Electrosprayed Microparticles with Loaded pDNA-Calcium Phosphate Nanoparticles to Promote the Regeneration of Mature Blood Vessels

Abstract

Purpose 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.

Electrohydrodynamic atomization: A two-decade effort to produce and process micro-/nanoparticulate materials

“…Their most recent study showed that microparticles with sequential release of PDGF and simvastatin could accelerate the dentoalveolar regeneration by enhancing osteoblastogensis and promoting bone maturation (Chang et al, 2014). In a separate study, Guo et al (2014) fabricated PLA-PEG microparticles with the loading of calcium phosphate-pDNA nanoparticles via electrospray. They found that subcutaneous infusion of microparticles with encapsulated both calcium phosphate-pVEGF and calcium phosphate-pbFGF nanoparticles can significantly increase the densities of blood vessels and induce a rapid maturation of blood vessels with marginal probability of cytotoxicity and inflammatory response.…”

Electrospun Gelatin Fibers with a Multiple Release of Antibiotics Accelerate Dermal Regeneration in Infected Deep Burns

“…One part of a tissue sample was frozen and cut into sections for histopathological examinations by hematoxylin‐eosin (HE) staining and for collagen identification by Masson's trichrome staining (BBC Biochemical, Stanwood, WA) . Another part of the tissue was fixed in formalin, paraffin‐embedded, and sectioned for immunohistochemical staining of α‐SMA as described previously . Briefly, tissue sections were incubated with 3% H 2 O 2 to inactivate endogenous peroxidase, followed by an exposure to microwave heating in 10 × 10 −3 m citrate buffer solution (pH 6.0) to recover antigens.…”

Trojan Microparticles Potential for Ophthalmic Drug Delivery

“…The microdroplets (and the nanoemulsion included in them) were hardened by UVinduced polymerization of the corresponding monomers. Guo et al, (2014) [25] prepared calcium phosphate nanoparticles loaded with a plasmid encoding two growth factors. The nanoparticles were included in microparticles prepared by electrospray using a mixture of poly(ethylene glycol) (PEG) blended with the copolymer poly(ethylene glycol)-poly(Lactide) (PELA).…”

“…Further treatment consisting on dissolving gelatin by using proteases and subsequent fluorescent quantitation assays were performed to determine the amount of plasmid DNA initially loaded in the trojan microparticles [17]. In the same sense, Guo et al, (2014) [25] dissolved the PEG-PELA trojan microparticles in methylene chloride. The calcium phosphate nanoparticles included in them were extracted several times in aqueous media.…”