Chemistry Reference
In-Depth Information
Various forms of PHAs have been used to package drugs and control their
delivery, including gels, films, microcapsules, microspheres, nanoparticles,
porous matrices, polymeric micelles and polymer linked drugs. 84 For ex-
ample, Kassab et al. used a simple solvent evaporation technique to produce
P(3HB) microspheres packaging Rifampicin as a chemoembolising agent,
with 90% of the drug released within 24 hours. 85 Similarly, Turesin et al.
compared P(3HB), P(3HB-co-3HV) and P(3HB-co-4HB) as rods for the release
of the antibiotics Sulperazone s and Duocid s and reported that their release
was controlled by the PHA to drug ratio. Sulperazone s dissolution was
significantly greater than the degradation of the PHA carrier. 86
d n 2 r 4 n g | 3
8.8.3 PHAs for Cell Delivery
PHAs have attracted considerable attention as scaffolds to deliver cells to the
body, in order to support tissue regeneration and engineering. 74,87 For ex-
ample, P(3HB) fibres have been used as scaffolds to deliver matrix com-
ponents and cell lines supporting neuronal survival and regeneration after
spinal cord injury. Novikov et al. constructed a scaffold consisting of P(3HB)
fibres coated with fibronectin and alginate hydrogel. 88 Fibres were im-
planted in the lesion cavity after cervical spinal cord injury in adult rats with
neurons of the rubrospinal tract used as an experimental model. In un-
treated animals, 45% of the injured neurons were lost 8 weeks post-
operatively. In contrast, the P(3HB) fibre scaffolds reduced this loss to
approximately 23%, a similar effect to treating the wound with neurotrophic
factors BDNF or NT-3. 88 The authors also used these P(3HB) scaffolds to
deliver neonatal Schwann cells prior to implantation and this resulted in
regenerating axons entering the fibre from both ends and extending along
its entire length. Thus, PHB-based fibre scaffolds were successfully used to
deliver Schwann cells to support neuronal survival and regeneration after
spinal cord injury. 88
Opitz et al. implanted P(4HB) scaffolds seeded with autologous vascular
smooth muscle cells (vSMC) and ovine endothelial cells from carotid arter-
ies, for 14 days in the descending aorta of juvenile sheep. 89 These constructs
were implanted after in vitro endothelialisation and periodically examined
up to 24 weeks for evaluation. The authors report that up to three months
after implantation, the grafts were fully patent, with no signs of dilatation,
occlusion or intimal thickening. In addition, a confluent luminal endo-
thelial cell layer was observed. In contrast, the six-month grafts displayed
significant dilatation and partial thrombus formation while histology dis-
played layered tissue formation resembling native aorta. 89 Similarly,
Hoerstrup et al. have used PHO to fabricate trileaflet heart valves and seeded
these with vascular cells harvested from ovine carotid arteries. 90 After long
term (152 weeks) implantation in lambs, these tissue-engineered constructs
were eventually covered with tissue, with no thrombus formation on any of
the specimens. 91
.
 
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