Biomedical Engineering Reference
In-Depth Information
In order to assess the biocompatibility of degradable polymers, it is ne-
cessary to study not only the polymer properties but also those of the low
molecular weight degradation products. 3HB, the ultimate degradation prod-
uct of P3HB, has been found to be biocompatible in tests with CHO-K1
fibroblasts [119]. Other studies included short-chain P3HB oligomers. For ex-
ample, the incubation of P3HB oligomers with hamster V79 fibroblasts and
marine melanoma B16(F10) cells did not affect the cell viability [120]. Fur-
thermore, particles of short-chain P3HB were found to cause dose-dependent
cell damage in macrophages but not in fibroblasts. Therefore, controlling the
degradation rate and thus concentration of degradation products was con-
cluded to be important for controlling the biocompatibility. Cocultures of
liver cells (Kupffer cells and hepatocytes) were not affected by treatment with
this material [121].
A murine monocytes-macrophages cell line was used as a model to study
foreign-body response and phagocytosis capability. The adhesion and pro-
liferation of these cells increased after alkaline surface hydrolysis of P3HB-
8%3HV films. Pretreatment of the unmodified polymer with collagen had
a repulsive effect on the cells, which disappeared on the hydrolyzed polymer,
while fibronectin promoted cell adhesion on both surfaces [122].
Despite these screening studies to assess the cell compatibility of P3HB-
based materials in general (including suitable methods for processing, modi-
fication, purification, and sterilization), a number of studies have been con-
ducted to study the potential and biocompatibility of P3HB in tissue en-
gineering applications using different tissue-specific cell types, such as os-
teoblasts, chondrocytes, and vascular cells.
For example, the biocompatibility of P3HB has been assessed by studying
the structural organization of cellular molecules involved in adhesion using
osteoblastic and epithelial cell lines. Both cell lines exhibited a rounded cell
shape due to reduced spreading on the polymer surface. The interactions be-
tween matrix proteins and the actin cytoskeleton mediated by integrins were
found to be impaired, including the colocalization of fibronectin fibrils with
actin filaments. Moreover, the cell morphology was modified showing larger
lateral extensions in the cell-cell contacts [123]. Osteoblast compatibility has
also been tested after seeding of rabbit bone marrow cells on P3HB films
and more cells could be found on P3HB than on PLLA surfaces [94]. P3HB
porous scaffolds showed slightly higher osteoblast viability, but comparable
alkaline phosphatase production to that of PLLA samples [49]. P3HB-3HH
copolymer matrices showed superior cell compatibility in both studies (see
Sect. 5.2). Addition of hydroxyapatite to the P3HB scaffolds resulted in en-
hanced viability and alkaline phosphatase activity [124]. Cell culture studies
with primary human osteoblasts showed very limited cell attachment and
proliferation on P3HB-7%3HV in comparison to P3HB surfaces [125]. Surface
modification of P3HB-8%3HV porous scaffolds by oxygen plasma treatment
resulted in more viable rat bone marrow osteoblasts and increased alka-
