Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone...

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Regenerative Medicine

Background:

• Stem cell-derived extracellular vesicles (EVs) show promise for bone regeneration but require optimization for specific tissue repair.
• Normal EVs (Nor-EVs) have limited osteogenic capacity, necessitating enhanced strategies for extensive bone defect treatment.

Purpose of the Study:

• To develop and evaluate osteoinductive EVs (Ost-EVs) loaded within a mussel-inspired adhesive hydrogel for enhanced bone tissue regeneration.
• To investigate the osteogenic potential and tissue integration capabilities of the Ost-EV/hydrogel system in vitro and in vivo.

Main Methods:

• Dental pulp stem cell-derived EVs were isolated and characterized as osteoinductive (Ost-EVs).
• A mussel-inspired adhesive hydrogel was synthesized using hyaluronic acid (HA) and polyethylene glycol derivatives (mHA).
• Ost-EVs were loaded into the mHA hydrogel, and the system's osteogenic capacity, tissue adhesion, and regenerative potential were assessed using in vitro assays and animal models (ectopic osteogenesis and rat femoral condyle defect).

Main Results:

• Ost-EVs significantly increased bone morphogenetic protein 2 (BMP2) expression (2.23-fold) compared to controls.
• In vitro studies showed Ost-EVs enhanced alkaline phosphatase (ALP) expression (1.88-fold) and calcium nodule formation (1.38-fold) relative to Nor-EVs.
• The mHA hydrogel exhibited tissue adhesion and self-healing properties.
• In vivo studies demonstrated that the Ost-EV/hydrogel system reduced inflammation, promoted revascularization, and enhanced tissue mineralization in bone defect models.

Conclusions:

• Osteoinductive EVs combined with advanced biomaterial hydrogels represent a promising strategy for bone defect regeneration.
• The mussel-inspired adhesive hydrogel serves as an effective carrier for Ost-EVs, improving their therapeutic efficacy.
• This combined system shows significant potential for clinical applications in treating extensive bone defects.