New Trends in Polymers - Progress in Organic and Physical Chemistry: Structures and Mechanisms - page 206

the walls of the conduit. The results demonstrate good quality nerve regeneration in
PHB guidance channels [16, 71].
Biocompatibility of PHB was evaluated by implanting microspheres from PHB
(M w = 450 kDa) into the femoral muscle of rats. The spheres were surrounded by one
or two layers of spindle cells, and in¿ ltration of inÀ ammatory cells and mononuclear
cells into these layers was recognized at 1 week after implantation. After 4 weeks, the
number of inÀ ammatory cells had decreased and the layers of spindle cells had thick-
ened. No inÀ ammatory cells were seen after 8 weeks, and the spheres were encapsulat-
ed by spindle cells. The toxicity of PHB microspheres was evaluated by weight change
and survival times in L1210 tumor-bearing mice. No differences were observed in the
weight change or survival time compared with those of control. These results suggest
that inÀ ammation accompanying microsphere implantation is temporary as well as
toxicity to normal tissues is minimal [58].
The levels of tissue factors, inÀ ammatory cytokines, and metabolites of ara-
chidonic acid were evaluated. Growth factors derived from endothelium and from
macrophages were found. These factors most probably stimulate both growth and
regeneration occurring when different biodegradable materials were used as grafts
[40, 53, 55, 70]. The positive reaction for thrombomodulin, a multifunctional protein
with anticoagulant properties, was found in both mesothelial and endothelial cells
after pericardial PHB patch implantation. Prostacycline production level, which was
found to have cytoprotective effect on the pericardium and prevent adhesion forma-
tion, in the regenerated tissue was similar to that in native pericardium [53, 55]. The
PHB patch seems to be highly biocompatible, since no signs of inÀ ammation were
observed macroscopically and also the level of inÀ ammation associated cytokine
mRNA did not change dramatically, although a transient increase of interleukin-1ȕ
and interleukin-6 mRNA through days 1-7 after PHB patch implantation was detect-
ed. In contrast, tumor necrosis factor-Į mRNA was hardly detectable throughout the
implantation period, which agrees well with a observed moderate ¿ brotic response
[40, 70].
16.3.2 PHB as Tissue Engineering Material and PHB in vitro
Biocompatibility
The biopolymer PHB is promising material in tissue engineering due to high biocom-
patibility i n vitro . Cell cultures of various origins including murine and human fibro-
blasts [12, 34, 72-74], human mesenchymal stem cells [75], rabbit bone marrow cells
(osteoblasts) [30, 73, 76], human osteogenic sarcoma cells [77], human epithelial cells
[74, 77], human endothelial cells [78, 79], rabbit articular cartilage chondrocytes [80,
81] and rabbit smooth muscle cells [82] in direct contact with PHB when cultured on
polymer films and scaffolds exhibited satisfactory levels of cell adhesion, viability and
proliferation. Moreover, it was shown that fibroblasts, endothelium cells, and isolated
hepatocytes cultured on PHB films exhibited high levels of cell adhesion and growth
(Figure 8) [83].