Composite Microgels for Imaging-Monitored Tracking of the Delivery of Vascular Endothelial Growth Factor to Ischemic Muscles

Abstract

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.

3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization

“…Li et al designed a tissue-like 3D structure by assembling PEG/gelatin microgels via covalent bonding (4-arm PEG-NHS as crosslinker) [ 45 ] to support the in vitro functionalities of human bone marrow mesenchymal stem cells (hBMSCs), upregulating chondrogenic markers in both gene (Sox-9, Aggrecan, COMP, Col2a1, Col1a1) and glycosaminoglycan (GAG) expression levels. Basiri et al optimized the fabrication of microgels assemblies composed of gelatin–phenol conjugate and silk fibroin working as angiogenesis promotive system suitable to monitor via imaging/tracking VEGF delivery in ischemic muscles [ 46 ].…”

Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications

“…First, in culture medium or even in vivo, microgels retain their structural integrity and functionality over a long period of time. For example, composite microgels formed from gelatin and silk fibroin remained fluorescent for more than 13 days ex vivo and were amenable to imaging . Second, microgels can provide a biomimetic microenvironment for the encapsulated cells to support their growth, proliferation, and differentiation.…”

“…Using droplet MFs, we explored the role of confinement in the structural organization of colloidal liquid crystals. − We then shifted our focus to the applications of droplet MFs to answer questions of biological importance, e.g., the preparation and characterization of microgels from biopolymers and the encapsulation of cells to explore the effects of matrix stiffness and cell coculture on cell fate . Microgels generated by droplet MFs were used for drug delivery and the delivery of vascular endothelial growth factor to ischemic muscle sites . Recently, we developed MF spheroid-on-a-chip platforms for the generation of multicellular spheroids and organoids, which were utilized for coculturing cells, screening active ingredients, and modeling drug delivery to multicellular spheroids. − …”

Monodispersed polymer particles with tunable surface structures: Droplet microfluidic‐assisted fabrication and biomedical applications

“…Biocompatible and biodegradable polymer particles have widely been used as carriers of drugs 56 . Compared with smooth particles, particles with rough surface structures and higher surface areas will enhance their targeting ability, promote phagocytosis, and accelerate the drug release rate.…”

“…Biocompatible and biodegradable polymer particles have widely been used as carriers of drugs. 56 Compared with smooth particles, particles with rough surface structures and higher surface areas will enhance their targeting ability, promote phagocytosis, and accelerate the drug release rate. For example, Zhu et al produced PLGA-b-PEG particles with tunable surface microstructures by tuning the blending ratio of PLGA to PLGA-b-PEG (Figure 7A).…”