Monolithic calcium phosphate/poly(lactic acid) composite versus calcium phosphate-coated poly(lactic acid) for support of osteogenic differentiation of human mesenchymal stromal cells.

Zeinab Tahmasebi Birgani,Pamela Habibovic,Clemens A Van Blitterswijk

doi:10.1007/s10856-016-5666-9

Abstract

Calcium phosphates (CaPs), extensively used synthetic bone graft substitutes, are often combined with other materials with the aim to overcome issues related to poor mechanical properties of most CaP ceramics. Thin ceramic coatings on metallic implants and polymer-ceramic composites are examples of such hybrid materials. Both the properties of the CaP used and the method of incorporation into a hybrid structure are determinant for the bioactivity of the final construct. In the present study, a monolithic composite comprising nano-sized CaP and poly(lactic acid) (PLA) and a CaP-coated PLA were comparatively investigated for their ability to support proliferation and osteogenic differentiation of bone marrow-derived human mesenchymal stromal cells (hMSCs). Both, the PLA/CaP composite, produced using physical mixing and extrusion and CaP-coated PLA, resulting from a biomimetic coating process at near-physiological conditions, supported proliferation of hMSCs with highest rates at PLA/CaP composite. Enzymatic alkaline phosphatase activity as well as the mRNA expression of bone morphogenetic protein-2, osteopontin and osteocalcin were higher on the composite and coated polymer as compared to the PLA control, while no significant differences were observed between the two methods of combining CaP and PLA. The results of this study confirmed the importance of CaP in osteogenic differentiation while the exact properties and the method of incorporation into the hybrid material played a less prominent role.

Highlights

To overcome issues related to the use of natural bone grafts [1, 2] and to satisfy a rapidly increasing need for successful and affordable strategies to treat damaged and diseased bone tissue [2, 3], significant efforts are currently invested in developing synthetic alternatives to natural bone
A reduction in the intensity of C peak was observed in the EDS spectra of both poly(lactic acid) (PLA)/Calcium phosphates (CaPs) composite and CaP-coated PLA particles whereas the intensity of the O peak increased in these samples
A uniform distribution of calcium and phosphorus were observed in the elemental maps of composite and coated PLA particles showing a homogenous distribution of CaP in the polymer matrix and a uniform surface coating, respectively

Summary

Introduction

To overcome issues related to the use of natural bone grafts [1, 2] and to satisfy a rapidly increasing need for successful and affordable strategies to treat damaged and diseased bone tissue [2, 3], significant efforts are currently invested in developing synthetic alternatives to natural bone. CaPs, suffer from intrinsic brittleness, which is an important limiting factor, in loadbearing applications [14, 15]. To overcome this issue, CaP ceramics have been combined with other materials, in particular polymers, in the bulk [14,15,16,17,18,19,20,21,22,23,24,25] or as surface coatings [8, 26]. CaPs have been used to develop monolithic composites with poly(a-esters) such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and their copolymers (PLGA) [17,18,19,20], protein based polymers including collagen [21] and gelatin [22, 23], polysaccharides like chitosan [24] as well as synthetic co-polymers

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Conclusion