Biomedical Engineering Reference
In-Depth Information
of human endothelial cells on P3HB films could be controlled by plasma treat-
ment introducing positive (NH
3
plasma) or negative (H
2
O plasma) surface
charge, which was explained by modulated anchorage and conformational
changes of adsorbed fibronectin [141].
In Vivo Studies
A number of in vivo studies have shown very mild tissue reactions after im-
plantation of P3HB, which were comparable to those of other polymers in
medical use. For example, an excellent in vivo biocompatibility of P3HB has
been reported after s.c. implantation in mice [29]. Nonwoven P3HB patches
tested as pericardial substitutes in sheep appeared to be slowly phagocy-
tosed by polynucleated macrophages without any other kind of inflammatory
cells, except for a small number of lymphocytes. The number of macrophages
surrounding the polymer particles decreased with the absorption of the poly-
mer [142]. Histologically, a dense collagen layer similar to that in native
pericardium was found on the epicardial side of the patch. A thin fibrotic
layer surrounding the patch disappeared along with the macrophages when
the patch was absorbed but the regenerated pericardial tissue remained [143].
A mild inflammatory response to the nonwoven P3HB patch material simi-
lar to that reported for the pericardial substitutes appeared after closure of
an atrial septal defect [144] and enlargement of the right ventricular outflow
tract in sheep [145].
P3HB and P3HB-3HV (5.5%, 9%, 19%, 22% 3HV) films manifested good
tissue tolerance when implanted s.c. in mice for up to 6 months. No acute in-
flammation, abscess formation, or tissue necrosis was observed. At 1 month
after implantation, implants were surrounded by a fibrous, vascularized cap-
sule consisting primarily of connective tissue cells. A mild inflammatory reac-
tion was manifested by the presence of mononuclear macrophages, foreign-
body cells, and lymphocytes. The number of inflammatory cells increased
with increasing valerate content in the copolymer. Thus, inflammation was
most pronounced for P3HB-22%3HV. Three months after implantation, the
fibrous capsule had thickened due to an increase in the amount of connective
tissue and a few collagen fiber deposits. A substantial decrease in inflamma-
tory cells was observed at this time, but inflammation still remained more
pronounced for P3HB-3HV with a higher content of valerate units. After
6monthsofimplantation,thenumberofinflammatorycellshadfurtherde-
creased and the fibrous capsule, consisting mainly of collagen fibers, had
thinned. Within 3 months of implantation a slightly stronger tissue reaction
to P3HB than to PDLLA or PLLA was observedinthisstudyandattributedto
low molecular weight components and impurities leaching out of the polymer
samples. At 6 months, the tissue response to the implants was similar for all
these types of polymers [55].
An increasing inflammatory response with increasing 3HV content was
also observed for P3HB-3HV (8%, 12%HV)filmss.c.implantedinratsfor
