Immunoisolation of hybrid liver support systems by semipermeable membranes.

Immunoisolation of hybrid liver support systems (LSS) utilizing suitable semipermeable membranes as an immune barrier enables neither immunocompetent cytotoxic factors to cause damage to the hepatocytes in the bioreactor nor xenogenic hepatocyte products to cause immunological side effects in patients. To determine the capability of membranes as an immune barrier, 6 flat membranes were investigated: Cuprophan (C-100), cut-off MW 1000, Cuprophan (C-240), cut-off MW 10,000, Polypropylen hydrophilic and hydrophobic (PPhi, PPho), cut-off MW 500,000-1,000,000, Polysulfon (PS), cut-off MW 1,000,000, Polyamid (PA), cut-off beyond MW 1,000,000. The permeability of the membranes to plasma factors and liver protein fractions (LP) was studied by routine biochemical methods and gel electrophoresis. In a second study, pigs (n=7) were immunised by LP after membrane passage. The results showed PA, PS, and PPhi to be completely permeable for plasma factors and LP C-100 and C-240 for urophanic substances, and C-240 again for LP under MW 14.000. All 7 pig sera studied by Western blot discovered pre-formed xenoreactive natural IgG-antibodies (NAB) against human liver antigen (AG) with MW 26.000. AB de-novo-synthesis was demonstrated for AG with MW 45.000. No AB-synthesis was induced for epitopes under MW 26,000. These results suggest that limiting the cut-off of bioreactor outflow membranes to MW < 26,000 could avoid immunological side effects to patients.

Breakable stent for interventions in infants and neonates: an animal study and histopathological findings.

OBJECTIVE: To test in a neonatal animal model the feasibility and biocompatibility of a new breakable stent that can be broken open by balloon dilatation during reintervention for use in neonates and infants. MATERIALS AND METHODS: Medical grade stainless steel breakable stents (n = 16) were interventionally implanted in systemic arteries in neonatal piglets (n = 7). Patency of the stented segments was shown by repeated angiography. Stents were redilated up to three times. After a follow up of 18-165 days the animals were killed and the tissue block containing the stent was excised. Besides standard histological examination, scanning electron microscopy was used for biocompatibility screening. RESULTS: The stents were broken by redilatation with a conventional angioplasty balloon catheter. During follow up, patency of all stented segments was shown angiographically. One stent became dislocated during implantation. One vessel ruptured during redilatation when an inadequately large balloon catheter was used for dilatation. No other complications were observed. Scanning electron microscopy showed complete cellular coverage of the stent struts. Histological examination showed thinning of the vessel wall and partial rupture of the media at the site of stent breakage. An only mild inflammatory reaction was detected. CONCLUSION: The new breakable stent can be broken open by simple angioplasty. Feasibility, effectiveness, and biocompatibility were shown in an animal model. Surgery to remove stents from paediatric patients due to disproportion between a previously implanted stent and the growing vessel may be avoided by the use of a breakable stent.

The impact of gelatin-resorcinol glue on aortic tissue: a histomorphologic evaluation.

PURPOSE: Although gelatin-resorcinol-formaldehyde glue has been used to treat acute aortic dissections for some time, concerns about formaldehyde's mutagenicity and carcinogenicity made it imperative to develop a new glue compound. Gelatin-dialdehyde glue was produced by omitting the formaldehyde component and replacing it with two less toxic aldehydes, glutaraldehyde and glyoxal. This study evaluated the histomorphologic effects of the new glue through in vivo use on the aortic tissue of domestic pigs. METHODS: Each animal's infrarenal aorta was glued around an implanted prosthesis. Histomorphologic evaluation was performed after operation after 1 and 4 weeks. RESULTS: The results demonstrated that the clinically observed tanning effect can be attributed primarily to the disintegration of the fiber texture, specifically collagenous, as well as smooth muscle fibers, and to the reciprocal alterations of the proteoglycan interstitial substance in the aortic wall. Macroscopic, microscopic, and electron microscopic analysis of the gluing process revealed an adequate healing process without any morphologically significant difference between formaldehyde and formaldehyde-free gelatin-resorcinol glue. CONCLUSIONS: Gelatin-dialdehyde glue is able to produce the same effects in the area of the aortic wall as the substantially more toxic gelatin-resorcinol-formaldehyde glue and thus could be recommended for clinical trials for treating acute aortic dissections thus far yielding excellent initial results.