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Cardiovascular diseases are the leading cause of mortality worldwide. Given the limited endogenous regenerative capabilities of cardiac tissue, patient-specific anatomy, challenges in treatment options, and shortage of donor tissues for transplantation, there is an urgent need for novel approaches in cardiac tissue repair. 3D bioprinting is a technology based on additive manufacturing which allows for the design of precisely controlled and spatially organized structures, which could possibly lead to solutions in cardiac tissue repair. In this review, we describe the basic morphological and physiological specifics of the heart and cardiac tissues and introduce the readers to the fundamental principles underlying 3D printing technology and some of the materials/approaches which have been used to date for cardiac repair. By summarizing recent progress in 3D printing of cardiac tissue and valves with respect to the key features of cardiovascular tissue (such as contractility, conductivity, and vascularization), we highlight how 3D printing can facilitate surgical planning and provide custom-fit implants and properties that match those from the native heart. Finally, we also discuss the suitability of this technology in the design and fabrication of custom-made devices intended for the maturation of the cardiac tissue, a process that has been shown to increase the viability of implants. Altogether this review shows that 3D printing and bioprinting are versatile and highly modulative technologies with wide applications in cardiac regeneration and beyond.
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Bioimpressão , Engenharia Tecidual , Bioimpressão/métodos , Coração , Humanos , Impressão Tridimensional , Engenharia Tecidual/métodosRESUMO
Antibacterial properties of copper against planktonic bacteria population are affected by surface microstructure and topography. However, copper interactions with bacteria in a biofilm state are less studied. This work aims at better understanding the difference in biofilm inhibition of bulk, cold-sprayed, and shot-peened copper surfaces and gaining further insights on the underlying mechanisms using optical and scanning electron microscopy to investigate the topography and microstructure of the surfaces. The biofilm inhibition ability is reported for all surfaces. Results show that the biofilm inhibition performance of cold sprayed copper, while initially better, decreases with time and results in an almost identical performance than as-received copper after 18h incubation time. The shot-peened samples with a rough and ultrafine microstructure demonstrated an enhanced biofilm control, especially at 18 hr. The biofilm control mechanisms were explained by the diffusion rates and concentration of copper ions and the interaction between these ions and the biofilm, while surface topography plays a role in the bacteria attachment at the early planktonic state. Furthermore, the data suggest that surface topography plays a key role in antiviral activity of the materials tested, with a smooth surface being the most efficient.
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PURPOSE OF REVIEW: This review describes the latest advances in cell therapy, biomaterials and 3D bioprinting for the treatment of cardiovascular disease. RECENT FINDINGS: Cell therapies offer the greatest benefit for patients suffering from chronic ischemic and nonischemic cardiomyopathy. Rather than replacing lost cardiomyocytes, the effects of most cell therapies are mediated by paracrine signalling, mainly through the induction of angiogenesis and immunomodulation. Cell preconditioning, or genetic modifications are being studied to improve the outcomes. Biomaterials offer stand-alone benefits such as bioactive cues for cell survival, proliferation and differentiation, induction of vascularization or prevention of further cardiomyocyte death. They also provide mechanical support or electroconductivity, and can be used to deliver cells, growth factors or drugs to the injured site. Apart from classical biomaterial manufacturing techniques, 3D bioprinting offers greater spatial control over biomaterial deposition and higher resolution of the details, including hollow vessel-like structures. SUMMARY: Cell therapy induces mainly angiogenesis and immunomodulation. The ability to induce direct cardiomyocyte regeneration to replace the lost cardiomyocytes is, however, still missing until embryonic or induced pluripotent stem cell use becomes available. Cell therapy would benefit from combinatorial use with biomaterials, as these can prolong cell retention and survival, offer additional mechanical support and provide inherent bioactive cues. Biomaterials can also be used to deliver growth factors, drugs, and other molecules. 3D bioprinting is a high-resolution technique that has great potential in cardiac therapy.
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Bioimpressão , Impressão Tridimensional , Materiais Biocompatíveis , Humanos , Miocárdio , Miócitos CardíacosRESUMO
We have studied the suitability of using a molecular rotor-based steady-state fluorometric assay for evaluating changes in both the conformation and the viscosity of collagen-like peptide solutions. Our results indicate that a positive charge incorporated on the hydrophobic tail of the BODIPY molecular rotor favours the dye specificity as a reporter for viscosity of these solutions.
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Peptídeos/química , Compostos de Boro/química , Colágeno/química , Corantes Fluorescentes/química , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Soluções , Espectrometria de Fluorescência , ViscosidadeRESUMO
A new hybrid cinnamoyl-coumarin probe was synthesised to study the formation and dynamics of a twisted internal charge transfer (TICT) excited state in homogeneous and biological membrane models. This probe showed a large bathochromic shift of the fluorescence band with the solvent polarity, which is associated with the decrease in the fluorescence intensity due to fast non-radiative deactivation pathways, ascribed to TICT excited state formation in polar solvents. The calculated potential energy surfaces using density functional theory (DFT) and time dependent-DFT (TD-DFT) along with the energetic barriers calculated using the ABF methodology established the energy requirements for a rotational twisting of the cinnamoyl-coumarin bond for TICT excited state formation. This strategy has allowed estimating the role of the ground state conformation and excited state distribution that, concomitant with fluorescence lifetime measurements, describes in detail dual fluorescence emission from TICT and ICT excited states. Moreover, the high sensitivity of fluorescence lifetimes of the TICT excited state in liposomes allows us to propose the use of this type of probes as a powerful tool for the study of gel and crystalline liquid phases in lipid membrane models. The development of this new approach will allow rationalizing and understanding the photochemical behavior of fluorescent TICT-based probes in constrained biological environments.
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Cumarínicos/química , Membranas/química , Modelos Biológicos , Fluorescência , Lipossomos/química , Conformação Molecular , Fotoquímica , Teoria Quântica , Solventes/químicaRESUMO
The interaction between nanoparticles and molecules plays a key role in determining the activity and performance of a given nanostructure. These interactions are pivotal for a variety of applications including drug delivery, surface manipulation for targeted therapies, and catalysis. However, to this day, gathering precise association parameters for the interaction of the molecules with nanostructures remains elusive and mostly imprecise. In this review, we present a critical discussion of the most commonly used techniques and models intended for determining the association of molecules with nanoparticles. Particular emphasis has been put on discussing the limitations and pitfalls related to determining association constants in this tutorial review.
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Sistemas de Liberação de Medicamentos , Modelos Químicos , Nanoestruturas/química , Catálise , NanopartículasRESUMO
We studied the interaction of four new pentapeptides with spherical silver nanoparticles. Our findings indicate that the combination of the thiol in Cys and amines in Lys/Arg residues is critical to providing stable protection for the silver surface. Molecular simulation reveals the atomic scale interactions that underlie the observed stabilizing effect of these peptides, while yielding qualitative agreement with experiment for ranking the affinity of the four pentapeptides for the silver surface.
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Cisteína/química , Lisina/química , Nanopartículas Metálicas/química , Peptídeos/química , Prata/químicaRESUMO
We have developed a rapid colorimetric method to determine the concentration of denatured collagen in solution, which is based on the collagen-silver nanoparticle corona formation. Using the proposed method, the lowest detectable concentration of denatured collagen protein in a solution of pure collagen was 14.7, 8.5, and 8.6 µg mL(-1) for porcine (PCOL), rat tail (RCOL), and type I human recombinant (HCOL) collagen, respectively.
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Colágeno/química , Nanopartículas Metálicas/química , Desnaturação Proteica , Prata/química , Animais , Colágeno/análise , Colorimetria/economia , Colorimetria/métodos , Humanos , Coroa de Proteína/análise , Coroa de Proteína/química , Ratos , Proteínas Recombinantes/análise , Proteínas Recombinantes/química , Suínos , TemperaturaRESUMO
In situ light initiated synthesis of silver nanoparticles (AgNP) was employed for AgNP incorporation within the polymeric matrices of medical grade polyurethane. The resulting materials showed improved antibacterial and antibiofilm activity against Pseudomonas aeruginosa with negligible toxicity for human primary skin cells and erythrocytes.
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Antibacterianos/síntese química , Materiais Biocompatíveis/síntese química , Nanopartículas Metálicas/química , Processos Fotoquímicos , Poliuretanos/síntese química , Compostos de Prata/síntese química , Antibacterianos/química , Materiais Biocompatíveis/química , Contagem de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Eritrócitos/química , Fibroblastos/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Varredura , Poliuretanos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Compostos de Prata/química , Pele/efeitos dos fármacos , Análise EspectralRESUMO
Hydrogels are a class of biomaterials that can provide a three-dimensional (3D) environment capable of mimicking the extracellular matrix of native tissues. In this chapter, we present a method to generate electrospun nanofibers for the purpose of reinforcing hydrogels. The addition of electrospun fibers can be used to improve the mechanical properties of hydrogels and broaden their range of applications. First, the polymer for making the electrospun fibers is formulated using chloroform/ethanol, polycaprolactone (PCL), polyethylene glycol (PEG), and polyethylene glycol diacrylate (PEGDA). Second, the polymer is used to generate thin electrospun nanofibers by an electrospinning technique using aluminum foil as a collector, which acts as the conductive substrate that collects the charged fibers. Third, the resulting electrospun fibers undergo a filtration process using nylon membrane filters, followed by lyophilization, ensuring complete removal of water from the sample.
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Hidrogéis , Nanofibras , Polietilenoglicóis , Nanofibras/química , Polietilenoglicóis/química , Hidrogéis/química , Materiais Biocompatíveis/química , Humanos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Poliésteres/química , Alicerces Teciduais/química , Engenharia Tecidual/métodosRESUMO
The field of small-diameter vascular grafts remains a challenge for biomaterials scientists. While decades of research have brought us much closer to developing biomimetic materials for regenerating tissues and organs, the physiological challenges involved in manufacturing small conduits that can transport blood while not inducing an immune response or promoting blood clots continue to limit progress in this area. In this short review, we present some of the most recent methods and advancements made by researchers working in the field of small-diameter vascular grafts. We also discuss some of the most critical aspects biomaterials scientists should consider when developing lab-made small-diameter vascular grafts.
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A plethora of biomaterials for heart repair are being tested worldwide for potential clinical application. These therapeutics aim to enhance the quality of life of patients with heart disease using various methods to improve cardiac function. Despite the myriad of therapeutics tested, only a minority of these studied biomaterials have entered clinical trials. This rapid scoping review aims to analyze literature available from 2012 to 2022 with a focus on clinical trials using biomaterials for direct cardiac repair, i.e., where the intended function of the biomaterial is to enhance the repair of the endocardium, myocardium, epicardium or pericardium. This review included neither biomaterials related to stents and valve repair nor biomaterials serving as vehicles for the delivery of drugs. Surprisingly, the literature search revealed that only 8 different biomaterials mentioned in 23 different studies out of 7038 documents (journal articles, conference abstracts or clinical trial entries) have been tested in clinical trials since 2012. All of these, intended to treat various forms of ischaemic heart disease (heart failure, myocardial infarction), were of natural origin and most used direct injections as their delivery method. This review thus reveals notable gaps between groups of biomaterials tested pre-clinically and clinically. STATEMENT OF SIGNIFICANCE: Rapid scoping review of clinical application of biomaterials for cardiac repair. 7038 documents screened; 23 studies mention 8 different biomaterials only. Biomaterials for repair of endocardium, myocardium, epicardium or pericardium. Only 8 different biomaterials entered clinical trials in the past 10 years. All of the clinically translated biomaterials were of natural origin.
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Materiais Biocompatíveis , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , AnimaisRESUMO
The anti-peroxyl radical quality of two aqueous rooibos infusions and solutions of their most abundant glycosylated polyphenols was evaluated using pyrogallol red and fluorescein-based oxygen radical absorbance ratios. It was observed that the artificial infusions, prepared using only the most abundant polyphenols present in rooibos and at concentrations similar to those found in the natural infusions, showed greater antioxidant quality than the latter infusions, reaching values close to those reported for tea infusions. Additionally, the antimicrobial activity of the natural and artificial infusions was assessed against three species of bacteria: Gram (+) Staphylococus epidermidis and Staphylococcus aureus and Gram (-) Escherichia coli. When compared to the natural infusions the artificial beverages did not demonstrate any bacterostatic/cidal activity, suggesting that the antibacterial activity of rooibos is related to compounds other than the glycosylated polyphenols employed in our study.
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Antibacterianos/química , Aspalathus/química , Flavonoides/química , Sequestradores de Radicais Livres/química , Glucosídeos/química , Extratos Vegetais/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Apigenina/química , Apigenina/isolamento & purificação , Apigenina/farmacologia , Bebidas , Chalconas/química , Chalconas/isolamento & purificação , Chalconas/farmacologia , Escherichia coli/efeitos dos fármacos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Testes de Sensibilidade Microbiana , Peróxidos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Quercetina/análogos & derivados , Quercetina/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Rutina/química , Rutina/isolamento & purificação , Rutina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacosRESUMO
Heart disease remains the leading cause of worldwide mortality. Although the last decades have broadened our understanding of the biology behind the pathologies of heart disease, ex vivo systems capable of mimicking disease progression and abnormal heart function using human cells remain elusive. In this contribution, an open-access electromechanical system (BEaTS-ß) capable of mimicking the environment of cardiac disease is reported. BEaTS-ß was designed using computer-aided modeling to combine tunable electrical stimulation and mechanical deformation of cells cultured on a flexible elastomer. To recapitulate the clinical scenario of a heart attack more closely, in designing BEaTS-ß we considered a device capable to operate under hypoxic conditions. We tested human induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and coronary artery endothelial cells in our simulated myocardial infarction environment. Our results indicate that, under simulated myocardium infarction, there was a decrease in maturation of cardiomyocytes, and reduced survival of fibroblasts and coronary artery endothelial cells. The open access nature of BEaTS-ß will allow for other investigators to use this platform to investigate cardiac cell biology or drug therapeutic efficacy in vitro under conditions that simulate arrhythmia and/or myocardial infarction.
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Methylene blue shows an isotope dependent triplet lifetime that is 50% longer in D(2)O compared with H(2)O as a result of electronic-to-vibrational relaxation. The effect is enhanced when the dye is bound to curcubit[7]uril due to a combination of restricted mobility and a unfavorable vibrational coupling.
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Hidrocarbonetos Aromáticos com Pontes/química , Óxido de Deutério/química , Imidazóis/química , Azul de Metileno/química , Solventes/química , Isótopos , Fatores de Tempo , VibraçãoRESUMO
Biomaterials are scaffolds designed to mimic the extracellular matrix and stimulate tissue repair. Biomaterial therapies have shown promise for improving wound healing in cardiac tissue after ischemic injury. An unintentional consequence of biomaterial delivery may be the stimulation of inflammation through recruitment of circulating monocytes into the tissue. Monocytes are a type of leukocyte (white blood cell) that play a critical role in pathogen recognition, phagocytosis of foreign material, and presentation of antigens to initiate an adaptive immune response. An increase in the pro-inflammatory subset of monocytes, marked by Ly6C antigen expression, in response to biomaterials can lead to rapid material degradation, ineffective treatment, and worsening of tissue injury. Flow cytometry is a leading method for screening the recruitment of monocytes to the heart in response to biomaterial injection. Here, we describe the isolation of leukocytes from the heart, blood, and spleen of mice treated with a biomaterial post-myocardial infarction and describe a flow cytometry protocol used to quantify the levels of major leukocyte subtypes, including Ly6C+ inflammatory monocytes.
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Procedimentos Cirúrgicos Cardíacos , Infarto do Miocárdio , Animais , Materiais Biocompatíveis/metabolismo , Matriz Extracelular/metabolismo , Camundongos , Monócitos/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapiaRESUMO
Expanding the toolbox of therapeutic materials for soft tissue and organ repair has become a critical component of tissue engineering. While animal- and plant-derived proteins are the foundation for developing biomimetic tissue constructs, using peptides as either constituents or frameworks for the materials has gained increasing momentum in recent years. This mini review discusses recent advances in peptide-based biomaterials' design and application. We also discuss some of the future challenges posed and opportunities opened by peptide-based structures in the field of tissue engineering and regenerative medicine.
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Bioprinting has rapidly progressed over the past decade. One branch of bioprinting known as in situ bioprinting has benefitted considerably from innovations in biofabrication. Unlike ex situ bioprinting, in situ bioprinting allows for biomaterials to be printed directly into or onto the target tissue/organ, eliminating the need to transfer pre-made three-dimensional constructs. In this mini-review, recent progress on in situ bioprinting, including bioink composition, in situ crosslinking strategies, and bioprinter functionality are examined. Future directions of in situ bioprinting are also discussed including the use of minimally invasive bioprinters to print tissues within the body.
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Agroinfiltration is a method used in biopharming to support plant-based biosynthesis of therapeutic proteins such as antibodies and viral antigens involved in vaccines. Major advantages of generating proteins in plants is the low cost, massive scalability and the rapid yield of the technology. Herein, we report the agroinfiltration-based production of glycosylated SARS-CoV-2 Spike receptor-binding domain (RBD) protein. We show that it exhibits high-affinity binding to the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and displays folding similar to antigen produced in mammalian expression systems. Moreover, our plant-expressed RBD was readily detected by IgM, IgA, and IgG antibodies from the serum of SARS-CoV-2 infected and vaccinated individuals. We further demonstrate that binding of plant-expressed RBD to ACE2 is efficiently neutralized by these antibodies. Collectively, these findings demonstrate that recombinant RBD produced via agroinfiltration exhibits suitable biochemical and antigenic features for use in serological and neutralization assays, and in subunit vaccine platforms.