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Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical
Meifei Lian1,2, Zhiguang Qiao2,3, Shichong Qiao1
1Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
Nerve growth factor-stimulated exosomes from mesenchymal stem cells promote bone healing by enhancing neural and bone cell function. Functionalized scaffolds deliver these exosomes, significantly improving innervated bone regeneration in animal models.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cell Biology
Background:
- Neural network integration is crucial for bone regeneration but often overlooked in biomaterial design.
- Mesenchymal stem cells (MSCs)-derived exosomes are potent cell-free therapeutic agents.
- Optimizing exosome cargo is key to enhancing their regenerative capabilities.
Purpose of the Study:
- To investigate the neuro-promotive and osteogenic potential of nerve growth factor (NGF)-stimulated MSCs-derived exosomes (N-Exos).
- To elucidate the molecular mechanisms underlying the therapeutic effects of N-Exos.
- To develop an N-Exos-functionalized scaffold for enhanced bone regeneration.
Main Methods:
- MSCs were stimulated with NGF to produce N-Exos.
- In vitro studies assessed N-Exos' effects on neural and osteogenic cells.
- Bioinformatic analysis (miRNA sequencing, pathway enrichment) identified key signaling pathways (MAPK, PI3K-Akt).
- N-Exos were loaded onto a 3D-printed hierarchical porous scaffold for sustained release.
- A rat distal femoral defect model was used to evaluate scaffold efficacy in vivo.
Main Results:
- N-Exos significantly improved neural cell function and osteogenic potential.
- Bioinformatic analysis revealed N-Exos modulate MAPK and PI3K-Akt pathways via exosomal miRNAs.
- The N-Exos-functionalized scaffold demonstrated sustained release and bioavailability.
- In vivo studies showed significant neurovascularization and bone regeneration in the defect area.
Conclusions:
- NGF stimulation effectively modulates MSC-derived exosome cargo for enhanced neuro-promotive and osteogenic effects.
- N-Exos represent a promising cell-free therapeutic strategy for bone regeneration.
- The developed N-Exos-functionalized scaffold is a viable approach for clinical translation in treating bone defects.
