The Colloid and Interface Chemistry Team at the School of Chemistry and Chemical Engineering has gained a series of research achievements in the research field of colloidal dispersion systems such as hydrogel and colloidal particle assembly. The team proposed a new strategy of polyphenol-based hydrogel to restore neuronal iron homeostasis and induce nerve regeneration, and revealed the role of iron homeostasis in neuronal regeneration. In addition, a photo-regulated ion conducting hydrogel was developed to simulate synaptic information processing. The application of colloidal dispersion system in bionic intelligent information sensing and processing was expanded. For colloid nanoparticle assembly, a strategy of chiral transfer from chiral organic molecules to non-chiral CdSe/CdS nanorods was proposed. Relevant studies have recently been published in Proc. Natl. Acad. Sci. U.S.A., Sci. Adv., J. Am. Chem. Soc., Angew. Chem. Int. Ed.etc.

1. Restoring neuronal iron homeostasis by polyphenol-based hydrogels revitalizes neurogenesis after spinal cord injury

The regeneration of neurons and axons is severely limited following spinal cord injury (SCI) that can induce impairment of neurological function. The recovery of nerves and functions after spinal cord injury has attracted great interests. The imbalance of ion homeostasis is a key pathological feature in the microenvironment of SCI, and its effect on nerve regeneration remains unclear. Polyphenols, as iron chelators and building blocks for hydrogel formation, are hypothesized to promote SCI repair and provide a suitable microenvironment for neurogenesis via chelating overloaded iron ions at the lesion sites to form inactive complexes, scavenging reactive oxygen species (ROS), and ameliorating inflammation.

The teams from Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education and Qilu Hospital of Shandong University have discovered that iron overloading after SCI initiates the Fenton reaction and plays a vital role in the axon disruption and neuronal regeneration failure. To address this issue, they develop a locoregional implant of polyphenol-based hydrogels composed of tannic acid and carboxymethyl chitosan that can restore the neuronal iron homeostasis, inhibit lipid peroxidation and suppress inflammation to revitalize intrinsic neurogenesis and improve locomotor behaviors after SCI. Notably, hydrogel-mediated iron homeostasis resulted in newborn neurons, which could contribute to the reconstruction of functional neural networks and the transmission of electrophysiological signals for improving coordination motor recovery in SCI rats (Fig. 1).

The study, a cross-disciplinary research of colloid and interface chemistry and biomedicine, reveals the importance of iron homeostasis in restorative neuroscience by using polyphenol-based hydrogels, which provides a promising strategy to facilitate neurogenesis for the treatment of other nervous injury-related diseases (e.g., trauma brain injury, cerebral hemorrhage). The work was published on Proc. Natl. Acad. Sci. The corresponding authors are Professors Cui Jiwei, Hao Jingcheng from the School of Chemistry and Chemical Engineering at Shandong University and Professor Ni Shilei from the Department of Neurosurgery, Qilu Hospital of Shandong University. Dr. Geng Huimin and Li Zhiwei from Shandong University are the co-first authors. This research is a significant progress based on the previous related achievements (Angew. Chem. Int. Ed. 2021,60, 21529; J. Am. Chem. Soc. 2022,144, 18419; Angew. Chem. Int. Ed. 2023,62, e202218021).

Figure 1. (A) Schematic illustration of TPC hydrogels for SCI repair via chelation of overloaded iron ions, remove of ROS, and suppression of inflammation, resulting in neural regeneration, attenuation of glial scar, and locomotor recovery in rats. (B) Experimental design for electrophysiological analysis. (C) Motor evoked potential (MEP) and somatosensory evoked potential (SEP) signals. (D) Representative immunostaining images of lesion areas in the SCI and TPC groups at 8 wpi stained with anti-NeuN antibodies (green), anti-GFAP antibodies (red), and DAPI (blue).

2. An optically modulated ion-conductive hydrogel, that simulates biological synaptic functions, opens up the application of colloidal systems in the bioinspired technology of information sensing and processing

Figure 2. Schematic illustration of information transmission controlled by neural synapse and generation of motion feedback in biological visual perception. In the hydrogel-based artificial synapse, the photothermal-induced controllable assembly of amphiphilic molecules converts the infrared optical pulse signal into the cumulative electrical signal, simulating the intelligent function of the neural synapse.

The transmission and processing of information in the biological nervous system always rely on the migration of ions to achieve intelligent neural activities, such as learning, memory, and perceptual feedback. In this process, the neural synapse serves as the fundamental functional unit and can regulate the information transmission ability between neurons by altering the synaptic weight through the transmembrane transport of ions and neurotransmitters under the stimulation of action potentials (Figure 2). Therefore, how to control the ion migration in gel materials and transform the environmental information into logical feedback is the key scientific problem for colloidal materials to perform information functions.

Through the design and synthesis of an ionic surfactant with temperature-controlled assembly behavior, a stretchable hydrogel performing infrared photoresponsive conductivity was constructed with the assistant of a photothermal conversion nanomaterial and a polymeric network. Relying on the dynamic assembly principle of ionic surfactants, the hydrogel can generate cumulative electrical signals by using infrared light pulse as input, which successfully simulates the functions of biological synapses, including excitatory postsynaptic membrane potential, pulse facilitation effect and short-term plasticity. The hydrogel has intrinsically stretchable electrical properties for realizing stable bioinspired synaptic functions under different strain states. Moreover, the hydrogel was used as an information processing unit to construct an optically modulated autonomous motion feedback system for sensing different optical signals and regulating the grasping behavior of a robotic hand, performing the “all-or-none” principle and the brain-like “learning-experience” ability. Based on the controllable assembly principle of colloidal dispersion system, this work broke through the technical bottleneck of traditional ionic hydrogels for performing diversified electrical functions, proposed a new mechanism for achieving bio-inspired information processing functions and constructed a novel strategy for transforming optical information into readable and logical electrical signals. The relevant research results are published in Science Advances. Professors Liu Yaqing and Hao Jingcheng from the School of Chemistry and Chemical Engineering are the corresponding authors of this paper. Tian Huasheng, a PhD student from Shandong University is the first author.

3. A strategy for regulating chirality transfer from chiral organic molecules to achiral CdSe/CdS nanorods was proposed using depletion interaction between colloidal nanoparticles.

Chiral effects can be found in natural systems across multiple length scales and are of fundamental importance in physics, chemistry, and materials science. Manipulation of the chirality at all scales has a cross-disciplinary importance and may address key challenges at the heart of colloid and interface chemistry research. Optically active chiral materials have been intensively investigated due to their potential uses in diverse fields, including asymmetric catalysis, biomedical engineering, and advanced optics. One of the ongoing goals in the synthetic realm is to develop chiral materials with high optical asymmetry known as g-factor at the ground or excited state, and the latter refers to circularly polarized luminescence (CPL)-active materials. One of the common strategies is to assemble nanoparticles on rigid chiral templates through electrostatic interaction, hydrogen bonding or coordination to form chiral structures. However, irreversible chemical adsorption leads to non-precise arrangement of nanoparticles on chiral templates, and the optical asymmetry factor of chiral assembly materials usually falls in the range between 10⁻⁴ and 10⁻³.

This work reports how the depletion interaction enabled by diversified small-molecular additives can regulate the chirality transfer from homochiral organic molecules to the achiral nanorods. The geometrical configuration of nanorods can be controlled by molecular additives, where distinct nanorod orientations of both End-To-End and Side-By-Side modes. When nanorods are co-assembled with chiral molecules, this depletion interaction can effectively regulate the chiral assembly structure of nanorods, as well as chirality inversion and amplification. On this basis, a chiral luminescent assembly material with a significantly promoted luminescence dissymmetry factor of approximately 0.3 was successfully constructed. In summary, this work breaks through the traditional thinking paradigm of regulating the chirality of colloidal nanoparticles. Focusing on regulating the interaction between colloidal nanoparticles, the authors elucidated the controllable chirality transfer mechanism from chiral supramolecular to nanoparticle assemblies, and established a new strategy for the controllable preparation of chiral colloidal materials with high asymmetry factors. Related results have been published in J. Am. Chem.（Soc，2023, 145, 17274).

Figure 3. Regulatory mechanisms of chirality transfer in multicomponent assemblies

Link to the articles:

PNAS:https://www.pnas.org/doi/10.1073/pnas.2220300120

SciAdv:https://www.science.org/doi/10.1126/sciadv.add6950

JACS2023:https://pubs.acs.org/doi/10.1021/jacs.3c04615

AngewChem2021:https://onlinelibrary.wiley.com/doi/10.1002/anie.202108462

JACS2022:https://doi.org/10.1021/jacs.2c06877

AngewChem2023:https://onlinelibrary.wiley.com/doi/10.1002/anie.202218021