Biomedical Engineering Reference
In-Depth Information
10.1
INTRODUCTION TO LAYER-BY-LAYER SELF-ASSEMBLY
10.1.1 I
NTRODUCTION
Nanotechnology has been one of the most important impetuses that accelerated the development
of biomaterials, especially third-generation biomaterials, focusing on stimulating specifi c cellular
responses at a molecular level [1]. Layer-by-layer (LbL) self-assembly technique is one of the nano-
technologies that has advanced in the past 10 years. LbL has demonstrated broad applications in
electronics, drug delivery, implant coating, and tissue engineering. We cover a few reviews based
on LbL self-assembly, including principles [2-4], self-assembled thin fi lms [4-6], and microen-
capsulation [5,7-9]. The principles of LbL self-assembly will be introduced and applications in
biomaterials will be discussed later in this chapter. Generally, to build biomaterials at nanoscale
through LbL self-assembly, two methods can be used: assemble ultrathin fi lms in a bottom-up way
or encapsulate nanomaterials on micro/nanotemplates. To characterize the assembly process and
the self-assembled structures, a few methods such as quartz crystal microbalance technique (QCM),
x-ray, and neutron refl ectivity measurements can be used.
LbL self-assembly is defi ned as building multiple layers of charged materials, including
particles, polymers, and even small molecules through electrostatic interactions. The concept of
the alternate LbL adsorption was fi rst proposed for charged colloidal particles in 1966 by Iler [10].
In 1991, Decher and coworkers developed this concept and later demonstrated various assemblies,
mainly using linear polyions, bipolar amphiphiles, or both [2,11-16]. LbL deposition is now rec-
ognized as an environmental friendly technology, both in fundamental and applied research [17].
The assembly process is simple and straightforward, with a wide selection of nanoblocks, including
natural or synthetic polymers, proteins, lipids, and organic or inorganic nanoparticles. The applica-
tions of LbL self-assembly in biomaterials fi eld range from ultrathin coatings in medical implants,
tissue engineering, and micropatterning to drug/gene delivery and cell encapsulation.
10.1.2 M
ETHODS
FOR
L
B
L S
ELF
-A
SSEMBLY
Figure 10.1a depicts a standard LbL self-assembly process on a solid substrate. This principle can
also be applied to the encapsulation of micro/nanotemplates (biocolloids) (Figure 10.1b). First, for
adsorption of a polyanion layer, a solid support (e.g., slide) with positive surface charge is incubated
in a solution containing polyanions for a certain amount of time, usually 30 min. Next, solid supports
are rinsed with pure water two or three times to remove excess free polyelectrolyte. Then, the slide
is immersed in a solution of cationic polyelectrolytes and a layer is adsorbed. The original surface
charge (positive) is restored, and the surface is ready for washing. Generally, the above-mentioned
steps are repeated alternately until a fi lm of desired thickness is obtained. One can also assemble
biomacromolecules or inorganic nanoparticles onto the precursor fi lm and form a complex structure
(Figure 10.1a, last step), for example, polyion/protein multilayer fi lms [18]. More than two compo-
nents can be used in the assembly with one condition: a proper alternation of positive and negative
compounds. The main idea of the method consists of resaturation of polyelectrolyte adsorption,
resulting in the alternation of the terminal charge after every subsequent layer deposition. Multi-
layer fi lms are typically deposited from polyelectrolyte concentrations of several milligrams per
milliliter (mg/mL), much higher than the amount that is needed to cover a substrate or a previous
layer. Ultrathin ordered fi lms can be designed with “molecular architecture” plans in the range of
5 nm to a few microns, composed of molecular layers even up to a few hundred, with a precision
better than 1 nm and a defi nite knowledge of their molecular composition. In addition, there is no
size or shape limitation for substrates that are involved in thin fi lm buildup, and this factor is very
important for biocompatible coating because of the wide range of biomedical devices and implants
involved. The major driving force for LbL self-assembly is the electrostatic interaction between two
adjacent layers, but other interactions such as short-range hydrophobic forces [3], specifi c interac-
tions between biomolecules [19,20], or hydrogen bonding could also be used [21,22].
