Novel, digital, chest drainage system in cardiac surgery.

BACKGROUND: A new, self-contained, digital, continuous pump-driven chest drainage system is compared in a randomized control trial to a traditional wall-suction system in cardiac surgery. METHODS: One hundred and twenty adult elective cardiac patients undergoing coronary artery bypass graft and/or valve surgery were randomized to the study or control group. Both groups had similar pre/intra-operative demographics: age 67.8 vs 67.0 years, Euroscore 2.3 vs 2.2, and body surface area 1.92 vs 1.91 m2 . Additionally, a satisfaction assessment score (0-10) was performed by 52 staff members. RESULTS: Given homogenous intra-operative variables, total chest-tube drainage was comparable among groups (566 vs 640 mL; ns), but the study group showed more efficient fluid collection during the early postoperative phase due to continuous suction (P = .01). Blood, cell saver transfusions and postoperative hemoglobin values were similar in both groups. The study group experienced drain removal after 29.8 vs 38.4 hours in the control group (ns). Seven crossovers from the Study to the Control group were registered but no patient had drain-related complications. The Personnel Satisfaction Assessment scored above 5 for all questions asked. CONCLUSIONS: The new, digital, chest drainage system showed better early drainage of the chest cavity and was as reliable as conventional systems. Quicker drain removal might impact on intensive care unit (ICU) stay and reduce costs. Additional advantages are portable size, battery operation, patient mobility, noiseless function, digital indications and alarms. The satisfaction assessment of the new system by the staff revealed a higher score when compared to the traditional wall suction chest drainage system.

Risk of Burns During Active External Rewarming for Accidental Hypothermia.

This article describes 3 incidents in which therapeutic or experimental warming of cold individuals caused first- to third-degree burns to the skin. Mechanisms for these injuries are considered. We conclude that active external rewarming of the trunk of a cold patient in the field can be administered safely and burn risk reduced if 1) manufacturer instructions are followed; 2) insulation is placed between the skin the and heat source; and 3) caregivers make regular efforts to observe heated skin for possible pending burn injury. Direct inspection is mandatory for the skin of areas that are on top of a heat source when the patient is lying on the heat source.

Biodegradable and plasma-treated electrospun scaffolds coated with recombinant Olfactomedin-like 3 for accelerating wound healing and tissue regeneration.

Three-dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM-related protein Olfactomedin-like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4-fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in-growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds.

Porcine carotid artery replacement with biodegradable electrospun poly-e-caprolactone vascular prosthesis.

OBJECTIVE: There is a continuous search for shelf-ready small-caliber vascular prostheses with satisfactory early and late results. Biodegradable scaffolds, repopulated by recipient's cells regenerating a neovessel, can be a suitable option for adult and pediatric, urgent and elective cardiovascular procedures. METHODS: This was a short-term experimental assessment of a new biodegradable vascular prosthesis for arterial replacement in the pig. Eleven pigs underwent bilateral carotid artery replacement with biodegradable electrospun poly-ε-caprolactone (PCL) nanofiber prostheses (internal diameter, 4 mm; length, 5 cm); or expanded polytetrafluoroethylene (ePTFE) prostheses as control. Perioperative anticoagulation was achieved with intravenous heparin (double baseline activated clotting time). Postoperatively, until conclusion of the study at 1 month, animals received aspirin and clopidogrel daily. Transit time flow was measured intraoperatively and at sacrifice. Doppler ultrasound (1 and 4 weeks) and a selective carotid angiography (4 weeks) were performed to assess patency. All explanted grafts were analyzed by histology, morphometry, and scanning electron microscopy in order to study graft-host interaction. RESULTS: Surgical handling and hemostasis of the new prostheses were excellent. Patency rate was 78% (7/9) for PCL grafts, compared with 67% (4/6) for ePTFE grafts. Transit time flow and Doppler ultrasound showed no significant changes in flow and velocity or diameter over time in both groups. Both prostheses showed no detectable in vivo compliance as compared with native carotid artery. Percent neoendothelialization was 86% for PCL and 58% for ePTFE grafts (P = .008). Neointima formation was equal in both grafts. More adventitial infiltration of macrophages, myofibroblasts, and capillaries was seen in PCL grafts with a milder foreign-body reaction when compared with ePTFE implants. Both grafts showed similar endoluminal thrombus formation. CONCLUSIONS: Biodegradable, electrospun PCL grafts showed good surgical and mechanical properties, no aneurysm formation, and similar short-term patency compared with ePTFE grafts. Rapid endothelialization and cell ingrowth confirms favorable PCL graft-recipient biological interaction. Despite good early results, long-term follow-up is required before clinical application.

A biodegradable ring enables growth of the native tricuspid annulus.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the growth potential and function of the tricuspid valve (TV) annulus after annuloplasty with the intra-annular biodegradable ring. METHODS: Among 11 children (median age 4.5 years; age range: 0.2-10.9 years) who underwent surgery for severe congenital TV regurgitation, valve repair was completed using a biodegradable annuloplasty ring. The children were followed regularly using transthoracic echocardiography, whereby the TV annulus lateral diameter (TVALD) and valve function were monitored. Rates of valve growth were derived from the slope of the regression equations which related TVALD to the natural logarithm of the body surface area (lnBSA). RESULTS: The children's somatic growth was harmonious throughout the entire follow up period (mean 478 days; range: 171-1,477 days). The TVALD differed significantly at six months and at one and two years after surgery compared to the postoperative value at discharge, rising from 19 mm (range: 15.5-26.0 mm) to 24 mm (range: 19.0-30.0 mm) at the last control examination (p = 0.003), while the related Z-scores remained stable. A significant linear correlation between TVALD and lnBSA was found in 63.6% of patients. The median rate of growth for the whole cohort was 1.96-fold (range: 0.52-5.53-fold) higher than a norm, and correlated strongly and positively with age (r = 0.91; p <0.05). The median postoperative TV insufficiency fraction of 9.8% (range: 0-28.8%) remained constant during the follow up period. The postoperative TV maximal pressure gradient was 5.5 mmHg (range: 3.1-12.2 mmHg), and did not increase over time. CONCLUSION: The implantation of a biodegradable ring does not restrict growth of the native TV annulus; this enabled its stabilization in proportion to the somatic growth in the majority of the children. The TV annulus began to change its dimension at six months postoperatively, which may coincide with its biodegradation. The rate of growth of the TV annulus differed from that in the normal population, and was proportional to the patient age. The increase in TV annulus diameter over time did not have any negative influence on the function of the repaired valve.

Hypothermic Cardiac Arrest - Retrospective cohort study from the International Hypothermia Registry.

AIM: The International Hypothermia Registry (IHR) was created to increase knowledge of accidental hypothermia, particularly to develop evidence-based guidelines and find reliable outcome predictors. The present study compares hypothermic patients with and without cardiac arrest included in the IHR. METHODS: Demographic, pre-hospital and in-hospital data, method of rewarming and outcome data were collected anonymously in the IHR between 2010 and 2020. RESULTS: Two hundred and one non-consecutive cases were included. The major causeof hypothermia was mountain accidents, predominantly in young men. Hypothermic Cardiac Arrest (HCA) occurred in 73 of 201 patients. Core temperature was significantly lower in the patients in cardiac arrest (25.0 vs. 30.0 °C, p < 0.001). One hundred and fifteen patients were rewarmed externally (93% with ROSC), 53 by extra-corporeal life support (ECLS) (40% with ROSC) and 21 with invasive internal techniques (71% with ROSC). The overall survival rate was 95% for patients with preserved circulation and 36% for those in cardiac arrest. Witnessed cardiac arrest and ROSC before rewarming were positive outcome predictors, asphyxia, coagulopathy, high potassium and lactate negative outcome predictors. CONCLUSIONS: This first analysis of 201 IHR patients with moderate to severe accidental hypothermia shows an excellent 95% survival rate for patients with preserved circulation and 36% for HCA patients. Witnessed cardiac arrest, restoration of spontaneous circulation, low potassium and lactate and absence of asphyxia were positive survival predictors despite hypothermia in young, healthy adults after mountaineering accidents. However, accidental hypothermia is a heterogenous entity that should be considered in both treatment strategies and prognostication.

S-nitroso human serum albumin as a nitric oxide donor in drug-eluting vascular grafts: Biofunctionality and preclinical evaluation.

Currently available synthetic small diameter vascular grafts reveal low patency rates due to thrombosis and intimal hyperplasia. Biofunctionalized grafts releasing nitric oxide (NO) in situ may overcome these limitations. In this study, a drug-eluting vascular graft was designed by blending polycaprolactone (PCL) with S-nitroso-human-serum-albumin (S-NO-HSA), a nitric oxide donor with prolonged half-life. PCL-S-NO-HSA grafts and patches were fabricated via electrospinning. The fabrication process was optimized. Patches were characterized in vitro for their morphology, drug release, biomechanics, inflammatory effects, cell proliferation, and expression of adhesion molecules. The selected optimized formulation (8%PCL-S-NO-HSA) had superior mechanical/morphological properties with high protein content revealing extended NO release (for 28 days). 8%PCL-S-NO-HSA patches significantly promoted endothelial cell proliferation while limiting smooth muscle cell proliferation. Expression of adhesion molecules (ICAM-1, VCAM-1) and pro-inflammatory macrophage/cytokine markers (CD80, IL-1α, TNF-α) was significantly reduced. 8%PCL-S-NO-HSA patches had superior immunomodulatory properties by up-regulating anti-inflammatory cytokines (IL-10) and M2 macrophage marker (CD163) at final time points. Grafts were further evaluated in a small rodent model as aortic implants up to 12 weeks. Grafts were assessed by magnetic resonance imaging angiography (MRI) in vivo and after retrieval by histology. All grafts remained 100 % patent with no signs of thrombosis or calcification. 8%PCL-S-NO-HSA vascular grafts supported rapid endothelialization, whereas smooth muscle cell proliferation was hampered in earlier phases. This study indicates that 8%PCL-S-NO-HSA grafts effectively support long-term in situ release of bioactive NO. The beneficial effects observed can be promising features for long-term success of small diameter vascular grafts. STATEMENT OF SIGNIFICANCE: Despite extensive research in the field of small diameter vascular graft replacement, there is still no appropriate substitute to autografts yet. Various limitations are associated with currently available synthetic vascular grafts such as thrombogenicity and intimal hyperplasia. Therefore, developing new generations of such conduits has become a major focus of research. One of the most significant signaling molecules that are involved in homeostasis of the vascular system is nitric oxide. The new designed nitric-oxide eluting vascular grafts described in this study induce rapid surface endothelialization and late migration of SMCs into the graft wall. These beneficial effects have potential to improve current limitations of small diameter vascular grafts.

Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards reduction of neointima formation?

BACKGROUND: Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug. METHODS AND RESULTS: PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months. CONCLUSIONS: Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts.

Dynamic human cadaver model for testing the feasibility of new endovascular techniques and tools.

Endovascular device specifications and technical improvements are strongly required, especially in particular anatomical locations such as the aortic arch and the thoracoabdominal aorta. We present a new technique for total endovascular repair of the aortic arch and an experimental design of a circulation model in the human cadaver in order to evaluate the feasibility of this technique.

Degradation and healing characteristics of small-diameter poly(epsilon-caprolactone) vascular grafts in the rat systemic arterial circulation.

BACKGROUND: Long-term patency of conventional synthetic grafts is unsatisfactory below a 6-mm internal diameter. Poly(epsilon-caprolactone) (PCL) is a promising biodegradable polymer with a longer degradation time. We aimed to evaluate in vivo healing and degradation characteristics of small-diameter vascular grafts made of PCL nanofibers compared with expanded polytetrafluoroethylene (ePTFE) grafts. METHODS AND RESULTS: We prepared 2-mm-internal diameter grafts by electrospinning using PCL (M(n)=80, 000 g/mol). Either PCL (n=15) or ePTFE (n=15) grafts were implanted into 30 rats. Rats were followed up for 24 weeks. At the conclusion of the follow-up period, patency and structural integrity were evaluated by digital subtraction angiography. The abdominal aorta, including the graft, was harvested and investigated under light microscopy. Endothelial coverage, neointima formation, and transmural cellular ingrowth were measured by computed histomorphometry. All animals survived until the end of follow-up, and all grafts were patent in both groups. Digital subtraction angiography revealed no stenosis in the PCL group but stenotic lesions in 1 graft at 18 weeks (40%) and in another graft at 24 weeks (50%) in the ePTFE group. None of the grafts showed aneurysmal dilatation. Endothelial coverage was significantly better in the PCL group. Neointimal formation was comparable between the 2 groups. Macrophage and fibroblast ingrowth with extracellular matrix formation and neoangiogenesis were better in the PCL group. After 12 weeks, foci of chondroid metaplasia located in the neointima of PCL grafts were observed in all samples. CONCLUSIONS: Small-diameter PCL grafts represent a promising alternative for the future because of their better healing characteristics compared with ePTFE grafts. Faster endothelialization and extracellular matrix formation, accompanied by degradation of graft fibers, seem to be the major advantages. Further evaluation of degradation and graft healing characteristics may potentially lead to the clinical use of such grafts for revascularization procedures.

Alcohol pretreatment of small-diameter expanded polytetrafluoroethylene grafts: quantitative analysis of graft healing characteristics in the rat abdominal aorta interposition model.

Long-term patency rates of small-diameter expanded polytetrafluoroethylene (ePTFE) vascular prostheses are unsatisfactory. Treatment of ePTFE grafts by alcohol before implantation was reported to increase hydrophilic properties, yielding better endothelialization and cellular in-growth, thus improving graft healing. The effect of alcohol pretreatment on ePTFE grafts and postoperative healing characteristics of wet ePTFE grafts were evaluated in this study. Ten sterile ePTFE grafts (2 mm ID, 30 micro thru-pore, 12 mm long) were implanted in the infrarenal aorta of male Sprague-Dawley rats (324-380 g). Five grafts were treated with ethanol 70% and soaked with saline solution before implantation (wet); five nontreated grafts served as control. All rats were sacrificed after digital subtraction angiography and sampling of the graft for histological investigation after 3 weeks. Histomorphometric analysis was performed for endothelial coverage, cellular in-growth, and intimal hyperplasia. All grafts were patent at the end of 3 weeks in both groups. Histological evaluation revealed significantly better endothelial coverage and prominent infiltration by fibroblasts and lymphocytes in the wet group. Endothelial coverage (31.03 +/- 10.61% vs. 13.03 +/- 9.46%, P = 0.03) and cellular infiltration of grafts (50.91 +/- 8.55% vs. 39.29 +/- 10.70%, P = 0.11) were higher in the wet group. Area of intimal hyperplasia per graft length was also higher in the wet group (5.32 +/- 4.75 microm(2)/microm vs. 2.69 +/- 3.41 microm(2)/microm, P = 0.36). Wetting of ePTFE grafts with ethanol 70% pretreatment before implantation might have a beneficial effect on long-term patency of small-diameter vascular grafts due to facilitated graft healing.

Effect of implantation site on outcome of tissue-engineered vascular grafts.

OBJECTIVE: Vascular prostheses for small caliber bypass grafts in cardiac and vascular diseases or for access surgery are still missing. Poly (Ɛ-caprolactone) (PCL) has been previously investigated by our group and showed good biocompatibility and mechanical properties in vitro and rapid endothelialisation, cellular infiltration and vascularisation in vivo yielding optimal patency in the abdominal aortic position. The aim of the present study is to evaluate our PCL graft in the carotid position and to compare its outcome to the grafts implanted in the abdominal aortic position. METHODS: PCL grafts (1 mm ID/10 mm long) were implanted into the left common carotid artery in 20 Sprague-Dawley rats and compared to our previously published series of abdominal aortic implants. The animals were followed up to 3, 6, 12 and 24 weeks. At each time point, in vivo compliance, angiography and histological examination with morphology were performed. RESULTS: PCL grafts showed good mechanical properties and ease of handling. The average graft compliance was 14.5 ±â€¯1.7%/ mmHg compared to 7.8 ±â€¯0.9% for the abdominal position and 45.1 ±â€¯3.2%/ mmHg for the native carotid artery. The overall patency for the carotid position was 65% as compared to 100% in the abdominal position. Complete endothelialisation was achieved at 3 weeks and cell invasion was more rapid than in the aortic position. In contrast, intimal hyperplasia (IH) and vascular density were less pronounced than in the aortic position. CONCLUSION: Our PCL grafts in the carotid position were well endothelialised with early cellular infiltration, higher compliance, lower IH and calcification compared to the similar grafts implanted in the aortic position. However, there was a higher occlusion rate compared to our abdominal aorta series. Anatomical position, compliance mismatch, flow conditions may answer the difference in patency seen.

Suture-reinforced electrospun polydioxanone-elastin small-diameter tubes for use in vascular tissue engineering: a feasibility study.

This study characterizes the cross-linking of electrospun elastin and the mechanical properties of suture-reinforced 1.5mm internal diameter electrospun tubes composed of blended polydioxanone (PDO) and soluble elastin. Several tube configurations were tested to assess the effects of reinforcement on tube mechanical properties. Between the electrospun layers of each double-layered prosthetic, zero, one or two 6-0 sutures were wound, maintaining 1mm spacing with a pitch of 9 degrees . Single-layered tubes without suture were also examined. Samples were cross-linked and tested for compliance and burst strength. Compliance decreased significantly (p <0.05) and burst strength significantly increased (p <0.01) with reinforcement. Uncross-linked tubes were also tested to determine the effects of cross-linking. Results demonstrated that cross-linking significantly decreases burst strength (p <0.01), while decreases in compliance for cross-linked tubes were not significant. Cross-linked suture-reinforced PDO-elastin tubes had burst pressures more than 10 times greater than normal systolic pressures and exhibited a range of compliance values, including those matching native artery. These tubes display many characteristics of the "ideal" small-diameter graft, having mechanical properties that can be tailored to match those desired in vascular replacement applications.

The International Hypothermia Registry (IHR): Dieter's ESAO Winter Schools and Beat's International Hypothermia Registry.

Accidental hypothermia could be listed as an 'orphan disease,' since mild hypothermia is common but has no severe medical consequences, whereas severe hypothermia is rare and life-threatening. In order to increase our knowledge, find new outcome predictors, and propose better guidelines for the treatment of deep accidental hypothermia victims, we created the International Hypothermia Registry (IHR: https://www.hypothermia-registry.org), which will allow us to gather a large number of cases in order to achieve statistical significance and issue evidence-based recommendations.

Pre-clinical validation of a new intra-operative "dual beam Doppler" blood flowmeter in an artificial circuit.

BACKGROUND: Intra-operative flow measurement during coronary or peripheral bypass operations is helpful for ruling out technical failures and for prediction of complication and patency rates. Preclinical validation of the flowmeters is required in order to rely on the intra-operatively measured results. The aim of this study is to evaluate a new "dual beam Doppler" blood flowmeter before clinical application and to compare it with the established "transit time flow measure-ment" technique in an artificial circuit. METHODS: Measurements were performed in an experimental flow model using pig blood and pig arteries. Three different flowmeters were used: Quantix OR (dual beam doppler flowmeter), CardioMed (transit time flowmeter), and Transonic (transit time flowmeter). Three validation tests were performed to assess correlation, precision, and repeatability of devices. (1) Correlation and agreement analysis was performed with various flow amounts (10-350 mL/min) (n = 160). (2) Device reproducibility and measurement stability were tested with a constant flow (flow amount = 300 mL/min) (n = 30). (3) A user accuracy test (intra- and inter-observer variability) was performed by 5 different observers with a constant flow (flow amount = 205 mL/min) (n = 75). Time collected true flow was used as a reference method in all steps and all tests were performed in a blind manner. Results are shown as mean values +/- standard deviations. Pear-son's correlation and Bland-Altman plot analyses were used to compare measurements. RESULTS: The mean flow was 167 +/- 98 mL/min for true flow and 162 +/- 94 mL/min, 165 +/- 94 mL/min, and 166 +/- 100 mL/min for Quantix OR, CardioMed, and Transonic, respectively. Correlation coefficients between Quantix OR, Medi-Stim, Transonic, and time collected true flow were over 0.98 (P = .01). Most of the measured results ( > 90%) were between +/- 1.96 SD agreement limits in Bland and Altman plot analysis. All devices showed good results in the reproducibility test. During the user accuracy test, larger variance changes were observed between intra- and inter-observer results with the dual beam Doppler flowmeter compared to the 2 used transit time flowmeters when used for single sided vessel access without stabilization device (available from the manufacturer). CONCLUSION: All 3 tested flowmeters showed an excellent correlation to the true flow in an artificial circuit and the accuracy of the tested devices was within agreement limits. Reproducibility of all devices was good and linear. The new dual beam Doppler flow measurement technique compares favorably to the classic transit time method. Clinical use may depend on operator, location, and condition, thus more studies may be required to ensure uniform results using the currently available blood flow measurement devices.

External Saphenous Vein Support Mesh Does Not Interfere With Transit-Time Flow Measurement on Venous Coronary Bypass Conduit: Clinical Confirmation.

A 65-year-old patient underwent double coronary artery bypass grafting using the left internal thoracic artery on the left anterior descending coronary artery and nitinol alloy mesh [external Saphenous Vein Support (eSVS)]-covered saphenous vein graft to the right posterior descending coronary artery. Transit-time flow measurements (TTFMs) were obtained on meshed and bare parts of the vein graft. There was no difference in TTFM parameters (flow, pulsatility index, and diastolic fraction values) obtained from the eSVS mesh-covered and the uncovered parts of the venous graft. This observation confirms that eSVS mesh does not interfere with TTFM on venous coronary bypass conduits.

Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site.

Drug-eluting vascular prostheses represent a new direction in vascular surgery to reduce early thrombosis and late intimal hyperplasia for small calibre grafts. Subcutaneous implantation in rats is a rapid and cost-effective screening model to assess the drug-elution effect and could, to some extent, be useful to forecast results for vascular prostheses. We compared biological and histological responses to scaffolds in different implantation sites. Polycaprolactone (PCL), paclitaxel-loaded PCL (PCL-PTX) and dexamethasone-loaded PCL (PCL-DXM) electrospun scaffolds were implanted subcutaneously and in an infrarenal abdominal aortic model in rats for up to 12 weeks. At the conclusion of the study, a histological analysis was performed. Cellular graft invasion revealed differences in the progression of cellular infiltration between PCL-PTX and PCL/PCL-DXM groups in both models. Cell infiltration increased over time in the aortic model compared to the subcutaneous model for all groups. Cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation in all groups and models over time. Macrophages and giant cells increased in the PCL aortic model; whereas in the subcutaneous model these cell types increased only after three weeks or even decreased in the drug-eluting PCL groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. The subcutaneous implant model can be used for screening, especially when drug-eluting effects are studied. However, major histological differences were observed in cell type reaction and depth of cell penetration compared to the aortic model. Our results demonstrate that the implantation site is a critical determinant of the biological response.