The fluid‐filled cystic cavity sealed by a dense scar developed following traumatic spinal cord injury (SCI) has been a major obstacle to neural regeneration and functional recovery. Here the transected lesion is bridged using a functional self‐assembling peptide (F‐SAP) hydrogel loaded with membrane‐permeable intracellular sigma peptide (ISP) and intracellular LAR peptide (ILP), targeted at perturbing chondroitin sulfate proteoglycan (CSPG) inhibitory signaling. As compared to F‐SAP hydrogel loaded with chondroitinase ABC, the F‐SAP+ISP/ILP promotes a beneficial anti‐inflammatory response via manipulation of microglia/macrophages infiltration and assembly of extracellular matrix (ECM) molecules into fibrotic matrix rather than scarring tissues. The remodeled ECM creates a permissive environment that supports axon regrowth and the formation of synaptic connections with neurons derived from endogenous neural stem cells. The remodeled networks contribute to functional recovery, as demonstrated by improved hind limb movements and electrophysiological properties. This work proposes a unique mechanism that ECM remodeling induced by CSPG‐manipulation‐based anti‐inflammation can construct a permissive environment for neural regeneration, and shed light on the advancement of manipulation of cascading cellular and molecular events potential for endogenous repair of SCI.
Hydrogel‐based regenerated scaffold shows promise as a platform for neural regeneration following spinal cord injury (SCI). Nevertheless, the persistent problem of poor mechanical strength and limited integration with the host tissue still exists. In this study, we developed a bioinspired hydrogel with highly sophisticated features for neural regeneration after SCI. The hydrogel is composed of DOPA‐grafted chitosan and a designer peptide, offering a unique set of qualities such as being injectable, having self‐healing abilities, and adhering to tissues. Compared to the conventional hydrogel, our hydrogel insured as significant promotion of the immune response modulation and axon regrowth while featuring synapse formation of various neurotransmitters and myelin regeneration. Subsequently, functional recoveries were enhanced, including motor function, sensory function and particularly bladder defect repair. These positive findings demonstrate that the hydrogel has great potential as a strategy for repairing SCI. Moreover, the versatility of this strategy goes beyond neural regeneration and holds promise for tissue regeneration in other contexts. Overall, our proposed hydrogel represented an innovative and multifaceted tool for engineering structures in the biomedical field.This article is protected by copyright. All rights reserved
Local reconstruction of a permissive environment with biomaterials is a promising strategy to treat spinal cord injury (SCI). We reported a hybrid hydrogel fabricated from a small functional self-assembling peptide (F-SAP) and large silk fibroin (SF). The diffusion of SF micelles into F-SAP solution was driven by the dynamic synergy between osmotic pressure and F-SAP/SF electrostatic interactions, resulting in the rearrangement of SF micelles and the formation of rod-like filaments with axes nearly perpendicular to F-SAP nanofibers. Spectroscopy analysis, including circular dichroism, Raman and fluorescence, indicated conformation changes of SF from random coil to β sheet, which contributed to enhanced mechanical properties of the resultant hybrid hydrogel. Furthermore, the F-SAP/SF hybrid hydrogel coupled with controlled release of NT-3 provided a permissive environment for neural regeneration by providing nanofibrous substrates for regenerating axons, inflammatory modulation and remyelination, consequently resulting in improved locomotion and electrophysiological properties. This hydrogel could be used as a long-term stent in vivo for the treatment of SCI.
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