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

Ilya Nifant'Ev,Tatiana Bukharova,Andrey Shlyakhtin,Maxim Kosarev,Elena Galitsyna,Alexander Dyakonov,Dmitry Gavrilov,Dmitry Goldshtein,Pavel Ivchenko

doi:10.3390/ijms20246242

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.

Highlights

Every year, millions of surgical procedures involving bone excision, bone grafting and fracture repair are performed worldwide [1]
One of the most promising approaches involves the use of mesenchymal stem cells (MSCs) that are seeded into 3D scaffolds and induce bone generation by osteoinductive cues [1,4–7]
The design of such 3D scaffolds as a bone void filler can be implemented at the interface of organic chemistry, polymer chemistry, material science and cell biology by the development of the composites containing biodegradable synthetic polymers and calcium phosphates [8–11]

Summary

Introduction

Millions of surgical procedures involving bone excision, bone grafting and fracture repair are performed worldwide [1]. One of the most promising approaches involves the use of mesenchymal stem cells (MSCs) that are seeded into 3D scaffolds and induce bone generation by osteoinductive cues [1,4–7] The design of such 3D scaffolds as a bone void filler can be implemented at the interface of organic chemistry, polymer chemistry, material science and cell biology by the development of the composites containing biodegradable synthetic polymers and calcium phosphates [8–11]. This approach seems to be prospective due to the variability of poIlnyt.mJ. Tehffiecmieinldt mtheetrhmoodlyosfisPoEfPA prethpearpaotiloynm(eSrschoefmteer1t-cb)u[t3y2l,3e3th].ylene phosphate (tBuOEP) was found to be a simple and efficient method of PEPA preparation (Scheme 1c) [32,33]

Methods

Results

Conclusion