In vivo resorption of a biodegradable polyurethane foam, based on 1,4-butanediisocyanate: a three-year subcutaneous implantation study.

Degradable polyurethanes (PUs), based on aliphatic diisocyanates, can be very useful in tissue regeneration applications. Their long-term in vivo degradation has not been extensively investigated. In this study a biodegradable PU with copolyester soft segments of DL-lactide/epsilon-caprolactone and hard segments synthesized from 1,4-butanediisocyanate was evaluated with regard to tissue response during degradation and, ultimately, the resorption of the material. Highly porous PU foam discs were subcutaneously implanted in rats and rabbits for intervals up to 3 years. A copolymer foam of DL-lactide and epsilon-caprolactone served as a control. The foams, the surrounding tissues and the draining lymph nodes were evaluated with light and electron microscopy. In the first stages of degradation the number of macrophages and giant cells increased. As the resorption stage set in their numbers gradually decreased. Electron microscopy showed macrophages containing pieces of PU. The size of the intracellular PU particles diminished and cells containing these remnants gradually disappeared after periods from 1 to 3 years. After 3 years an occasional, isolated macrophage with biomaterial remnants could be traced in both PU and copolymer explants. Single macrophages with biomaterial remnants were observed in the lymph nodes between 39 weeks and 1.5 years following implantation. It is concluded that the PU foam is biocompatible during degradation. After 3 years PU samples had been resorbed almost completely. These results indicate that the PU foam can be safely used as a biodegradable implant.

Animal study on surface-modified defibrillator systems: Indications for enhanced infection resistance.

One of the most important problems with ICD systems is infection. The aim of this study was an in vivo evaluation of the efficacy of defibrillator systems in terms of infection resistance. The polyurethane leads were coupled with heparin and loaded with the antibiotic gentamicin, while the PGs were modified to release gentamicin. Group I was comprised of 10 pigs implanted with either a standard or a modified system for 2 weeks; group II was implanted during 4 weeks. The lead was inserted into the heart wall via the jugular vein. The other end was subcutaneously tunneled to the armpit where the PG was positioned. A cocktail of Staphylococcus aureus and epidermidis was injected at the site of the PG. Evaluation was performed macroscopically, by taking bacterial swabs during explantation and by microscopic processing. The results showed that 3 out of 5 modified defibrillator-systems in group I and 1-2 out of 5 in group II were judged as noninfected, whereas all standard systems were infected. Infection rates of the remaining modified defibrillators showed variances, as found with the standards, from slight to moderate to high, to even high/severe in group II (1x standard and 1x modified). With the modified systems, this may be related to production of humoral factors by an intensified early tissue reaction, as indicated by a swelling at day 6 at the site of the PG. When infected, whether or not modified, usually only Staphylococcus aureus was present. Spreading of infection seemed to occur by inoculation via blood, for example, based on the observation that group II in general showed an increase in infected fibrotic overgrowth in the heart, while infectious problems were low in the jugular vein. It is concluded that the modification at short term shows enhanced infection resistance. An increased infection rate already at 4 weeks, however, indicates that the modification may not hold in the long run. Special attention is needed concerning the more intense early tissue reaction.

Electronmicroscopical evaluation of short-term nerve regeneration through a thin-walled biodegradable poly(DLLA-epsilon-CL) nerve guide filled with modified denatured muscle tissue.

The aim of this study was to evaluate short-term peripheral nerve regeneration across a 15-mm gap in the sciatic nerve of the rat, using a thin-walled biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide filled with modified denatured muscle tissue (MDMT). The evaluation was performed using transmission electron microscopy and morphometric analysis. Evaluation times ranged from 3 to 12 weeks after reconstruction. Already, 3 weeks after reconstruction, myelinated nerve fibers could be observed in the distal nerve stump. Twelve weeks after reconstruction, the number of (non)myelinated nerve fibers had significantly increased in the distal nerve stump. From this study, we can conclude that a thin-walled biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guides filled with MDMT can be successfully applied in the reconstruction of severed nerves in the rat model. Furthermore, we showed fast nerve regeneration across the 15-mm nerve gap and found that the use of MDMT functioned as a mechanical support preventing a collapse of this thin-walled nerve guide.