Cardiovascular Biomaterials Research Articles

A CO-releasing coating based on carboxymethyl chitosan-functionalized graphene oxide for improving the anticorrosion and biocompatibility of magnesium alloy stent materials

Due to its biofunctions similar to NO, the CO gas signaling molecule has gradually shown great potential in cardiovascular biomaterials for regulating the in vivo performances after the implantation and has received increasing attention. To construct a bioactive surface with CO-releasing properties on the surface of magnesium-based alloy to augment the anticorrosion and biocompatibility, graphene oxide (GO) was firstly modified using carboxymethyl chitosan (CS), and then CO-releasing molecules (CORM401) were introduced to synthesize a novel biocompatible nanomaterial (GOCS-CO) that can release CO in the physiological environments. The GOCS-CO was further immobilized on the magnesium alloy surface modified by polydopamine coating with Zn2+ (PDA/Zn) to create a bioactive surface capable of releasing CO in the physiological environment. The outcomes showed that the CO-releasing coating can not only significantly enhance the anticorrosion and abate the corrosion degradation rate of the magnesium alloy in a simulated physiological environment, but also endow it with good hydrophilicity and a certain ability to adsorb albumin selectively. Owing to the significant enhancement of anticorrosion and hydrophilicity, coupled with the bioactivity of GOCS, the modified sample not only showed excellent ability to prevent platelet adhesion and activation and reduce hemolysis rate but also can promote endothelial cell (EC) adhesion, proliferation as well as the expression of nitric oxide (NO) and vascular endothelial growth factor (VEGF). In the case of CO release, the hemocompatibility and EC growth behaviors were further significantly improved, suggesting that CO molecules released from the surface can significantly improve the hemocompatibility and EC growth. Consequently, the present study provides a novel surface modification method that can simultaneously augment the anticorrosion and biocompatibility of magnesium-based alloys, which will strongly promote the research and application of CO-releasing bioactive coatings for surface functionalization of cardiovascular biomaterials and devices.

CARDIOVASCULAR DISEASE, SIGNALING, GENE/CELL THERAPY AND ADVANCED NANOBIOMATERIALS

Cardiovascular biomaterials (also known as CB) are the most common type of biomaterials, both in terms of investments and demand. This review article compiles information on the CB and categorizes it into three primary categories: metals, polymers, and biological materials. Blood compatibility is one of the primary parameters that restricts the use of biomaterials for cardiovascular applications. Within the scope of this study, a number of significant figures concerning blood compatibility are investigated. There were a variety of surface modification techniques that were being utilized at the moment in order to enhance the compatibility of the CB. For the purpose of gaining a deeper comprehension, a number of contemporary applications of surface modification techniques on materials for cardiovascular devices were also discussed. Last but not least, the utilization of induced human pluripotent stem cells, the endothelization of cardiac implants, and the current trend of CB. As a result of the rapid expansion of the field of CB, a significant number of new researchers and academics are developing an interest in it. This overview will serve as a one-stop shop for quickly gaining an understanding of the fundamental studies that have been conducted in the field of CB.

Effects of heterogeneous surface characteristics on hemocompatibility and cytocompatibility of bacterial nanocellulose

The surface properties of cardiovascular biomaterials play a critical role in their biological responses. Although bacterial nanocellulose (BNC) materials have exhibited potential applications in cardiovascular implants, the impact of their surface characteristics on biocompatibility has rarely been studied. This study investigated the mechanism for the biocompatibility induced by the physicochemical properties of both sides of BNC. With greater wettability and smoothness, the upper BNC surface reduced protein adsorption by 25 % compared with the lower surface. This prolonged the plasma re-calcification time by 14 % in venous blood. Further, compared with the lower BNC surface, the upper BNC surface prolonged the activated partial thromboplastin time by 5 % and 4 % in arterial and venous blood, respectively. Moreover, the lower BNC surface with lesser rigidity, higher roughness, and sparser fiber structure promoted cell adhesion. The lower BNC surface enhanced the proliferation rate of L929 and HUVECs cells by 15 % and 13 %, respectively, compared with the upper BNC surface. With lesser stiffness, the lower BNC surface upregulated the expressions of CD31 and eNOS while down-regulating the ICAM-1 expression - This promoted the proliferation of HUVECs. The findings of this study will provide valuable insights into the design of blood contact materials and cardiovascular implants.

In vivo application of a glutaraldehyde-free, UVA/riboflavin cross-linked bovine pericardium confirms suitability for cardiovascular substitutes

Glutaraldehyde (GA)-treated bovine pericardium is still the gold standard for the fabrication of bioprostheses needed for the surgical treatment of valvular malfunction. Although excellent stability and low immunogenicity are accomplished, the application of GA is considered to be causal for structural valve deterioration, diminishing the long-term durability of bioprosthetic tissue. The novel GA-free SULEEI-treatment of bovine pericardium combines decellularization, riboflavin/UVA-cross-linking, and low-energy electron beam irradiation. In the present study, we initiated an in vivo application. We used a subcutaneous rat model to compare the immune and tissue responses, calcification propensity, and biomechanical properties of the alternatively prepared SULEEI bovine pericardial tissue with standard glutaraldehyde-fixed and industrially produced bovine pericardial patch material. SULEEI pericardium evokes a similar immune reaction and tissue response as the control standard bovine patch material. The calcification propensity of SULEEI tissue was low, and biomechanical analysis revealed a heterogeneous but similar pattern in tissue stiffness compared to the control patch. The results of this study highlight the potential of SULEEI-treated bovine pericardial tissue as a candidate for cutting-edge cardiovascular and valvular biomaterials in reconstructive surgery.

How to fix a broken heart-designing biofunctional cues for effective, environmentally-friendly cardiac tissue engineering.

Cardiovascular diseases bear strong socioeconomic and ecological impact on the worldwide healthcare system. A large consumption of goods, use of polymer-based cardiovascular biomaterials, and long hospitalization times add up to an extensive carbon footprint on the environment often turning out to be ineffective at healing such cardiovascular diseases. On the other hand, cardiac cell toxicity is among the most severe but common side effect of drugs used to treat numerous diseases from COVID-19 to diabetes, often resulting in the withdrawal of such pharmaceuticals from the market. Currently, most patients that have suffered from cardiovascular disease will never fully recover. All of these factors further contribute to the extensive negative toll pharmaceutical, biotechnological, and biomedical companies have on the environment. Hence, there is a dire need to develop new environmentally-friendly strategies that on the one hand would promise cardiac tissue regeneration after damage and on the other hand would offer solutions for the fast screening of drugs to ensure that they do not cause cardiovascular toxicity. Importantly, both require one thing-a mature, functioning cardiac tissue that can be fabricated in a fast, reliable, and repeatable manner from environmentally friendly biomaterials in the lab. This is not an easy task to complete as numerous approaches have been undertaken, separately and combined, to achieve it. This review gathers such strategies and provides insights into which succeed or fail and what is needed for the field of environmentally-friendly cardiac tissue engineering to prosper.

Fibrin Adsorption on Cardiovascular Biomaterials and Medical Devices.

Medical devices that are inserted in blood vessels always risk eliciting thrombosis, and the surface properties of such devices are thus of major importance. The initiating step for surface-induced pathological coagulation has been associated with adsorption of fibrinogen protein on biomaterial surfaces and subsequent polymerization into an insoluble fibrin clot. This issue gives rise to an inherent challenge in biomaterial design as varied surface materials must fulfill specialized roles while also minimizing thrombotic complications from spontaneous fibrin(ogen) recruitment. We have aimed to characterize the thrombogenic properties of state-of-the-art cardiovascular biomaterials and medical devices by quantifying the relative surface-dependent adsorption and formation of fibrin followed by analysis of the resulting morphologies. We identified stainless steel and amorphous fluoropolymer as comparatively preferable biomaterials based on their low fibrin(ogen) recruitment, in comparison to other metallic and polymeric biomaterials, respectively. In addition, we observed a morphological trend that fibrin forms fiber structures on metallic surfaces and fractal branched structures on polymeric surfaces. Finally, we used vascular guidewires as clotting substrates and found that fibrin adsorption depends on parts of the guidewire that are exposed, and we correlated the morphologies on uncoated guidewires with those formed on raw stainless-steel biomaterials.

Copper and Zinc Co-doped Titanium Dioxide Nanotubes Arrays on Controlling Nitric Oxide Releasing and Regulating the Inflammatory Responses for Cardiovascular Biomaterials.

Titanium dioxide (TiO2) nanotubes arrays have shown tremendous application foreground due to their unique characters of structure and performance. However, the single bio-function is still the limit on cardiovascular biomaterials. The loadability function provides the possibility for the TiO2 nanotubes arrays to realize composite multifunction. The copper can catalyze the release of nitric oxide to promote the proliferation of endothelium cells and improve the anticoagulant. Also, zinc can adjust the inflammatory responses to improve anti-inflammation. In this patent work, we co-doped the copper and zinc onto TiO2 nanotubes arrays to estimate the hemocompatibility, cytocompatibility and responses of inflammation. The results showed that copper and zinc could introduce better multi-biofunctions to the TiO2 nanotubes arrays for the application in cardiovascular biomaterials. In summary, the NTs@Cu/Zn sample as a new composite material in this study had significant biocompatibility in vascular implantation and can be used as a potential material for polymer- free drug-eluting stents.

A novel MgF2/PDA/S-HA coating on the bio-degradable ZE21B alloy for better multi-functions on cardiovascular application

Recently, functional molecules such as Polydopamine (PDA), Hyaluronic Acid (HA) and heparin have been widely studied in the field of surface modification of magnesium (Mg) alloy stents for better degradation behavior and biocompatibility, but their further application is limited by undesirable anticoagulant function, uncontrollable degradation and easy bleeding, respectively. Regarding to this consideration, a magnesium Fluoride/Polydopamine/Sulphonated hyaluronic acid (MgF 2 /PDA/S-HA) composite coating was successfully prepared by applying S-HA with sulfur content of 9.71 wt% on the surface of ZE21B alloy in this study. The results showed that the composite coating with a unique mesh structure not only inherited the anticoagulant effect of sulfonic acid group and the excellent cyto-compatibility of S-HA with high sulfur content, but also significantly improved the corrosion performance of ZE21B alloy. These results indicate a great application potential of the composite coating in the field of cardiovascular biomaterials.

Development of Innovative Biomaterials and Devices for the Treatment of Cardiovascular Diseases (Adv. Mater. 46/2022)

Cardiovascular Biomaterials and Devices In article number 2201971, Yunbing Wang and co-workers provide an overview of the challenges and research frontiers of innovative biomaterials and devices for the treatment of cardiovascular diseases, and their future development directions are discussed. With the development and improved performance of new cardiovascular biomaterials and devices, more advanced treatment options will be available to bring new hope to the cardiovascular patients.

Extracellular Matrix Coatings on Cardiovascular Materials—A Review

Vascular transplantation is an effective and common treatment for cardiovascular disease (CVD). However, the low biocompatibility of implants is a major problem that hinders its clinical application. Surface modification of implants with extracellular matrix (ECM) coatings is an effective approach to improve the biocompatibility of cardiovascular materials. The complete ECM seems to have better biocompatibility, which may give cardiovascular biomaterials a more functional surface. The use of one or several ECM proteins to construct a surface allows customization of coating composition and structure, possibly resulting in some unique functions. ECM is a complex three-dimensional structure composed of a variety of functional biological macromolecules, and changes in the composition will directly affect the function of the coating. Therefore, understanding the chemical composition of the ECM and its interaction with cells is beneficial to provide new approaches for coating surface modification. This article reviews novel ECM coatings, including coatings composed of intact ECM and biomimetic coatings tailored from several ECM proteins, and introduces new advances in coating fabrication. These ECM coatings are effective in improving the biocompatibility of vascular grafts.

Selenium-functionalized polycarbonate-polyurethane for sustained in situ generation of therapeutic gas for blood-contacting materials

Polyurethanes (PU) have been widely used in blood-contacting devices including indwelling implants and extracorporeal devices due to its good biocompatibility. However, the conventional PU also faces problems like thrombus formation and cell compatibility that could cause the treatment failure. In this study, a novel selenium-functionalized polycarbonate-polyurethane (PCU–SeSe) is developed based on the dynamic diselenide bond. Having diselenide bond-containing glycol as functional component, PCU-SeSe is endowed with glutathione peroxidase (GPx)-like catalytic activity, which could catalyze the release of nitric oxide (NO) continuously and controllably in the donor environment. This feature provides the materials with multiple functions from markedly suppressing platelet adhesion and activation, reducing the thrombogenesis, and enhancing the hemocompatibility. Meanwhile, PCU-SeSe could promote the growth of endothelial cell (EC) as well as significantly inhibit the growth of smooth muscle cell (SMC) and macrophage (MA) in vitro. The animal experiments including aortic implantation of sprague-dawley (SD) rats and stent implantation also demonstrate the abilities of endothelialization, thromboresistance, anti-inflammation, and anti-hyperplasia of PCU-SeSe in vivo. Overall, this study provides a new strategy for the designing of blood-contacting devices, which could be promising in the fabrication of cardiovascular biomaterials.

Designing Polymeric Cardiovascular Biomaterials for Hemocompatibility and Mechanical Performance

Designing Polymeric Cardiovascular Biomaterials for Hemocompatibility and Mechanical Performance

Predicting the In Vivo Performance of Cardiovascular Biomaterials: Current Approaches In Vitro Evaluation of Blood-Biomaterial Interactions.

The therapeutic efficacy of a cardiovascular device after implantation is highly dependent on the host-initiated complement and coagulation cascade. Both can eventually trigger thrombosis and inflammation. Therefore, understanding these initial responses of the body is of great importance for newly developed biomaterials. Subtle modulation of the associated biological processes could optimize clinical outcomes. However, our failure to produce truly blood compatible materials may reflect our inability to properly understand the mechanisms of thrombosis and inflammation associated with biomaterials. In vitro models mimicking these processes provide valuable insights into the mechanisms of biomaterial-induced complement activation and coagulation. Here, we review (i) the influence of biomaterials on complement and coagulation cascades, (ii) the significance of complement-coagulation interactions for the clinical success of cardiovascular implants, (iii) the modulation of complement activation by surface modifications, and (iv) in vitro testing strategies.

Nisin-based antibacterial and antiadhesive layer-by-layer coatings

Some removable medical devices such as catheters and cardiovascular biomaterials require antiadhesive properties towards both prokaryotic and eukaryotic cells in order to prevent the tissues from infections upon implantation and, from alteration upon removal. In order to inhibit cell adhesion, we developed ultrathin hydrated Layer-by-Layer (LbL) coatings composed of biocompatible polyelectrolytes, namely chondroitin sulfate A (CSA) and poly-l-lysine (PLL). The coatings were crosslinked with genipin (GnP), a natural and biocompatible crosslinking agent, to increase their resistance against environmental changes. In order to confer antibacterial activity to the coatings, we proceeded to the electrostatically-driven immobilization of nisin Z, an antimicrobial peptide (AMP) active against gram-positive bacteria. The nisin-enriched coatings had a significantly increased anti-proliferative impact on fibroblasts, as well as a strong contact-killing activity against Staphylococcus aureus in the short and long term.

Tissue response, macrophage phenotype, and intrinsic calcification induced by cardiovascular biomaterials: Can clinical regenerative potential be predicted in a rat subcutaneous implant model?

The host immune response to an implanted biomaterial, particularly the phenotype of infiltrating macrophages, is a key determinant of biocompatibility and downstream remodeling outcome. The present study used a subcutaneous rat model to compare the tissue response, including macrophage phenotype, remodeling potential, and calcification propensity of a biologic scaffold composed of glutaraldehyde-fixed bovine pericardium (GF-BP), the standard of care for heart valve replacement, with those of an electrospun polycarbonate-based supramolecular polymer scaffold (ePC-UPy), urinary bladder extracellular matrix (UBM-ECM), and a polypropylene mesh (PP). The ePC-UPy and UBM-ECM materials induced infiltration of mononuclear cells throughout the thickness of the scaffold within 2 days and neovascularization at 14 days. GF-BP and PP elicited a balance of pro-inflammatory (M1-like) and anti-inflammatory (M2-like) macrophages, while UBM-ECM and ePC-UPy supported a dominant M2-like macrophage phenotype at all timepoints. Relative to GF-BP, ePC-UPy was markedly less susceptible to calcification for the 180 day duration of the study. UBM-ECM induced an archetypical constructive remodeling response dominated by M2-like macrophages and the PP caused a typical foreign body reaction dominated by M1-like macrophages. The results of this study highlight the divergent macrophage and host remodeling response to biomaterials with distinct physical and chemical properties and suggest that the rat subcutaneous implantation model can be used to predict in vivo biocompatibility and regenerative potential for clinical application of cardiovascular biomaterials.

A metal-organic-framework incorporated vascular graft for sustained nitric oxide generation and long-term vascular patency

Copper-MOFs (Cu-MOFs) have been reported to demonstrate great potential as cardiovascular biomaterials, due to enhanced catalytic ability of Cu2+ to generate nitric oxide (NO) from endogenous S-nitrosothiols (RSNOs). However, free Cu-MOFs usually show rapid degradation under physiological conditions, resulting in short catalytic half-life and risk of copper ion toxicity. Therefore, how to increase the stability of Cu-MOFs is of great importance in cardiovascular biomaterials research. Herein, we chose M199 MOF as an example and developed Cu-MOF-based scaffold, using the electrospinning method to embed Cu-MOF nanoparticles into polycaprolactone (PCL) fibers. Entrapment of Cu-MOF nanoparticles within PCL could simultaneously enhance Cu-MOF stability in serum and allow for long-term NO catalytic activity, as assessed by in vitro assays and using in situ implantation models. Additionally, the optimized concentration of Cu-MOFs loaded within the scaffolds significantly promoted endothelial cell (EC) migration and increased acetylated low-density lipoprotein (Ac-LDL) uptake. Moreover, Cu-MOF-based scaffolds dramatically inhibited platelet adhesion and activation, which markedly reduced acute thrombosis in arterio-venous shunt models. In situ implantation experiments revealed that the PCL/Cu-MOF scaffolds accelerated the formation of an intact endothelial monolayer. Together, these results suggest that the incorporation of Cu-MOFs into electrospun fibers could serve as a promising approach to achieve stable catalytic performance and long-term activity required for implant materials.

Comprehensive analyses and prioritization of various swim bladder-derived extracellular matrix in the application of heart valve prosthesis

Calcification-caused failure and deterioration have become the biggest issues facing traditional biological heart valves (BHVs). Thus, developing new source of materials with the ability to resist calcification is an imperative demand of clinical. In our previous work, swim bladder was proved with superb calcification-resistance as a promising candidate for cardiovascular biomaterials. To find the optimal choice of swim bladder, we herein further investigated four types of swim bladders including grass carp (GC), culter alburnus (CA), carp (C) and silver carp (SC) as material source of the BHVs. Data showed that all the swim bladder was mainly composed of elastin fiber, collagen fiber and glycosaminoglycan (GAG). All the groups except GC group can meet the basic mechanical and materials stability requirements as BHVs. Moreover, the calcification of swim bladder derived from SC was proved significantly lower than that of CA and C groups with in vivo rat subcutaneous implantation model. Additionally, in vitro assays demonstrated that four types of swim bladder exhibited well hemocompatibility and cytocompatibility. Collectively, the superior properties including low calcification, adequate mechanical, high stability, as well as excellent hemocompatibility and cytocompatibility of SC-derived swim bladder endow it great competence as BHVs.

Swim bladder as an alternative biomaterial for bioprosthetic valves.

Valvular structural deterioration and calcification are the main indications for secondary intervention after bioprosthetic valve replacement, promoting an urgent requirement for more durable cardiovascular biomaterials for clinical applications. The swim bladder of carp we introduced in this study has several advantages as a raw biomaterial when compared to the bovine pericardium. First, the results of in vitro assays demonstrated that the cross-linked carp swim bladder exhibited superior biocompatibility compared to the bovine pericardium, and the anti-calcification property was verified by subcutaneous implantation experiments in rats. Furthermore, the cross-linked swim bladder tissue was sutured on a cobalt-chromium alloy stent to fabricate a pulmonary bioprosthetic valve, and then the feasibility and durability of the bioprosthetic valve were proved by a fatigue test in vitro. Finally, a sheep pulmonary bioprosthetic valve replacement in situ experiment further confirmed the superior calcification resistance, immune-compatibility, endothelialization, and hemodynamic properties of the swim bladder, suggesting that it might be used as an alternative biomaterial for bioprosthetic valves.

Sulfur Contents in Sulfonated Hyaluronic Acid Direct the Cardiovascular Cells Fate.

Hyaluronic acid (HA) is recognized as a functional carbohydrate polymer applied for the surface modification of cardiovascular implanted materials due to its molecular weight (MW) dependent cellular regulation. However, due to the enzyme digestion of hyaluronidase on HA in vivo, the stability of HA MW needs to be further improved. It has been reported that the stability of HA MW can be improved by sulfonation. In this study, sulfonated hyaluronic acids (S-HA) with sulfur content of 2.06, 3.69, 7.10, 8.98, and 9.71 were prepared through different sulfuric acid treatment procedures. Cell tests showed that S-HA with higher sulfur content played a significant role in promoting the proliferation and migration of endothelial cells and regulating smooth muscle cells to the physiological phenotype. In addition, it was also proved to inhibit the inflammatory macrophages adhesion/activation. Our data indicates that S-HA may be a better carbohydrate polymer for potential application of cardiovascular biomaterials.

A state of the “heart”: application of bioengineered materials for cardiac surgery

Introduction. Cardiovascular diseases have become the leading mortality cause, requiring a novel technologies and techniques for the treatment. Cardiovascular biomaterials play a vital role as the potentially eligible alternative modality for an operation, covering the gap between facilities and patients in need of medical devices and procedures.Purpose. The aim of this essay is to explore and analyze the currently used biomaterials for cardiac surgery as tools to repair or replace the damaged tissues. This study seeks to obtain data which will help to address research gaps and to stimuli the manufacturing process.Description of the state of knowledge. We conduct the systematic literature review, based on the information found in PubMed, Research Gate and Google Scholar databases using the eligible parameters. Obtained data in form of descriptive information were analyzed.Summary. This study has identified a wide area of cardiovascular biomaterials use in the modern clinical and scientific practice. The most obvious finding to emerge from this study is that decellularization of xenogenous heart valves is a crucial feature to obtain the optimal matrix for a tissue-engineered valve substitute. This information can be used to develop targetted interventions aimed at cardiac surgery.