Biomedical Engineering Reference
In-Depth Information
Even when films are not built in acidic or basic conditions, they may be subjected to dis-
solution in physiological medium. This was observed for films containing PEI as polyan-
ion and a mixture of heparin and acid fibroblast growth factors whose degradation could
be observed in PBS at 37°C (Mao et al. 2005). In contrast, films built with basic fibroblast
growth factor and chondroitin sulfate (Ma et al. 2007) were stable in PBS. However, it is
difficult to establish a common rule and each type of film needs to be tested. It also has
to be noted that the presence of cells, which are able to exert strong stress on their matrix
(Discher et al. 2005), can also affect the film stability.
It is important to stress that different strategies have been proposed to increase the
mechanical resistance of the most fragile films (i.e., polypeptide or polysaccharide-based
ones), in particular by cross-linking them using various strategies for increasing their
mechanical properties (see Section 8.2.6).
Besides spatial control of film organization, a great amount of work deals with the
temporal control of film durability and, in particular, controlled degradability. This has
become of utmost importance in the field of drug delivery, in which PEMs have found
many applications. The different stimulus pathways used to trigger deconstruction or dis-
solution have already been detailed by Tang et al. (2006) and Lynn (2007) for PEM films
and De Geest et al. (2007) for PEM capsules.
A new strategy relies on the preparation of films with adjustable biodegradability, depend-
ing on the d- over l-lysine enantiomer ratio in the polyelectrolyte solution (Benkirane-
Jessel et al. 2005). THP-1 macrophages produced TNF-
α
when they came into contact with
protein A embedded in the film. The production of TNF-
α
started after a varying induction
time and displayed a transition from no-production to full-production, which took place
over a period that depended on both the film's composition and the embedding depth. The
same type of macrophages degraded cross-linked CHI/HA films in an adjustable manner
that depended on the extent of film cross-linking (Picart et al. 2005b). Of note, the initial
adhesion of these macrophages was also related to the degree of cross-linking.
A development of the widely explored hydrolytically degradable polymers was recently
presented by Liu et al. (2005c). It consists in synthesizing “charge-shifting” cationic poly-
mers. Liu et al. demonstrated that the addition of citraconic anhydride to PAH yields an
anionic, carboxylate-functionalized polymer (called polymer 2) that can be converted
readily back to cationic PAH in acidic environments. The incorporation of polymer 2 into
PEMs thus provides an approach to the manufacture of films that are stable at neutral pH
but that erode over a period of several days in acidic media (e.g., a pH of 5).
As proof of concept, they demonstrated that ultrathin films roughly 100 nm thick manu-
factured using polymer 2 sustained the release of fluorescently labeled PAH for up to
4 days when incubated at pH 5.0. Furthermore, the synthetic approach was more recently
applied to the release of DNA (Liu et al. 2008) using two different degradable polymers.
DeliveryofBioactiveMoleculestoCellsviaPEMFilms
Small Molecules or Drugs
Delivery of bioactive molecules (ions, drugs, proteins) often relies on diffusive processes
that will depend on the film's internal structure and nanometer scale porosity. Such pro-
cesses are also extremely present in real tissues for the delivery of nutrients (Thorne et al.
2008).
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