Suppression Of Phase Separation Research Articles

Tackling P3HT:Y‐Series Miscibility Through Advanced Processing for Tunable Aggregation

AbstractPolymer and small molecule blend thin films are of strong interest for organic electronics and particularly organic solar cells. The high miscibility in blends of ordinary P3HT and state‐of‐the‐art Y‐series non‐fullerene acceptors (NFAs) suppresses phase separation and aggregation challenging successful charge separation and transport. In a recent work, current‐induced doping (CID) is introduced, a method to precisely control the aggregation of Poly(3‐hexylthiophene) (P3HT) in solution. The highly ordered pre‐aggregation in solution is used here to control the P3HT aggregation in neat films and blends with Y12 (BTP‐4F‐12). This results in a 25‐fold increase in hole mobility in P3HT organic field‐effect transistor (OFET) devices and tunability of the P3HT aggregate quality in the presence of Y12 over large ranges. At the same time, particularly the Y12 long‐range ordering is heavily suppressed by increasing P3HT aggregation. However, solvent vapor annealing (SVA) leads to an extraordinarily high Y12 ordering, changes in the crystal orientation of Y12, and a further improvement of P3HT aggregation. A broad range of different degrees of aggregation of both materials can therefore be obtained in the final thin films solely by changing processing parameters without changing the composition of the material system.

Identification of Essential Components of RNA Binding Domain of TLS/FUS

TLS/FUS is RNA-binding protein having multiple functions of regulations of genes, homeostasis, and cellular growth. Recent studies show that TLS is involved in phase separation and occasionally forms precipitation related to neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). RNA has been reported to suppress phase separation, droplet formation, and concomitant precipitation of TLS, suggesting that RNA is a possible candidate for ALS drug discovery. Our experiments demonstrated that a long noncoding RNA, promoter-associated noncoding RNA (pncRNA-D), specifically binds TLS and represses its phase separation and precipitation. To obtain competent drug seeds, it is essential to reveal mechanism of action of lncRNAs with specificity to TLS and inhibitory activity on phase separation and related precipitation. For this purpose, several lncRNAs (lncRNAs 1 to 6) were selected upon assays with GST-TLS binding and inhibition on the precipitation. With criteria of binding specificity for TLS, lncRNA3 has been selected for further analysis for RNA-binding ability. Initially, RNA-binding region at TLS amino acid sequence was identified from four fragments of TLS. RNA binding assay with biotinylated lncRNA3 precipitated with avidin magnetic beads indicated clearly that TLS binds the fragment 4 (373-526 aa), C-terminus end of TLS. Then, dissecting fragment 4 presents four regions, RGG2, zinc finger, RGG3, and the nuclear localization signal (NLS) region in this order. Experiments with extensive deletion mutants indicated that just one deletion out of the four regions irs not enough to delete the TLS binding, although combinatorial deletion of zinc finger with other three regions almost wiped off the lncRNA3 binding. Remarkably, each of four regions alone has no binding to TLS, either. Collectively, RGG2, zinc finger, RGG3, and NLS all are essential for binding to lncRNA3, but are required to work synergistically for full binding. These data indicate that dynamic assembly of RNA-binding domain works for action of lncRNAs and possibly has allosteric effect on intrinsically disordered region (IDR) of N-terminus of TLS, implying relation of RNA-binding with phase separation and the resultant precipitation.

Suppressed phase separation in high-voltage LiNi0.5Mn1.5O4 cathode via Co-doping

Spinel LiNi0.5Mn1.5O4 (LNMO) is a promising cathode material with high operating voltage and energy density. However, the poor rate performance caused by the two-phase reaction during charging and discharging limits its large-scale application. In this work, Co3+ doped LNMO cathode materials are prepared by co-precipitation method, and the effect of Co3+ doping replacing Mn4+, as well as the amount of Co3+ doping (LiNi0.5CoxMn1.5-xO4) are explored. Co3+ doping increases the content of Mn3+, thus improving the electronic conductivity of LNMO. Co3+ doping suppresses the phase transition of LNMO during discharging, which results in a smaller volume change and improves cycling stability. The presence of a solid solution intermediate allows for more uniform changes within the particles during the discharge process, thus increasing the diffusion rate of Li+ ion. LiNi0.5Co0.05Mn1.45O4 exhibits the best electrochemical performance compared to other samples, with a discharge specific capacity of 111.1 mAh g−1 after 500 cycles at 1 C and a capacity retention of 92.4%. At 10 C high rate, the specific discharge capacity is 106.8 mAh g−1. Our research reveals that Co3+ doping can improve the electrochemical performance of LNMO and provide a deeper insight into Co3+ doping of other cathode materials.

Inhibition strategies for phase separation of iron-based oxygen carriers in chemical looping gasification- enhanced oxygen transport efficiency through oxide-support interactions

Chemical looping gasification partially oxidizes biomass to obtain high-quality syngas using oxygen carriers, emerging as a potential method to cope with energy shortages. However, the oxygen carriers were susceptible to deactivation due to phase separation caused by different migration rates between atoms. In this work, the phase deviation of the oxygen carrier is inhibited by enhancing the lattice oxygen activity. Typically, the NiFe-based oxygen carriers were used as active sites and Ce atoms were introduced to change the lattice structure of the oxygen carriers. Calculated by density functional theory (DFT), Ce atoms formed a strong bonding interaction (Ni-O-Ce) with Ni atoms, causing lattice distortion of NiFe oxygen carriers that promote the formation of oxygen vacancies. Therefore, the syngas yields were increased from 537 ml/g (NF) to 633 ml/g (NF@0.5Ce) and 615 ml/g (NF@1.5Ce) in the N2 atmosphere. The syngas yields were increased from 895 to 1101 ml/g (NF@0.5Ce) and 1186 ml/g (NF@1.5Ce) with steam atmosphere. During the 20-cycle experiments, the phase separation of NiFe-based oxygen carriers was effectively suppressed by the intervention of Ce atoms. Therefore, it is a feasible option to induce lattice distortion of active grains by introducing inert elements to suppress phase separation.

Ligand Mediated Assembly of CdS Colloids in 3D Porous Metal–Organic Framework Derived Scaffold with Multi‐Sites Heterojunctions for Efficient CO2 Photoreduction

AbstractThe inclusion of colloidal particles into 3D porous constructs to realize heterostructure ensembles enhances surface interactions and energy transfer that can transform the catalytic properties of conventional catalysts. However, assembling hydrophobic colloidal nanoparticles within hydrophilic 3D porous matrices to create tailored heterostructures and catalytic properties is particularly challenging. Here, a modified ligand grafting method is presented to spontaneously assemble CdS inorganic colloidal quantum dots within a metal‐organic framework (MOF) derived porous framework for efficient photocatalytic CO2 reduction. The grafted long chain molecular ligands effectively suppress phase separation and endow a molecular‐recognition effect to form ordered assembly microstructures. The proof‐of‐concept assembly of CdS and Prussian blue analogues (PBA) derived Co3O4 facilitates a high density of heterojunctions formation, improving charge transfer and extended lifetimes of photo‐induced electrons. Consequently, CdS/Co3O4 assembly exhibits exceptionally active and stable photocatalytic CO2 reduction activity, with a CO production rate of 73.9 µmol g−1 h−1 and CO selectivity of 98.9%. Importantly, the ligand grafting method can be generalized to achieve spontaneous assembly of quantum dots within various metal organic framework derived porous scaffolds. This work provides a rational strategy for precise self‐assembly of colloidal nanoparticles within porous microstructures, allowing tailored heterointerfaces for functional materials and applications.

Mechanosensitivity of phase separation in an elastic gel

Liquid–liquid phase separation (LLPS) in binary or multi-component solutions is a well-studied subject in soft matter with extensive applications in biological systems. In recent years, several experimental studies focused on LLPS of solutes in hydrated gels, where the formation of coexisting domains induces elastic deformations within the gel. While the experimental studies report unique physical characteristics of these systems, such as sensitivity to mechanical forces and stabilization of multiple, periodic phase-separated domains, the theoretical understanding of such systems and the role of long-range interactions have not emphasized the nonlinear nature of the equilibrium binodal for strong segregation of the solute. In this paper, we formulate a generic, mean-field theory of a hydrated gel in the presence of an additional solute which changes the elastic properties of the gel. We derive equations for the equilibrium binodal of the phase separation of the solvent and solute and show that the deformations induced by the solute can result in effective long-range interactions between phase-separating solutes that can either enhance or, in the case of externally applied pressure, suppress phase separation of the solute relative to the case where there is no gel. This causes the coexisting concentrations at the binodal to depend on the system-wide average concentration, in contrast to the situation for phase separation in the absence of the gel.Graphical abstract

Phosphomimetic substitutions in TDP-43’s transiently α-helical region suppress phase separation

Phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer’s disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients is located in the low-complexity domain (LCD), the same domain that has been shown to be critical for TDP-43 liquid-liquid phase separation (LLPS). However, the effect of these LCD phosphorylation sites on TDP-43 LLPS has been largely unexplored, and any work that has been done has mainly focused on sites near the C-terminal end of the LCD. Here, we used a phosphomimetic approach to explore the impact of phosphorylation at residues S332 and S333, sites located within the transiently α-helical region of TDP-43 that have been observed to be phosphorylated in disease, on protein LLPS. Our turbidimetry and fluorescence microscopy data demonstrate that these phosphomimetic substitutions greatly suppress LLPS, and solution NMR data strongly suggest that this effect is at least in part due to the loss of α-helical propensity of the phosphomimetic protein variant. We also show that the S332D and S333D substitutions slow TDP-43 LCD droplet aging and fibrillation of the protein. Overall, these findings provide a biophysical basis for understanding the effect of phosphorylation within the transiently α-helical region of TDP-43 LCD on protein LLPS and fibrillation, suggesting that phosphorylation at residues 332 and 333 is not necessarily directly related to the pathogenic process.

A bivalent inhibitor against TDRD3 to suppress phase separation of methylated G3BP1.

The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells. Our result paves a new path to mediate multivalent interactions involved in SG assembly for potential combinational chemotherapy by bivalent inhibitors.

Chemotactic Motility-Induced Phase Separation.

Collectives of actively moving particles can spontaneously separate into dilute and dense phases-a fascinating phenomenon known as motility-induced phase separation (MIPS). MIPS is well-studied for randomly moving particles with no directional bias. However, many forms of active matter exhibit collective chemotaxis, directed motion along a chemical gradient that the constituent particles can generate themselves. Here, using theory and simulations, we demonstrate that collective chemotaxis strongly competes with MIPS-in some cases, arresting or completely suppressing phase separation, or in other cases, generating fundamentally new dynamic instabilities. We establish principles describing this competition, thereby helping to reveal and clarify the rich physics underlying active matter systems that perform chemotaxis, ranging from cells to robots.

Inverted Wide-Bandgap 2D/3D Perovskite Solar Cells with >22% Efficiency and Low Voltage Loss.

Wide-bandgap perovskites play a key role in high-performance tandem solar cells, which have the potential to break the Schockley-Queisser limit. Here, a 2D/3D hybrid wide-bandgap perovskite was developed using octane-1,8-diaminium (ODA) as spacer. The incorporation of the ODA spacer can not only significantly reduce charge carrier nonradiative recombination loss but also inhibit phase separation. Moreover, with a synergy effect using butylammonium iodide (BAI) as a surface defect passivator, both the phase stability and device performance were further improved. Compared to the control inverted device with a VOC of 1.16 V and a PCE of 18.50%, the optimized PSCs based on a surface processed 2D/3D perovskite exhibit a superior high VOC of 1.26 V and a champion PCE of 22.19%, which is a record efficiency for wide-bandgap PSCs (Eg > 1.65 eV). This work provides a very effective strategy to suppress phase separation in wide-bandgap perovskites for highly efficient and stable solar cells.

Asymmetric Polymer Additive for Morphological Regulation and Thermally Stable Organic Solar Cells.

High thermal stability is crucial for the commercialization of organic solar cells (OSCs). The thermal stability of OSCs has been improved using the tailoring blend morphology of bulk heterojunctions (BHJs). Herein, we demonstrated thermally stable OSCs in a ternary blended system containing low-crystalline semiconducting polymers (asy-PNDI1FTVT and PTB7-Th) and a non-fullerene acceptor (Y6). The asymmetric n-type semiconducting polymer (asy-PNDI1FTVT) differed from general symmetric semiconducting polymers as it randomly substituted fluorine atoms at the donor moiety (TVT), resulting in significantly lower crystallinity. asy-PNDI1FTVT in PTB7-Th:Y6 exhibited a well-mixed morphology at the BHJ and efficiently facilitated the charge dissociation process with an enhanced fill factor and power conversion efficiency. Furthermore, the ternary system of PTB7-Th:Y6:asy-PNDI1FTVT suppressed phase separation with negligible burn-in loss and performance degradation under thermal stress. The experiments showed that our devices without encapsulation retained over 90% of their initial efficiencies after 100 h at 65 °C. These results show significant potential for the development of thermally stable OSCs with reasonable efficiency.

Suppressed Phase Separation of Mixed-Halide Perovskite Quantum Dots Confined in Mesoporous Metal Organic Frameworks.

Mixed-halide perovskite quantum dots (PeQDs) are the most competitive candidates in designing solar cells and light-emitting devices (LEDs) due to their tunable bandgap and high-efficiency quantum yield. However, phase separation in mixed-halide perovskites under illumination can form rich iodine and bromine regions, which change its optical responses. Herein, we synthesize PeQDs combined with mesoporous zinc-based metal organic framework (MOF) crystals, which can greatly improve the stability of anti-anion exchange, including photo-, thermal, and long-term stabilities under illumination. This unique structure provides a solution for improving the performance of perovskite optoelectronic devices and stabilizing mixed-halide perovskite devices.

Effect of in-situ Zn doping on suppression of phase separation in InxAl1−xAs epitaxial layer on InP(001) grown by MOCVD

The effect of Zn impurities on the surface morphology evolution and phase separation behavior of the InAlAs layer on InP(001) substrates is investigated using metal organic chemical vapor deposition (MOCVD). The phase separation of InAlAs occurs at a relatively low growth temperature (T < 620 °C), accompanied by surface roughening and bandgap lowering. According to the microstructural analyses, indium (In) and aluminum (Al) atoms have high reactivity with In-rich or Al-rich columns in a certain growth region. The addition of Zn impurities during InAlAs growth at the phase-separating temperature results in the suppression of phase separation, which can be attributed to a high probability of Zn incorporation into the sites, which generates an In-rich and Al-rich phase column in the phase-separated InAlAs layer. Based on atomic force microscopy (AFM) and high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM) analysis, we classify four types of InAlAs surface morphology as a function of the growth temperature and flow rate of Zn impurities.

Co-phase separation of Y14 and RNA in vitro and its implication for DNA repair.

The multifunctional RNA recognition motif-containing protein Y14/RBM8A participates in mRNA metabolism and is essential for the efficient repair of DNA double-strand breaks (DSBs). Y14 contains highly charged, low-complexity sequences in both the amino- and carboxy-terminal domains. The feature of charge segregation suggests that Y14 may undergo liquid-liquid phase separation (LLPS). Recombinant Y14 formed phase-separated droplets, which were sensitive to pH and salt concentration. Domain mapping suggested that LLPS of Y14 involves multivalent electrostatic interactions and is partly determined by the net charge of its low-complexity regions. Phospho-mimicry of the carboxy-terminal arginine-serine dipeptides of Y14 suppressed phase separation. Moreover, RNA could phase separate into Y14 droplets and modulate Y14 LLPS in a concentration-dependent manner. Finally, the capacity of Y14 in LLPS and coacervation with RNA in vitro correlated with its activity in DSB repair. These results reveal a molecular rule for LLPS of Y14 in vitro and an implication for its co-condensation with RNA in genome stability.

Heterogeneous intercalated metal-organic framework active materials for fast-charging non-aqueous Li-ion capacitors

Intercalated metal-organic frameworks (iMOFs) based on aromatic dicarboxylate are appealing negative electrode active materials for Li-based electrochemical energy storage devices. They store Li ions at approximately 0.8 V vs. Li/Li+ and, thus, avoid Li metal plating during cell operation. However, their fast-charging capability is limited. Here, to circumvent this issue, we propose iMOFs with multi-aromatic units selected using machine learning and synthesized via solution spray drying. A naphthalene-based multivariate material with nanometric thickness allows the reversible storage of Li-ions in non-aqueous Li metal cell configuration reaching 85% capacity retention at 400 mA g−1 (i.e., 30 min for full charge) and 20 °C compared to cycling at 20 mA g−1 (i.e., 10 h for full charge). The same material, tested in combination with an activated carbon-based positive electrode, enables a discharge capacity retention of about 91% after 1000 cycles at 0.15 mA cm−2 (i.e., 2 h for full charge) and 20 °C. We elucidate the charge storage mechanism and demonstrate that during Li intercalation, the distorted crystal structure promotes electron delocalization by controlling the frame vibration. As a result, a phase transition suppresses phase separation, thus, benefitting the electrode’s fast charging behavior.

Control of Host-Matrix Morphology Enables Efficient Deep-Blue Organic Light-Emitting Devices.

Mixing a sterically bulky, electron-transporting host material into a conventional single host-guest emissive layer isdemonstratedtosuppress phase separation of the host matrix while increasing the efficiency and operational lifetime of deep-blue phosphorescent organic light-emitting diodes (PHOLEDs) with chromaticity coordinates of (0.14, 0.15). The bulky host enables homogenous mixing of the molecules comprising the emissive layer while suppressing single host aggregation; a significant loss channel of nonradiative recombination. By controlling the amorphous phase of the host-matrix morphology, the mixed-host device achieves a significant reduction in nonradiative exciton decay, resulting in 120 ± 6% increase in external quantum efficiency relative to an analogous, single-host device. In contrast to single host PHOLEDs where electrons are transported by the host and holes by the dopants, both charge carriers are conducted by the mixed host, reducing the probability of exciton annihilation, thereby doubling of the deep-blue PHOLED operational lifetime. These findings demonstrate that the host matrix morphology affects almost every aspect of PHOLED performance.

Magnetic Fields Reduce Apoptosis by Suppressing Phase Separation of Tau-441.

The biological effects of magnetic fields (MFs) have been a controversial issue. Fortunately, in recent years, there has been increasing evidence that MFs do affect biological systems. However, the physical mechanism remains unclear. Here, we show that MFs (16 T) reduce apoptosis in cell lines by inhibiting liquid-liquid phase separation (LLPS) of Tau-441, suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the "mysterious" magnetobiological effects. The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite. The phase-separated droplets of Tau-441 recruited hexokinase (HK), resulting in a decrease in the amount of free HK in the cytoplasm. In cells, HK and Bax compete to bind to the voltage-dependent anion channel (VDAC I) on the mitochondrial membrane. A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I, leading to increased Bax-mediated apoptosis. In the presence of a static MF, LLPS was marked inhibited and HK recruitment was reduced, resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I, thus reducing Bax-mediated apoptosis. Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS. In addition, these results show the potential applications of physical environments, such as MFs in this study, in the treatment of LLPS-related diseases.

Activity-Suppressed Phase Separation.

We use a continuum model to examine the effect of activity on a phase-separating mixture of an extensile active nematic and a passive fluid. We highlight the distinct role of (i)previously considered interfacial active stresses and (ii)bulk active stresses that couple to liquid crystalline degrees of freedom. Interfacial active stresses can arrest phase separation, as previously demonstrated. Bulk extensile active stresses can additionally strongly suppress phase separation by sustained self-stirring of the fluid, substantially reducing the size of the coexistence region in the temperature-concentration plane relative to that of the passive system. The phase-separated state is a dynamical emulsion of continuously splitting and merging droplets, as suggested by recent experiments. Using scaling analysis and simulations, we identify various regimes for the dependence of droplet size on activity. These results can provide a criterion for identifying the mechanisms responsible for arresting phase separation in experiments.

Compliant, Tough, Anti-Fatigue, Self-Recovery, and Biocompatible PHEMA-Based Hydrogels for Breast Tissue Replacement Enabled by Hydrogen Bonding Enhancement and Suppressed Phase Separation

Although hydrogel is a promising prosthesis implantation material for breast reconstruction, there is no suitable hydrogel with proper mechanical properties and good biocompatibility. Here, we report a series of compliant and tough poly (hydroxyethyl methacrylate) (PHEMA)-based hydrogels based on hydrogen bond-reinforcing interactions and phase separation inhibition by introducing maleic acid (MA) units. As a result, the tensile strength, fracture strain, tensile modulus, and toughness are up to 420 kPa, 293.4%, 770 kPa, and 0.86 MJ/m3, respectively. Moreover, the hydrogels possess good compliance, where the compression modulus is comparable to that of the silicone breast prosthesis (~23 kPa). Meanwhile, the hydrogels have an excellent self-recovery ability and fatigue resistance: the dissipative energy and elastic modulus recover almost completely after waiting for 2 min under cyclic compression, and the maximum strength remains essentially unchanged after 1000 cyclic compressions. More importantly, in vitro cellular experiments and in vivo animal experiments demonstrate that the hydrogels have good biocompatibility and stability. The biocompatible hydrogels with breast tissue-like mechanical properties hold great potential as an alternative implant material for reconstructing breasts.

Mechanically robust, biocompatible, and durable PHEMA-based hydrogels enabled by the synergic effect of strong intermolecular interaction and suppressed phase separation

Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel is highly biocompatible and stable, but its actual application in soft-tissue replacement is limited by its poor mechanical properties. This study develops a facile strategy to construct PHEMA-based hydrogels with the highest strength and toughness ever reported. The strategy relies on introducing robust coordination interactions between the carboxylate groups of copolymerized maleic acid (MA) units and Fe 3+ to suppress the phase separation of PHEMA chains from aqueous solution, thereby inducing a homogeneous network. The homogeneous network can avoid stress concentrations, and dynamic coordination crosslinking can effectively dissipate energy and simultaneously maintain network elasticity. The synergistic effects of these two factors impart exceptionally high tensile strength (3.44 MPa), elastic modulus (14.22 MPa), and toughness (4.17 MJ/m 3 ) to the hydrogels, which are 22.7, 43.1, and 24.2 times higher than those of pure PHEMA hydrogels, respectively. Such mechanical properties are comparable to human nasal and auricular cartilage. The hydrogels manifest outstanding self-recovery properties and fatigue resistance, which are essential for long-term and sustainable use. In vitro cell and in vivo animal experiments show that this strategy does not sacrifice the excellent biocompatibility and stability of the PHEMA hydrogels. These PHEMA-based hydrogels, with excellent mechanical properties, fatigue resistance, and biocompatibility, are promising candidates for replacing diseased or damaged nasal and auricular cartilage. Mechanically robust, biocompatible, and durable PHEMA-based hydrogels with cartilage mimetic properties are prepared by designing a homogeneous network with strong ionic coordination interactions. The hydrogels possess excellent mechanical properties by modulating the MA content or FeCl 3 solution concentration, which is comparable to human nasal and auricular cartilage. Good fatigue resistance properties support the hydrogels for long-term and sustainable use. Combined with long-term biocompatibility and stability in vivo , the high-performance PHEMA-based hydrogels show great application prospects as a desirable candidate material for replacing diseased or damaged nasal and auricular cartilage. • Hydrogels are designed by a homogenous network with robust coordination interactions. • The homogeneous network is induced by suppressing phase separation. • The mechanical properties of hydrogels are significantly improved by such design. • Hydrogels also manifest good biocompatibility and stability. • Hydrogels are promising candidates in nasal and auricular cartilage replacement.