Advances in electroactive bioscaffolds for repairing spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological disorder, leading to loss of motor or somatosensory function, which is the most challenging worldwide medical problem. Re-establishment of intact neural circuits is the basis of spinal cord regeneration. Considering the crucial role of electrical signals in the nervous system, electroactive bioscaffolds have been widely developed for SCI repair. They can produce conductive pathways and a pro-regenerative microenvironment at the lesion site similar to that of the natural spinal cord, leading to neuronal regeneration and axonal growth, and functionally reactivating the damaged neural circuits. In this review, we first demonstrate the pathophysiological characteristics induced by SCI. Then, the crucial role of electrical signals in SCI repair is introduced. Based on a comprehensive analysis of these characteristics, recent advances in the electroactive bioscaffolds for SCI repair are summarized, focusing on both the conductive bioscaffolds and piezoelectric bioscaffolds, used independently or in combination with external electronic stimulation. Finally, thoughts on challenges and opportunities that may shape the future of bioscaffolds in SCI repair are concluded.

Poly(N-acryloyl glycinamide-co-N-acryloxysuccinimide) Nanoparticles: Tunable Thermo-Responsiveness and Improved Bio-Interfacial Adhesion for Cell Function Regulation.

Poly(N-acryloyl glycinamide) (PNAGA) can form high-strength hydrogen bonds (H-bonds) through the dual amide motifs in the side chain, allowing the polymer to exhibit gelation behavior and an upper critical solution temperature (UCST) property. These features make PNAGA a candidate platform for biomedical devices. However, most applications focused on PNAGA hydrogels, while few focused on PNAGA nanoparticles. Improving the UCST tunability and bio-interfacial adhesion of the PNAGA nanoparticles may expand their applications in biomedical fields. To address the issues, we established a reactive H-bond-type P(NAGA-co-NAS) copolymer via reversible addition-fragmentation chain transfer polymerization of NAGA and N-acryloxysuccinimide (NAS) monomers. The UCST behaviors and the bio-interfacial adhesion toward the proteins and cells along with the potential application of the copolymer nanoparticles were investigated in detail. Taking advantage of the enhanced H-bonding and reactivity, the copolymer exhibited a tunable UCST in a broad temperature range, showing thermo-reversible transition between nanoparticles (PNPs) and soluble chains; the PNPs efficiently bonded proteins into nano-biohybrids while keeping the secondary structure of the protein, and more importantly, they also exhibited good adhesion ability to the cell membrane and significantly inhibited cell-specific propagation. These features suggest broad prospects for the P(NAGA-co-NAS) nanoparticles in the fields of biosensors, protein delivery, cell surface decoration, and cell-specific function regulation.

H-bond-type thermo-responsive schizophrenic copolymers: The phase transition correlation with their parent polymers and the improved protein co-assembly ability.

Schizophrenic copolymers are one type of the popular smart polymers that show invertible colloidal structures in response to temperature stimulus. However, the lack of principles to predict the phase transition temperature of a schizophrenic copolymer from its corresponding parent thermo-responsive polymers limits their development. Additionally, studies on their applications remain scarce. Herein, a series of schizophrenic copolymers were synthesized by polymerization of a RAFT-made polymer precursor poly(acrylamide-co-N-acryloxysuccinimide-co-acrylic acid) (P(AAm-co-NAS-co-AAc)) with the mixture of N-isopropylmethacrylamide (NIPAm) and acrylamide (AAm) in varying molar ratios. In aqueous solution, the block P(AAm-co-NAS-co-AAc) and the block poly(NIPAm-co-AAm) exhibited upper and lower critical solution temperature (UCST and LCST) behavior, respectively. The schizophrenic copolymers featured either UCST-LCST, LCST-UCST, or only LCST thermo-responsive transition. A preliminary correlation of phase transition between the schizophrenic copolymers and their parent polymers was summarized. Furthermore, the co-assembly of the schizophrenic copolymers and proteins were conducted and the kinetics of protein loading and protein activity were investigated, which showed that the schizophrenic copolymers were efficient platforms for protein co-assembly with ultra-high protein loading while preserving the protein bioactivities. Additionally, all the materials were non-toxic towards NIH 3T3 and MCF-7 cells. This work offers the prospects of the schizophrenic polymers in soft colloidal and assembly systems, particularly in guiding the design of new materials and their use in biomedical applications.

Phospholipid-Decorated Glycogen Nanoparticles for Stimuli-Responsive Drug Release and Synergetic Chemophotothermal Therapy of Hepatocellular Carcinoma.

Dendritic macromolecules are potential candidates for nanomedical application. Herein, glycogen, the natural hyperbranched polysaccharide with favorable biocompatibility, is explored as an effective drug vehicle for treating liver cancer. In this system, glycogen is oxidized and conjugated with cancer drugs through a disulfide link, followed by in situ loading of polypyrrole nanoparticles and then coated with functional phospholipids to form the desired system, Gly-ss-DOX@ppy@Lipid-RGD. The phospholipid layer has good cell affinity and can assist the system to penetrate into cells smoothly. Additionally, combined with the "fusion targeting" of glycogen and the active targeting effect of RGD toward liver cancer cells, Gly-ss-DOX@ppy@Lipid-RGD presents efficient specificity and enrichment of hepatocellular carcinoma. Owing to the glutathione-triggered cleavage of disulfide linkers, Gly-ss-DOX@ppy@Lipid-RGD can controllably release drugs to induce cell nucleus damage. Meanwhile, the polypyrrole nanoparticles can absorb near-infrared light and radiate heat energy within tumors. Besides enhancing drug release, the heat can also provide photothermal treatment for tumors. As proved by in vitro and in vivo experiments, Gly-ss-DOX@ppy@Lipid-RGD is a remarkable candidate for synergistic chemophotothermal therapy with high anticancer therapeutic activity and reduced systematic toxicity, efficiently suppressing tumor growth. All results demonstrate that glycogen nanoparticles are expected to be a new building block for accurate hepatocellular carcinoma treatment.