The effect of cationically-modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo

Jonathan M Lawton,William Bonfield,Serena M Best,Neil Rushton,Bingkui Ma,Mariam Habib,Andrew L Lewis,Roger A Brooks

doi:10.1007/s10856-017-5958-8

Abstract

The effect of introducing cationic charge into phosphorylcholine (PC)-based polymers has been investigated in this study with a view to using these materials as coatings to improve bone formation and osseointegration at the bone-implant interface. PC-based polymers, which have been used in a variety of medical devices to improve biocompatibility, are associated with low protein adsorption resulting in reduced complement activation, inflammatory response and cell adhesion. However, in some applications, such as orthopaedics, good integration between the implant and bone is needed to allow the distribution of loading stresses and a bioactive response is required. It has previously been shown that the incorporation of cationic charge into PC-based polymers may increase protein adsorption that stimulates subsequent cell adhesion. In this paper, the effect of cationic charge in PC-based polymers on human osteoblasts (HObs) in vitro and the effect of these polymers on bone formation in the rat tibia was assessed. Increasing PC positive surface charge increased HOb cell adhesion and stimulated increased cell differentiation and the production of calcium phosphate deposits. However, when implanted in bone these materials were at best biotolerant, stimulating the production of fibrous tissue and areas of loosely associated matrix (LAM) around the implant. Their development, as formulated in this study, as bone interfacing implant coatings is therefore not warranted.Graphical abstract

Highlights

Advances in modern medicine, such as the introduction of penicillin, antiseptics, and vaccinations, have significantly increased human life expectancy [1]
Phosphorylcholine (PC) materials are bio-inspired polymers that mimic the extracellular surface of red blood cells, containing an exact chemical copy of the predominant zwitterionic phospholipid headgroup found in the cell lipid membrane
The number of human osteoblasts (HObs) cells increased with time on PC20 and

Summary

Introduction

Advances in modern medicine, such as the introduction of penicillin, antiseptics, and vaccinations, have significantly increased human life expectancy [1]. Predominantly due to degenerative diseases (such as osteoporosis), osteosarcoma and trauma [4], has led to the design of a variety of surgical techniques, medical devices and specialised materials. These range from total hip and knee replacements to fracture fixation devices and bone stock replacements. The well-hydrated and neutrally-charged PC surface allows for the interaction of proteins without inducing shape changes in the protein’s three-dimensional structure and reduce irreversible protein adsorption [5] This decrease in protein adsorption results in decreased blood clotting [6], cellular adhesion, and in a reduction in the inflammatory response and fibrous capsule formation [7]. PC materials have found utility in the orthopaedic field, as superlubricious, low-wear surfaces grafted onto polyethylene acetabular liners [12], for which there are 3 year data from an 80 patient study [13], colbalt-chromium-molybdenum metal alloy bearings [14, 15] and poly(ether-ether ketone) orthopaedic bearing surfaces [16]

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Conclusion