Natural nerve tissue is composed of nerve bundles with multiple aligned assembles, and matrix electroconductivity is beneficial to the transmission of intercellular electrical signals, or effectively deliver external electrical cues to cells. Herein, aiming at the biomimetic design of the extracellular matrix for neurons, we first synthesized electroconductive polypyrrole (PPy) nanoparticles with modified hydrophilicity to improve their uniformity in collagen hydrogel. Next, cell-laden collagen−PPy hybrid hydrogel microfibers with highly oriented microstructures were fabricated via a microfluidic chip. The hydrogel microfibers formed a biomimetic three-dimensional microenvironment for neurons, resulting from the native cell adhesion domains, oriented fibrous structures, and conductivity. The oriented fibrous microstructures enhanced neuron-like cells aligning with fibers' axon; the matrix conductivity improved cell extension and upregulated neuralrelated gene expression; moreover, external electrical stimulation further promoted the neuronal functional expression. This mechanism was attributed to the electroconductive matrix and its delivered electrical stimulation to cells synergistically upregulated the expression of an L-type voltage-gated calcium channel, resulting in an increase in the intracellular calcium level, which in turn promoted neurogenesis. This approach has potential in constructing the biomimetic microenvironment for neurogenesis.

Hydroxyapatite nanoparticles (HA NPs) have been acknowledged for their benign biocompatibility and proliferation inhibition effect on tumor cells, attracting considerable attention for tumor therapeutics without late effects. However, unnoticeable tumor cytotoxicity of HA NPs limited the final clinical therapeutic efficacy. Herein, a two-phase synthetic approach was developed to synthesize sphere-like HA NPs by varying the conventional growth habit of HA precipitate. We present our in vitro and in vivo experimental evidence that spherical HA NPs have surprisingly high inhibitory activities against tumor cells. We demonstrate further, based on our experimental data, that the underlying cause for the death of the tumor cells is related to two concurrent pathways, the mitochondria-dependent apoptosis pathway and negative regulation of the phosphatidylinositol-3-kinase/protein kinase B (PIK3/AKT) pathway. The present study indicated that HA nanospheres can be engineered as nontoxic specific inhibitors for efficient tumor therapeutics with nanobiomaterials.

Electrical stimulation is regarded pivotal to promote repair of nerve injuries, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche. Herein, a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation is demonstrated. By the preparation of magnetoelectric core/shell structured Fe3O4@BaTiO3 NPs‐loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto‐electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches‐mimicked hydrogel network, arising prospects not only in neurogenesis but also in human–computer interaction with higher resolution.

Following spinal cord injury (SCI), the transmission of electrical signals is interrupted, and an oxidative microenvironment is generated, hindering nerve regeneration and functional recovery. The strategies of regulating oxidative pathological microenvironment while restoring endogenous electrical signal transmission hold promise for SCI treatment. However, challenges are still faced in simply fabricating bioactive scaffolds with both antioxidation and conductivity. Herein, aiming to construct an antioxidative and conductive microenvironment for nerve regeneration, the difunctional polypyrrole (PPy) nanoparticles were developed and incorporated into bioactive collagen/hyaluronan hydrogel. Owing to the embedded PPy in hydrogel, the encapsulated bone marrow mesenchymal stem cells (BMSCs) can be protected from oxidative damage, and their neuronal differentiation was promoted by the synergy between conductivity and electrical stimulation, which is proved to be related to PI3K/Akt and the mitogen-activated protein kinase (MAPK) pathway. In SCI rats, the BMSC-laden difunctional hydrogel restored the transmission of bioelectric signals and inhibited secondary damage, thereby facilitating neurogenesis, resulting in prominent nerve regeneration and functional recovery. Overall, taking advantage of a difunctional nanomaterial to meet two essential requirements in SCI repair, this work provides intriguing insights into the design of biomaterials for nerve regeneration and tissue engineering.

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