Collagen is the oldest and most abundant extracellular matrix protein that has found many applications in food, cosmetic, pharmaceutical, and biomedical industries. First, an overview of the family ...of collagens and their respective structures, conformation, and biosynthesis is provided. The advances and shortfalls of various collagen preparations (e.g., mammalian/marine extracted collagen, cell‐produced collagens, recombinant collagens, and collagen‐like peptides) and crosslinking technologies (e.g., chemical, physical, and biological) are then critically discussed. Subsequently, an array of structural, thermal, mechanical, biochemical, and biological assays is examined, which are developed to analyze and characterize collagenous structures. Lastly, a comprehensive review is provided on how advances in engineering, chemistry, and biology have enabled the development of bioactive, 3D structures (e.g., tissue grafts, biomaterials, cell‐assembled tissue equivalents) that closely imitate native supramolecular assemblies and have the capacity to deliver in a localized and sustained manner viable cell populations and/or bioactive/therapeutic molecules. Clearly, collagens have a long history in both evolution and biotechnology and continue to offer both challenges and exciting opportunities in regenerative medicine as nature's biomaterial of choice.
Collagen is the most abundant extracellular matrix protein and is used extensively in food, cosmetic, pharmaceutical, and biomedical industries. The fundamentals of collagen biosynthesis, assembly, and native crosslinking are provided, along with methods to produce natural and synthetic collagens and to fabricate, stabilize, and characterize collagen‐based devices.
Bacterial infection of implanted scaffolds may have fatal consequences and, in combination with the emergence of multidrug bacterial resistance, the development of advanced antibacterial biomaterials ...and constructs is of great interest. Since decades ago, metals and their ions had been used to minimize bacterial infection risk and, more recently, metal-based nanomaterials, with improved antimicrobial properties, have been advocated as a novel and tunable alternative. A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria. Antibacterial mechanisms such as oxidative stress induction, ion release and disruption of biomolecules are currently well accepted. However, the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood. The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing, and allow to mitigate potential side effects to the host. Starting with a general overview of antibacterial mechanisms, we subsequently focus on specific metal ions such as silver, zinc, copper, iron and gold, and outline their distinct modes of action. Finally, we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure.
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•Distinct mechanisms concertedly contribute to the antibacterial effect of metal ions and nanoparticles in tissue engineering.•Metal-mediated antibacterial mechanisms include membrane disruption, ROS generation, and protein/DNA damage.•As different metals/nanoparticles prompt different antibacterial mechanisms, biomaterials may benefit from combinatorial use.•Application specific antibacterial biomaterials with controlled metal release rates are achievable by combining techniques.
Collagen-based devices, in various physical conformations, are extensively used for tissue engineering and regenerative medicine applications. Given that the natural cross-linking pathway of collagen ...does not occur in vitro, chemical, physical, and biological cross-linking methods have been assessed over the years to control mechanical stability, degradation rate, and immunogenicity of the device upon implantation. Although in vitro data demonstrate that mechanical properties and degradation rate can be accurately controlled as a function of the cross-linking method utilized, preclinical and clinical data indicate that cross-linking methods employed may have adverse effects on host response, especially when potent cross-linking methods are employed. Experimental data suggest that more suitable cross-linking methods should be developed to achieve a balance between stability and functional remodeling.
Biomaterials and scaffolds for Tissue Engineering are widely used for an effective healing and regeneration. However, the implantation of these scaffolds causes an innate immune response in which the ...macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype is crucial to avoid chronic inflammation. Recent studies have showed that the use of bioactive ions such as cobalt (Co
), copper (Cu
) and magnesium (Mg
) could improve tissue regeneration, although there is limited evidence on their effect on the macrophage response. Therefore, we investigated the immunomodulatory potential of Co
, Cu
and Mg
in macrophage polarization. Our results indicate that Mg
and concentrations of Cu
lower than 10 μM promoted the expression of M2 related genes. However, higher concentrations of Cu
and Co
(100 μM) stimulated pro-inflammatory marker expression, indicating a concentration dependent effect of these ions. Furthermore, Mg
were able to decrease M1 marker expression in presence of a mild pro-inflammatory stimulus, showing that Mg
can be used to modulate the inflammatory response, even though their application can be limited in a strong pro-inflammatory environment.
Extracted forms of collagen are subjected to chemical cross-linking to enhance their stability. However, traditional cross-linking approaches are associated with toxicity and inflammation. This work ...investigates the stabilization capacity, cytotoxicity and inflammatory response of collagen scaffolds cross-linked with glutaraldehyde (GTA), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, 4-arm polyethylene glycol (PEG) succinimidyl glutarate (4SP), genipin (GEN), and oleuropein. Although all cross-linking methods reduced free amine groups, variable data were obtained with respect to denaturation temperature, resistance to collagenase digestion, and mechanical properties. With respect to biological analysis, fibroblast cultures showed no significant difference between the treatments. Although direct cultures with human-derived leukemic monocyte cells (THP-1) clearly demonstrated the cytotoxic effect of GTA, THP-1 cultures supplemented with conditioned medium from the various groups showed no significant difference between the treatments. With respect to cytokine profile, no significant difference in secretion of proinflammatory (e.g., interleukin IL-1β, IL-8, tumor necrosis factor-α) and anti-inflammatory (e.g., vascular endothelial growth factor) cytokines was observed between the noncross-linked and the 4SP and GEN cross-linked groups, suggesting the suitability of these agents as collagen cross-linkers.
The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the ...endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4‐induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. Conclusions: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process. (Hepatology 2014;59:2358–2370)
Mesoscale convective systems (MCSs) are frequent, but understudied, components of the warm season climatology in northwestern Mexico. This study provides an update of previous research on convective ...development and examines MCS life cycle, structure, and motion from July through September. It focuses on a region south of the North American monsoon core and, from 2009 to 2018 satellite observations, on patterns of cloud tops higher than 10 km above sea level. The diurnal cycle of convection shows cells initiating in the early afternoon over the Sierra Madre Occidental mountains and becoming better organized over the next few hours. These features typically move westward, grow upscale to reach maximum vertical extent near local sunset, and weaken during the night. However, there is a distinct region of deep convection over and off the coast of Nayarit (20–23°N), in the Pacific Ocean, that remains active through the night and into the early morning, producing heavy rainfall and frequent lightning. Occasionally, the inner structure of these MCSs can move across the Gulf of California and reach the southern Baja California Peninsula. One particular long‐lived, fast‐moving MCS from July 23 and 24, 2014 was selected for in‐depth analysis, because it was associated with weather conditions that included unusual precipitation and extreme winds. The MCS caused damage from sustained winds of tropical‐storm strength and an intense gust front in the Los Cabos area, in the southern tip of the peninsula. This extraordinary MCS developed in the most unstable and humid environment recorded during the 1976–2018 period, and was supported by a collocated upper‐level, inverted trough and a lower‐troposphere tropical wave. We also found that the 10 most unstable conditions have all occurred after 2011, possibly indicative of a trend toward more frequent and favourable environments to spawn MCSs over the Gulf of California entrance.
This extraordinary mesoscale convective system (MCS), over the Gulf of California, approached the Baja California Peninsula, Mexico, on July 24, 2014 with tropical‐storm‐force winds that resulted in significant property damage and heavy rainfall to the population in Los Cabos. The environment, in which the MCS formed, was characterized by one of the highest values of convective available potential energy ever measured for the region.
Cardiovascular diseases are considered one of the worldwide causes of death, with atherosclerosis being the most predominant. Nowadays, the gold standard treatment is blood vessel replacement by ...bypass surgery; however, autologous source is not always possible. Thereby, tissue-engineered blood vessels (TEBVs) are emerging as a potential alternative source. In terms of composition, collagen has been selected in many occasions to develop TEBVs as it is one of the main extracellular matrix components of arteries. However, it requires specific support or additional processing to maintain the tubular structure and appropriate mechanical properties. Here, we present a method to develop support-free collagen TEBVs with co-axial extrusion in a one-step procedure with high concentrated collagen. The highest concentration of collagen of 20 mg/mL presented a burst pressure of 619.55 ± 48.77 mmHg, being able to withstand perfusion of 10 dynes/cm
. Viability results showed a high percentage of viability (86.1 and 85.8% with 10 and 20 mg/mL, respectively) of human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVEC) after 24 h extrusion. Additionally, HUVEC and HASMCs were mainly localized in their respective layers, mimicking the native distribution. All in all, this approach allows the direct extrusion of collagen TEBVs in a one-step procedure with enough mechanical properties to be perfused.
Two oxoiron(IV) isomers (R2a and R2b) of general formula FeIV(O)(RPyNMe3)(CH3CN)2+ are obtained by reaction of their iron(II) precursor with NBu4IO4. The two isomers differ in the position of the oxo ...ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R2a and R2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R2a reacts one order of magnitude faster than R2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.
The isomerization of pairs of electronically tuned oxoiron(IV) geometrical isomers is described, as a model for the “ferryl flip” observed in non‐heme enzymes. The position of the oxo ligand in the coordination sphere of the iron center has a strong impact on the hydrogen‐atom transfer (HAT) activity of the oxoiron(IV) compounds, while electronic effects do not play a significant role in HAT reactions.
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