DegraPol-foam: a degradable and highly porous polyesterurethane foam as a new substrate for bone formation.

Bone morphogenetic protein (BMP) is known to require a suitable carrier to induce ectopic bone formation in vivo. To evaluate the suitability of DegraPol-foam, a degradable, elastic, and highly porous polyesterurethane foam as carrier for BMP-induced bone formation, a fraction containing all the active BMPs (BMP cocktail) was combined with DegraPol-foam and implanted subcutaneously into rats. DegraPol-BMP scaffolds were found to induce osteogenesis 2 weeks after implantation as evidenced by morphological and biochemical observations. In addition, the osteoblast-compatibility of DegraPol-foam was examined here. In vitro, primary rat osteoblasts and osteoblasts from the human cell line (HFO1) attached and proliferated preferentially on the surface of the DegraPol-foam. Both cell types exhibited relatively high attachment and low doubling time that resulted in a confluent cell multilayer with spindle-shaped morphology on the surface of the foam. Osteoblasts produced high concentrations of collagen type I and osteocalcin, and expressed increasing levels of alkaline phosphatase (ALP) activity. Taken collectively, both osteoblasts from rat tibia and from the human cell line HFO1 showed high cell attachment and growth, and preserved their phenotype. The geometrical structure of DegraPol is a suitable carrier for BMP for the induction of bone formation.

Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein.

BACKGROUND/AIM: In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS: Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS: None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS: The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.

In vitro evaluation of the biofunctionality of osteoblasts cultured on DegraPol-foam.

The biofunctionality of osteoblasts cultured on DegraPol-foam, a biodegradable, elastic, and highly porous polyesterurethane-foam, was determined here to examine the possible use of this structure as bone repair material. Osteoblasts from rat tibia and from the cell line (MC3T3-E1) exhibited relatively high attachment and low doubling time that result in a confluent cell multilayer on the surface of the foam. They produced high concentrations of collagen type I and osteocalcin, and expressed increasing alkaline phosphatase activity. Exposure to 1,25-dihydroxy vitamin D (Vit. D) increased dose- and time-dependent alkaline phosphatase activity and osteocalcin concentration, and decreased the level of collagen type I and cell density. Maximal effects of Vit. D on alkaline phosphatase activity (2.2 fold), osteocalcin (1.5 fold), collagen type I (50% reduction), and on cell density (35% reduction) were found at 100 ng Vit. D ml(-1). Osteoblasts cultured on DegraPol-foam in the presence of Vit. D exhibited more spreading and less spindle-like morphology than cells cultured in the absence of Vit. D. Cell ingrowth into the pores of the foam was not affected by Vit. D treatment. Taken collectively, the osteoblasts, capability of responding to Vit. D confirms the osteoblast compatibility of DegraPol-foam and the possible use of this scaffold in the bone healing process.

Chondrocyte-biocompatibility of DegraPol-foam: in vitro evaluations.

Histological and biochemical investigations were carried out in order to evaluate the chondrocyte compatibility of a recently developed biodegradable polyesterurethane-foam (DegraPol-foam). Therefore, cell adhesion, cell growth, and the preservation of chondrocyte phenotype was measured in rat xyphoid chondrocytes seeded on DegraPol-foam. Chondrocytes, isolated from xyphoids of adult male rats, exhibited relatively high cell adhesion on DegraPol-foam (about 60% of that found on TCPS). Scanning electron microscopy (SEM) showed that chondrocytes grew on the surface and into the open cell pores of the foam. Morphologically, cells found on the surface of the foam exhibited a flat cell appearance and built a confluent cell multilayer. In contrast, the interior of the foam cells showed rounded morphology in cell aggregates and cell islets. In addition, chondrocytes proliferated on the DegraPol-foam (doubling-time of about 12.5 days) and preserved their phenotype for up to 14 days. Compared to freshly isolated chondrocytes, cells seeded on the foam produced high concentrations of collagen type II for up to 2 weeks: the ratio of type II/I collagen was 1.2-1.4 fold higher than the ratio found in freshly isolated cells. No significant difference was observed in chondroitin sulfate levels produced by freshly isolated cells and cells cultured on DegraPol-foam for up to 14 days. To sum up, our results indicate that DegraPol-foam is a compatible substrate for chondrocytes.

New versatile, elastomeric, degradable polymeric materials for medicine.

The present investigation was focused on the cell compatibility of recently developed biodegradable polyesterurethane-foam (DegraPol-foam) to chondrocytes and osteoblasts. Both chondrocytes and osteoblasts, isolated from adult male rats, exhibited relatively high cell adhesion on DegraPol-foam. Scanning electron microscopy (SEM) showed that cells grew on the surface and into the open cell pores of the foam. Morphologically, cells found on the surface of the foam exhibited a flat cell appearance and built a confluent cell multilayer. In contrast, inside the foams cell showed rounded morphology building cell aggregates and cell islets. In addition, chondrocytes and osteoblasts proliferated on the DegraPol-foam and preserved their phenotype for up to 2 weeks. During degradation of these polymers, small crystalline particles of short-chain poly[(R)-3-hydroxybutyric acid] (Mn approximately 2300) (PHB-P) and lysine methyl ester are released. Therefore, lysine methyl ester and PHB-P, as possible degradation products of the polymer, are investigated here for their effects on macrophages and osteoblasts. Results obtained in the present study clearly indicate that macrophages and, to a lesser degree, osteoblasts have the ability to take up (phagocytose) PHB-P. At low concentrations, particles of PHB failed to induce cytotoxic effects or to activate macrophages. Osteoblasts showed only limited PHB-P phagocytosis and no signs of any cellular damage. At high concentrations of PHB-P, the cell viability of macrophages and to a lesser extent of osteoblasts was affected.

Tissue engineering: a new approach in cardiovascular surgery--seeding of human fibroblasts on resorbable mesh.

INTRODUCTION: In tissue engineering the material properties of synthetic compounds are manipulated to enable delivery of dissociated cells onto a scaffold in a manner that will result in in vitro formation of new functional tissue. The seeding of human fibroblasts on resorbable mesh is a precondition of a successful creation of human tissue such as autologous cardiac valves. MATERIAL AND METHODS: Polymeric scaffolds (n = 12) composed of polyglycolic acid (PGA) with a fiber diameter of 12-15 mm and a polymer density of 70 mg/ml were used as square sheets of 0.3 x 1 x 1 cm. Fibroblasts (passage 5), harvested from human foreskin, were seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA mesh. RESULTS: Microscopic examination of the seeded mesh demonstrated that the human fibroblasts were attached to the polymeric fibers and had begun to spread out and to divide. Electron microscopy showed a continuous distribution and formation of the cells throughout the "polymeric architecture". Spotlike hydrolysis of PGA fibers was observed. After 3 weeks the seeded scaffolds resembled a solid sheet of tissue. CONCLUSION: These preliminary results, successful seeding of human fibroblasts on a PGA mesh, represent a first basic step on the way to construct human tissue such as autologous cardiac valves and demonstrate that tissue engineering might be a promising new device in therapy of cardiovascular disease.

Tissue engineering: a new approach in cardiovascular surgery: Seeding of human fibroblasts followed by human endothelial cells on resorbable mesh.

OBJECTIVE: In tissue engineering the material properties of synthetic compounds are chosen to enable delivery of dissociated cells onto a scaffold in a manner that will result in in vitro formation of a new functional tissue. The seeding of human fibroblasts followed by human endothelial cells on resorbable mesh is a precondition of a successful creation of human tissues such as vessels or cardiac valves. METHODS: Polymeric scaffolds (n = 18) composed of polyglycolic acid (PGA) with a fiber diameter of 12-15 microm and a polymer density of 70 mg/ml were used as square sheets of 1 x 1 x 0.3 cm. Fibroblasts (passage 7) harvested from human foreskin were seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA-mesh, followed by seeding of endothelial cells (passage 5, 2.8 x 10(6)) harvested from human ascending aorta. Thereafter the new tissue was stained for HE, van Gieson, Trichrom Masson, Factor VIII and CD 34 and proved by scanning electron microscopy. RESULTS: Microscopic examination of the seeded mesh demonstrated that the human fibroblasts were attached to the polymeric fibers and had begun to spread out and divide. The scanning electron microscopic examination demonstrated a homogeneous scaffold resembling a solid sheet of tissue. The seeded endothelial cells formed a monolayer on the fibroblasts and no endothelial cell invasion or new formation of capillaris could be detected. CONCLUSIONS: These results are a first step to demonstrate that seeding of human fibroblasts and endothelial cells on PGA-mesh might be a feasible model to construct human tissues such as vessels or cardiac valves.

Degradable and highly porous polyesterurethane foam as biomaterial: effects and phagocytosis of degradation products in osteoblasts.

Recently, a new class of biodegradable PHB-based polyesterurethane (DegraPol/btc) has been prepared and found to exhibit favorable cell and tissue compatibility. The present study has been designed to evaluate the response of primary isolated rat tibia osteoblasts to small crystalline particles of short-chain poly[(R)-3-hydroxybutyric acid] (PHB-P diameter: 2-20 microm), of fluorescent-labeled analogs (DPHP-P), and of lysine methyl ester as possible degradation products of DegraPol/btc. Observations made using confocal microscopy clearly indicate that osteoblasts have the capability of taking up PHB-P particles. Although in single-cell analysis the number of DPHB-P-positive osteoblasts gradually increased up to 16 days, the fluorescence intensity per osteoblast increased only during the first 4 h after DPHB-P incubation, and then it retained the 4 h level up to 16 days. No significant change in the production levels of collagen type I and osteocalcin was detectable after treatment with low concentrations of PHB-P for up to 32 days. In contrast, a time- and dose-dependent alteration of the alkaline phosphatase (ALP) activity was found. Maximal activity was measured after 4 days of treatment with 2 microg of PHB-P/mL (170% of control cells). Rat peritoneal macrophages co-cultured with osteoblasts in a transwell culture system mimicked the observed PHB-P induced ALP elevation. Therefore, the PHB-P-induced ALP increase could be the result of direct or indirect stimulation of osteoblasts, possibly via soluble factors produced by contaminating osteoclasts. Taken collectively, the data demonstrate that osteoblasts are capable of phagocytosing PHB-P and that this process is accompanied at low PHB-P concentrations by dose- and time-dependent alteration of alkaline phosphatase activity but not of collagen type I or osteocalcin.

Magnetic resonance-guided laparoscopic interstitial laser therapy of the liver.

BACKGROUND: There is a necessity for an imaging method during laparoscopy to get a three-dimensional access to the target. In this study we evaluated laparoscopic interstitial laser therapy of the liver under magnetic resonance imaging guidance. METHODS: Five domestic pigs underwent laparoscopy in an open-configuration magnetic resonance system. Under simultaneous real-time magnetic resonance imaging interstitial laser therapy was applied to the liver. Magnetic resonance images, macroscopic aspects of the lesions, and light microscopic findings were compared. RESULTS: The interventions could be safely performed. There was no image artifact caused by instruments or by the carbon dioxide. Dynamic gadolinium-enhanced imaging proved to significantly predict the macroscopic volume of the laser lesions. CONCLUSIONS: Magnetic resonance-guided laparoscopic interstitial laser therapy of the liver combines the advantages of minimal invasive surgery and magnetic resonance imaging. Further development should focus on laparoscopic instruments and temperature sensitive sequences.

Multiblock copolyesters as biomaterials: in vitro biocompatibility testing.

Cell adhesion, cell growth and cell activities of macrophages and fibroblasts, cultured on newly developed degradable multiblock-copolyesters were studied to examine the biocompatibility and the possible use of these polymers for medical applications. The biocompatibility and the biodegradability of the polymers were confirmed by subcutaneous implantation of polymer foils in rats. The newly developed polymers, two polyesters (DegraPol/bsc43 and DegraPol/bsd43) and a polyesterether (DegraPol/bst41), were found to exhibit good cell compatibility; the cell-to-substrate interactions induced neither cytotoxic effects nor activation of macrophages. The adhesion and growth of fibroblasts and macrophages were different among the substrate. Fibroblasts adhered on the polyesters to about 60% of control cell cultured on tissue culture polystyrene (TCPS) and proliferated in the same doubling time as on TCPS. On the polyetherester cells exhibited weak adhesion; however, they proliferated up to day 4 after plating at the same doubling time as on TCPS (of about 42 h), and then decreased their doubling time to 27 h. Macrophages attached to the polyesters to about 40-60% of TCPS but no significant change was seen in the doubling time of cells cultured on TCPS and the polyesters. Again on the polyetherester, macrophages exhibited relatively low adhesion (25% of TCPS) and high doubling time (about 100 h). Fibroblasts produced high amounts (up to 500% of control cells) of collagen type I and type IV, and fibronectin. Macrophages responded to lipopolysaccharide treatment by the production of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha), indicating that the cell-to-polymer interactions allow fibroblasts and macrophages to maintain their phenotype. All three test polymers exhibit favourable tissue compatibility. The formed capsule was just a few cell layers thick (<30 microm). After 2 months implanted subcutaneously in rats, the molecular weight of the test polymers was reduced by >20% depending on their chemical structure. Taken collectively, the present data demonstrate that the newly developed multiblock copolyesters are biocompatible and biodegradable.

Development of degradable polyesterurethanes for medical applications: in vitro and in vivo evaluations.

To evaluate the biocompatibility of a newly developed degradable class of polyesterurethanes and their possible use as biomaterials, we investigated the cell and tissue interactions with these polymers using a small number of chemical base entities. The polymers were prepared by chain extension with diisocyanates of PHB/HV-diol and either PCL-diol or Diorez, another aliphatic polyester-diol. Regardless of the chemical composition of the four tested polyesterurethanes used as substrates, no morphological difference was observed either in the macrophages (macrophage cell line J774) or in the fibroblasts (fibroblast cell line 3T3) cultured on the polymers. In contrast, however, cell adhesion and growth of macrophages and fibroblasts were affected by the polymer properties. Compared to macrophages cultured on tissue culture polystyrene (TCPS), cells cultured on the test polymers exhibited levels of cell adhesion that varied from 65-100% of TCPS, and the doubling time was 25-43% higher on the polymers than on TCPS. Likewise, fibroblasts adhered to the polymers at lower rates (50-85% of TCPS) and grew at higher doubling times (125-140% of TCPS). Furthermore, cells cultured on the test polymers preserved their phenotypes: fibroblasts produced high amounts (up to 280% of control cells) of collagens Type I and Type IV and fibronectin; and macrophages produced nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) in the same concentrations as control cells and responded to lipopolysaccharide treatment by the elevation of the production of NO and TNF-alpha, indicating that the cell-to-polymer interactions allow fibroblasts and macrophages to maintain their phenotypes. In vivo investigations showed that all four test polymers exhibit favorable tissue compatibility. The formed capsule was 60-250 microns thick. In addition, the polymers are degradable. After one year's subcutaneous implantation in rats, the molecular weight of the test polymers were reduced to about 50%, depending on the composition. Taken collectively, the present data demonstrate that the newly developed polyesterurethanes are cell and tissue compatible and biodegradable.

MR imaging-guided intravascular procedures: initial demonstration in a pig model.

With use of an open 1.5-T magnetic resonance (MR) imager and a tracking catheter, the authors successfully placed the catheter into the left or right sacral artery in pigs. The tracking catheter comprised a 5.3-F percutaneous transluminal angioplasty catheter with a small copper radio-frequency coil in its tip. With use of the coil as an antenna, the catheter tip position was projected in real time onto MR angiography road maps in two planes. Guidance of placement of the catheter with the MR angiography road maps allowed successful embolization, balloon occlusion, and transjugular intrahepatic puncture of the portal system. Specialized catheters can be tracked in vivo to allow MR guidance in intravascular interventional procedures.

[Testing bone implants in cell lines and human osteoblasts]. / Testung von Knochenimplantaten auf Zellinien und humanen Osteoblasten.

Two different types of cell-line and fresh human osteoblasts, cultured from cancellous bone grafts from the iliac crest, were used for the study. Three different biomaterials were compared regarding biocompatibility: titanium, steel and hydroxyapatite. The cells were fibroblast cell line (3T3), "osteoblast-like" cell line (MC3T3-E1), and fresh human osteoblasts (HOB) which we cultured in our laboratory. 5 x 10(4) cells of each type were seeded on the three different bone implants. All experiments were performed in triplicate. Cell proliferation and alkaline phosphatase activity were determined 24 and 72 h after the cells were plated on the biomaterials. Human osteoblast growth was better on titanium than on steel and hydroxyapatite. The most remarkable observation was the continuously decreasing alkaline phosphatase activity (ALP) of "osteoblast-like" cells (MC3T3-E1) and human osteoblasts (HOB) on hydroxyapatite. In conclusion, our in vitro observations suggest that the best cell/material interactions were with human osteoblasts (HOB) and titanium.

Experimental cryosurgery of the liver under magnetic resonance guidance.

The feasibility and the advantages of magnetic resonance (MR)-guided interstitial cryosurgery of the liver in an 0.5 Tesla open MR system have been evaluated. Cryosurgery was performed using an Erbocryo PS system with a nonmagnetic cryoprobe of 6 mm diameter. The probe was inserted into the liver parenchyma under real-time MR control. Using continuous MR imaging two freezing cycles of 12 min each were applied. After conventional and dynamic gadolinium-enhanced MR imaging, the animals were sacrificed after 30 min, 3 hr, 24 hr, 7 days, and 21 days. Each lesion was analyzed using light microscopy. A total of seven cryolesions were made in five animals without any complications from cryosurgery. During real-time imaging, cryolesions appeared as a hemispherical growing signal loss with a mean volume of 16.4 cm3. Macroscopic volumes of the lesions showed a good correlation with dynamic enhanced MR images during follow-up, whereas real-time images usually showed an underestimation of the lesion volumes. Cryosurgery of the liver in an open-configuration MR system is a feasible and safe method. MR imaging allows the guidance and the follow-up of cryolesions of the liver with good accuracy.

Interactions of osteoblasts and macrophages with biodegradable and highly porous polyesterurethane foam and its degradation products.

The macrophage cell line J774, primary rat osteoblasts, and the osteoblast cell line MC3T3-E1 were used to examine the biocompatibility of a newly developed polyesterurethane foam and the possible use of this structure as bone-repair materials. The newly developed, biodegradable, and highly porous (pore size 100-150 microns) DegraPol/btc polyesterurethane foam was found to exhibit good cell compatibility; the cell-to-substrate interactions induced neither cytotoxic effects nor activation of macrophages. Osteoblasts and macrophages exhibited normal cell morphology. No signs of cell damage were detected using scanning electron microscopy (SEM). No significant increase in the production of tumor necrosis factor-alpha (TNF-alpha) or nitric oxide (NO) was detected in macrophages. Compared with cells cultured on tissue culture polystyrene (TCPS), macrophages exhibited relatively high cell attachment (150% of TCPS) but significantly high doubling time (about 8 days) compared with TCPS (4.6 days). Primary rat osteoblasts and the osteoblast cell line exhibited relatively high attachment (140% and 180% of TCPS, respectively) and a doubling time of about 5 days, compared with TCPS (6 days and 8.8 days, respectively). Eight days after cell seeding, osteoblasts exhibited a confluent cell multilayer and migrated into the pores of the polymer. In addition they produced high concentrations of collagen type I, the main protein of the bone, and expressed increasing alkaline phosphatase activity and osteocalcin production throughout the 12 days of the experiment. During degradation of these polymers, small crystalline particles of short-chain poly[(R)-3-hydroxybutyric acid] (M(n) approximately 2300) (PHB-P) are released. Therefore PHB-P (diameter, 2-20 microns), as possible degradation products of the polymer, are investigated here for their effects on macrophages and osteoblasts. Results obtained in the present study clearly indicate that macrophages and, to a lesser degree, osteoblasts have the ability to take up (phagocytose) PHB-P. At low concentrations particles of PHB failed to induce cytotoxic effects or to activate macrophages. Osteoblasts showed only limited PHB-P phagocytosis and no signs of cellular damage. At high concentrations of PHB-P, this process was accompanied by cytotoxic effects in macrophages (> 200 pg PHB-P/cell) and to a lesser extent in osteoblasts (> 400 pg PHB-P/cell).

Characterization of the cell response of cultured macrophages and fibroblasts to particles of short-chain poly[(R)-3-hydroxybutyric acid].

The known biodegradability of poly[(R)-3-hydroxybutyric acid] (PHB) in certain biological environments had led to its proposed use as a biodegradable, biocompatible polymer. Recently, a new, rapidly biodegradable block copolymer that contains crystalline domains of PHB blocks has been synthesized. During degradation of these polymers, the PHB domains are transformed in a first step into small crystalline particles of short-chain PHB. Therefore, particles of short-chain poly[(R)-3-hydroxybutyric acid] (Mn 2300) (PHB-P), as possible degradation products, are investigated here for their effects on the viability and activation of mouse macrophages (J774), primary rat peritoneal macrophages, and mouse fibroblasts (3T3), and their biodegradation or exocytosis (or both) in these cells. Results obtained in the present study indicate that incubation of macrophages with PHB-P concentrations higher than 10 micrograms/mL were found to cause a significant decrease in the number of attached and viable cells as measured in MTT assay, and significant increase in the production levels of tumor necrosis factor-alpha (TNF-alpha) or nitric oxide (NO). At low concentrations, particles of PHB failed to induce cytotoxic effects or to activate macrophages. In addition, signs of possible biodegradation were seen in macrophages. Fibroblasts showed only limited PHB-P phagocytosis and no signs of any cellular damage or cell activation (production of collagen type I and IV, and fibronectin). Taken collectively, the present data indicate that phagocytosis of PHB-P at high concentrations ( > 10 micrograms/mL) is dose dependent and associated with cell damage in macrophages but not in fibroblasts.

[Initial clinical results in the treatment of peripheral arterial occlusive diseases using new percutaneous atherectomy equipment (REDHA-CUT)]. / Erste klinische Resultate der Behandlung der peripheren, arteriellen Verschlusskrankheit mit einem neuen perkutanen Atherektomiegerät (REDHA-CUT)

In 11 female and 13 male patients 29 symptomatic femoropopliteal occlusions were treated with a novel intraluminal endarterectomy device (REDHA-CUT). The pre-existing stenoses (71 +/- 9%) could be reduced to 29 +/- 18% (means +/- s.d.). The arteriectomy procedure with this device took on average 5 +/- 3 min. Neither perforations nor dissections nor distal embolisms or any other complications were observed. In comparison with other percutaneous transluminal angioplasty procedures the clinical use of the novel REDHA-CUT device is safe, simple and fast and allows for the retrieval of plaque biopsies.

Laparoscopic treatment of biliary and gastric outlet obstruction.

To avoid laparotomy in patients with biliary or gastric outlet obstruction in inoperable carcinoma of the pancreas, we evaluated the feasibility of double-bypass operation in 20 pigs. In model A (n = 10), biliary bypass was a Roux-en-Y loop for cholecystojejunostomy after choledochal clip occlusion. In model B (n = 10) an additional Roux-en-Y loop was attached to the stomach after transection of the duodenum. Model A showed functioning biliary bypass with patent and leak-free anastomoses at necropsy on day 28. In model B, four pigs were sacrificed earlier, but nine had normal functioning double bypass (two intussusceptions of the ileum, one bleeding ulcer at the gastroenterostomy, one necrotic Roux-en-Y-loop). Based on the presented bypass function, we are encouraged to perform laparoscopic biliary and gastroenteral bypass in humans to treat malignant jaundice and gastric outlet obstruction.