The composition and mechanical properties of porcine placental ECM from three different breeds.

Biologic scaffolds are extensively used in various clinical applications such as musculotendinous reconstruction, hernia repair or wound healing. Biologic scaffolds used in these applications vary in species, breed and tissue of origin, and other variables that affect their properties. Decellularization and sterilization processes also determine the characteristics of these scaffolds. The goal of the present study is to compare the composition and mechanical properties of decellularized porcine placental scaffolds from three different porcine breeds: Landrace, York and Duroc. Placental extracellular matrix (ECM) scaffolds from the three porcine breeds preserved the amnion/chorion ECM structure and the basement membrane markers laminin and collagen type IV. ECM placental scaffolds showed similar contents of collagen, elastin and lipids, and minimal differences in glycosaminoglycans content. Mechanical properties from the three breeds ECM placental scaffolds were also similar and stable for 24 months. While this study serves as preliminary characterization of porcine ECM scaffolds, future studies will determine their compatibility and suitability for tissue engineering applications.

Preserved extracellular matrix components and retained biological activity in decellularized porcine mesothelium.

Mesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium was characterized for strength, composition of the matrix and biological activity. The tensile strength of the material was 40.65 +/- 21.65 N/cm. Extracellular matrix proteins collagen IV, fibronectin, and laminin as well as glycosaminoglycans were present in the material. Cytokines inherent in the extracellular matrix were preserved. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) were retained and the levels of VEGF and TGF-beta in the decellularized mesothelium were higher than those found in decellularized small intestinal submucosa (SIS). The decellularized mesothelium also stimulated human fibroblasts to produce more VEGF than fibroblasts grown on tissue culture plastic. Decellularized mesothelium is a sheet material with a combination of strength and biological activity that may have many potential applications in surgical repair and regenerative medicine.

The retention of extracellular matrix proteins and angiogenic and mitogenic cytokines in a decellularized porcine dermis.

Decellularized dermis materials demonstrate considerable utility in surgical procedures including hernia repair and breast reconstruction. A new decellularized porcine dermis material has been developed that retains many native extracellular matrix (ECM) proteins and cytokines. This material has substantial mechanical strength with maximum tensile strength of 141.7 +/- 85.4 (N/cm) and suture pull through strength of 47.0 +/- 14.0 (N). After processing, many ECM proteins remained in the material including collagen III, collagen IV, collagen VII, laminin and fibronectin. Glycosaminoglycans, including hyaluronic acid, were also preserved. Among several cytokines whose levels were quantified, more vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) were retained within this material than in comparable decellularized dermis materials. The retention of bioactivity was demonstrated in a cell culture assay. Because this decellularized porcine dermis material both retains significant strength and has substantial biological activity, it may promote rapid integration and repair in clinical applications.

A novel bioengineered small-caliber vascular graft incorporating heparin and sirolimus: excellent 6-month patency.

OBJECTIVE: A bioengineered microporous polycarbonate-siloxane polyurethane graft has been developed for coronary artery bypass grafting. Biological agents can be impregnated into its absorbable collagen and hyaluronan microstructure and stable macrostructure to promote patency. The objective of this study was to examine the in vivo biological performance and biomechanical characteristics of this graft. METHODS: Three types of graft (3.6-mm internal diameter, 24-mm length) were manufactured: heparin alone (H) grafts, heparin and sirolimus (HS) grafts, and grafts without any drug impregnation (C). All H and HS grafts were impregnated with 54 U of heparin in the microstructure for early elution to prevent acute graft thrombosis and 56 U of heparin in the macrostructure to prevent late thrombosis. In addition to the heparin, the HS graft was impregnated with 2.1 mg of sirolimus in the macrostructure for prolonged elution to inhibit intimal hyperplasia. All grafts (3.6-mm internal diameter, 24-mm length) were implanted into the abdominal aortas of rabbits (n = 55). Expanded polytetrafluoroethylene grafts (4.0-mm internal diameter, 24-mm length; n = 7) were implanted as controls. At 1, 3, and 6 months after surgery, the grafts were removed for histologic, scanning electron microscopic, immunohistochemical, and biomechanical evaluations. RESULTS: The patency rate was 100% in the H, HS, and C grafts at each time point. Although the expanded polytetrafluoroethylene grafts were patent at 1 and 3 months after surgery, 1 of 2 grafts (50%) were occluded at 6 months. None of the H or HS grafts had any stenosis or thrombus. Scanning electron microscopic examination proved that endothelial cells propagated smoothly from the anastomotic sites after 6 months in the H and HS grafts in comparison with the expanded polytetrafluoroethylene grafts, which had rare endothelialization. Neointima formation was inhibited in the HS graft compared with the H or C graft at 6 months (123 +/- 126 microm vs 206 +/- 158 microm or 202 +/- 67 microm; P < .05). In addition, the H, HS, and C grafts had greater cellular infiltration inside the graft than the expanded polytetrafluoroethylene grafts. All grafts except the expanded polytetrafluoroethylene graft had marked neocapillary formation 6 months after surgery. The graft compliance between 80 and 120 mm Hg was 6.0% +/- 2.5% and 6.2% +/- 0.9% at 6 months in the H and HS grafts, respectively. The graft macrostructure was unchanged according to the biomechanical evaluation in the H and HS grafts. CONCLUSION: A unique drug-eluting graft had excellent patency throughout the 6 months after implantation. The heparin-sirolimus graft encouraged luminal endothelialization without excessive intimal hyperplasia. This graft performed significantly better than the expanded polytetrafluoroethylene graft. This graft has the potential to become an implantable graft for coronary artery bypass grafting.

Evaluation of a flexible collagen surgical patch for reinforcement of a fascial defect: Experimental study in a sheep model.

There is a need for a surgical mesh that can be used in general surgical procedures for reinforcement or repair of soft tissue. Collagen based surgical meshes may possess the appropriate qualities. In this study, the potential of a collagen product BioBlanket Surgical Mesh to facilitate soft tissue repair in an ovine fascial defect model in vivo was evaluated. BioBlanket Surgical Mesh facilitated soft tissue repair in an ovine fascial defect model in vivo. Superficial fascial surgical sites were evaluated grossly, histologically, and mechanically at 6 and 12 week time points. BioBlanket Surgical Mesh and the predicate device Restore Orthobiologic Implant both performed favorably when implanted in superficial fascial defects compared with the negative control empty defect.

Novel bioengineered small caliber vascular graft with excellent one-month patency.

BACKGROUND: A bioengineered microporous polycarbonate-siloxane polyurethane graft has been developed for coronary artery bypass grafting. Biological agents can be impregnated into its absorbable collagen and hyaluronan microstructure and stable macrostructure to promote patency. The objective of this study was to examine the biological performance and biomechanical characteristics of this graft. METHODS: Heparin-sirolimus (HS) or heparin-sirolimus-vascular endothelial growth factor (HSV) grafts were manufactured for this study. Heparin (40 U) was embedded in the microstructure of the graft for early elution from the graft wall. Heparin (100 U) and sirolimus (450 microg) were incorporated into the macrostructure of the graft for late elution. Vascular endothelial growth factor was also embedded in the microstructure of the graft. Both grafts (3.6 mm internal diameter, 24 mm length) were implanted into the abdominal aortas of rabbits (n = 36) to compare with heparin-alone (H) grafts (n = 9). At 4 hours, 1 day, and 1, 2, and 4 weeks after surgery, the grafts were removed for histologic, immunohistochemical, and biomechanical evaluations. RESULTS: The patency rate of all grafts was 100% at each time point. None of grafts had stenosis after surgery. Endothelial cells were observed at 4 weeks after surgery in the HS, HSV, and H grafts. Although there was no significant difference of neointima thickness among the HS, HSV, and H grafts (136 +/- 75, 93 +/- 64, and 125 +/- 90 microm; p = 0.08), the H grafts did have more cellular infiltration in the graft than the HS or HSV grafts. There was neocapillary formation inside the graft wall at 4 weeks in all grafts. The graft macrostructure was unchanged based on biomechanical evaluation 4 weeks after surgery. CONCLUSIONS: A unique drug-eluting graft had excellent patency at 1 month and may encourage luminal endothelialization without excessive intimal hyperplasia. Although vascular endothelial growth factor did not improve intimal formation, cell infiltration, or vascularization, sirolimus might inhibit cell proliferation. Further long-term study would need to evaluate the efficacy of impregnated sirolimus.