 120 mL N-methylpyrrolidone, 2-naphthyl isocyanate (29.7 mg, 0.18 mmol) and dibutyltin dilaurate (3 drops) was added, and the mixture was stirred for 24 h at room temperature. The product was obtained by precipitation into excessive amount of acetone for three times, and then dried overnight under vacuum at 60 o C (1.01 g, 98%). 1  For the synthesis of rhodamine B-labeled HEC-Np, rhodamine B isocyanate (1 mg, 2 μmol) was added during the reaction between the reaction of HEC and 2-naphthyl isocyanate, following the above-mentioned protocol.

Microfluidic device fabrication
The microfluidic device for producing water-in-oil microdroplets was produced via soft lithography by pouring poly(dimethylsiloxane) (PDMS) along with crosslinker (Sylgard 184 elastomer kit, Dow Corning, pre-polymer: crosslinker = 10 : 1) onto a silicon wafer patterned with SU-8 photoresist. [3][4] The PDMS was allowed to solidify at 70 °C overnight before it was peeled off, while inlets and outlets were generated using a biopsy punch. The enclosed microfluidic channels were formed by attaching the moulded PDMS

Droplets-based microfluidic formation of supramolecular shielded microgels
The formation of supramolecular shielded microgels was achieved by assembly of HBPCB[8] and HEC-Np in microfluidic droplets. To generate water-in-oil microdroplets, three different liquids were injected into a microfluidic device by three syringe pumps (PHD, Harvard Apparatus) with controlled flow rates ( Figure S1). One discontinuous aqueous phase for inlet 1 was prepared by dissolving

Generation of a macroscopic scaffold from supramolecular shielded microgels
The macroscopic scaffold was prepared by injection of supramolecular shielded microgels suspensions in a pre-designed mould.
Supramolecular shielded microgels (19.5 mg) were mixed with HBPCB[8] solution (CB[8] = 8 mM, 500 μL) and loaded in a 1 mL syringe. The mixture was extruded through an 25G needle for injected into a pre-designed mould and filled in the whole cubic area.
Macroscopic scaffold annealing was conducted at 65 o C for 30 min and then cooled down to the room temperature. To prevent evaporation of water during the thermo-treatment, the mould was kept in a petri dish sealed by the parafilm.

Fabrication of self-healable electronic conductor using mouldable hydrogel scaffolds
A silver nanowires dispersion was drop-cast on the precleaned PDMS substrate to form a network of silver nanowires. After drying, a mixture of supramolecular shielded microgels (19.5 mg) in HBPCB  Figure S1 shows the molecular structures of the cucurbit[8]uril-threaded highly-branched polyrotaxanes (HBPCB[8]) and

Supplementary figures
naphthyl-functionalised hydroxyethyl cellulose (HEC-Np), which were used for constructing of supramolecular shielded microgels in microfluidic droplets. Figure S2. 1H NMR spectrum of the highly branched HBPCB[8] (D2O, 298 K, 500 MHz). [5] Microdroplets containing a mixture of HBPCB[8], CB[8], and HEC-Np were genereated by a flow-focusing microfluidic device ( Figure   S3). Upon water evaporation in microdroplets, it was found that the structure was collapsed because of a lack of internal support, with creases and folds clearly observed on the supramolecular polymer skins ( Figure S4).  In the dynamic rheological measurements, the dynamic amplitude sweep was carried out. A sharp increase in G' was observed from ca. 2 Pa (dispersed supramolecular microgels) to ca. 1000 (annealed microgels samples) upon 30-min annealing at 65 o C.