Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model

Abstract

This study aimed to design a growth factor loaded copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) nanoparticles containing 3D collagen matrix to achieve growth factor sustained release for long-term stimulation of human mesenchymal stem cells (hMSCs) proliferation/differentiation for tissue engineer application. Platelet-derived growth factor-BB (PDGF-BB), which is known to enhance hMSCs proliferation in human serum, was selected as a model growth factor, and biodegradable copolyester of PHBHHx was chosen to be the sustained release vehicle. PDGF-BB phospholipid complex encapsulated PHBHHx nanoparticles were fabricated, and their effect on hMSCs proliferation was investigated via assays of CCK-8 and live-dead staining to cells inoculated in 2D tissue culture plates and 3D collagen gel scaffolds, respectively. The resulting spherical PHBHHx nanoparticles were stable in terms of their mean particle size, polydispersity index and zeta potential before and after lyophilization. In vitro study revealed a sustained release of PDGF-BB with a low burst release. Furthermore, sustained released PDGF-BB was revealed to significantly promote hMSCs proliferation in both cell monolayer and cell seeded 3D collagen scaffolds inoculated in serum-free media. Therefore, the 3D collagen matrices with locally sustained release growth factor nanoparticles hold promise to be used for stem cell tissue engineering.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations

“…This combination resulted in a long-acting release system for reliable and stable induction of osteogenic differentiation. 4,9 This method is termed soybean lecithin-mediated introduction of growth factors into polyesters (SMIGP), and was also applied to load growth factors into PLGA microspheres, 213 PHB nanoparticles, 376 PHBHHx nanoparticles, 377 and insulin-PHA. 384 5.2.4 Antigen carriers and bionic vaccines.…”

Insights Into the Role of Platelet-Derived Growth Factors: Implications for Parkinson’s Disease Pathogenesis and Treatment

“…(Liu et al, 2014) PDGF-BB PDGF-BB promoted the proliferation of human mesenchymal stem cells. (Dong et al, 2015) PDGF-BB Membrane sections with higher PDGF-BB concentrations created a better environment for human adipose-derived stem celltenogenesis. (Min et al, 2014)…”

Development of hydrogels for regenerative engineering

“…Compared to the direct loading of GFs, this strategy protects GFs from inactivation in biological environments, and supplies the required GF concentrations over extended periods until the formation of stable tissues. Recently, Dong et al developed platelet-derived growth factor-BB (PDGF-BB) phospholipid complex loaded biodegradable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) nanoparticles for the sustained release of PDGF-BB in collagen hydrogel scaffolds, and demonstrated improved proliferation of hMSCs [125]. In another study, VEGF-loaded chitosan-dextran sulfate nanoparticles were incorporated into injectable alginate/fibrinogen hydrogels containing free VEGF to induce both rapid initial burst release and slower sustained release of VEGF in the injured spinal cords [126].…”