Current clinical treatment strategies for the bypassing of small diameter (<6 mm) blood vessels in the management of cardiovascular disease frequently fail due to a lack of suitable autologous ...grafts, as well as infection, thrombosis, and intimal hyperplasia associated with synthetic grafts. The rapid advancement of 3D printing and regenerative medicine technologies enabling the manufacture of biological, tissue-engineered vascular grafts (TEVGs) with the ability to integrate, remodel, and repair in vivo, promises a paradigm shift in cardiovascular disease management. This review comprehensively covers current state-of-the-art biofabrication technologies for the development of biomimetic TEVGs. Various scaffold based additive manufacturing methods used in vascular tissue engineering, including 3D printing, bioprinting, electrospinning and melt electrowriting, are discussed and assessed against the biomechanical and functional requirements of human vasculature, while the efficacy of decellularization protocols currently applied to engineered and native vessels are evaluated. Further, we provide interdisciplinary insight into the outlook of regenerative medicine for the development of vascular grafts, exploring key considerations and perspectives for the successful clinical integration of evolving technologies. It is expected that continued advancements in microscale additive manufacturing, biofabrication, tissue engineering and decellularization will culminate in the development of clinically viable, off-the-shelf TEVGs for small diameter applications in the near future.
Current clinical strategies for the management of cardiovascular disease using small diameter vessel bypassing procedures are inadequate, with up to 75% of synthetic grafts failing within 3 years of implantation. It is this critically important clinical problem that researchers in the field of vascular tissue engineering and regenerative medicine aim to alleviate using biofabrication methods combining additive manufacturing, biomaterials science and advanced cellular biology. While many approaches facilitate the development of bioengineered constructs which mimic the structure and function of native blood vessels, several challenges must still be overcome for clinical translation of the next generation of tissue-engineered vascular grafts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
3D printing enables the rapid manufacture of patient-specific anatomical models that substantially improve patient consultation and offer unprecedented opportunities for surgical planning and ...training. However, the multistep preparation process may inadvertently lead to inaccurate anatomical representations which may impact clinical decision making detrimentally. Here, we investigated the dimensional accuracy of patient-specific vascular anatomical models manufactured
digital anatomical segmentation and Fused-Deposition Modelling (FDM), Stereolithography (SLA), Selective Laser Sintering (SLS), and PolyJet 3D printing, respectively. All printing modalities reliably produced hand-held patient-specific models of high quality. Quantitative assessment revealed an overall dimensional error of 0.20 ± 3.23%, 0.53 ± 3.16%, -0.11 ± 2.81% and -0.72 ± 2.72% for FDM, SLA, PolyJet and SLS printed models, respectively, compared to unmodified Computed Tomography Angiograms (CTAs) data. Comparison of digital 3D models to CTA data revealed an average relative dimensional error of -0.83 ± 2.13% resulting from digital anatomical segmentation and processing. Therefore, dimensional error resulting from the print modality alone were 0.76 ± 2.88%, + 0.90 ± 2.26%, + 1.62 ± 2.20% and +0.88 ± 1.97%, for FDM, SLA, PolyJet and SLS printed models, respectively. Impact on absolute measurements of feature size were minimal and assessment of relative error showed a propensity for models to be marginally underestimated. This study revealed a high level of dimensional accuracy of 3D-printed patient-specific vascular anatomical models, suggesting they meet the requirements to be used as medical devices for clinical applications.
Background: A patent arteriovenous fistula (AVF) with adequate flow is essential for performing successful hemodialysis. However, the literature currently reports 1-year patency rates of 69%–74%. ...Surveillance of AVFs has been proposed to prevent failure of fistulas with the associated morbidity and mortality. We implemented a renal access surveillance clinic with the aims of detecting stenoses and arranging treatment to avoid underdialysis and thrombosis of AVFs. Methods: The nurse-led vascular renal access surveillance clinic (VRAC) of the Royal Brisbane and Women's Hospital was created in 2015. The surveillance program is run by a full-time vascular clinical nurse with experience in renal access. Over the 3-year period of 2015–2017, 1006 patients were in the surveillance program. We compared the rates of intervention on fistulas and the incidence of thrombosed fistula in the 5 years preceding the initiation of our VRAC surveillance program, with the 3 years after it was commenced. Results: Our results show that our rates of intervention on threatened fistulas have increased since the program was established, and that the percentage of thrombosed fistulas has remained stable. Allowing this early triage has expedited management and freed more outpatient clinic time. Conclusion: We have compared outcomes before and after implementation of a nurse-led dialysis access surveillance program and have found that the percentage of thrombosed fistulas has remained stable as the rates of intervention have increased for threatened fistulas.
Aim: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator (SRC) was developed to estimate the rates of complications for patients ...undergoing a variety of surgical procedures, based on the patient's preoperative demographics and medical conditions. Its predictive ability has been evaluated in a number of studies for a variety of surgical fields. There has so far been no assessment of the SRC in patients undergoing vascular surgery. This study assesses whether the ACS NSQIP SRC can accurately predict risk of complications in patients undergoing major vascular surgery at a tertiary hospital. Methods: A retrospective review of prospectively collected data was performed on all patients who underwent an open abdominal aortic aneurysm (AAA) repair, an endovascular aneurysm repair (EVAR), or a femoral-popliteal bypass graft (FPBG) from July 2016 to April 2017. A total of 95 patients had their demographics entered into the ACS NSQIP SRC, and the predicted rates of complications were compared to the observed rates of complications. Results: Statistical analysis was performed with Brier scores and C-statistics. This analysis found the ACS NSQIP SRC accurately estimated the risk of complications with a Brier score of 0.044 for EVAR, 0.068 for open AAA repair, and 0.0752 for FPBG. The C-statistics for serious complications, any complications, and discharge to a nursing home or rehabilitation indicated the model was good at accurately predicting the risk of these outcomes. Conclusion: The ACS NSQIP SRC accurately predicts the rates of complications in patients undergoing vascular surgery.
Background This study evaluates the impact on short and mid-term outcomes and quality of life of dialysis dependent patients undergoing cardiac surgery. The benefit to patients from a ...bio-psycho-social perspective is put into context via an inter-personal patient interview. Methods The study period was from February 1999 to February 2009. Data on 45 dialysis dependent patients undergoing cardiac surgery was prospectively collected and analysed retrospectively. The mean age was 59.9 years and sex ratio (M:F) of 32:13. All patients were New York Heart Association (NYHA) class >2 preoperatively. Fifty-five percent (25/45) of these patients had coronary artery bypass graft surgery (CABG) and 28% (12/45) aortic valve replacement surgery alone. Forty-two variables were studied to define predictors of outcome. Follow-up was 100% (18/18) with a mean follow-up time of 48.1 months (0–124 months). They were followed up with quality of life and functional coping score surveys (SF-36). Results The main postoperative morbidities were pulmonary complications 20% (9/45), multi-organ failure 11% (5/45) and blood transfusion rates 40% (18/45). The 30 day mortality of the dialysis patients was 13.3% (6/45) and late death was 54% (21/39). Increasing age, pulmonary complications and blood product usage were the significant predictors of both 30 day mortality (age: p = 0.02, pulmonary: p = 0.003, blood product usage: p = 0.03) and late death (age: p = 0.008, pulmonary: p = 0.02, blood product usage: p = 0.02). New York Heart Association class was I–II in 83% (15/18) on long term follow up. All five patients awaiting renal transplants received their transplant in the first six months post-operatively. The overall survival at one year was 78% and five years was 40%. On SF-36 health questionnaire all patients scored less on physical functioning than the Australian norms (24.89 ± 4.10). Conclusions Cardiac surgery in the presence of renal failure is associated with significant morbidity and mortality. The overall survival and quality of life of dialysis patients undergoing cardiac surgery is poor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Objectives The study aims to define predictors of neurological dysfunction, 30-day mortality, long-term survival and quality of life following repair of acute type A aortic dissection (AAAD). Methods ...Between 2000 and 2008, 65 patients underwent repair of AAAD. Sixty-four pre-, intra- and post-operative variables were studied. Mean follow-up was 26.6 months. Results The mean age was 61 years; 60% were male and five had Marfan's syndrome. At presentation, ischaemic ECG changes were seen in 45%, malperfusion syndrome in 59%, moderate–severe aortic regurgitation in 48% and tamponade in 16%. EF was <40% in 17%. There was a delay of >12 hours between diagnosis and operation in 64%. Axillary cannulation was performed in 37%. Cerebral protection was by hypothermic arrest (HCA) alone (19%), HCA with retrograde cerebral perfusion (RCP) (11%), or HCA with antegrade cerebral perfusion (ACP) (46%). The procedure was performed on cross-clamp in 24%. Full arch replacement was performed in 14% and concomitant coronary artery grafting was performed in 11%. Post-operative neurological dysfunction was present in 33.8%. The only significant predictor of poor neurological outcome was full arch replacement ( p = 0.04) on univariate analysis. In-hospital OR 30 mortality was 23.53%. Significant predictors of mortality were low ejection fraction ( p = 0.017) and post-operative renal failure ( p = 0.012). Long-term survival was 70% at two years, 50% at five years and 25% at nine years. Functional outcomes and long-term quality of life were assessed in 69% of patients who were alive at last follow-up. Ninety percent of patients reported minimal limitation on functional scores. Quality of life was assessed using the EQ-5D questionnaire. Forty-eight percent of patients recorded full health with an overall mean index of 0.854 (where the best possible score is 1) using the US preference weighted index score. Conclusions Discharged patients have reasonable long-term survival and good quality of life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
This study evaluates the early and mid-term outcomes, predictors of mortality and morbidity and quality of life of patients operated for infective endocarditis. Data on 108 patients undergoing 113 ...surgical procedures during October 1998 to January 2010 was prospectively collected. NYHA Class was >III in 49 (43.4%) cases. Thirty-seven (33%) patients had isolated mitral valve procedures, 58 (51%) had aortic valve, two had tricuspid valve and 16 had multivalvular procedures. Active endocarditis was noted in 86 (76%) procedures, native valve endocarditis in 105 (93%) and prosthetic valve endocarditis in eight procedures. Logistic EuroSCORE at presentation was >14 in 18 (17%) patients. Staphylococcus aureus was the most common organism isolated. Follow-up was carried out in 76/85 (88.37%) of surviving patients, and the mean follow-up time was 37.2 months. Functional class and quality of life (using EQ-5D Health Questionnaire) were assessed by telephone interviews. NYHA Class on follow-up was I–II in 62/76 (83%). Multivariate predictor of 30-day mortality was peripheral vascular disease ( p = 0.025) whilst multivariate predictors of long-term survival were male sex ( p = 0.01), peripheral vascular disease ( p = 0.02) and bypass time ( p = 0.006). The overall survival was 87% at one year and 80% at five years. Thirty-three percent (25/76) patients reported a score reflecting full health. Optimal antibiotic therapy and timely surgical intervention were associated with improved functional class, quality of life and mid-term survival.
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Biofabrication approaches toward the development of tissue-engineered vascular grafts (TEVGs) have been widely investigated. However, successful translation has been limited to large diameter ...applications, with small diameter grafts frequently failing due to poor mechanical performance, in particular mismatched radial compliance. Herein, melt electrowriting (MEW) of poly(
-caprolactone) has enabled the manufacture of highly porous, biocompatible microfibre scaffolds with physiological anisotropic mechanical properties, as substrates for the biofabrication of small diameter TEVGs. Highly reproducible scaffolds with internal diameter of 4.0 mm were designed with 500 and 250
m pore sizes, demonstrating minimal deviation of less than 4% from the intended architecture, with consistent fibre diameter of 15 ± 2
m across groups. Scaffolds were designed with straight or sinusoidal circumferential microfibre architecture respectively, to investigate the influence of biomimetic fibre straightening on radial compliance. The results demonstrate that scaffolds with wave-like circumferential microfibre laydown patterns mimicking the architectural arrangement of collagen fibres in arteries, exhibit physiological compliance (12.9 ± 0.6% per 100 mmHg), while equivalent control geometries with straight fibres exhibit significantly reduced compliance (5.5 ± 0.1% per 100 mmHg). Further mechanical characterisation revealed the sinusoidal scaffolds designed with 250
m pores exhibited physiologically relevant burst pressures of 1078 ± 236 mmHg, compared to 631 ± 105 mmHg for corresponding 500
m controls. Similar trends were observed for strength and failure, indicating enhanced mechanical performance of scaffolds with reduced pore spacing. Preliminary
culture of human mesenchymal stem cells validated the MEW scaffolds as suitable substrates for cellular growth and proliferation, with high cell viability (>90%) and coverage (>85%), with subsequent seeding of vascular endothelial cells indicating successful attachment and preliminary endothelialisation of tissue-cultured constructs. These findings support further investigation into long-term tissue culture methodologies for enhanced production of vascular extracellular matrix components, toward the development of the next generation of small diameter TEVGs.
Ventricular free wall rupture is an acute, severe complication of myocardial infarction (MI). Accounting for 20–30% of MI mortality, ventricular rupture is fatal if not detected early and repaired ...surgically. The unique case of a delayed, chronic rupture is reported in a 64 year-old male who presented with a painless, pulsatile, sub-xiphisternal bruise, five years post MI. Trans-thoracic echocardiography (TTE) revealed haematoma extending posteriorly with only contrast echocardiography revealing an active communication between the sub-dermal area and the heart. Urgent surgery and a prolonged period in ICU enabled sufficient enough recovery for discharge.
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