Targeted Delivery of NGF-Pretreated Schwann Cell-Derived Exosomes for Osteoporosis Therapy: Overcoming Pain while Enhancing Bone Formation

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Biomaterials Science & Engineering Pub Date : 2026-10-12 Epub Date: 2026-09-28 DOI:10.1021/acsbiomaterials.6c00906

Yinnan Guo, Sha Cui, Wenting Zhang, Yali Wu, Qi Song, Le Chang, Xiangying Jiao

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引用次数: 0

Abstract

Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mass and increased fragility, leading to fractures and chronic pain. Nerve growth factor (NGF) plays a pivotal role in bone homeostasis and neuro-regeneration but paradoxically exacerbates pain. This study investigated the therapeutic potential of engineered, bone-targeting exosomes derived from NGF-pretreated Schwann cells (NGF-Exo-Pep) for the treatment of OP. We demonstrated that NGF-Exo-Pep effectively promoted osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs) in vitro, while also enhancing Schwann cell proliferation, migration, and neurotrophic factor secretion. Mechanistically, miRNA sequencing revealed that NGF-Exo-Pep was enriched in osteogenic miRNAs. In vivo, NGF-Exo-Pep treatment in ovariectomized mice significantly improved bone microarchitecture, increased osteoblast activity, reduced osteoclast activity, and neurotization of bone tissue. Notably, NGF-Exo-Pep alleviated pain-related behaviors by downregulating pain mediators and reducing c-Fos expression in the spinal cord. This study presented a novel and promising strategy for OP treatment, harnessing the pro-regenerative properties of NGF while mitigating its pain-inducing side effects.

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靶向递送经神经生长因子预处理的雪旺细胞衍生外泌体用于骨质疏松症治疗：克服疼痛同时增强骨形成。

骨质疏松症（OP）是一种常见的骨骼疾病，其特征是骨量减少和脆性增加，导致骨折和慢性疼痛。神经生长因子（NGF）在骨稳态和神经再生中起着关键作用，但却矛盾地加剧了疼痛。本研究探讨了由ngf预处理的雪旺细胞（NGF-Exo-Pep）衍生的工程化骨靶向外泌体治疗op的潜力。我们证明了NGF-Exo-Pep在体外有效地促进骨髓间充质干细胞（BMSCs）的成骨分化和矿化，同时也增强了雪旺细胞的增殖、迁移和神经营养因子的分泌。在机制上，miRNA测序显示NGF-Exo-Pep在成骨miRNA中富集。在体内，NGF-Exo-Pep治疗卵巢切除小鼠显著改善骨微结构，增加成骨细胞活性，降低破骨细胞活性，骨组织神经化。值得注意的是，NGF-Exo-Pep通过下调疼痛介质和降低脊髓中c-Fos的表达来减轻疼痛相关行为。本研究提出了一种新颖而有前途的治疗OP的策略，利用NGF的促再生特性，同时减轻其引起疼痛的副作用。

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来源期刊

ACS Biomaterials Science & Engineering Materials Science-Biomaterials

CiteScore

10.30

自引率

3.40%

发文量

413

期刊介绍： ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture