Manufacturing and validation of small-diameter vascular grafts: A mini review.

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.

Biomaterials for direct cardiac repair-A rapid scoping review 2012-2022.

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.

BEaTS-ß: an open-source electromechanical bioreactor for simulating human cardiac disease conditions.

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.

Scalable agroinfiltration-based production of SARS-CoV-2 antigens for use in diagnostic assays and subunit vaccines.

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.

Development of in situ bioprinting: A mini review.

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.

Peptide Biomaterials for Tissue Regeneration.

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.

Characterization of the Monocyte Response to Biomaterial Therapy for Cardiac Repair.

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.

The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication.

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.

Nanoengineered Sprayable Therapy for Treating Myocardial Infarction.

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.

3D Bioprinted Cardiac Tissues and Devices for Tissue Maturation.

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.

Biofilm Inhibition and Antiviral Response of Cold Sprayed and Shot Peened Copper Surfaces: Effect of Surface Morphology and Microstructure.

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.

Molecular rotors as reporters for viscosity of solutions of collagen like peptides.

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.

Evaluation of Therapeutic Collagen-Based Biomaterials in the Infarcted Mouse Heart by Extracellular Matrix Targeted MALDI Imaging Mass Spectrometry.

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.

Building new cardiac vasculature and myocardium: where are we at?

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.

Biosupramolecular complexes of amphiphilic photosensitizers with human serum albumin and cucurbit[7]uril as carriers for photodynamic therapy.

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.

Riboflavin Surface Modification of Poly(vinyl chloride) for Light-Triggered Control of Bacterial Biofilm and Virus Inactivation.

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.

Mimicking biofilm formation and development: Recent progress in in vitro and in vivo biofilm models.

Biofilm formation in living organisms is associated to tissue and implant infections, and it has also been linked to the contribution of antibiotic resistance. Thus, understanding biofilm development and being able to mimic such processes is vital for the successful development of antibiofilm treatments and therapies. Several decades of research have contributed to building the foundation for developing in vitro and in vivo biofilm models. However, no such thing as an "all fit" in vitro or in vivo biofilm models is currently available. In this review, in addition to presenting an updated overview of biofilm formation, we critically revise recent approaches for the improvement of in vitro and in vivo biofilm models.

A low cost and open access system for rapid synthesis of large volumes of gold and silver nanoparticles.

Rapid synthesis of nanomaterials in scalable quantities is critical for accelerating the discovery and commercial translation of nanoscale-based technologies. The synthesis of metal nanogold and silver in volumes larger than 100 mL is not automatized and might require of the use of harsh conditions that in most cases is detrimental for the production of nanoparticles with reproducible size distributions. In this work, we present the development and optimization of an open-access low-cost NanoParticle Flow Synthesis System (NPFloSS) that allows for the rapid preparation of volumes of up to 1 L of gold and silver nanoparticle aqueous solutions.

Integrated photothermal decontamination device for N95 respirators.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 global pandemic has infected over 25 million people worldwide and resulted in the death of millions. The COVID-19 pandemic has also resulted in a shortage of personal protective equipment (PPE) in many regions around the world, particularly in middle- and low-income countries. The shortages of PPE, such as N95 respirators, is something that will persist until an effective vaccine is made available. Thus, devices that while being easy to operate can also be rapidly deployed in health centers, and long-term residences without the need for major structural overhaul are instrumental to sustainably use N95 respirators. In this report, we present the design and validation of a decontamination device that combines UV-C & B irradiation with mild-temperature treatment. The device can decontaminate up to 20 masks in a cycle of < 30 min. The decontamination process did not damage or reduce the filtering capacity of the masks. Further, the efficacy of the device to eliminate microbes and viruses from the masks was also evaluated. The photothermal treatment of our device was capable of eradicating > 99.9999% of the bacteria and > 99.99% of the virus tested.

BEaTS-α an open access 3D printed device for in vitro electromechanical stimulation of human induced pluripotent stem cells.

3D printing was used to develop an open access device capable of simultaneous electrical and mechanical stimulation of human induced pluripotent stem cells in 6-well plates. The device was designed using Computer-Aided Design (CAD) and 3D printed with autoclavable, FDA-approved materials. The compact design of the device and materials selection allows for its use inside cell incubators working at high humidity without the risk of overheating or corrosion. Mechanical stimulation of cells was carried out through the cyclic deflection of flexible, translucent silicone membranes by means of a vacuum-controlled, open-access device. A rhythmic stimulation cycle was programmed to create a more physiologically relevant in vitro model. This mechanical stimulation was coupled and synchronized with in situ electrical stimuli. We assessed the capabilities of our device to support cardiac myocytes derived from human induced pluripotent stem cells, confirming that cells cultured under electromechanical stimulation presented a defined/mature cardiomyocyte phenotype. This 3D printed device provides a unique high-throughput in vitro system that combines both mechanical and electrical stimulation, and as such, we foresee it finding applications in the study of any electrically responsive tissue such as muscles and nerves.