Vascular replacement using a layered elastin-collagen vascular graft in a porcine model: one week patency versus one month occlusion.

A persistent clinical demand exists for a suitable arterial prosthesis. In this study, a vascular conduit mimicking the native 3-layered artery, and constructed from the extracellular matrix proteins type I collagen and elastin, was evaluated for its performance as a blood vessel equivalent. A tubular 3-layered graft (elastin-collagen-collagen) was prepared using highly purified type I collagen fibrils and elastin fibers, resembling the 3-layered native blood vessel architecture. The vascular graft was crosslinked and heparinised (37 ± 4 µg heparin/mg graft), and evaluated as a vascular graft using a porcine bilateral iliac artery model. An intra-animal comparison with clinically-used heparinised ePTFE (Propaten®) was made. Analyses included biochemical characterization, duplex scanning, (immuno)histochemistry and scanning electron microscopy. The tubular graft was easy to handle with adequate suturability. Implantation resulted in pulsating grafts without leakage. One week after implantation, both ePTFE and the natural acellular graft had 100% patencies on duplex scanning. Grafts were partially endothelialised (Von Willebrand-positive endothelium with a laminin-positive basal membrane layer). After one month, layered thrombi were found in the natural (4/4) and ePTFE graft (1/4), resulting in occlusion which in case of the natural graft is likely due to the porosity of the inner elastin layer. In vivo application of a molecularly-defined tubular graft, based on nature's matrix proteins, for vascular surgery is feasible.

Controlled fabrication of triple layered and molecularly defined collagen/elastin vascular grafts resembling the native blood vessel.

There is a consistent need for a suitable natural biomaterial to function as an arterial prosthesis in achieving arterial regeneration. Natural grafts are generally obtained by decellularization of native blood vessels, but batch to batch variations may occur and the nature/content of remaining contaminants is generally unknown. In this study we fabricated a molecularly defined natural arterial graft from scratch resembling the native three layered architecture from the fibrillar extracellular matrix components collagen and elastin. Using casting, moulding, freezing and lyophilization techniques, a triple layered construct was prepared consisting of an inner layer of elastin fibres, a middle (porous) film layer of collagen fibrils and an outer scaffold layer of collagen fibrils. The construct was carbodiimide cross-linked and heparinized. Characterization included biochemical/biophysical analyses, scanning electron microscopy, micro-computed tomography, (immuno)histology and haemocompatibility. Burst pressures were up to 400mm Hg and largely conferred by the intermediate porous collagen film layer. The highly purified type I collagen fibrils and elastin fibres used did not evoke platelet aggregation in vitro. Suturability of the graft in end to side anastomosis was successful and considered adequate for in vivo application.

EDI developments in Dutch health care.

In the past two years EDI developments in Dutch Health Care have gained some momentum. These developments are focussed on the communication between hospitals on the one hand, and General Practitioners, Health Care insurers and suppliers of health care products on the other hand. Experiences show that although the results are promising there is a great need for broadly accepted standard EDI messages based on a thorough analysis of the existing information exchange between organisations.

Hepatitis B pre-S1 and pre-S2 proteins: clinical significance and relation to hepatitis B virus DNA.

Pre-S proteins may have an important role in virus assembly and virus entry into the host cell. The presence of pre-S proteins in serum has also been thought to correlate with active viral replication. To investigate whether pre-S proteins in serum might have additional diagnostic and/or predictive value for liver sequelae in HBV infection, sera from six different serological groups of patients with HBV markers (total number 363) and different manifestations of liver histology were examined for the presence of pre-S1 and pre-S2 proteins using micro-ELISAs. Pre-S1 and pre-S2 proteins were detected significantly more often in HBV-DNA-positive than in HBV-DNA-negative sera from HBsAg carriers. However, pre-S1 and pre-S2 proteins were also found in HBV-DNA-negative HBsAg carriers irrespective of serum HBeAg/anti-HBe or liver histologic findings. These results suggest that the presence of the pre-S1 and or pre-S2 proteins in serum either does not seem to reflect the presence of active viral replication and active liver disease or pre-S proteins are more readily detectable than HBeAg and HB-DNA as measured by a dot-blot technique. Furthermore, the presence of pre-S proteins in serum is strongly correlated with that of HBsAg.

Pre-S proteins in hepatitis B.

Two reactive sequences of the pre-S regions of hepatitis B surface antigen were synthesized chemically and used in micro-ELISAs for the assay of pre-S1 and pre-S2 antigens in serum from patients with acute and chronic hepatitis B. Pre-S1 antigen correlated well with the presence of HBV-DNA and was no longer detectable on cessation of viral replication, after natural recovery and after successful treatment with alpha-interferon. Pre-S2 proteins were also lost after treatment with alpha-interferon. The results show that the assay of pre-S1 and pre-S2 proteins in serum provides additional useful markers for assessing patients with acute and chronic hepatitis B infection and for monitoring the response to treatment with interferon.