Biomolecular Engineering 21 (2004) 73–80
Polystyrene surface coated with vitamin E modulates human
granulocyte adhesion and MMP-9 release
F. Renò, F. Lombardi, M. Cannas
∗
Human Anatomy Laboratory, Research Center for Biocompatibility, Department of Medical Sciences,
University of Eastern Piedmont “A.Avogadro”, Via Solaroli 17, 28100 Novara, Italy
Received 16 June 2003; received in revised form 3 November 2003; accepted 19 November 2003
Abstract
Vitamin E (Vit.E, -tocopherol) is a natural biological antioxidant and antinflammatory agent, which protects cells from the effects of free
radicals and inhibits inflammation. For such properties Vit.E has been used to improve the biocompatibility of materials such as cellulose
membrane for hemodialysis. In this study granulocytes adhesion and activation have been studied after contact with normal cell culture grade
polystyrene (PS) and Vit.E-coated polystyrene (Vit.E 0.1 and 0.3% (v/v)) using optical microscopy, flow cytometry and substrate zymography.
Vit.E increased the number of adherent granulocytes both at 0.1% (11470 ± 1064 cells/cm
2
, P< 0.01) and 0.3% (13706 ± 818 cells/cm
2
,
P< 0.001) concentration compared to normal PS (5529 ± 692 cells/cm
2
). The morphology of granulocytes adherent to Vit.E–PS appeared
lightly altered and no differences have been observed in their respiratory burst compared to control granulocyte, while matrix metalloproteinase
9 or gelatinase B (MMP-9) release and activation were increased compared to the normal PS samples. Our data indicate that Vit.E-coated
surface induced an increase in granulocytes adhesion and MMP-9 release in the absence of the typical oxidative stress, hallmark of granulocytes
activation. A possible explanation of the phenomenon is that Vit.E modifies the surface protein adsorption thus increasing cell adhesion and
in turn MMP-9 releasing.
© 2004 Elsevier B.V. All rights reserved.
Keywords: Vitamin E; Granulocytes; Adhesion; MMP-9; Biocompatibility
1. Introduction
Materials implantation in the human body causes a tissue
trauma due both to the surgery procedure and the presence
of a new contact surface in the biological environment. The
interactions of circulating and tissue cells with the mate-
rial surface evoke both a specific leukocytes inflammatory
response and a wound healing reaction [1]. In fact, after
the prosthesis implantation, neutrophil granulocytes adhere
along with other leukocytes to polymeric artificial surfaces
[2] by the adsorbed plasma protein layer [3,4].
Following adhesion to biomaterial surfaces, granulocytic
phagocytosis, respiratory burst and protease (gelatinase B or
MMP-9 and elastase) release may occur, resulting in a dam-
age in the surrounding tissue. Furthermore, many aspects of
acute and chronic inflammatory processes are mediated by
oxidants released by activated granulocytes and monocytes,
∗
Corresponding author. Tel.: +39-0321-660632;
fax: +39-0321-660632.
E-mail address: cannas@med.unipmn.it (M. Cannas).
thank to their ability to induce cellular production of cy-
tokines [5]. As granulocytes activation is an early event in
the inflammation process it has been taken as an indicator
for risk assessment of biopolymer-mediated inflammation
[6].
Vitamin E (Vit.E, -tocopherol) is a natural biological
antioxidant, that prevents peroxides accumulation and pro-
tects cells from free radicals effects [7]. Vit.E has been
also described as an antinflammatory agent able to inhibit
many key events in inflammation such as IL-1 release
from activated monocytes [8], monocyte adhesion to en-
dothelial cells [9] and respiratory burst [10]. The Vit.E
anti-oxidative and anti-inflammatory properties have been
extensively utilized to improve the biostability and the bio-
compatibility of different biomaterials. In fact Vit.E has
been used in the production of amphiphilic monomers [11]
and it has been added to different biocompatible materials
such as poly(etherurethane urea) elastomers [12], acrylic
bone cements [13], and recently to ultrahigh molecular
weight polyethylene [14]. Another important application of
Vit.E is the production of Vit.E-modified dialysis cellulose
1389-0344/$ – see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.bioeng.2003.11.001