Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

Abstract

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts) and RUNX2 (chondrocyte differentiation). In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for treatment of bone metastases. The polyP particles are highlighted as genuine, smart, bioinspired nano/micro biomaterials.

Amorphous polyphosphate, a smart bioinspired nano-/bio-material for bone and cartilage regeneration: towards a new paradigm in tissue engineering

“…The anionic polymer Na-polyP can be readily co-precipitated with the anionic zoledronic acid, a drug frequently used in management of metastatic bone diseases 201 in the presence of Ca 2+ . 188 During this process the mixed deposits Ca-polyP/zoledronic acid remain almost perfectly amorphous (Fig. 13E) like the Ca-polyP particles, in contrast to the deposits with pure zoledronic acid and Ca 2+ which formed strong crystals (Fig.…”

“…13A and B). The expressions of the differentiation/transcription factor SOX9 (differentiation towards osteoblasts) and of the factor RUNX2 (chondrocyte differentiation) were used as markers; 188 Fig. 13.…”

Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters

“… 26 More recently, calcium/polyP nanoparticles were also found to promote osteogenic and chondrogenic differentiation of bone marrow cells. 27 However, many fundamental questions remain, including how polyP is distributed intracellularly after uptake, if there is any difference in polyP uptake among different cell types, how stable polyP particles are to enzymatic degradation, and what the roles of polyP are in cellular function. In addition, these methods to deliver polyP afforded minimal or unreported levels of cellular delivery and are yet to enable widespread study of intracellular polyP signaling and function.…”

Increased osteogenic differentiation potential of MSCs cultured on nanofibrous structure through activation of Wnt/β-catenin signalling by inorganic polyphosphate

“…Inorganic polyphosphate (PolyP) is one of the molecules with pro-thrombotic and pro-inflammatory properties in the circulatory system [14,15] that recently has been reported as calcification enhancer of osteoblasts culture medium [16]. Our recent study showed that there is a RAGE-dependent poly P-mediated crosstalk between mTOR and the GSK-3/Wnt/b-catenin signalling network in endothelial cells [14], on the other hand, has been reported polyP can be an important role for repairing long bone osteoarticular damages [17].…”