Electrosprayed microparticles with loaded pDNA-calcium phosphate nanoparticles to promote the regeneration of mature blood vessels.
OBJECTIVE
The lack of control over microvasculature formation remains a key roadblock to the therapeutic vascularization and regeneration of functional tissues. In the current study, the integration of plasmid DNA (pDNA) condensation and electrospraying technologies was proposed to promote the regeneration of mature blood vessels through injectable or infusible administration of microparticles.


METHODS
Calcium phosphate (CP) nanoparticles with encapsulated plasmids encoding vascular endothelial growth factors (pVEGF) and basic fibroblast growth factor (pbFGF) were synthesized using reverse microemulsions. Electrosprayed microparticles with the loading of CP-pDNA nanoparticles were evaluated on both endothelial cells and smooth muscle cells and after subcutaneous infusion into animals.


RESULTS
CP-pDNA nanoparticles was obtained with an average size of around 110 nm and electrosprayed into microparticles, resulting in high loading efficiency and extended protection on pDNA from external DNase environment. The inoculation of poly(ethylene glycol) into microparticle matrices realized a gradual release for 4 weeks of CP-pDNA nanoparticles, leading to an incremental transfection efficiency and strong secretion of extracellular matrices. After subcutaneous infusion of microparticles with encapsulated both CP-pVEGF and CP-pbFGF nanoparticles, significantly higher densities of blood vessels were achieved than those containing individual nanoparticles, and induced a rapid generation of mature blood vessels with few cytotoxicity and inflammation reactions.


CONCLUSIONS
Electrosprayed microparticle with CP-pDNA nanoparticles encapsulated promoted the formation of vascular networks, providing clinical relevance for therapeutic vascularization and regeneration of functional tissues after injection to ischemic sites or entrapment into tissue engineering scaffolds.
Key Laboratory of Advanced Technologies of Materials Ministry of Education of China School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.
Xueqin
X
Guo
Tian
T
Xia
Huan
H
Wang
Fang
F
Chen
Rong
R
Cheng
Xiaoming
X
Luo
Xiaohong
X
Li
D000818:Animals; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D008863:Microspheres; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*
D002130:Calcium Phosphates; D004247:DNA; C020243:calcium phosphate