(730f) Angiogenic Microfiber Patches for Directed Blood Vessel Growth

Introduction:  Therapeutic angiogenesis has emerged as a promising strategy to treat various acute and chronic vascular diseases, and to enhance tissue repair and regeneration.  Common revascularization therapies include the administration of angiogenic factors, such as vascular endothelial growth factor (VEGF).  These therapies greatly rely on the ability to engineer mature and functional neovessels, uniformly distributed within target tissues.  The objective of this study was to develop an angiogenic patch that releases angiogenic growth factors and ultimately regulates the directional growth of mature and functional blood vessels.

Materials and Methods:  Angiogenic microfiber patches were prepared by integrating electrospinning and electrospraying processes.  PLA microfibers with negative surface chargers were extruded through an electrohydrodynamic nozzle, and VEGF encapsulating PLGA microparticles with positive surface charges were simultaneously sprayed over the fiber surfaces.  The microparticle covered fibers were collected on Teflon frames in a directionally aligned manner.  The proangiogenic patches were individually implanted on the chorioallantoic membrane (CAM) of chicken embryos and examined over a week for blood vessel formation.  The CAMs were excised and histological CAM cross-sections were analyzed for blood vessel densities, distributions, and alignment.

Results and Discussion:  The electrospinning/electrospraying technique produced an angiogenic patch that sustainably released VEGF from degrading PLGA microparticles, while the PLA microfibers act as a stable structure preventing the dislocation of microparticles at the delivery site.  The temporal control of electrostatic interactions using this technique has the advantage of improving bond strength between fibers and particles compared to previously reported techniques.  Cells adhered to the patch anisotropically, directed by the alignment of the microfiber patches.  The implantation of angiogenic patches on CAMs of chicken embryos resulted in a significant increase in the size and density of mature blood vessels compared to control samples.  The formation of blood vessels was evenly distributed and aligned parallel to the microfiber alignment.  We suggest that the VEGF released from the microparticles locally distributes around and associates with the PLA microfibers, subsequently presenting concentration gradients that direct blood vessel formation along the microfibers.  

Conclusion:  We have demonstrated that the angiogenic patch fabricated by integrating an electrospinnning and elecrospraying process allows the control of both the density and spatial organization of blood vessels at an implant site.  Overall, the angiogenic patch developed in this study will be broadly useful for improving the quality of treatments for various vascular diseases and tissue defects.