Extracellular matrix-inspired BMP-2-delivering biodegradable fibrous particles for bone tissue engineering

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Growth factors are crucial for tissue regeneration, stimulating cell proliferation, migration, and differentiation.
• Effective delivery systems are needed for sustained release of growth factors to target sites.
• Current methods require improved carriers for enhanced therapeutic outcomes in tissue repair.

Purpose of the Study:

• To fabricate and characterize novel fibrous particles (FPs) mimicking the extracellular matrix (ECM) for growth factor delivery.
• To develop heparinized FPs (Hep-FPs) for sustained release of bone morphogenetic protein-2 (BMP-2).
• To evaluate the efficacy of Hep-FPs-BMP-2 in promoting bone regeneration in a mouse calvarial defect model.

Main Methods:

• Fibrous particles (FPs) were fabricated from poly(l-lactic acid) via aminolysis and subsequently heparinized to create Hep-FPs.
• Hep-FPs were characterized for their ability to bind and sustain the release of BMP-2.
• In vitro studies assessed BMP-2's effect on human mesenchymal stem cells (hMSCs), measuring alkaline phosphatase activity and mineralization.
• In vivo studies involved implanting FPs, Hep-FPs, FPs-BMP-2, and Hep-FPs-BMP-2 into mouse calvarial defects (4 mm) for 8 weeks.

Main Results:

• Hep-FPs demonstrated stable binding and sustained release of BMP-2.
• Released BMP-2 from Hep-FPs significantly enhanced alkaline phosphatase activity and mineralization in hMSCs.
• In vivo, Hep-FPs-BMP-2 implantation resulted in significantly greater new bone formation and higher bone density compared to control groups.
• The ECM-mimicking morphology of FPs contributed to their effectiveness as a regenerative scaffold.

Conclusions:

• Hep-FPs serve as an effective carrier for sustained BMP-2 delivery, promoting osteogenic differentiation of stem cells.
• Hep-FPs-BMP-2 significantly enhances bone regeneration in critical-sized calvarial defects.
• ECM-mimicking fibrous particles represent a promising platform for diverse tissue engineering and regenerative medicine applications.