Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, ...or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.
DNA transcription is functionally coupled to messenger RNA (mRNA) translation in bacteria, but how this is achieved remains unclear. Here we show that RNA polymerase (RNAP) and the ribosome of ...Escherichia coli can form a defined transcribing and translating ÒexpressomeÓ complex. The cryo–electron microscopic structure of the expressome reveals continuous protection of ~30 nucleotides of mRNA extending from the RNAP active center to the ribosome decoding center. The RNAP-ribosome interface includes the RNAP subunit α carboxyl-terminal domain, which is required for RNAP-ribosome interaction in vitro and for pronounced cell growth defects upon translation inhibition in vivo, consistent with its function in transcription-translation coupling. The expressome structure can only form during transcription elongation and explains how translation can prevent transcriptional pausing, backtracking, and termination.
Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent ...developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.
Polymer scaffolds have many different functions in the field of tissue engineering. They are applied as space filling agents, as delivery vehicles for bioactive molecules, and as three-dimensional ...structures that organize cells and present stimuli to direct the formation of a desired tissue. Much of the success of scaffolds in these roles hinges on finding an appropriate material to address the critical physical, mass transport, and biological design variables inherent to each application. Hydrogels are an appealing scaffold material because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. Consequently, hydrogels have been utilized as scaffold materials for drug and growth factor delivery, engineering tissue replacements, and a variety of other applications.
Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) delivery may provide a new approach for the treatment of ischemic diseases, but current strategies to deliver VEGF rely on ...either bolus delivery or systemic administration, resulting in limited clinical utility, because of the short half‐life of VEGF in vivo and its resultant low and transient levels at sites of ischemia. We hypothesize that an injectable hydrogel system can be utilized to provide temporal control and appropriate spatial biodistribution of VEGF in ischemic hindlimbs. A sustained local delivery of relatively low amounts of bioactive VEGF (3 μg) with this system led to physiologic levels of bioactive VEGF in ischemic murine (ApoE−/−) hindlimbs for 15 days after injection of the gel, as contrasted with complete VEGF deprivation after 72 h with bolus injection. The gel delivery system resulted in significantly greater angiogenesis in these limbs as compared to bolus (266 vs. 161 blood vessels mm−2). Laser Doppler perfusion imaging showed return of tissue perfusion to normal levels by day 28 with the gel system, whereas normal levels of perfusion were never achieved with saline delivery of VEGF or in control mice. The system described in this article could represent an attractive new generation of therapeutic delivery vehicle for treatment of cardiovascular diseases, as it combines long‐term in vivo therapeutic benefit (localized bioactive VEGF for 1–2 weeks) with minimally invasive delivery.
Recent projections of climatic change have focused a great deal of scientific and public attention on patterns of carbon (C) cycling as well as its controls, particularly the factors that determine ...whether an ecosystem is a net source or sink of atmospheric carbon dioxide (CO₂). Net ecosystem production (NEP), a central concept in C-cycling research, has been used by scientists to represent two different concepts. We propose that NEP be restricted to just one of its two original definitions-the imbalance between gross primary production (GPP) and ecosystem respiration (ER). We further propose that a new term-net ecosystem carbon balance (NECB)-be applied to the net rate of C accumulation in (or loss from negative sign) ecosystems. Net ecosystem carbon balance differs from NEP when C fluxes other than C fixation and respiration occur, or when inorganic C enters or leaves in dissolved form. These fluxes include the leaching loss or lateral transfer of C from the ecosystem; the emission of volatile organic C, methane, and carbon monoxide; and the release of soot and CO₂ from fire. Carbon fluxes in addition to NEP are particularly important determinants of NECB over long time scales. However, even over short time scales, they are important in ecosystems such as streams, estuaries, wetlands, and cities. Recent technological advances have led to a diversity of approaches to the measurement of C fluxes at different temporal and spatial scales. These approaches frequently capture different components of NEP or NECB and can therefore be compared across scales only by carefully specifying the fluxes included in the measurements. By explicitly identifying the fluxes that comprise NECB and other components of the C cycle, such as net ecosystem exchange (NEE) and net biome production (NBP), we can provide a less ambiguous framework for understanding and communicating recent changes in the global C cycle.
Background:There is evidence that ultra-endurance exercise causes myocardial injury. The extent and duration of these changes remains unresolved. Recent reports have speculated that structural ...adaptations to exercise, particularly of the right ventricle, may predispose to tachyarrhythmias and sudden cardiac death.Objective:To quantify the extent and duration of post-exercise cardiac injury with particular attention to right ventricular (RV) dysfunction.Methods:27 athletes (20 male, 7 female) were tested 1 week before, immediately after and 1 week after an ultra-endurance triathlon. Tests included cardiac troponin I (cTnI), B-type natriuretic peptide (BNP) and comprehensive echocardiographic assessment.Results:26 athletes completed the race and testing procedures. Post-race, cTnI was raised in 15 athletes (58%) and the mean value for the entire cohort increased (0.17 vs 0.49 μg/l, p<0.01). BNP rose in every athlete and the mean increased significantly (12.2 vs 42.5 ng/l, p<0.001). Left ventricular ejection fraction (LVEF) was unchanged (60.4% vs 57.5%, p = 0.09), but integrated systolic strain decreased (16.9% vs 15.1%, p<0.01). New regional wall motion abnormalities developed in seven athletes (27%) and LVEF was reduced in this subgroup (57.8% vs 45.9%, p<0.001). RV function was reduced in the entire cohort with decreases in fractional area change (0.47 vs 0.39, p<0.01) and tricuspid annular plane systolic excursion (21.8 vs 19.1 mm, p<0.01). At follow-up, all variables returned to baseline except in one athlete where RV dysfunction persisted.Conclusion:Myocardial damage occurs during intense ultra-endurance exercise and, in particular, there is a significant reduction in RV function. Almost all abnormalities resolve within 1 week.
Angiogenesis and biomineral substrates play major roles in bone development and
regeneration. We hypothesized that macroporous scaffolds of biomineralized 85:15
poly(lactide-co-glycolide), which ...locally release vascular endothelial growth
factor-165 (VEGF), would direct simultaneous regeneration of bone and vascular
tissue. The presence of a bone-like biomineral substrate significantly increased
regeneration of osteoid matrix (32 ± 7% of total tissue area; mean ± SD; p < 0.05)
and mineralized tissue (14 ± 2%; P < 0.05) within a rat cranium critical defect
compared with a non-mineralized polymer scaffold (19 ± 8% osteoid and 10 ± 2%
mineralized tissue). Further, the addition of VEGF to a mineralized substrate
significantly increased the generation of mineralized tissue (19 ± 4%; P < 0.05)
compared with mineralized substrate alone. This appeared to be due to a significant
increase in vascularization throughout VEGF-releasing scaffolds (52 ± 9
vessels/mm2; P < 0.05) compared with mineralized scaffolds without
VEGF (34 ± 4 vessels/mm2). Surprisingly, there was no significant
difference in total osteoid between the two samples, suggesting that increased
vascularization enhances mineralized tissue generation, but not necessarily osteoid
formation. These results indicate that induced angiogenesis can enhance tissue
regeneration, supporting the concept of therapeutic angiogenesis in
tissue-engineering strategies.
Hydrogels for Tissue Engineering Lee, Kuen Yong; Mooney, David J
Chemical reviews,
07/2001, Letnik:
101, Številka:
7
Journal Article
Recenzirano
Lee and Mooney discuss the critical design parameters of hydrogels to be used in tissue engineering. Hydrogels are divided into two categories according to their natural or synthetic origin.
There is significant interest in the development of injectable carriers for cell transplantation to engineer bony tissues. In this study, we hypothesized that adhesion ligands covalently coupled to ...hydrogel carriers would allow one to control pre-osteoblast cell attachment, proliferation, and differentiation. Modification of alginate with an RGDcontaining peptide promoted osteoblast adhesion and spreading, whereas minimal cell adhesion was observed on unmodified hydrogels. Raising the adhesion ligand density increased osteoblast proliferation, and a minimum ligand density (1.5-15 femtomoles/cm2) was needed to elicit this effect. MC3T3-E1 cells demonstrated increased osteoblast differentiation with the peptide-modified hydrogels, as confirmed by the up-regulation of bone-specific differentiation markers. Further, transplantation of primary rat calvarial osteoblasts revealed statistically significant increases of in vivo bone formation at 16 and 24 weeks with G4RGDY-modified alginate compared with unmodified alginate. These findings demonstrate that biomaterials may be designed to control bone development from transplanted cells.
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