Patient-derived endothelial progenitor cells improve vascular graft patency in a rodent model.

Late outgrowth endothelial progenitor cells (EPCs) derived from the peripheral blood of patients with significant coronary artery disease were sodded into the lumens of small diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts. Grafts (1mm inner diameter) were denucleated and sodded either with native EPCs or with EPCs transfected with an adenoviral vector containing the gene for human thrombomodulin (EPC+AdTM). EPC+AdTM was shown to increase the in vitro rate of graft activated protein C (APC) production 4-fold over grafts sodded with untransfected EPCs (p<0.05). Unsodded control and EPC-sodded and EPC+AdTM-sodded grafts were implanted bilaterally into the femoral arteries of athymic rats for 7 or 28 days. Unsodded control grafts, both with and without denucleation treatment, each exhibited 7 day patency rates of 25%. Unsodded grafts showed extensive thrombosis and were not tested for patency over 28 days. In contrast, grafts sodded with untransfected EPCs or EPC+AdTM both had 7 day patency rates of 88-89% and 28 day patency rates of 75-88%. Intimal hyperplasia was observed near both the proximal and distal anastomoses in all sodded graft conditions but did not appear to be the primary occlusive failure event. This in vivo study suggests autologous EPCs derived from the peripheral blood of patients with coronary artery disease may improve the performance of synthetic vascular grafts, although no differences were observed between untransfected EPCs and TM transfected EPCs.

Relationship between the canthal-tragus distance and the puncture point in temporomandibular joint arthroscopy.

This study investigated whether a relationship exists between the length of the canthal-tragus line and the distance from the tragus at which the puncture point for arthroscope insertion should be made. On one side of 11 cadaver heads, a puncture point was marked 7 mm from the midtragus and 2 mm below the canthal-tragus line. On the other side, the distances were 10 mm and 2 mm, respectively. The arthroscope trocar and cannula were inserted at the marked points. The anatomical location of the arthroscope after insertion was confirmed by open dissection with the arthroscope in place. Following dissection, the canthal-tragus line was measured on each side of the cadaver's head. For measurements > 70 mm, puncture points 10 mm from the midtragus led to insertion of the arthroscope inside the upper joint compartment. For measurements < or = 70 mm, puncture points 7 mm from the midtragus led to insertion of the arthroscope inside the upper joint compartment. This suggests that for canthal-tragus distances of > 70 mm, the arthroscope should be inserted 10mm from the midtragus and for distances < or = 70 mm it should be inserted at 7 mm for the greatest likelihood of entering the upper joint compartment of the TMJ.

Intravital microscopy evaluation of angiogenesis and its effects on glucose sensor performance.

An optical window model for the rodent dorsum was used to perform chronic and quantitative intravital microscopy and laser Doppler flowmetry of microvascular networks adjacent to functional and non-functional glucose sensors. The one-sided configuration afforded direct, real-time observation of the tissue response to bare (unmodified, smooth surface) sensors and sensors coated with porous poly-L-lactic acid (PLLA). Microvessel length density and red blood cell flux (blood perfusion) within 1 mm of the sensors were measured bi-weekly over 2 weeks. When non-functional sensors were fully implanted beneath the windows, the porous coated sensors had two-fold more vasculature and significantly higher blood perfusion than bare sensors on Day 14. When functional sensors were implanted percutaneously, as in clinical use, no differences in baseline current, neovascularization, or tissue perfusion were observed between bare and porous coated sensors. However, percutaneously implanted bare sensors had two-fold more vascularity than fully implanted bare sensors by Day 14, indicating the other factors, such as micromotion, might be stimulating angiogenesis. Despite increased angiogenesis adjacent to percutaneous sensors, modest sensor current attenuation occurred over 14 days, suggesting that factors other than angiogenesis may play a dominant role in determining sensor function.

Increased signs of acute rejection with ischemic time in a rat musculocutaneous allotransplant model.

BACKGROUND: Composite tissue allotransplantation (CTA) may restore a variety of tissue defects, but carries the potential risks of graft failure and/or immunosuppression-related complications. Ischemia-reperfusion injury has been documented in CTA is known to contribute to acute rejection of solid organ grafts. This study describes the influence of subcritical ischemic time (ie, ischemia sufficient to generate reversible cell damage) on signs of rejection of musculocutaneous allograft components of subcritical ischemic time, namely, ischemia sufficient to generate reversible cell injury. Although skin is considered the most antigenic component of a composite allograft and is currently used for rejection surveillance, muscle and adipose are more susceptible to ischemia-related injury. METHODS: Vascularized epigastric flaps were transplanted from WKY to Fisher 344 rats after 1 or 3 hours of ischemia. Biopsies taken on postoperative day 6 were graded for signs of acute rejection according to criteria modified from previously published grading systems for CTA rejection. RESULTS: Skin and muscle exposed to 3 hours of ischemia showed significantly higher rejection scores than after 1 hour of ischemia, as evidenced by a more aggressive diffuse lymphocytic infiltration with disruption of tissue architecture. The rejection score in skin with 3-hour ischemia was 5.0 +/- 0.1 versus 3.7 +/- 0.2 with 1-hour (Mann-Whitney U test; P < .05). The rejection score in muscle exposed to 3-hour ischemia was 3.6 +/- 0.3 versus 2.5 +/- 0.1 with 1-hour (P < .05). CONCLUSIONS: Muscle and skin demonstrated increased acute rejection of allotransplants with increased subcritical ischemic time. This study supports the use of aggressive methods to reduce subcritical ischemic injury during allotransplantation of composite tissue and inclusion of muscle in postoperative biopsies in this early investigational period of CTA.

In vitro and in vivo characterization of porous poly-L-lactic acid coatings for subcutaneously implanted glucose sensors.

The purpose of this study was to test the hypothesis that porous poly-L-lactic acid (PLLA) sensor coatings reduce fibrosis and promote blood microvessel formation in tissue adjacent to the sensor surface. Porous PLLA coatings were produced using ammonium bicarbonate as the gas foaming/salt leaching agent, and deployed on functional and nonfunctional sensors. The porous coatings minimally affected sensor accuracy and response rate in vitro. Three-week subcutaneous rat studies of nonfunctional glucose sensors showed the anticipated effect of porous coatings enhancing vascularity and decreasing collagen deposition. In contrast, percutaneous functional sensors with and without porous coatings showed no significant difference in terms of histology or sensor response. In spite of the observation that texturing increases the vascularity of the tissue that surrounds implanted sensors, other factors such as the additional mechanical stresses imposed by percutaneous tethering may override the beneficial effects of the porous coatings.

Vascular endothelial growth factor and dexamethasone release from nonfouling sensor coatings affect the foreign body response.

Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in the surrounding tissue after 2 weeks of implantation compared to hydrogel-coated fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers and had reduced capsule vascularity compared to VEGF-releasing hydrogel-coated fibers. Hydrogels that released both VEGF and DX simultaneously also showed reduced inflammation at 2 weeks implantation; however, no enhanced vessel formation was observed indicating that the DX diminished the VEGF effect. At 6 weeks, there were no detectable differences between drug-releasing hydrogel-coated fibers and control fibers. From this study, hydrogel drug release affected initial events of the foreign body response with DX inhibiting VEGF, but once the drug depot was exhausted these effects disappeared.

[Current perspectives of orthogonal polarization spectral imaging in plastic surgery]. / Orthogonal Polarization Spectral Imaging und derzeitige Perspektiven in der Plastischen Chirurgie.

The technology of Orthogonal Polarization Spectral Imaging (OPSI), patented in the United States in 1999, has been heralded as an alternative to conventional intravital microscopy for several reasons, including ease of application and ability to perform continued observations. In the following examples, OPSI was applied to reconstructive plastic surgery. Two experimental and one clinical model are presented. Currently, the image quality does not allow a qualitative analysis of the microvasculature. The data analysis of images remains inconclusive. However, a technically modified version with improved image resolution and software could become a valuable experimental as well as clinical tool in the field of reconstructive plastic surgery in the future.

Analyte flux through chronically implanted subcutaneous polyamide membranes differs in humans and rats.

The rat is commonly used to evaluate physiological responses of subcutaneous tissue to implanted devices. In vivo longevity of various devices and the biocompatibility of biomaterials depend on how adjacent tissue interacts. How closely the rat model predicts the human response has not been well characterized. The objective of this study was to compare rat and human subcutaneous foreign body responses by monitoring the biochemical environment at a polymer-tissue interface over 8 days using microdialysis. Polyamide microdialysis probes were implanted subcutaneously in humans and rats (n = 12). Daily microdialysis samples were analyzed for glucose, lactate, pyruvate, glycerol, and urea. Blood glucose was also monitored. Analyte concentrations differed significantly between rats and humans at the implant-tissue interface. There were also qualitative differences in the 8-day trends. For example, over 8 days, microdialysate glucose increased two- to fourfold in humans but decreased in rats (P < 0.001). This study reveals profound physiological differences at material-tissue interfaces in rats and humans and highlights the need for caution when extrapolating subcutaneous rat biocompatibility data to humans.

Urea as a recovery marker for quantitative assessment of tumor interstitial solutes with microdialysis.

Microdialysis is a technique that enables measurement of extracellular concentrations of unbound analytes. A small probe with a semipermeable membrane is implanted in tissue and constantly perfused. Small analytes in the interstitial fluid diffuse into the perfusate and are collected. Often, microdialysate concentrations of an analyte are only a fraction of the unbound concentrations in the extracellular space attributable to incomplete equilibration between these two compartments. Thus, it is necessary to determine the degree of equilibration between microdialysate and interstitium for each probe to accurately estimate concentrations. In this study, we investigated tissue urea as a solute to continually correct for nonequilibrium conditions. We used this method, along with relative diffusivities of urea and glucose, to monitor glucose levels before and during hyperglycemia as an example of how this method can be applied. No-net-flux experiments were performed on 10 anesthetized female rats with mammary adenocarcinomas. Microdialysis probes 1 cm in length with a molecular weight cutoff of M(r) 100,000 were used. Urea was added to the perfusate in concentrations of 0.83, 2.5, 5.0, and 13.33 mM. Microdialysate samples were collected every 15 min. For each rat, there was a linear relationship between the net urea concentration (outflow-inflow) and the urea concentration in the perfusate (inflow). Net flux should equal zero when perfusate and interstitial concentrations are equal. In an additional series of 13 rats, microdialysate samples were obtained before, during, and after administration of glucose at a dose of 1 g/kg. The interstitial tumor urea concentration was 7.8 +/- 0.3 mM compared with 6.2+/- 0.3 mM in plasma. There was a significant linear relationship between plasma urea (measured directly) and tumor urea (microdialysis measurement). Plasma urea concentrations were constant over time in all of the experiments, including those where hyperglycemia was induced. Hyperglycemia caused 7.7- and 3.6-fold increases in tumor and plasma glucose, respectively. There was no effect of hyperglycemia on tumor blood flow. Urea appears to be a useful low molecular weight relative recovery marker for tumor microdialysis. In combination with the determination of relative diffusivity between urea and the solute of interest, this calibration method may allow for quantitative measurements of tumor metabolites and unbound drugs.

Decreased analyte transport through implanted membranes: differentiation of biofouling from tissue effects.

Membrane biofouling and tissue changes in the foreign body response are known to cause detrimental reductions of analyte transport into implanted biosensors. The relative contribution of each phenomenon is unknown. Hollow fiber microdialysis probes were employed to assess the effect of subcutaneous implantation on glucose flux through polymeric membranes in rats over 8 days and to differentiate the transport effects of biofouling versus tissue changes. Three commercially available membranes were examined: poly(ether sulfone) (PES), polyacrylonitrile (PAN), and polycarbonate (PC). As measured by glucose recovery (the ratio of microdialysis glucose to blood glucose concentrations), transport through PES membranes was significantly less on day 2 than day 0 (39% decrease, p < 0.05) whereas PAN and PC showed no significant decreases in flux until day 8 (42 and 43%, respectively). Application of a transport model to glucose recovery data obtained before implantation in vivo and after explantation indicated that mass transport resistances originating from biofouling and tissue compartments increased between days 0 and 8. However, on average the biofouling layer adherent to the probe created substantially less resistance to glucose transport (12-24% of total) than did the tissue that surrounded the probe. These results suggested that future material developments for biosensors should be directed at understanding and modifying transport properties of tissues at the implant site.

Laser Doppler flowmeter monitoring of free-tissue transfers: blood flow in normal and complicated cases.

In this article, laser Doppler flowmeter (LDF) monitoring of blood flow in 94 free flaps is summarized. Seventy-six patients had uneventful postoperative courses, and 18 patients developed postoperative complications, with a salvage rate of 88 percent. Except for one case, the flowmeter identified developing complications before clear clinical indices appeared, and in two cases it was the only indication of vascular compromise of the flap. On the basis of the data obtained, the ranges of absolute flow values in different types of uncomplicated flaps are reported, along with their temporal pattern of flow. Decrease inflow pattern may be an early indicator of a developing perfusion disturbance. On the basis of LDF readings, the following classifications of free-flap blood flow are suggested. (1) If the flow is within or slightly above the established range, then normal diligence in observation is justified. If the flow is well above the normal range, artifacts that could falsely elevate readings should be investigated. (2) If the flow is somewhat below the established range, then a modest increase in observation is warranted (alert level 1). (3) If the relative flow falls to 50 percent of the initial flow of that flap and remains at that level for 30 minutes or longer, then more aggressive flap observation is indicated (alert level 2). (4) If the flow is below 0.4 LDF units for 30 minutes, then aggressive clinical observation should be performed (alert level 3, or "red alert") and exploration should be strongly considered. Falsely elevated measurements can be caused by vibration, motion of the probe or tissue, or location of the probe over a macroscopic blood vessel. False low readings are quite rare but can result from partial probe detachment from the flap or coagulum accumulating on the probe. Once artifacts are ruled out, LDF readings have a high level of credibility and, in the authors' experience, significantly improve salvage rates.

Long- and short-term effects of biological hydrogels on capsule microvascular density around implants in rats.

Fibrous capsule formation around implants can inhibit solute exchange between implantable devices and the circulation. Parylene-n coated polycarbonate disks surrounded with growth factor reduced Matrigel (MG) or several gelatin-based matrices were implanted intramuscularly into rats for 21 or 50 days. MG supplemented with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) increased capsule microvascular density at 21 days (p < 0.05) when compared to bare parylene-coated polycarbonate disks (control). The increased microvascular density around VEGF- and bFGF-treated implants regressed by 50 days and was no longer significantly different from controls. The microvascular density induced by the gelatin-based matrices was not significantly different from controls at 21 days, but was increased at 50 days (p < 0.05), suggesting a slower, long-term effect. Disks treated with MG and gelatin-based matrices had thinner capsules at 21 days (p < 0.05). By 50 days, the capsule thicknesses around these implants were no longer statistically thinner than controls. The capsule thickness around implants treated with VEGF, bFGF, and essential gelatin-based matrix was thinner than controls at 50 days (p < 0.05). These results indicate that it is possible to increase functional microvascular density within fibrous capsules using angiogenic growth factors and gelatin-based matrices. However, this effect may be short-lived, requiring chronic administration of growth factors.

Review of methods used to study oxygen transport at the microcirculatory level.

The existence of hypoxic regions in tumors has long been recognized as a key factor leading to radiation resistance. More recently, it has been found that low oxygen levels also affect drug resistance, angiogenesis, cytokine production, cell cycle control, apoptosis, and metastatic propensity of tumors. Until now, most approaches to eliminating hypoxia have been empirical. However, improved understanding of the underlying mechanisms may permit the development of more soundly based, effective approaches. As discussed in this review, critical evaluation of the factors governing oxygen transport in tumors requires a thorough understanding of the methods used to study this process. Many experimental methodologies can be used to address these issues. In this review, the emphasis is placed on techniques that measure parameters on the scale of the diffusion distance of oxygen. Studies at the microregional level provide the most detailed physiological information on such processes. Over the past few years, significant progress in technology has allowed us to measure tumor oxygenation, yet spatial and temporal heterogeneities continue to provide significant challenges to obtaining clear knowledge of oxygen transport.

The role of allopurinol and deferoxamine in preventing pressure ulcers in pigs.

Ischemia and reperfusion may be important in the pathogenesis of pressure ulcers. On the basis of this hypothesis, the effects of intermittent pressure and the anti-free radical agents allopurinol and deferoxamine were studied in a pig model in which a pressure of 150 mmHg was applied intermittently to the scapulae. Cutaneous blood flow, transcutaneous oxygen tension, skin and muscle damage, and muscle levels of adenosine triphosphate were quantified. A control group of pigs (n = 6) was untreated, the allopurinol group (n = 6) received oral allopurinol beginning 2 days before the experiment, and the deferoxamine group (n = 6) received an intramuscular injection of deferoxamine 2 hours before the experiment. Pressure (150 mmHg) was applied to the scapulae for 210 minutes, and it was relieved for 30 minutes. This 4-hour cycle was repeated continuously for 48 hours, and it resulted in pressure injuries in all animals. Allopurinol and deferoxamine improved cutaneous blood flow and tissue oxygenation, but only deferoxamine could significantly reduce cutaneous and skeletal muscle necrosis (p < 0.001). This study suggests a future role for anti-free radical agents in the reduction of pressure-induced injury.

The effect of muscle flap transposition to the fracture site on TNFalpha levels during fracture healing.

The trauma and sepsis that follow open fractures and wounds may lead to the production of various cytokines. Understanding wound healing requires a direct knowledge of the specific cytokines and the respective wound fluid levels that are present at the wound site. An animal model was designed that mimics the open fracture and the clinical repair of the human, high-energy open fracture. Canine right tibiae were fractured with a penetrating, captive-bolt device, then repaired in a standard clinical fashion using an interlocking intramedullary nail. Before primary wound closure, microdialysis probes were placed at the fracture site and in a muscle located at a contralateral site. Canines received one of the following experimental protocols: (1) tibial fracture (n = 5); (2) tibial fracture plus Staphylococcus aureus inoculation at the fracture site (n = 5); and (3) tibial fracture, S. aureus inoculation, and a rotational gastrocnemius muscle flap (n = 5). Microdialysis fluid samples were collected intermittently for 7 days. Tumor necrosis factor alpha (TNFalpha) levels at the fracture site were significantly elevated 3 to 34-fold (p<0.02), as compared with respective serum levels at all time points for all treatment groups. Fracture site TNFalpha levels were elevated (p<0.02) in days 1 through 6, as compared with the baseline and contralateral in all treatment groups. At days 1 through 6, the TNFalpha levels of the muscle flap group fracture site were significantly decreased by approximately 50 percent (p<0.05), as compared with the fractures without muscle flaps and regardless of additional S. aureus inoculation. On day 7, fracture site TNFalpha levels in all animal groups were similar, yet remained well above those of baseline TNFalpha. These results demonstrate that S. aureus does not further elevate TNFalpha levels in the presence of an open fracture and that a muscle flap reduces pro-inflammatory TNFalpha levels during early wound healing. This experimental model allows for the characterization of specific biological signals and cellular pathways that are influenced by bacterial infection and surgical closure. These data provide a scientific framework on which to judge or validate therapeutic regimens for open-fracture wound healing.

Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia.

We previously reported that the arteriolar input in window chamber tumours is limited in number and is constrained to enter the tumour from one surface, and that the pO2 of tumour arterioles is lower than in comparable arterioles of normal tissues. On average, the vascular pO2 in vessels of the upper surface of these tumours is lower than the pO2 of vessels on the fascial side, suggesting that there may be steep vascular longitudinal gradients (defined as the decline in vascular pO2 along the afferent path of blood flow) that contribute to vascular hypoxia on the upper surface of the tumours. However, we have not previously measured tissue pO2 on both surfaces of these chambers in the same tumour. In this report, we investigated the hypothesis that the anatomical constraint of arteriolar supply from one side of the tumour results in longitudinal gradients in pO2 sufficient in magnitude to create vascular hypoxia in tumours grown in dorsal flap window chambers. Fischer-344 rats had dorsal flap window chambers implanted in the skin fold with simultaneous transplantation of the R3230AC tumour. Tumours were studied at 9-11 days after transplantation, at a diameter of 3-4 mm; the tissue thickness was 200 microm. For magnetic resonance microscopic imaging, gadolinium DTPA bovine serum albumin (BSA-DTPA-Gd) complex was injected i.v., followed by fixation in 10% formalin and removal from the animal. The sample was imaged at 9.4 T, yielding voxel sizes of 40 microm. Intravital microscopy was used to visualize the position and number of arterioles entering window chamber tumour preparations. Phosphorescence life time imaging (PLI) was used to measure vascular pO2. Blue and green light excitations of the upper and lower surfaces of window chambers were made (penetration depth of light approximately 50 vs >200 microm respectively). Arteriolar input into window chamber tumours was limited to 1 or 2 vessels, and appeared to be constrained to the fascial surface upon which the tumour grows. PLI of the tumour surface indicated greater hypoxia with blue compared with green light excitation (P < 0.03 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). In contrast, illumination of the fascial surface with blue light indicated less hypoxia compared with illumination of the tumour surface (P < 0.05 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). There was no significant difference in pO2 distributions for blue and green light excitation from the fascial surface nor for green light excitation when viewed from either surface. The PLI data demonstrates that the upper surface of the tumour is more hypoxic because blue light excitation yields lower pO2 values than green light excitation. This is further verified in the subset of chambers in which blue light excitation of the fascial surface showed higher pO2 distributions compared with the tumour surface. These results suggest that there are steep longitudinal gradients in vascular pO2 in this tumour model that are created by the limited number and orientation of the arterioles. This contributes to tumour hypoxia. Arteriolar supply is often limited in other tumours as well, suggesting that this may represent another cause for tumour hypoxia. This report is the first direct demonstration that longitudinal oxygen gradients actually lead to hypoxia in tumours.

Multimodality evaluation of pressure relief surfaces.

Multimodality evaluation of six different support surfaces was performed measuring interface pressure, transcutaneous oxygen tension, and blood flow in pressure ulcer-prone areas on healthy subjects. Interface pressure was measured with a flexible force-sensing resistor array. The interface pressure distribution patterns of 10 healthy male volunteers were measured in the supine and lateral positions using a pressure sensor (force sensing resistor) array. Transcutaneous oxygen (TcPO2) and laser Doppler flowmeter probes were placed over the sacrum, the right trochanter, and the right ischium. Data were recorded for 15 minutes each with the subject in the supine and lateral decubitus positions. Statistically significant differences (p < 0.05) between the various surfaces could be observed for blood flow and pressure measurements, especially in the lateral position over the trochanter and for the TcPO2 measurements in the supine position over the sacrum. We conclude that measuring interface pressure, transcutaneous oxygen tension, and blood flow allows a more thorough evaluation of the physiologic effects of special support surfaces than any single technique. Future studies on patients will assess algorithms for using these measurement techniques to predict the efficacy of various support surfaces in minimizing pressure ulceration.

Improving endothelial cell adhesion to vascular graft surfaces: clinical need and strategies.

Synthetic vascular grafts do not spontaneously endothelialize in humans and require some form of anticoagulation to maintain patency. Preseeding synthetic graft materials such as expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (PET) with endothelial cells (EC) has been examined in various in vitro and in vivo models. Although various studies provide encouraging results, clinical trials for EC seeding on synthetic grafts have not been equally successful. This paper provides a brief review of the various reports on EC seeding in animal and clinical studies. We discuss the inefficiencies associated with the EC seeding process and examine plasma protein treatment of the graft surfaces as a viable option for improving EC attachment, retention and spreading. As an alternative to existing therapies we present data on a heterogeneous ligand treatment of fibronectin (Fn) and avidin-biotin for enhanced human umbilical vein endothelial cell (HUVEC) adhesion to ePTFE graft surfaces. Control consisted of HUVECs seeded on Fn treated ePTFE graft surfaces. Functionality of HUVECs was assessed by measuring prostacyclin production of cells on both homogeneous and heterogeneous ligand treated surfaces. Laminar flow studies with a variable width flow chamber and scanning electron microscopy were used to measure initial cell retention and observe initial cell spreading on ePTFE surfaces, respectively. HUVEC retention on heterogeneous ligand treated graft surface was significantly (p < 0.001) higher compared to homogeneous ligand treated surfaces for shear stress in the range of 10-30 dyn cm(-2). HUVEC showed more cellular spreading on the heterogeneous ligand treated surface after seeding for 1-2 h. In vivo experimentation was performed in immune deficient (nude) rats by replacing a section of both the femoral arteries with 8 mnm long, 1 mm internal diameter denucleated ePTFE grafts treated with homogeneous and heterogeneous ligands respectively. Both grafts were seeded with similar cell density for 15 min prior to implantation. EC attachment and retention was measured by staining EC with hematoxylin and counting the cells before and after flow using light microscopy. The results indicate that a heterogeneous ligand treatment of graft surfaces using avidin-biotin and Fn-integrin attachment mechanisms increase cell seeding efficiency, initial cell retention and cellular spreading.

Comparison of supine and lateral positioning on various clinically used support surfaces.

In this study, interface pressures, transcutaneous oxygen tension (TcPO2), and blood flow were compared with the classic pressure ulcer-prone areas in the supine and lateral position on six different high- and low-air-loss support surfaces. Interface pressures were substantially higher in the lateral decubitus than in the supine position. Consistent with this, mean TcPO2 and blood flow readings over the trochanter in the lateral position were lower than over the sacrum and ischium in the supine position. With weighting, the average TcPO2 readings decreased from 78.6 mmHg to 11.9 mmHg on the trochanter and from 65.4 mmHg to 45.7 mmHg on the sacrum and ischium. In parallel, average laser Doppler readings decreased from 2.3 to 0.7 laser Doppler flow units over the trochanter, but did not change significantly over the sacrum and ischium. These data support the clinical suggestion that the lateral decubitus position should not be maintained for long periods of time, not even on many special support surfaces.

Pressure ulcers and pressure relief surfaces.

Pressure ulcer incidence has been reduced but not eliminated. A few patients still develop pressure ulcers despite using air-fluidized beds and other specialty beds. In the future, very high-risk patients may possibly be sent to space clinics to recuperate in zero gravity for extended periods. Another possibility is the creation of suspension devices to keep a patient off the areas of the body where pressure sores might occur. Being informed of what is available and and aware how to use it optimally is currently the best solution.