One of the challenges of using growth factors for tissue regeneration is to monitor their biodistributions and delivery to injured tissues for minimally invasive detection. In the present study, tracking of human vascular endothelial growth factor (VEGF) was achieved by chemically linking it to photoluminescent carbon dots (CDs). Carbon dots were synthesized by the hydrothermal method and, subsequently, conjugated with VEGF using carbodiimide coupling. ELISA and western blot analysis revealed that VEGF-conjugated CDs preserve the binding affinity of VEGF to its antibodies. We also show that VEGF-conjugated CDs maintain the functionality of VEGF for tube formation and cell migration. The VEGF-conjugated CDs were also used for in vitro imaging of human umbilical vein endothelial cells. The results of this work suggest that cell-penetrating VEGF-conjugated CDs can be used for growth factor protein tracking in therapeutic and tissue engineering applications.

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Monitoring the supply of vascular endothelial growth factor (VEGF) to ischemic tissues provides information on its biodistribution and delivery to meet the requirements of therapeutic angiogenesis and tissue engineering applications. We herein report the use of microfluidically generated microgels containing VEGFconjugated fluorescent carbon dots (CDs) (VEGF−CDs), a gelatin− phenol conjugate, and silk fibroin for imaging-monitored tracking of VEGF delivery to ischemic muscles. An in vitro release study and a bioactivity assay indicated that the VEGF−CDs were released in a sustained manner with high bioactivity. The microgels showed a high angiogenesis potential, along with a strong fluorescent signal, for the chicken chorioallantoic membrane and chick embryo. Imaging and studies of therapeutic modalities of the composite microgels indicated their effective localization in ischemic tissues and sustained VEGF release, which resulted in enhanced therapeutic angiogenesis of ischemic muscles. This work reveals the success of using VEGF-loaded composite polymer microgels for efficient and monitored VEGF delivery by intramuscular administration for ischemic disease treatment.