Transformation of Amorphous Polyphosphate Nanoparticles into Coacervate Complexes: An Approach for the Encapsulation of Mesenchymal Stem Cells

Abstract

Inorganic polyphosphate [polyP] has proven to be a promising physiological biopolymer for potential use in regenerative medicine because of its morphogenetic activity and function as an extracellular energy-donating system. Amorphous Ca -polyP nanoparticles [Ca-polyP-NPs] are characterized by a high zeta potential with -34 mV (at pH 7.4). This should contribute to the stability of suspensions of the spherical nanoparticles (radius 94 nm), but make them less biocompatible. The zeta potential decreases to near zero after exposure of the Ca-polyP-NPs to protein/peptide-containing serum or medium plus serum. Electron microscopy analysis reveals that the particles rapidly change into a coacervate phase. Those mats are amorphous, but less stable than the likewise amorphous Ca-polyP-NPs and are morphogenetically active. Mesenchymal stem cells grown onto the polyP coacervate show enhanced growth/proliferation and become embedded in the coacervate. These results suggest that the Ca-polyP coacervate, formed from Ca-polyP-NPs in the presence of protein, can act as an adaptable framework that mimics a niche and provides metabolic energy in bone/cartilage engineering.

In Situ Polyphosphate Nanoparticle Formation in Hybrid Poly(vinyl alcohol)/Karaya Gum Hydrogels: A Porous Scaffold Inducing Infiltration of Mesenchymal Stem Cells

“…[20] This transformation from the amorphous state as nanoparticles to the coacervate has been demonstrated to occur after transfer to a proteinaceous environment. [20] This transformation from the amorphous state as nanoparticles to the coacervate has been demonstrated to occur after transfer to a proteinaceous environment.…”

“…In a first step, the PVA/KG solution was subjected to freezing-thawing cycles to introduce a porous channel system and to allow physical cross-linking of the PVA chains to occur, and subsequently to Ca 2+ that causes ionic gelation (Scheme in Figure 15A). [20] This property of the scaffold substantially controls the relaxation and retardation times of the MSCs, and by that also the viability and the differentiation capacity of those cells. By alteration of the pH conditions in the vicinity of the cells or by peptides released by them and interacting with the ionic and hydrogen bonds the strength of the network is substantially affected.…”

“…[20] In the absence of peptides the nanoparticles in the dried "KG2/PVA/ polyP:NP-cryogel" remain permanently present ( Figure 7A-F). [20] In the absence of peptides the nanoparticles in the dried "KG2/PVA/ polyP:NP-cryogel" remain permanently present ( Figure 7A-F).…”

“…[15] Applying a new technology, we succeeded to entrap polyP, in a biomimetic way, into amorphous nanoparticles (Ca-polyP-NP) formed by the Ca 2+ salt of this polymer, [16] like those present in acidocalcisomes; similar particles have also been synthesized with other divalent counterions of the polyP. [20] The polyP is prone to enzymatic hydrolysis with the alkaline phosphatase (ALP), the dominant intra-and extracellular enzyme that hydrolyzes the phosphoanhydride bonds which link the phosphate groups. [19] Recently we showed that Ca-polyP-NP undergo coacervation after contact with proteins/peptides that reduce the zeta potential of the particles.…”

“…[20,39] The material is a dynamic hydrogel with pronounced viscoelastic properties. Like in the free state, the nanoparticles within the cryogel undergo coacervation after transfer of the material into a protein/peptide-containing medium and by that become biochemically active.…”