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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
OBJECTIVE: Open science is a movement and set of practices to conduct research more transparently. Implementing open science will significantly improve public access and supports equity. It also has the potential to foster innovation and reduce duplication through data and materials sharing. Here, we survey an international group of researchers publishing in cardiovascular journals regarding their perceptions and practices related to open science. METHODS: We identified the top 100 'Cardiology and Cardiovascular Medicine' subject category journals from the SCImago journal ranking platform. This is a publicly available portal that draws from Scopus. We then extracted the corresponding author's name and email from all articles published in these journals between 1 March 2021 and 1 March 2022. Participants were sent a purpose-built survey about open science. The survey contained primarily multiple choice and scale-based questions for which we report count data and percentages. For the few text-based responses we conducted thematic content analysis. RESULTS: 198 participants responded to our survey. Participants had a mean response of 6.8 (N=197, SD=1.8) on a 9-point scale with endpoints, not at all familiar (1) and extremely familiar (9), when indicating how familiar they were with open science. When asked about where they obtained open science training, most participants indicated this was done on the job self-initiated while conducting research (n=103, 52%), or that they had no formal training with respect to open science (n=72, 36%). More than half of the participants indicated they would benefit from practical support from their institution on how to perform open science practices (N=106, 54%). A diversity of barriers to each of the open science practices presented to participants were acknowledged. Participants indicated that funding was the most essential incentive to adopt open science. CONCLUSIONS: It is clear that policy alone will not lead to the effective implementation of open science. This survey serves as a baseline for the cardiovascular research community's open science performance and perception and can be used to inform future interventions and monitoring.
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Cardiologia , Humanos , Cardiologia/tendências , Pesquisa Biomédica/tendências , Editoração/tendênciasRESUMO
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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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.
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COVID-19 , SARS-CoV-2 , Humanos , Animais , Enzima de Conversão de Angiotensina 2 , COVID-19/prevenção & controle , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus , Vacinas de Subunidades Antigênicas , Mamíferos/metabolismoRESUMO
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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BACKGROUND: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) can be disruptive for patients and their families. OBJECTIVE: We aimed to classify patients based on NPS and to explore the relationship of these classes with sex and with caregiver burden. METHODS: The study cohort comprised individuals with AD dementia diagnosed at Ace Alzheimer Center in Barcelona, Spain, between 2011-2020. NPS were ascertained by using the Neuropsychiatric Inventory-Questionnaire. Latent class analysis was used to identify clusters of individuals sharing a similar NPS profile. We evaluated the caregiver burden using the Zarit Burden Interview. Multivariable regression models were used to obtain adjusted estimates of the association between sex, NPS classes, and caregiver burden. RESULTS: A total of 1,065 patients with AD dementia and their primary caregivers were included. We classified patients into five different classes according to their NPS profile: "Affective", "High-behavioral-disturbance", "Negative-affect", "Affective/deliriant", and "Apathy". We found that age, sex, and type of AD diagnosis differed greatly across classes. We found that patients from the "High-behavioral-disturbance" (ORâ=â2.56, 95% CI: 1.00-6.56), "Negative-affect" (ORâ=â2.72, 95% CI: 1.26-3.64), and "Affective/deliriant" (ORâ=â2.14, 95% CI: 1.26-3.64) classes were over two times more likely to have a female caregiver than those in "Apathy" class. These three classes were also the ones associated to the greatest caregiver burden in the adjusted analyses, which seems to explain the increased burden observed among female caregivers. CONCLUSION: Caregiver burden is highly dependent on the patient's NPS profiles. Female caregivers provide care to patients that pose a greater burden, which makes them more susceptible to become overwhelmed.
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Doença de Alzheimer , Doença de Alzheimer/psicologia , Sobrecarga do Cuidador , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Análise de Classes Latentes , Espanha/epidemiologiaRESUMO
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
The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. We found that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed histone H3 lysine 27 monomethylation in plants depends on H3.1, TSK, and DNA polymerase theta (Pol θ). This work reveals an H3.1-specific function during replication and a common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone monomethyltransferases and reading of the H3.1 variant.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Reparo do DNA , Replicação do DNA , DNA de Plantas/metabolismo , Histonas/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Quebras de DNA de Cadeia Dupla , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Genoma de Planta , Instabilidade Genômica , Histonas/química , Lisina/metabolismo , Metilação , Metiltransferases/genética , Mutação , Domínios e Motivos de Interação entre Proteínas , DNA Polimerase tetaRESUMO
We report the development, as well as the in vitro and in vivo testing, of a sprayable nanotherapeutic that uses surface engineered custom-designed multiarmed peptide grafted nanogold for on-the-spot coating of an infarcted myocardial surface. When applied to mouse hearts, 1 week after infarction, the spray-on treatment resulted in an increase in cardiac function (2.4-fold), muscle contractility, and myocardial electrical conductivity. The applied nanogold remained at the treatment site 28 days postapplication with no off-target organ infiltration. Further, the infarct size in the mice that received treatment was found to be <10% of the total left ventricle area, while the number of blood vessels, prohealing macrophages, and cardiomyocytes increased to levels comparable to that of a healthy animal. Our cumulative data suggest that the therapeutic action of our spray-on nanotherapeutic is highly effective, and in practice, its application is simpler than other regenerative approaches for treating an infarcted heart.
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Infarto do Miocárdio , Animais , Modelos Animais de Doenças , Condutividade Elétrica , Macrófagos , Camundongos , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Miócitos CardíacosRESUMO
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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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
The goal of this study was to develop strategies to localize human collagen-based hydrogels within an infarcted mouse heart, as well as analyze its impact on endogenous extracellular matrix (ECM) remodeling. Collagen is a natural polymer that is abundantly used in bioengineered hydrogels because of its biocompatibility, cell permeability, and biodegradability. However, without the use of tagging techniques, collagen peptides derived from hydrogels can be difficult to differentiate from the endogenous ECM within tissues. Imaging mass spectrometry is a robust tool capable of visualizing synthetic and natural polymeric molecular structures yet is largely underutilized in the field of biomaterials outside of surface characterization. In this study, our group leveraged a recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technique to enzymatically target collagen and other ECM peptides within the tissue microenvironment that are both endogenous and hydrogel-derived. Using a multimodal approach of fluorescence microscopy and ECM-IMS techniques, we were able to visualize and relatively quantify significantly abundant collagen peptides in an infarcted mouse heart that were localized to regions of therapeutic hydrogel injection sites. On-tissue MALDI MS/MS was used to putatively identify sites of collagen peptide hydroxyproline site occupancy, a post-translational modification that is critical in collagen triple helical stability. Additionally, the technique could putatively identify over 35 endogenously expressed ECM peptides that were expressed in hydrogel-injected mouse hearts. Our findings show evidence for the use of MALDI-IMS in assessing the therapeutic application of collagen-based biomaterials.
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Materiais Biocompatíveis , Colágeno , Matriz Extracelular/metabolismo , Infarto do Miocárdio/diagnóstico por imagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/análise , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacocinética , Colágeno/administração & dosagem , Colágeno/análise , Colágeno/química , Colágeno/farmacocinética , Modelos Animais de Doenças , Matriz Extracelular/química , Feminino , Coração/diagnóstico por imagem , Histocitoquímica , Camundongos , Camundongos Endogâmicos C57BL , Imagem Molecular/métodos , Infarto do Miocárdio/metabolismo , Miocárdio/química , Miocárdio/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacocinética , Distribuição TecidualRESUMO
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
In the present work, we evaluated the supramolecular interactions between three photosensitizers, namely toluidine blue O (TBO, positively charged) and two fatty acid conjugates of 6 and 14 carbon atoms chain lengths (TBOC6 and TBOC14), with human serum albumin (HSA) and the macrocycle cucurbit[7]uril (CB[7]), alone or in combination within a biosupramolecular system as potential carriers of photosensitizers for Photodynamic therapy (PDT). Binding studies were carried out using photophysical and calorimetric techniques and accompanied with molecular docking simulations. Amphiphilic photosensitizers, particularly TBOC14, showed stronger binding to HSA and (CB[7]). Comparing the different delivery systems, (CB[7]) had a marginal effect on cell uptake and phototoxicity in HeLa cells, while HSA showed enhanced cell uptake with phototoxicities that depended on the photosensitizer. Despite low cell uptake, the combination of both (CB[7]) and HSA was the most phototoxic, which illustrates the potential of combining these systems for PDT applications.
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Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Fármacos Fotossensibilizantes/química , Albumina Sérica Humana/química , Sítios de Ligação , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos/química , Células HeLa , Humanos , Imidazóis/metabolismo , Simulação de Acoplamento Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Ligação Proteica , Albumina Sérica Humana/metabolismo , Cloreto de Tolônio/química , Cloreto de Tolônio/metabolismoRESUMO
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
Poly(vinyl chloride) (PVC) is the most used biomedical polymer worldwide. PVC is a stable and chemically inert polymer. However, microorganisms can colonize PVC producing biomedical device-associated infections. While surface modifications of PVC can help improve the antimicrobial and antiviral properties, the chemically inert nature of PVC makes those modifications challenging and potentially toxic. In this work, we modified the PVC surface using a derivative riboflavin molecule that was chemically tethered to a plasma-treated PVC surface. Upon a low dosage of blue light, the riboflavin tethered to the PVC surface became photochemically activated, allowing for Pseudomonas aeruginosa bacterial biofilm and lentiviral in situ eradication.