Biomedical Engineering Reference
In-Depth Information
Introduction
In the field of implantable biomaterials and tissue engineered constructs, the bulk prop-
erties of materials are usually recognized as being important for the overall properties,
such as mechanical strength, of the materials. Surface properties, however, are of utmost
importance because they have an impact on subsequent tissue and cellular events, includ-
ing protein adsorption, cell adhesion, and inflammatory response (Thevenot et al. 2008),
all of which are necessary for tissue remodeling. Considerable efforts are thus currently
devoted toward the functionalization of biomaterial surfaces commonly used in biomedi-
cal applications (typically metals, polymers, ceramics) in order to provide them with new
functional biological properties and to render them more biomimetic. In this work, biomi-
metic indicates an attempt to reproduce the self-organization of natural matrices. In par-
ticular, one of the major aims is to recreate the complex cell structure and environment at
various length scales: from the cell membrane structure and pericellular coat (also called
glycocalyx), which are important for signal transduction and the mechanical and chemi-
cal sensing of the cell (Zaidel-Bar et al. 2004), to the extracellular matrix composed of an
entangled and hydrated network of proteins and glycosaminoglycans (Alberts et al. 1994).
To this end, thin film coatings deposited on the “bulk” materials offer great potentialities.
Designing thin films with nanometer-scale control over their internal structures while
preserving the bioactivity of embedded molecules and adjusting their delivery is thus a
great challenge, in particular when the delivery must be performed under physiological
conditions (limited pH range, fixed ionic strength, presence of physiological fluids and
cells). Not only are thin films of utmost importance for the biomedical field, but also in
many other fields such as electronics, optical devices, sensors, and catalysis. Several tech-
niques have thus been developed to design thin films at the molecular level, including
Langmuir-Blodgett (LB) and self-assembled monolayers (SAMs). As already indicated by
Tang et al. (2006) in their review, both present a certain number of limitations and disad-
vantages. The most problematic are probably the limited amounts of biological molecules
incorporated into LB films because of their limited stability, their monolayer nature, and
the need for the presence of thiols on the substrate (e.g., for only noble metals or silane) in
order to deposit SAMs. For biological applications, there is thus a need for easier and more
versatile deposition methods.
The layer-by-layer (LbL) method initially introduced by Moehwald, Decher, and Lvov
15 years ago consists of alternately depositing polyelectrolytes that self-assemble and self-
organize on the material's surface, leading to the formation of polyelectrolyte multilayer
(PEM) Films (Decher et al. 1992; Lvov et al. 1994). The procedure is simple and in principle
applicable to many different kinds of substrate. In the first 10 years of the development of
this technique for biomedical applications, the proofs of concept were given and different
types of films containing charged species were successfully prepared, including biological
molecules (polypeptides, polysaccharides, DNA, proteins, and viruses) and various kinds
of nanoparticles (clay platelets, carbon nanotubes, etc.) (Ai et al. 2003; Decher and Schlenoff
2003). In a second phase of the technical development, the behavior of the cells deposited
on films began to be explored in 2001 (Chluba et al. 2001). At the same period, a differ-
ent mechanism for film growth—exponential growth—was discovered, which opened up
new opportunities for the design of thick films with reservoir capacities (Picart et al. 2002).
Within the past 5 years, possibilities for the spatiotemporal control of cell growth have
emerged and the first in vivo studies have been performed. It is only recently that more
complex cell processes such as cell differentiation have begun to be explored and controlled
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