Microfluidic-Assisted Encapsulation of Vascular Endothelial Growth Factor for Bone Regeneration

Objectives: Conventional bone tissue-engineered constructs are poorly vascularized that often leads to weak survival and integration. Slow penetration of the host vasculature in the use of tissue replacements in critically sized defects often causes necrosis within the central region of the engineered tissues. Embedding angiogenic growth factors, such as vascular endothelial growth factor (VEGF), along with other growth factors and bioactive agents, within the tissue engineered construct can be used to promote the vascularization of bone constructs. However, the blind and uncontrolled administration of VEGF is particularly risky.
In this project, we develop a new on-chip approach for encapsulation of VEGF with precise sustained release capabilities through novel microfluidic platforms. This approach allows us to produce monodisperse particles (in contrast to current techniques based on bulk mixing) in a highly controllable and reproducible manner, providing us with the ability to fine tune the desired characteristics as required.
Methods: Using conventional photolithographic methods, we fabricate a microfluidic platform working based on double emulsion technique suitable for encapsulation of VEGF in Poly Lactic-co-Glycolic Acid (PLGA) particles. By tuning the flow parameters, specific sizes of VEGF-loaded PLGA micro-nanoparticles are achieved. The release rate of VEGF-loaded PLGA micro-nanoparticles are characterized using an ELISA-based assay.
Results: It is shown that the employed on-chip double emulsion technique produces particles with improved monodispersity compared with corresponding harsh bulk emulsion synthesis method, which provides well-regulated release rates. The flow rates and PLGA/VEGF ratio are adjusted to make particles with various sizes and loading capacity. It was found that encapsulation efficiency increases by decreasing water droplet size (i.e. higher flow rate ratios) in the first emulsion. Release profiles of different sizes of VEGF-loaded PLGA particles are obtained.
Conclusions: The synthesized VEGF particles have the potential to be embedded in scaffolds designed for bone tissue regeneration in craniomaxillofacial defects. The controlled release of the VEGF promotes angiogenesis in designed matrices, allowing for enhanced tissue regeneration of the target defects.