Smart materials in cardiovascular implants: Shape memory alloys and shape memory polymers.

Smart materials have intrinsic properties that change in a controlled fashion in response to external stimuli. Currently, the only smart materials with a significant clinical impact in cardiovascular implant design are shape memory alloys, particularly Nitinol. Recent prodigious progress in material science has resulted in the development of sophisticated shape memory polymers. In this article, we have reviewed the literature and outline the characteristics, advantages, and disadvantages of shape memory alloys and shape memory polymers which are relevant to clinical cardiovascular applications, and describe the potential of these smart materials for applications in coronary stents and transcatheter valves.

Modular assembly of thick multifunctional cardiac patches.

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues.

Systematical evolution on a Zn-Mg alloy potentially developed for biodegradable cardiovascular stents.

To reduce the long-term side effects of permanent metallic stents, a new generation of cardiovascular stents called "biodegradable stents" is being extensively developed. Zinc has been considered as a promising candidate material for biodegradable cardiovascular stents due to its excellent biocompatibility and appropriate biodegradability. However, weak mechanical properties limit its further clinic application. In this study, hot extruded pure Zn and Zn-0.02 Mg alloy were prepared. Compared with pure Zn, Zn-0.02 Mg alloy showed more homogeneous microstructure, much smaller grain size and higher mechanical strength. Zn-0.02 Mg alloy presented uniform corrosion morphologies during the immersion process, and its corrosion rates was higher than that of pure Zn. Hemocompatibility results showed that the Zn-based alloy had extremely low hemolysis rate (0.74 ± 0.15%) and strong inhibitory effect on blood coagulation, platelet adhesion and aggregation. Zn-0.02 Mg alloy also exhibited excellent cytocompatibility. Its extracts could significantly promote the proliferation of endothelial cells. Moreover, the antibacterial activities of the Zn-based alloy were demonstrated by spread plate assay, live/dead viability assay and bacterial morphology observation. These results indicate that the extruded Zn-0.02 Mg alloy has a potential in biodegradable cardiovascular stents.

[Effect of polyoxyalkanoate -based cover on properties of suture material].

The results of a surgical intervention and, in particular, reconstructive operations on arteries are largely influenced by suture material. Despite a wide range of choice, the market concerned lacks suture material which would make it possible to decrease the risk of thrombosis in the area of the vascular anastomosis. In order to increase bio- and haemocompatibility, the surface of a polypropylene thread was covered with a layer based on polyoxyalkanoates - polyhydroxybutyrate and copolymer polyhydroxybutyrate-oxyvaleriate (PHBV). The strongest and most uniformly distributed coating of the polypropylene thread was provided by PHBV. We assessed the bio- and haemocompatibility properties of suture material modified by PHBV, revealing that this modification does not exert negative effect on the main components of blood - thrombocytes and erythrocytes. Treatment of the thread's surface with PHBV promoted a significant (p<0.05) decrease in the amount of absorbed proteins in the area of the vascular anastomosis in experiment: the amount of IgM decreased by 26%, that of fibrinogen by 29%, and that of D-Dimer by 281%, being on the whole indicative of bio- and haemocompatibility of the modified suture material.

Biomaterials to enhance stem cell function in the heart.

Transplantation of stem cells into the heart can improve cardiac function after myocardial infarction and in chronic heart failure, but the extent of benefit and of reproducibility of this approach are insufficient. Survival of transplanted cells into myocardium is poor, and new strategies are needed to enhance stem cell differentiation and survival in vivo. In this review, we describe how biomaterials can enhance stem cell function in the heart. Biomaterials can mimic or include naturally occurring extracellular matrix and also instruct stem cell function in different ways. Biomaterials can promote angiogenesis, enhance engraftment and differentiation of stem cells, and accelerate electromechanical integration of transplanted stem cells. Biomaterials can also be used to deliver proteins, genes, or small RNAs together with stem cells. Furthermore, recent evidence indicates that the biophysical environment of stem cells is crucial for their proliferation and differentiation, as well as their electromechanical integration. Many approaches in regenerative medicine will likely ultimately require integration of molecularly designed biomaterials and stem cell biology to develop stable tissue regeneration.

Current status of developing tissue engineering vascular technologies.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in western countries. Although surgical outcomes for CVD are dramatically improving with the development of surgical techniques, medications, and perioperative management strategies, adverse postoperative events related to the use of artificial prosthetic materials are still problematic. Moreover, in pediatric patients, using these artificial materials make future re-intervention inevitable due to their lack of growth potential. AREAS COVERED: This review focuses on the most current tissue-engineering (TE) technologies to treat cardiovascular diseases and discusses their limitations through reports ranging from animal studies to clinical trials. EXPERT OPINION: Tissue-engineered structures, derived from a patient's own autologous cells/tissues and biodegradable polymer scaffolds, can provide mechanical function similar to non-diseased tissue. However, unlike prosthetic materials, tissue-engineered structures are hypothetically more biocompatible and provide growth potential, saving patients from additional or repetitive interventions. While there are many methods being investigated to develop TE technologies in the hopes of finding better options to tackle CVD, most of these approaches are not ready for clinical use or trials. However, tissue engineering has great promise to potentially provide better treatment options to vastly improve cardiovascular surgical outcomes.

Cyclopeptide-ß-cyclodextrin/γ-glycerol methoxytrimethoxysilane film for potential vascular tissue engineering scaffolds.

The mortality rate of cardiovascular diseases is the highest among all mortality rates worldwide. Allotransplantation and autotransplantation are limited by rejection reaction and availability. Tissue engineering provides new avenues for the treatment of cardiovascular diseases. However, the current small-diameter (<6 mm) vascular tissue-engineered scaffolds have many challenges, including thrombosis, stenosis, and infection. Small-diameter vascular scaffolds have structural and compositional requirements such as biocompatibility, porosity, and appropriate phase separation. We used liquid-crystal cyclopeptide（CYC）to modify ß-cyclodextrin and mixed it with γ-glycerol methoxytrimethoxysilane (GPTMS) to prepare CYC-ß-cyclodextrin (ßCD)/GPTMS film by sol-gel. The chemical structure of CYC-ßCD was confirmed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The chemical characterization of CYC-ßCD/GPTMS film was performed by differential scanning calorimetry, X-ray diffraction, and small-angle X-ray scattering. The surface morphology and phase separation microstructure of the film were determined by scanning electron microscopy and atomic force microscopy, and the image of polarizing microscopy showed the liquid-crystal structure of the film. Cell culture experiments showed that CYC-ßCD/GPTMS film had good cytocompatibility and induced growth and proliferation of cells. These results indicated the potential applications of CYC-ßCD/GPTMS film in tissue engineering scaffolds.

Current usage and future directions for the bovine pericardial patch.

Bovine pericardium (BP) is widely used in surgery and is commonly used as a patch after arteriotomy in cardiovascular surgery. BP patches have several advantages compared with prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding, and possibly reduced rates of infection. These advantages of BP have led to its common use during carotid endarterectomy (CEA). However, long-term clinical results reported after CEA have suggested several issues that may be related to the patch, including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification, and thrombosis. These complications may diminish the long-term efficacy of CEA and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which BP heals after patch angioplasty may lead to next generation tissue-engineered patches.

A Bioresorbable Dynamic Pressure Sensor for Cardiovascular Postoperative Care.

Bioresorbable electronics that can be absorbed and become part of the organism after their service life are a new trend to avoid secondary invasive surgery. However, the material limitation is a significant challenge. There are fewer biodegradable materials with pressure-sensitive properties. Here, a pressure sensor based on the triboelectric effect between bioabsorbable materials is reported. This effect is available in almost all materials. The bioresorbable triboelectric sensor (BTS) can directly convert ambient pressure changes into electrical signals. This device successfully identifies abnormal vascular occlusion events in large animals (dogs). The service life of the BTS reaches 5 days with a high service efficiency (5.95%). The BTS offers excellent sensitivity (11 mV mmHg-1 ), linearity (R2  = 0.993), and good durability (450 000 cycles). The antibacterial bioresorbable materials (poly(lactic acid)-(chitosan 4%)) for the BTS can achieve 99% sterilization. Triboelectric devices are expected to be applied in postoperative care as bioresorbable electronics.

Low-flow polytetrafluoroethylene accesses: ultrasound surveillance and preemptive interventions ensure long-term patency.

BACKGROUND: Vascular accesses (especially polytetrafluoroethylene grafts) with a permanently low flow (Qa <600 ml/min) are prone to thrombosis and thus have short patency. The reason for a permanently low flow is usually medial calcinosis of the inflow artery in diabetics. We retrospectively studied the long-term patency of low-flow grafts with careful ultrasound surveillance and preemptive interventions. METHODS: Twenty subjects with Qa permanently <600 ml/min were included. Ultrasound surveillance was performed every 3 months in addition to classical monitoring techniques. Significant stenosis was strictly defined as the combination of B-mode narrowing >50% + >2-fold peak systolic velocity increase + 1 additional criterion (residual diameter <2.0 mm or flow volume decrease by >20%). Such stenoses were treated by preemptive percutaneous intervention. Primary and secondary patencies were calculated. RESULTS: The primary patency was 357 ± 316 days and the secondary (cumulative) patency was 996 ± 702 days. The number of interventions was 2.09/patient year, but >10 in 6 (33%) subjects. 93 and 80% of grafts were patent 1 and 2 years after access creation, respectively. CONCLUSION: Low-flow accesses undergoing ultrasound surveillance with strict diagnostic criteria and preemptive interventions had patencies similar to accesses with normal Qa in our study. This was enabled by a relatively high rate of interventions.

Strategies in cell-free tissue-engineered vascular grafts.

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in the world, among which coronary artery diseases (CAD) are the most common type of CVD. Coronary artery bypass grafting (CABG) using autologous vein and artery grafts is the typical surgical intervention for CAD patients. However, for patients whose autologous grafts are not available, there are no appropriate substitutes for vascular grafts. Investigation of tissue-engineered vascular graft (TEVG) has persisted over decades with significant advancement, utilizing different types of biomaterials. In the past two decades, a great number of studies based on cell-seeding strategies were reported. However, limitations of cell-based strategies made clinical application difficult. With the understanding of stem cells and tissue remodeling process, strategies without cell-seeding emerged as potential methods to achieve in situ regeneration. A cell-free graft may recruit host cells and guide their participation in vascular remodeling. The grafts modified by bio-active molecules showed good results in promoting in situ regeneration and exhibited potential to make the vascular grafts off-the-shelf. In this review, the strategies for cell-free TEVG manufacturing were discussed, including the materials for fabricating TEVGs, the methods of functionalization to promote in situ regeneration, the challenges researchers faced in TEVG investigation, and finally the prospects in TEVG design.

Biodegradable phosphorylcholine copolymer for cardiovascular stent coating.

Phosphorylcholine (PC) based polymer coatings with excellent biocompatibility have shown successful commercialization in drug-eluting stents. However, poor degradability represents a challenge in the application of biodegradable stents. Herein, a biodegradable phosphorylcholine copolymer is developed based on one-step radical ring-opening polymerization (RROP). This copolymer was synthesized by copolymerization of a PC unit, degradable ester (2-methylene-1,3-dioxepane, MDO) unit and non-degradable butyl methacrylate (BMA) unit, which showed ratio controllability by changing the monomer ratio during polymerization. We demonstrated that the copolymer with the ratio of 34% MDO, 19% MPC and 47% BMA could form a stable coating by ultrasonic spray, and showed good blood compatibility, anti-adhesion properties, biodegradability, and rapamycin eluting capacity. In vivo study revealed its promising application as a biodegradable stent coating. This work provides a facile path to add biodegradability into PC based polymers for further bio-applications.

Fabrication, characterization, and in vitro evaluation of electrospun polyurethane-gelatin-carbon nanotube scaffolds for cardiovascular tissue engineering applications.

Myocardial infarction occurs because coronary arteries insufficiency is one of the major causes of mortality worldwide. Recent studies have shown that tissue engineering of myocardial tissue to regenerate infarcted tissue or engineering of the coronary artery may help overcome this problem. In the present research, gelatin and single-walled carbon nanotube were firstly administrated to physico-chemically and biologically modulate polyurethane nanofibers. Electrospinning, as versatile and effective technique for production of functional nanoscale fiber, was applied. Incorporation of both gelatin and SWNTs reduced mean diameter of nanofibrous scaffolds from 210 to 140 nm, which influenced on initial cell behavior. Possible interaction between gelatin and SWNTs with polyurethane chains was evaluated using FTIR and DSC techniques. Regarding the incorporation of both gelatin and SWNTs, it was found that hydrophilicity of nanofibrous scaffolds dramatically improved. Scaffold degradation profile was adjusted by incorporation of gelatin. Biomimetic mechanical properties of composite scaffolds like normal blood vessel were developed and SWNTs improved the Young modulus and ultimate strength of scaffolds up to 16.47 ± 0.5 and 23.73 ± 0.5 MPa, respectively. However, addition of gelatin increased elongation at break due to its softening effect. The incorporation of the SWNTs led to significant enhancement of electrical conductivity of the scaffolds. Biological evaluation using SEM and MTT assay demonstrated that nanofibrous surface was covered by confluent and dense layer of both myocardial myoblast and endothelial cells after 7 days of culture, which is crucial for cardiovascular tissue engineering. Results verified that the fabricated scaffolds could be effective for cardiovascular tissue engineering.

Improving outcomes through the use of surgical sealants for anastomotic sealing during cardiovascular surgery.

The continued need to minimize blood product usage both during and after cardiac surgical procedures has been challenged by a changing patient population, and most recently by the withdrawal of the antifibrinolytic aprotinin (Trasylol, Bayer Pharmaceuticals, West Haven, CT, USA) from the market. To meet these challenges, a variety of topical hemostatic tools have continued to emerge in the surgical armamentarium. These include hemostatic agents, adhesives, and sealants designed to control perioperative bleeding and decrease blood product utilization. Optimal application of novel topical adjuncts can be limited due to the lack of clarity on how to differentiate between these adjunctive hemostatic products and their appropriate uses. This paper will review the classes of these products, how and where such products can be used during cardiovascular surgery for achieving hemostasis, and the potential for improved outcomes through the appropriate selection and use of these agents.

Aortic aneurysm/dissection and osteogenesis imperfecta: Four new families and review of the literature.

Osteogenesis imperfecta (OI) is the commonest form of heritable bone fragility. It is mainly characterized by fractures, hearing loss and dentinogenesis imperfecta. OI patients are at increased risk of cardiovascular disease of variable severity. Aortic aneurysm/dissection is one of the rarer but potentially serious cardiovascular complications of OI. So far, only six patients with aortic dissection and OI have been reported. As such, present OI diagnostic guidelines do not recommend systematic screening of patients for aortopathy. Here, we report on the clinical and molecular characteristics of three new OI patients and one additional patient with a first degree relative who presented with aortic dissection and/or aneurysm surgery. This observation further opens up the discussion on the need for and extent of cardiovascular screening in adult patients with OI.

Oral Health Status, Health Behaviour and Treatment Needs of Patients Undergoing Cardiovascular Surgery.

OBJECTIVE: The aim of the present study was to assess the oral health status and treatment needs of cardiovascular surgery patients. Second, the awareness of cardiovascular surgery patients regarding the association between oral health and heart disease was considered. METHODS: Assessment of oral health status, oral hygiene practices and treatment needs of 106 hospitalized patients in preparation for cardiovascular surgery. Patients were interviewed using a structured questionnaire designed for this study and oral examination was carried out by a dentist. RESULTS: The oral hygiene practices of the study cohort were not up to the standard. Patients' awareness of infective endocarditis was poor. Approximately 68% patients experienced dental caries as decayed teeth or missing teeth due to caries and filled teeth. The mean plaque index in the study group was 1.25. In this study cohort, the mean probing depth of periodontal pockets was 5.7±1.3, whereas the mean number of teeth with periodontal pockets > 6 mm was 0.5±0.9. A total of 84 (74.2%) of the patients required dental treatment. CONCLUSION: The principal finding in this study was that patients with heart disease had poor oral health. This study also highlights the importance of better interaction among all healthcare professionals to integrate oral health as part of comprehensive inpatient healthcare.

Safety of the use of Tissucol Duo S in cardiovascular surgery: retrospective analysis of 2149 patients after coronary artery bypass grafting.

OBJECTIVE: Fibrin sealant is widely used in almost all fields of surgery and has proved to be an effective therapeutic tool in cardiothoracic surgery. Nevertheless, there have been concerns about early bypass graft occlusion associated with the use of fibrin glue. This analysis has been performed to assess the risks and benefits of Tissucol Duo S in coronary artery bypass grafting (CABG) surgery. METHODS: Two thousand one hundred forty-nine patients were included in this retrospective study, 879 (40.9%) were intra-operatively treated with Tissucol Duo S fibrin glue, 1270 (59.1%) did not receive fibrin glue (control group). Patient characteristics were documented according to the EuroScore. Intra- and postoperative data were collected. Primary endpoint of this study was the 30-day all-cause mortality rate in the Tissucol Duo S treated group compared to the control group. RESULTS: Mean age was 66.6+/-9.4 years, 76.3% of the patients were male. There was an increased 30-day-mortality rate in the Tissucol Duo S group compared to the control group (8.5 vs 3.5%, p<0.001). In order to determine if and to what extent the apparent fibrin effect might be due to confounding effects from covariates, an adjustment for potential confounding was done. However, multivariable adjustment did not reduce the risk of fibrin glue below an odds ratio of 2.2. CONCLUSION: Although the apparent increase in mortality risk associated with the use of fibrin glue could not be eliminated statistically, we consider Tissucol Duo S fibrin glue a safe and effective therapeutic tool in CABG surgery when it is applied correctly. Due to the retrospective character of this study some detailed information about the indication for the use of fibrin glue and its application is missing which may be important cofactors for mortality. For further clarification a prospective randomized study may be useful.

Novel approaches toward the generation of bioscaffolds as a potential therapy in cardiovascular tissue engineering.

Cardiovascular disease associated with myocardial infarction (MI) is among the leading causes of mortality worldwide, in part, due to the limited regenerative capacity of tissues. Although various approaches have been employed to generate bioartificial myocardial tissues, including surgical reconstruction and the use of biosynthetic or biological cell-free grafts, many challenges still remain. Natural biomaterials based on decellularization have made significant inroads into the development of favorable biomatrices for myocardial tissue regeneration. This process occurs with the concept of removing whole cellular contents, while preserving the extracellular matrix components and all the necessary features of native tissues. Furthermore, acellular-derived matrices serve to stimulate proliferation and recruitment of endothelial cells by providing proliferation signals to cells. This review highlights a novel approach to generate natural three dimensional myocardial scaffolds for clinical applications.

Stirred, shaken, or stagnant: What goes on at the blood-biomaterial interface.

There is a widely recognized need to improve the performance of vascular implants and external medical devices that come into contact with blood by reducing adverse reactions they cause, such as thrombosis and inflammation. These reactions lead to major adverse cardiovascular events such as heart attacks and strokes. Currently, they are managed therapeutically. This need remains unmet by the biomaterials research community. Recognized stagnation of the blood-biomaterial interface research translates into waning interest from clinicians, funding agencies, and practitioners of adjacent fields. The purpose of this contribution is to stir things up. It follows the 2014 BloodSurf meeting (74th International IUVSTA Workshop on Blood-Biomaterial Interactions), offers reflections on the situation in the field, and a three-pronged strategy integrating different perspectives on the biological mechanisms underlying blood-biomaterial interactions. The success of this strategy depends on reengaging clinicians and on the renewed cooperation of the funding agencies to support long-term efforts.