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Microsphere-Mediated Sustained Delivery of Growth Factors Stimulates Osteogenesis in Target Cells in a

Ketki Holkar1, Prasad Pethe1, Vaijayanti Kale1

  • 1Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, India.

Journal of Biomedical Materials Research. Part A
|June 11, 2025
PubMed

Insights

Sustained delivery of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in hydrogels significantly enhances bone regeneration by promoting osteogenesis and angiogenesis more effectively than direct delivery.

Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Efficient bone repair requires coordinated osteogenic and angiogenic signals, often mediated by growth factors.
  • Optimal delivery strategies for growth factors like BMP-2 and VEGF remain crucial for therapeutic success in bone regeneration.
  • Previous studies highlighted the potential of BMP-2 and VEGF but lacked precise dosing and delivery optimization.

Purpose of the Study:

  • To investigate the dual delivery of BMP-2 and VEGF for enhanced scaffold-mediated bone regeneration.
  • To compare direct versus sustained delivery methods for optimizing growth factor efficacy.
  • To evaluate the impact of sustained delivery on osteogenesis and angiogenesis within a 3D hydrogel microenvironment.

Main Methods:

  • Utilized an interpenetrating network (IPN) hydrogel composed of alginate and PEGDA to encapsulate MC3T3 cells and deliver BMP-2 and VEGF.
  • Compared direct and sustained delivery methods of BMP-2 and VEGF.
  • Assessed osteogenesis via alkaline phosphatase (ALP) activity and calcium content.
  • Analyzed angiogenic effects and confirmed growth factor encapsulation and release kinetics through biomaterial characterization (FTIR, swelling, release assay).

Main Results:

  • Sustained delivery significantly increased ALP activity (up to 1.12-fold) and calcium content (up to 1.85-fold) compared to direct delivery.
  • Molecular studies confirmed that sustained delivery of both BMP-2 and VEGF exhibited a stronger osteoinductive and angiogenic effect.
  • Biomaterial characterization confirmed successful growth factor encapsulation and validated the release profiles of the dual delivery system.

Conclusions:

  • Sustained delivery of BMP-2 and VEGF within an IPN hydrogel is a more effective strategy for promoting bone regeneration than direct delivery.
  • This dual delivery approach holds promise for improving therapeutic outcomes in bone healing by optimizing growth factor release kinetics.
  • The study provides valuable insights into optimizing growth factor delivery systems for tissue engineering applications in bone repair.
Keywords:
angiogenesisbone morphogenetic protein‐2 (BMP‐2)growth factorsosteogenesisvascular endothelial growth factor (VEGF)

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