Osteogenic Differentiation of Human Adipose Tissue-Derived MSCs by Non-Toxic Calcium Poly(ethylene phosphate)s

Abstract

P.I.) 2 A.V. Topchiev Institute of Petrochemical Synthesis RAS, 29 Leninsky Pr.,Abstract: There is a current clinical need for the development of bone void fillers and bioactive bone graft substitutes. The use of mesenchymal stem cells (MSCs) that are seeded into 3D scaffolds and induce bone generation in the event of MSCs osteogenic differentiation is highly promising. Since calcium ions and phosphates promote the osteogenic differentiation of MSCs, the use of the calcium complexes of phosphate-containing polymers is highly prospective in the development of osteogenic scaffolds. Calcium poly(ethylene phosphate)s (PEP-Ca) appear to be potentially suitable candidates primarily because of PEP's biodegradability. In a series of experiments with human adipose-tissue-derived multipotent mesenchymal stem cells (ADSCs), we demonstrated that PEP-Ca are non-toxic and give rise to osteogenesis gene marker, bone morphogenetic protein 2 (BMP-2) and mineralization of the intercellular matrix. Owing to the synthetic availability of poly(ethylene phosphoric acid) block copolymers, these results hold out the possibility for the development of promising new polymer composites for orthopaedic and maxillofacial surgery.

Design, Synthesis and Actual Applications of the Polymers Containing Acidic P–OH Fragments: Part 1. Polyphosphodiesters

“…Cholesterol-initiated PEPA/poly(EtOEP) copolymer demonstrated no hemolysis activity or cytotoxicity against MC3T3-E1 cells [ 80 , 89 ]. No cytotoxicity was detected during experiments on adipose-tissue-derived multipotent mesenchymal stem cells (ADSCs) adhesion and proliferation in the presence of Na and Ca salts of PEPA [ 125 ] ( Figure 10 ).…”

A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells

“…We have recently developed an approach to synthesis of PEPAs and PEPA-based block copolymers [ 29 ] and demonstrated their biocompatibility [ 41 ]. Hypothetically, salts formed by by TFV base with such copolymers offer an opportunity to regulate the rate of TFV release by varying the length of PEPA chains and acid to base molar ratios.…”

“…Copolymers of poly(ethylene phosphoric acid)s (PEPA) that can be obtained by different methods [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], are polyacids potentially able to bind and deliver organic bases, including drugs. Despite the obvious promise of PEPA for different biomedical applications [ 27 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 ], the ability of PEPA-containing polymers to act as a carrier of antiviral drugs with basic functional groups have not been studied to date.…”

Bone Mineral Affinity of Polyphosphodiesters

“…Nifant'ev et al [35] also recently reported the enhancement of osteoblastic differentiation by PPDEs. They synthesized PEP via the route shown in Figure 2b and made the polysalts PEP•Na and PEP•Ca in the aqueous phase.…”