Directing Stem Cell Commitment by Amorphous Calcium Phosphate Nanoparticles Incorporated in PLGA: Relevance of the Free Calcium Ion Concentration

Abstract

The microenvironment of mesenchymal stem cells (MSCs) is responsible for the modulation in MSC commitment. Nanocomposites with an inorganic and an organic component have been investigated, and osteogenesis of MSCs has been attributed to inorganic phases such as calcium phosphate under several conditions. Here, electrospun meshes and two-dimensional films of poly(lactic-co-glycolic acid) (PLGA) or nanocomposites of PLGA and amorphous calcium phosphate nanoparticles (PLGA/aCaP) seeded with human adipose-derived stem cells (ASCs) were analyzed for the expression of selected marker genes. In a two-week in vitro experiment, osteogenic commitment was not found to be favored on PLGA/aCaP compared to pure PLGA. Analysis of the medium revealed a significant reduction of the Ca2+ concentration when incubated with PLGA/aCaP, caused by chemical precipitation of hydroxyapatite (HAp) on aCaP seeds of PLGA/aCaP. Upon offering a constant Ca2+ concentration, however, the previously observed anti-osteogenic effect was reversed: alkaline phosphatase, an early osteogenic marker gene, was upregulated on PLGA/aCaP compared to pristine PLGA. Hence, in addition to the cell–material interaction, the material–medium interaction was also important for the stem cell commitment here, affecting the cell–medium interaction. Complex in vitro models should therefore consider all factors, as coupled impacts might emerge.

Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent

“…Then, the undifferentiated pulp stem cells migrate to the injury site, proliferate, and differentiate to form an extracellular matrix and promote mineralization [ 52 , 57 ]. The ACP-mediated directional differentiation of mesenchymal stem cells is affected by the concentration of free calcium ions; if the concentration decreases in the surrounding environment, osteogenic differentiation is reduced [ 58 ]. As a drug delivery carrier and scaffold material, PLLA has some problems, such as its weak stability of hydrophilic components and the burst release phenomenon, which need to be improved [ 59 ].…”

Intraosseous Injection of Calcium Phosphate Polymer-Induced Liquid Precursor Increases Bone Density and Improves Early Implant Osseointegration in Ovariectomized Rats

“… 60 Many studies have attempted to use high-concentration polymers to encapsulate and stabilize sufficient ACP but have focused solely on crystallinity and ignored the effects of ultra-small particle size. 29 , 37 , 61 Collagen fibrils are twisted collagen triple-helix molecules that contain only approximately 1.8–4 nm-sized tortuous subchannels. 37 Such an exceptional structure is inaccessible to most ACP polymers by direct precipitation, which limits the performance of ACP.…”

“…Polymer-induced liquid-precursor (PILP) is a liquid-phase amorphous mineral precursor stabilized by charged polymeric additives. 29 , 30 In nature, this amorphous precursor phase plays key roles in the formation process of zebrafish fin, and rat skull and long bones. 33 Recently, it has been suggested that calcium phosphate-PILP can penetrate collagen fibers and occupy the internal nanoscale space, promote intrafibrillar mineralization through the formation of co-oriented arrays of lamellar HAP crystal within the fibrils, 31 , 32 and eventually form hierarchical ordered bone structure.…”

Suspension of Amorphous Calcium Phosphate Nanoparticles Impact Commitment of Human Adipose-Derived Stem Cells In Vitro

“…Besides the individual response of the three donors towards the aCaP suspension, the complex kinetics of aCaP transformation to HAp [8], all thermodynamic equilibria of calcium phosphate phases with dissolution and precipitation [7,12,57] also have to be accounted for the response of the (heterogeneous) ASCs to aCaP nanoparticle exposition.…”

“…Amorphous calcium phosphate has gained a lot of attention, due to its bioactivity; it easily transforms to hydroxyapatite (HAp) [8], the main inorganic component of natural bone [9]. Like this, aCaP is an interesting material for bone tissue engineering purposes, particularly if combined with an organic phase to give nanocomposites, such as PLGA/aCaP [10][11][12].…”