Basic fibroblast growth factor(Kyoto University)

Microglia‐mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood–brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane‐coated PEGylated liposomes (hFGF21@BCM‐LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM‐LIP specifically targets Aβ1‐42‐induced BV2 cells, with uptake hindered by anti‐VCAM‐1 antibody, indicating the importance of VCAM‐1 and integrin α4/β1 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM‐LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid‐beta (Aβ1‐42)‐induced mice. Furthermore, the administration of hFGF21@BCM‐LIP to activated microglia improves cognitive deficits caused by Aβ1‐42 and reduces levels of tau, p‐Tau, and BACE1. It also decreases interleukin‐6  (IL‐6) and tumor necrosis factor‐α (TNF‐α) release while increasing interleukin‐10 (IL‐10) release both in vivo and in vitro. These results indicate that hFGF21@BCM‐LIP can be a promising treatment for AD, by effectively crossing the blood–brain barrier and targeting delivery to brain microglia via the neck‐meningeal lymphatic vasculature‐brain parenchyma pathways.

Bioactive scaffolds accurately mimicking the structure and composition of the extracellular matrix have garnered significant interest in tissue engineering. In this study, we developed a platform utilizing natural silk nanofibrils, hyaluronic acid, and basic fibroblast growth factor for the purpose of promoting spinal cord regeneration by creating an optimal microenvironment. The bioactive scaffold exhibited notable characteristics such as high porosity and hydrophilicity, attributed to its unique nanostructure, high connectivity, and polysaccharide composition. Furthermore, the pore size of the scaffold can be adjusted within the range of 90 μm to 120 μm by varying the content of hyaluronic acid. In vitro, human umbilical vein endothelial cells were seeded into the scaffold, demonstrating enhanced cell viability. The scaffold facilitated cell proliferation and migration. In vivo experiments on rats indicated that the scaffold had a beneficial impact on spinal cord regeneration, creating a conducive environment for motor function recovery of the rats. This effect may be attributed to the scaffold's ability to stimulate axon growth and neuronal survival, as well as inhibit the formation of glial scars, as evidenced by the decreased expression of growth associated protein-43, microtubule-associated protein 2, and neurofilament-200. This study presents a promising method to develop a feasible bioscaffold for the treatment of spinal cord injury.