Capillary devices for therapy - Artificial Cells, Cell Engineering and Therapy - page 303

This aspect of biocompatibility is not a constant attribute. It depends on the sort
of the encapsulated biological material, the environment and the method of
evaluation, so the obtained values may be different; however, the ratio of the
measured parameters (except the cell growth) should be close to 1 in

biocompatible systems.

11.2 Biomedical applications of hollow fiber-based
devices
11.2.1 Introduction

Originally, HFs were applied as treatment for endocrine system functions
deficiency as bioartificial pancreas systems. The permiselective HFs of acrylic
copolymer (2±3 cm long, inner diameter (i.d.) 1.8±4.8 mm, wall thickness 69±
105m, a nominal MWCO 50-80 kDa; W. R. Grace & Co.) were used for
immunoisolation of canine, bovine or porcine pancreatic islets. 48 Pancreatic
islets of Lewis rats suspended in agarose (10 000 islets/ml), encapsulated in
polyacrylonitrile±sodium methallylsulfonate (AN69) HF and implanted intra-
peritoneally into streptozotocin-induced diabetic rats maintained glycemia
below 250 mg/dl for 70 days after the implantation. 49 Rat islets immobilized in
collagen gel in the presence of vascular endothelial growth factor (VEGF) to
increase the cell viability, encapsulated in AN69 HF and implanted intra-
peritoneally into diabetic mice, maintained a stable glucose level for at least 28
days. 50 Unfortunately, such limitations as the functional cell longevity, 51
formation of fibrous capsule around the transplant delimiting the oxygen and
nutrition supply, 52,53 and the presence of pre-existing natural xeno-antibodies in
case of xenografts 54,55 hinder a successful application of the implants in large
animals as well as in clinical trials. 53 Other studies carried out with biohybrid
implants deal with the construction of a bioartificial liver, 56 the control of

erythropoietin secretion by cells 57±59 and the delivery of fibroblast growth

factor-2 (FGF-2) by myoblasts. 60
Systems of genetically engineered cells encapsulated in HF can provide an
efficient means for future applications involving delivery of neurotrophic
factors. 61±63 Dopamine secreting cell line PC12 encapsulated in polyvinyl
alcohol (PVA) foam as a matrix material in the lumen of the polyvinyl alcohol
HF and implanted into rodent striatum 60,61 may serve as such a system.
At the moment, treatment with bioartificial organs using HF systems does not
go beyond the animal model except preliminary clinical trials in diabetes
treatment, 64 in amyotrophic lateral sclerosis (ALS) treatment 64 or in reducing
chronic pain. 65,66 A clinical trial was performed in ALS patients to evaluate the
safety and tolerability of the intrathecal implants of the encapsulated genetically
engineered baby hamster kidney (BHK) cells releasing human ciliary
neurotrophic factor (CNTF). The BHK cells, encapsulated in HF, mounted on