Factors That Complicated the Implementation of a Program of Donation After Unexpected Circulatory Death of Lungs and Kidneys. Lessons Learned From a Regional Trial in the Netherlands.

BACKGROUND: Organ shortage remains a problem in transplantation. An expansion of the donor pool could be the introduction of unexpected donation after circulatory death (uDCD) donors. The goal of this study was to increase the number of transplantable kidneys and lungs by implementing a uDCD protocol. METHODS: A comprehensive protocol for uDCD donation was developed and implemented in the emergency departments (EDs) of 3 transplant centers. All out-of-hospital cardiac arrest (OHCA) patients were screened for uDCD donation. Inclusion criteria were declaration of death in the ED, age (<50 y for kidneys, <65 y for lungs), witnessed arrest, and basic and advanced life support started within 10 and 20 min, respectively. RESULTS: A total of 553 OHCA patients were reported during the project, of which 248 patients survived (44.8%). A total of 87 potential lung and 42 potential kidneys donors were identified. A broad spectrum of reasons resulted in termination of all uDCD procedures. Inclusion and organ-specific exclusion criteria were the most common reason for not proceeding followed by consent. None of the potential donors could be converted into an actual donor. CONCLUSION: Although uDCD potential was shown by successful recognition of potential donors in the ED, we were not able to transplant any organs during the study period. The Dutch Emergency medical service guidelines to stop futile OHCA in the prehospital setting and the strict use of inclusion and exclusion criteria like age and witnessed arrest hampered the utilization. A prehospital uDCD protocol to bring all OHCA patients who are potential uDCD candidates to an ED would be helpful in creating a successful uDCD program.

Innate glycosidic activity in metallic implants for localized synthesis of antibacterial drugs.

Iron-containing metallic implants are shown herein to mediate hydrolysis of glycosidic linkages. Using glucuronide prodrugs for broad-spectrum fluoroquinolone antibacterial agents, we capitalize on this behaviour and perform localized synthesis of antimicrobials which affords a significant zone of inhibition of bacterial growth around the metallic material.

Self-expandable tubular collagen implants.

Collagen has been extensively used as a biomaterial, yet for tubular organ repair, synthetic polymers or metals (e.g., stents) are typically used. In this study, we report a novel type of tubular implant solely consisting of type I collagen, suitable to self-expand in case of minimal invasive implantation. Potential benefits of this collagen scaffold over conventional materials include improved endothelialization, biodegradation over time, and possibilities to add bioactive components to the scaffold, such as anticoagulants. Implants were prepared by compression of porous scaffolds consisting of fibrillar type I collagen (1.0-2.0% (w/v)). By applying carbodiimide cross-linking to the compressed scaffolds in their opened position, entropy-driven shape memory was induced. The scaffolds were subsequently crimped and dried around a guidewire. Upon exposure to water, crimped scaffolds deployed within 15-60 s (depending on the collagen concentration used), thereby returning to the original opened form. The scaffolds were cytocompatible as assessed by cell culture with human primary vascular endothelial and smooth muscle cells. Compression force required to compress the open scaffolds increased with collagen content from 16 to 32 mN for 1.0% to 2.0% (w/v) collagen scaffolds. In conclusion, we report the first self-expandable tubular implant consisting of solely type I collagen that may have potential as a biological vascular implant.

Continuously Grooved Stent Struts for Enhanced Endothelial Cell Seeding.

PURPOSE: Implantation of pre-endothelialized stents could enhance cellular recovery of a damaged vessel wall provided attached cells remain viable, functional and are present in sufficient numbers after deployment. The purpose of this study was to evaluate the feasibility of grooved stainless steel (SS) stents as a primary endothelial cell (EC) carrier with potentially enhanced EC protection upon stent deployment. MATERIALS AND METHODS: Attachment and behavior of enzymatically harvested human adult venous ECs seeded onto gelatin-coated vascular stents were evaluated in an in vitro setting. Smooth and grooved SS stents and smooth nitinol stents were studied. RESULTS: All cells expressed EC markers vWF and CD31. Using rotational seeding for a period of 16-24 h, ECs attached firmly to the stents with sufficient coverage to form a confluent EC monolayer. The grooved SS wire design was found to enable attachment of three times the number of cells compared to smooth wires. This also resulted in an increased number of cells remaining on the stent after deployment and after pulsatile flow of 180 ml/min for 24 h, which did not result in additional EC detachment. CONCLUSIONS: The grooved stent provides a potential percutaneous means to deliver sufficient numbers of viable and functional cells to a vessel segment during vascular intervention. The grooves were found to offer a favorable surface for EC attachment and protection during stent deployment in an in vitro setting.

Abdominal organ procurement in the Netherlands - an analysis of quality and clinical impact.

Between March 2012 and August 2013, 591 quality forms were filled out for abdominal organs in the Netherlands. In 133 cases (23%), there was a discrepancy between the evaluation from the procuring and transplanting surgeons. Injuries were seen in 148 (25%) organs of which 12 (2%) led to discarding of the organ: one of 133 (0.8%) livers, five of 38 (13%) pancreata and six of 420 (1.4%) kidneys (P < 0.001). Higher donor BMI was a risk factor for procurement-related injury in all organs (OR: 1.06, P = 0.011) and donor after cardiac death (DCD) donation in liver procurement (OR: 2.31, P = 0.034). DCD donation is also associated with more pancreata being discarded due to injury (OR: 10.333, P = 0.046). A higher procurement volume in a centre was associated with less injury in pancreata (OR = -0.95, P = 0.013) and kidneys (OR = -0.91, P = 0.012). The quality form system efficiently monitors the quality of organ procurement. Although there is a relatively high rate of organ injury, the discard rate is low and it does not significantly affect 1-year graft survival for any organ. We identified higher BMI as a risk factor for injury in abdominal organs and DCD as a risk factor in livers. A higher procurement volume is associated with fewer injuries.

The Effect of Mycophenolate Mofetil on Early Wound Healing in a Rodent Model.

BACKGROUND: Immunosuppressant agents are inevitable for solid organ recipients, but may have a negative effect on wound healing that is difficult to measure because of clinical use of a polydrug regime. The evidence on mycophenolate mofetil (MMF) is scarce and contradictory. This study aims to investigate the effect of MMF administration on wound healing. METHODS: Ninety-six male Wistar rats divided into 4 groups underwent anastomotic construction in ileum and colon at day 0. Three groups received daily oral doses of 20 or 40 mg/kg MMF or saline (control group) from day 0 until the end of the experiment. Half of each group was analyzed after 3 days and half after 7 days. Another group started the medication 3 days after the laparotomy and was analyzed after 7 days, half of this group received 20 mg/kg and half 40 mg/kg MMF. Wound strength in anastomoses and in the abdominal wall was measured using bursting pressure, breaking strength, and histology. Trough levels were measured. RESULTS: Significant differences in wound strength were seen in ileum tissue after 3 days, which surprisingly showed a stronger anastomosis in the experimental groups. Bursting pressure as well as breaking strength was higher in the low-dose and high-dose MMF group compared with the control group. A negative effect was measured in abdominal wall tissue for the highest-dose group, which disappeared when the medication was delayed for 3 days. Histology showed poorer bridging of the submucosal layer and more polymorphonuclear cell infiltration in the ileum specimens of the control group compared with the treatment groups. CONCLUSIONS: As a single agent in a preclinical wound healing model in the rat, MMF has no negative effect on healing of bowel anastomoses but might have a negative effect on the healing of abdominal wall.

Endovascular versus surgical revascularization in proximal subclavian artery obstruction.

BACKGROUND: The aim of this paper was to compare the outcomes of endovascular versus surgical treatment in patients with symptomatic proximal subclavian artery obstruction through a retrospective clinical study. Treatment of symptomatic subclavian artery obstruction can be performed with percutaneous transluminal angioplasty or open surgical reconstruction. Comparative studies are scarce. METHODS: Technical success, patency and complication rates of 47 endovascular reconstructions in 46 patients were retrospectively compared with those of 19 open surgical reconstructions in 17 patients performed between 1996 and 2012. An additional series of 51 surgical reconstructions performed in the same institution between 1976 and 1993 served as a reference. RESULTS: The technical success rate was 79% for endovascular and 100% for open surgical reconstructions (P<0.05). Primary patency was 72% and 89% at 1 year or 54% and 55% at 5 years for the endovascular and open surgical groups, respectively (log rank 0.210, P=0.65). Assisted primary patency was 77% and 100% at 1 year or 67% and 67% at 5 years, respectively (log rank 0.528, P=0.47). There was no mortality and major complications were infrequent, occurring equally in both groups (P=0.22). CONCLUSIONS: Although with its less invasive character endovascular treatment has gained preference over surgical treatment of proximal subclavian obstruction in many cases, extrathoracic surgical reconstruction can be performed with a higher technical success rate, similar patency and a comparable number of complications.

Tacrolimus does not affect early wound healing in a rodent model of bowel anastomoses and abdominal wall closure.

BACKGROUND: Use of immunosuppressant drugs has been associated with complications in wound healing. The calcineurin inhibitor tacrolimus is thought to have a relatively low complication rate, but preclinical research has yielded contradictory data, prompting the current comprehensive study. METHODS: Three groups of 33 male Wistar rats received a daily subcutaneous dose of 0,5, 2 or 5 mg/kg tacrolimus. A control group received saline. On day 0 a resection of 1 cm ileum and 1 cm colon was performed, and end-to-end anastomoses were constructed. Ten rats of each group were killed on day 3 and day 5 and the remaining animals on day 7. Both anastomoses and the wound in the abdominal wall were analyzed. Wound strength was the primary outcome parameter. RESULTS: Mean strength of the abdominal wall increased significantly over time in all groups (p<0.0001). Both the breaking strength and the bursting pressure of the ileum and colon anastomoses followed the same pattern. No differences were observed between control and experimental groups. In addition, no consistent differences were found between groups regarding wound hydroxyproline content and the activities of matrix metalloproteinase-2 and -9. CONCLUSION: Tacrolimus does not affect early wound healing.

Towards a role of interleukin-32 in atherosclerosis.

BACKGROUND: IL-32 has been previously shown to promote inflammation in rheumatoid arthritis patients and to contribute to IL-1ß-induced ICAM-1 as well as other proinflammatory cytokines synthesis in human umbilical endothelial cells (HUVECs). Given the high rate of atherosclerosis in RA, these observations suggest that IL-32 may be involved in the inflammatory pathways of atherosclerosis. METHODS: mRNA and protein levels of IL-32 were determined in human atherosclerotic arterial vessel wall tissue by quantitative real-time PCR and immunohistochemistry. HUVEC and M1/M2 macrophages were stimulated with proinflammatory cytokines and TLR ligands to assess IL-32 mRNA induction. Human THP1 macrophages were transduced with AdIL-32γ, to investigate induction of several proatherosclerotic mediators. Finally, aortas from IL-32γ transgenic mice were studied and compared with aortas from age-matched wild-type mice. RESULTS: IL-32 expression was detectable in human atherosclerotic arterial vessel wall, with the expression of IL-32ß and IL-32γ mRNA significantly enhanced. TLR3-ligand Poly I:C in combination with IFNγ were the most potent inducers of IL-32 mRNA expression in both HUVEC and M1/M2 macrophages. Adenoviral overexpression of IL-32γ in human THP1 macrophages resulted in increased production of CCL2, sVCAM-1, MMP1, MMP9, and MMP13. The IL-32γ transgenic mice chow a normal fat diet exhibited vascular abnormalities resembling atherosclerosis. CONCLUSIONS: IL-32 acts as a proinflammatory factor and may be implicated in the inflammatory cascade contributing to atherosclerosis. By promoting the synthesis of matrix metalloproteinases, it may further contribute to plaque instability. Further studies are warranted to investigate whether IL-32 may serve as a potential therapeutic target in fighting atherosclerosis.

Overexpression of angiopoietin-like protein 4 protects against atherosclerosis development.

OBJECTIVE: Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in macrophages and examined the impact of Angptl4 on atherosclerosis development. APPROACH AND RESULTS: Macrophage activation elicited by pathogen-recognition receptor agonists decreased Angptl4 expression, whereas lipid loading by intralipid and oxidized low-density lipoprotein increased Angptl4 expression. Consistent with an antilipotoxic role of Angptl4, recombinant Angptl4 significantly decreased uptake of oxidized low-density lipoprotein by macrophages, via lipolysis-dependent and -independent mechanisms. Angptl4 protein was detectable in human atherosclerotic lesions and localized to macrophages. Transgenic overexpression of Angptl4 in atherosclerosis-prone apolipoprotein E*3-Leiden mice did not significantly alter plasma cholesterol and triglyceride levels. Nevertheless, Angptl4 overexpression reduced lesion area by 34% (P<0.05). In addition, Angptl4 overexpression decreased macrophage content (-41%; P<0.05) and numbers of monocytes adhering to the endothelium wall (-37%; P<0.01). Finally, plasma Angptl4 was independently and negatively associated with carotid artery sclerosis measured by 3-T MRI in subjects with metabolic syndrome and low-grade systemic inflammation. CONCLUSIONS: Angptl4 suppresses foam cell formation to reduce atherosclerosis development. Stimulation of Angptl4 in macrophages by oxidized low-density lipoprotein may protect against lipid overload.

Humoral signalling compounds in remote ischaemic preconditioning of the kidney, a role for the opioid receptor.

BACKGROUND: Renal ischaemia-reperfusion injury (IRI) is a common clinical problem associated with significant mortality and morbidity. One strategy to reduce this damage is remote ischaemic preconditioning (RIPC), in which brief ischaemia of a limb protects the kidney against a prolonged ischaemic insult. The mechanism of renal RIPC has not yet been elucidated. Here, we address the gap in our understanding of renal RIPC signalling, using a rat model of renal IRI and RIPC by brief hind limb ischaemia. METHODS: Rats were treated with either no RIPC, RIPC+vehicle or RIPC+ an inhibitor or antagonist of one of the following candidate signalling molecules: noradrenalin, cannabinoids, glucocorticoids, inducible nitric oxide synthase, calcitonin gene-related peptide, ganglion-mediated signalling, haem oxygenase and free radicals. Subsequently, the animals underwent 25 min of renal ischaemia and 2 days of reperfusion, after which renal function and damage were assessed. RESULTS: RIPC by three 4 min cycles of hind limb ischaemia effectively reduced renal IRI. Pre-treatment with the opioid receptor antagonist naloxone completely blocked this protective effect, when compared with animals treated with RIPC+vehicle; serum creatinine and urea increased (307.8±43.7 versus 169.5±16.7 µmol/L and 42.2±4.9 versus 27.6±2.2 mmol/L, respectively), as did the renal histological damage (score 4.2±0.7 versus 2.8±0.5) and expression of kidney injury molecule-1 (KIM-1; relative-fold increase in mRNA expression 164±18 versus 304±33). All other antagonists were without effect. CONCLUSIONS: Renal RIPC by brief hind limb ischaemia may be the result of endorphin release from the hind limb. The importance of opioid signalling in renal RIPC provides vital clues for its successful translation to the clinical setting.

The need to reduce cold ischemia time in kidney transplantation.

PURPOSE OF REVIEW: Hypothermic preservation is a prerequisite for kidney exchange in transplantation. The severity of tissue damage caused by hypothermic preservation influences the level of ischemia/reperfusion injury and subsequent graft function. With the purpose of reviewing the implications of prolonged cold ischemia time (CIT) in kidney transplantation, its pathophysiology, effects on early and late outcome of transplantation for different types of deceased organ donors, and preservation methods are discussed based on recent literature. RECENT FINDINGS: The main findings are that the consequences of a prolonged CIT are mainly identifiable in the early posttransplant period as delayed graft function, especially in expanded criteria donors, and possibly in an increased acute rejection rate. The preferred method of hypothermic preservation in expanded criteria donors and donors after cardiac death appears to be machine preservation. SUMMARY: The effects of CIT on the long-term outcome of renal transplantation in the form of impaired graft function and graft survival are less evident.

Ischemic preconditioning in the animal kidney, a systematic review and meta-analysis.

Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h = early vs. ≥ 24 h = late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments.

Automatic segmentation of the wire frame of stent grafts from CT data.

Endovascular aortic replacement (EVAR) is an established technique, which uses stent grafts to treat aortic aneurysms in patients at risk of aneurysm rupture. Late stent graft failure is a serious complication in endovascular repair of aortic aneurysms. Better understanding of the motion characteristics of stent grafts will be beneficial for designing future devices. In addition, analysis of stent graft movement in individual patients in vivo can be valuable for predicting stent graft failure in these patients. To be able to gather information on stent graft motion in a quick and robust fashion, we propose an automatic method to segment stent grafts from CT data, consisting of three steps: the detection of seed points, finding the connections between these points to produce a graph, and graph processing to obtain the final geometric model in the form of an undirected graph. Using annotated reference data, the method was optimized and its accuracy was evaluated. The experiments were performed using data containing the AneuRx and Zenith stent grafts. The algorithm is robust for noise and small variations in the used parameter values, does not require much memory according to modern standards, and is fast enough to be used in a clinical setting (65 and 30s for the two stent types, respectively). Further, it is shown that the resulting graphs have a 95% (AneuRx) and 92% (Zenith) correspondence with the annotated data. The geometric model produced by the algorithm allows incorporation of high level information and material properties. This enables us to study the in vivo motions and forces that act on the frame of the stent. We believe that such studies will provide new insights into the behavior of the stent graft in vivo, enables the detection and prediction of stent failure in individual patients, and can help in designing better stent grafts in the future.

Everolimus-induced loss of wound strength can be prevented by a short postoperative delay in its administration.

The use of mammalian target of rapamycin inhibitors coincides with an increased incidence of surgical complications. In previous experiments, serious negative effects of postoperative everolimus on anastomotic strength were found. This study aims to investigate if delayed drug administration can prevent loss of wound strength. Ten groups of Wistar rats each received daily oral doses of 1.0 or 2.0 mg/kg everolimus, starting the day of anastomotic construction in both ileum and colon, or 1, 2, 3, or 4 days later. The 11th group received saline. Seven days later, wound strength in anastomoses and in the abdominal wall and wound hydroxyproline levels were measured. Mean wound strength was significantly and dose-dependently reduced if everolimus was started on the day of operation. In ileum and colon, strength was not affected if drug administration was delayed until the third or second day, respectively. In abdominal fascia, this was the case only if everolimus was withheld until day 4. In general, changes in wound hydroxyproline content showed similarities to changes in wound strength. Thus, delaying administration of everolimus for 2-4 days after operation can prevent a serious loss of wound strength, both in the intestine and in the abdominal fascia.

Persisting iliaco-caval fistula after EVAR maintained by a type II endoleak.

We present the case of a patient with a persisting type II endoleak after endovascular repair of an iliac aneurysm with an iliaco-caval fistula. We describe the pathophysiological mechanism behind this phenomenon and discuss why conservative treatment is unlikely to seal this type of endoleak. A more aggressive treatment strategy is therefore advocated.

Influence of prolonged cold ischemia in renal transplantation.

AIM: To determine to what extent current cold ischemia times (CITs) affect the results of renal transplantation in the Netherlands. METHODS: Retrospective survey of the Dutch Organ Transplant Registry concerning transplants from deceased donors between 1990 and 2007. RESULTS: A total of 6322 recipients were identified, of whom 5306 received a kidney from deceased heartbeating (HBD) and 1016 from donors after cardiac death (DCD). Mean CIT was 24.0 ± 7.9 h in HBD and 21.6 ± 6.7 h in DCD. The percentage delayed graft function (DGF) was 12.3 and 50.4, respectively (p < 0.001). Primary non-function (PNF) occurred in, respectively, 1.7% and 5.0% (p < 0.001). Serum creatinine after three months was 166 µM in HBD and 213 µM in DCD (p < 0.001). Five-yr graft survival was 79.5% and 78.3%, respectively (p = ns). In multivariate analysis, CIT proved to be an independent risk factor for DGF and PNF. Shorter CIT was associated with better graft survival in both groups with a hazard ratio of 1.024 (1.011-1.037, 95% CI)/h. CIT <20 h was associated with a graft survival benefit of 3% after five yr in HBD and CIT of <16 h with a benefit of 10% in DCD. CONCLUSIONS: Longer CITs are associated with the occurrence of DGF, PNF and decreased graft survival in the Netherlands.

Remote ischaemic preconditioning by brief hind limb ischaemia protects against renal ischaemia-reperfusion injury: the role of adenosine.

BACKGROUND: Remote ischaemic preconditioning (RIPC) is a strategy to protect a target organ against ischaemia-reperfusion injury (IRI) by inducing short-term ischaemia/reperfusion (I/R) in a remote organ. RIPC of the kidney by temporary limb occlusion would be a safe, inexpensive and noninvasive method to prevent renal damage in, e.g., transplantation and aortic surgery. We investigated whether brief hind limb occlusion can protect against renal IRI and whether this protection is adenosine dependent. METHODS: Rats underwent either no RIPC, unilateral RIPC or bilateral RIPC. The preconditioning stimulus was either continuous (12'/12' I/R) or fractionated (three times 4'/4' I/R). After the last reperfusion period, we induced 25' ischaemia in the right kidney. RESULTS: After 24 h of reperfusion, renal function was improved by 30-60% in both bilateral RIPC groups and in the fractionated unilateral group. Renal tubule damage and kidney injury molecule-1 expression were reduced in three of four RIPC groups. Treatment with the adenosine receptor blocker 8-(p-sulfophenyl)theophylline had no effect on fractionated or continuous RIPC. CONCLUSIONS: Brief hind limb ischaemia induces protection against renal IRI, which makes this a promising strategy to prevent renal IRI in a clinical setting. Bilateral RIPC was more effective than unilateral RIPC, and this protection occurs via an adenosine-independent mechanism.

Preparation and characterization of injectable fibrillar type I collagen and evaluation for pseudoaneurysm treatment in a pig model.

OBJECTIVE: Despite the efficacy of collagen in femoral artery pseudoaneurysm treatment, as reported in one patient study, its use has not yet gained wide acceptance in clinical practice. In this particular study, the collagen was not described in detail. To further investigate the potential of collagen preparations, we prepared and characterized highly purified injectable fibrillar type I collagen and evaluated its use for femoral artery pseudoaneurysm (PSA) treatment in vivo using a pig model. METHODS: Purified fibrillar type I collagen was characterized using electron microscopy. The effect of three different sterilization procedures, ie, hydrogen peroxide gas plasma (H2O2), ethylene oxide gas (EtO), and gamma irradiation, was studied on both SDS-PAGE and platelet aggregation. Different collagen injectables were prepared (3%, 4%, and 5%) and tested using an injection force test applying a 21-gauge needle. To evaluate the network characteristics of the injectable collagen, the collagen was suspended in phosphate buffered saline (PBS) at 37°C and studied both macroscopically and electron microscopically. To determine whether the collagen induced hemostasis in vivo, a pig PSA model was used applying a 4% EtO sterilized collagen injectable, and evaluation by angiography and routine histology. RESULTS: Electron microscopy of the purified type I collagen revealed intact fibrils with a distinct striated pattern and a length<300 µm. Both SDS-PAGE and platelet aggregation analysis of the sterilized collagen indicated no major differences between EtO and H2O2 sterilization, although gamma-irradiated collagen showed degradation products. Both 3% and 4% (w/v) collagen suspensions were acceptable with respect to the force used (<50 N). The 4% suspension was selected as the preferred injectable collagen, which formed a dense network under physiologic conditions. Testing the collagen in vivo (n=5), the angiograms revealed that the PSA partly or completely coagulated. Histology confirmed the network formation, which was surrounded by thrombus. CONCLUSIONS: Collagen injectables were prepared and EtO sterilized without major loss of structural integrity and platelet activity. In vivo, the injectable collagen formed a dense network and triggered (partial) local hemostasis. Although optimization is needed, an injectable collagen may be used as a therapeutic agent for femoral PSA treatment.