首页期刊导航|Acta biomaterialia
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Acta biomaterialia
Elsevier
Acta biomaterialia

Elsevier

1742-7061

Acta biomaterialia/Journal Acta biomaterialiaEIISTPSCI
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    Membrane-active amino acid-coupled polyetheramine derivatives with high selectivity and broad-spectrum antibacterial activity

    Li H.Li Y.Wang Y.Liu L....
    13页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Membrane active antimicrobial peptide mimics have been considered as promising alternatives to antibiotics, which interact with bacterial cell membranes to combat bacteria and avoid the emergence of multidrug-resistant bacteria. Herein, a series of star-shaped and membrane-active cationic polyetheramides derived from amino acids, were synthesized via condensation of amino acids and polyetheamine (T403). The antibacterial and anti-biofilm activitives as well as the biocompatibility of these amino acids derived polyetheramides (AAPEAs) were investigated in detail. The star-shaped AAPEAs showed high-efficient and broad-spectrum antibacterial activity against the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens. In addition, the antibacterial activity was significantly affected by the type of amino acid. L-Trp-T403, which was obtained from L-tryptophan and polyetheramine, exhibited the best antibacterial activity with the minimum inhibitory concentration (MIC) of 1 μg/mL against methicillin-resistant S. aureus (MRSA). Time-kill kinetics and multi-passage resistance tests experiments indicated that L-Trp-T403 could rapidly kill bacteria within 1 h. This compound also showed potent antibacterial activity against bacteria over many passages. Moreover, the AAPEAs exhibited outstanding stability and long-term antibacterial activity in complex mammalian body fluids, as well as good biocompatibility, low hemolytic activity, slight toxicity for mammalian cell (L929) and low in vivo toxicity. The antibacterial activity of L-Trp-T403 was found to be based on the disruption of bacterial membranes, which leads to the leakage of the internal cytoplasm. The AAPEAs possessed high antibacterial and anti-biofilm activity, thus, they are promising to be used as long-term and biofilm-disrupting antimicrobial agents. Statement of significance: The growing epidemic of MDR-bacteria is becoming a severe public health threat. Here, a series of amino acids derived polyetheramides (AAPEAs) with a star-shaped polyether amide scaffold was synthesized. The star-shaped AAPEAs displayed broad-spectrum antibacterial activity against Gram-positive, Gram-negative bacteria and drug-resistant bacteria MRSA. Notably, the star-shaped AAPEAs were stable under plasma conditions and showed outstanding stability and long-term antibacterial activity in various complex mammalian fluids. Moreover, these star-shaped AAPEAs not only inhibited the formation of biofilms but also disrupted the established biofilms. Furthermore, the membrane-active AAPEAs eradicated bacteria via the fast membrane lytic mechanism, thus plausibly overcoming the MDR effect. These results demonstrate that membrane-active AAPEAs can serve as emerging long-term and biofilm-disrupting antimicrobial agents to treat biofilm-related infections.
      原文链接:
    • NSTL
    • Elsevier

    Cell alignment modulated by surface nano-topography – Roles of cell-matrix and cell-cell interactions

    Coyle S.Doss B.Huo Y.Singh H.R....
    11页
    查看更多>>摘要：? 2022The propensity of cells to align in particular directions is relevant to a number of areas, including tissue engineering and biohybrid robotics. Cell alignment is modulated through various extracellular conditions including surface topographies, mechanical cues from cell-matrix interactions, and cell-cell interactions. Understanding of these conditions provides guidance for desirable cellular structure constructions. In this study, we examine the roles of surface topographies and cell-cell interactions in inducing cell alignment. We employed wavy surface topographies at the nanometer scale as a model extracellular environment for cell culture. The results show that, within a certain range of wavelengths and amplitudes of the surface topographies, cell alignment is dependent on cell confluency. This dependence on both topology and confluency suggests interplay between cell-cell and cell-matrix interactions in inducing cell alignment. Images of sparsely distributed and confluent cells also demonstrated clear differences in the structures of their focal adhesion complexes. To understand this effect, we introduced anti-N-cadherin to cell culture to inhibit cell-cell interactions. The results show that, when anti-N-cadherin was applied, cells on wavy surfaces required greater confluency to achieve the same alignment compared to that in the absence of anti-N-cadherin. The understanding of the cell alignment mechanisms will be important in numerous potential applications such as scaffold design, tissue repair, and development of biohybrid robotic systems. Statement of significance: Cell alignment plays a critical role in numerous biological functions. Advances in tissue engineering utilizes cell alignment to restore, maintain, or even replace different types of biological tissues. The clinical impact that tissue engineering has made is facilitated by advancements in the understanding of interactions between scaffolds, biological factors, and cells. This work further elucidates the role of cell-cell interactions in promoting the organization of biological tissues.
      原文链接:
    • NSTL
    • Elsevier

    Cavitation nucleation and its ductile-to-brittle shape transition in soft gels under translational mechanical impact

    Kim C.Choi W.J.Kang W.
    14页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Cavitation bubbles in the human body, when subjected to impact, are being increasingly considered as a possible brain injury mechanism. However, the onset of cavitation and its complex dynamics in biological materials remain unclear. Our experimental results using soft gels as a tissue simulant show that the critical acceleration (acr) at cavitation nucleation monotonically increases with increasing stiffness of gelatin A/B, while acr for agarose and agar initially increases but is followed by a plateau or even decrease after stiffness reach to ～100 kPa. Our image analyses of cavitation bubbles and theoretical work reveal that the observed trends in acr are directly linked to how bubbles grow in each gel. Gelatin A/B, regardless of their stiffness, form a localized damaged zone (tens of nanometers) at the gel-bubble interface during bubble growth. In contrary, the damaged zone in agar/agarose becomes significantly larger (> 100 times) with increasing shear modulus, which triggers the transition from formation of a small, damaged zone to activation of crack propagation. Statement of Significance: We have studied cavitation nucleation and bubble growth in four different types of soft gels (i.e., tissue simulants) under translational impact. The critical linear acceleration for cavitation nucleation has been measured in the simulants by utilizing a recently developed method that mimics acceleration profiles of typical head blunt events. Each gel type exhibits significantly different trends in the critical acceleration and bubble shape (e.g., A gel-specific sphere-to-saucer transition) with increasing gel stiffness. Our theoretical framework, based on the concepts of a damaged zone and crack propagation in each gel, explains underlying mechanisms of the experimental observations. Our in-depth studies shed light on potential links between traumatic brain injuries and cavitation bubbles induced by translational acceleration, the overlooked mechanism in the literature.
      原文链接:
    • NSTL
    • Elsevier

    Fracture behaviour and toughening mechanisms of dry and wet collagen

    Bose S.Li S.Mele E.Silberschmidt V.V....
    11页
    查看更多>>摘要：? 2022 Acta Materialia Inc.The growing interest to the use of collagen films for biomedical applications motivates the analysis of their fracture behaviour in different environments. Studies revealed the decreased mechanical strength and stiffness as well as increased plasticity in water compared to collagen specimens tested in air. However, the fracture behaviour of pure collagen films in both air and water has not been reported so far. In this paper, the entire process of mode-I loading of single-edge notched tension (SENT) specimens was recorded and analysed. In case of in-air (dry) specimens, cracks propagated rapidly in a brittle fashion while large plastic deformations were observed in aqua prior to failure due to crack opening and a blunting mechanism in wet specimens. The fracture-toughness parameters for pure collagen in air and in aqua were estimated using linear-elastic (KI and GI) and elasto-plastic (JI) fracture-mechanics approaches, respectively, following the force-displacement response and deformational behaviour. GIC and JI were 1365 ± 112 J/m2 and 2500 ± 440 J/m2, respectively. Scanning electron microscopy was used to observe the structural changes linked to collagen fibrils in the crack-tip area and the fracture surface. For in-air specimens, the former mostly exhibited extrinsic toughening (usually at micro scale) acting behind the crack-tip, while in-aqua intrinsic toughening acting ahead of a crack tip was found. Fractography of in-air specimens showed no occurrence of voids while multiple micro-voids were found for in-aqua specimens. Statement of significance: The fracture toughness and crack propagation of both mineralised (bone, dentine) and non-mineralised (skin) tissues has been extensively investigated over the past decades. Though these tissues are rich in collagen, the fracture properties of pure collagen have not been quantified yet at macroscale. Considering the applications of collagen films in tissue regeneration, it is essential to perform investigations of their fracture behaviour in both dry and wet conditions. Determining the effect of environment on the fracture behaviour of collagen and understanding its toughening mechanism are essential for prevention of failures during application. Moreover, this would give an insight for fabrication of tougher collagen-based biomaterials for biomedical uses.
      原文链接:
    • NSTL
    • Elsevier

    Tropocollagen springs allow collagen fibrils to stretch elastically

    Bell J.S.Hayes S.Whitford C.Sanchez-Weatherby J....
    9页
    查看更多>>摘要：? 2022The mechanical properties of connective tissues are tailored to their specific function, and changes can lead to dysfunction and pathology. In most mammalian tissues the mechanical environment is governed by the micro- and nano-scale structure of collagen and its interaction with other tissue components, however these hierarchical properties remain poorly understood. In this study we use the human cornea as a model system to characterise and quantify the dominant deformation mechanisms of connective tissue in response to cyclic loads of physiological magnitude. Synchronised biomechanical testing, x-ray scattering and 3D digital image correlation revealed the presence of two dominant mechanisms: collagen fibril elongation due to a largely elastic, spring-like straightening of tropocollagen supramolecular twist, and a more viscous straightening of fibril crimp that gradually increased over successive loading cycles. The distinct mechanical properties of the two mechanisms suggest they have separate roles in vivo. The elastic, spring-like mechanism is fast-acting and likely responds to stresses associated with the cardiac cycle, while the more viscous crimp mechanism will respond to slower processes, such as postural stresses. It is anticipated that these findings will have broad applicability to understanding the normal and pathological functioning of other connective tissues such as skin and blood vessels that exhibit both helical structures and crimp. Statement of significance: The tropocollagen spring mechanism allows collagen fibrils from some tissues to elongate significantly under small loads, and its recent discovery has the potential to change our fundamental understanding of how tissue deforms. This time-resolved study quantifies the contribution of the spring mechanism to the local strain in stretched tissue and compares it to the contribution associated with the straightening of fibril waviness, the widely accepted primary low-load strain mechanism. The spring mechanism contributed more to the local tissue strain than fibril straightening, and was found to be elastic while fibril straightening was more viscous. The results suggest that the viscoelastic behaviour of a biomaterial is controlled, at least in part, by the relative amount of fibril-scale crimp and tropocollagen supramolecular twist.
      原文链接:
    • NSTL
    • Elsevier

    Amorphous-to-crystal transition in the layer-by-layer growth of bivalve shell prisms

    Duboisset J.Ferrand P.Baroni A.Grunewald T.A....
    14页
    查看更多>>摘要：? 2022Biomineralization integrates complex physical and chemical processes bio-controlled by the living organisms through ionic concentration regulation and organic molecules production. It allows tuning the structural, optical and mechanical properties of hard tissues during ambient-condition crystallisation, motivating a deeper understanding of the underlying processes. By combining state-of-the-art optical and X-ray microscopy methods, we investigated early-mineralized calcareous units from two bivalve species, Pinctada margaritifera and Pinna nobilis, revealing chemical and crystallographic structural insights. In these calcite units, we observed ring-like structural features correlated with a lack of calcite and an increase of amorphous calcium carbonate and proteins contents. The rings also correspond to a larger crystalline disorder and a larger strain level. Based on these observations, we propose a temporal biomineralization cycle, initiated by the production of an amorphous precursor layer, which further crystallizes with a transition front progressing radially from the unit centre, while the organics are expelled towards the prism edge. Simultaneously, along the shell thickness, the growth occurs following a layer-by-layer mode. These findings open biomimetic perspectives for the design of refined crystalline materials. Statement of significance: Calcareous biominerals are amongst the most present forms of biominerals. They exhibit astonishing structural, optical and mechanical properties while being formed at ambient synthesis conditions from ubiquitous ions, motivating the deep understanding of biomineralization. Here, we unveil the first formation steps involved in the biomineralization cycle of prismatic units of two bivalve species by applying a new multi-modal non-destructive characterization approach, sensitive to chemical and crystalline properties. The observations of structural features in mineralized units of different ages allowed the derivation of a temporal sequence for prism biomineralization, involving an amorphous precursor, a radial crystallisation front and a layer-by-layer sequence. Beyond these chemical and physical findings, the herein introduced multi-modal approach is highly relevant to other biominerals and bio-inspired studies.
      原文链接:
    • NSTL
    • Elsevier

    3D hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance

    Ertekin O.Monavari M.Kruger R.Fuentes-Chandia M....
    13页
    查看更多>>摘要：? 2022 Acta Materialia Inc.In this work, we analyzed the reliability of alginate-gelatin microcapsules as artificial tumor model. These tumor-like scaffolds are characterized by their composition and stiffness (～25 kPa), and their capability to restrict -but not hinder- cell migration, proliferation and release from confinement. Hydrogel-based microcapsules were initially utilized to detect differences in mechano-sensitivity between MCF7 and MDA-MB-231 breast cancer cells, and the endothelial cell line EA.hy926. Additionally, we used RNA-seq and transcriptomic methods to determine how the culture strategy (i.e. 2D v/s 3D) may pre-set the expression of genes involved in multidrug resistance, being then validated by performing cytotoxicological tests and assays of cell morphology. Our results show that both breast cancer cells can generate elongated multicellular spheroids inside the microcapsules, prior being released (mimicking intravasation stages), a behavior which was not observed in endothelial cells. Further, we demonstrate that cells isolated from 3D scaffolds show resistance to cisplatin, a process which seems to be strongly influenced by mechanical stress, instead of hypoxia. We finally discuss the role played by aneuploidy in malignancy and resistance to anticancer drugs, based on the increased number of polynucleated cells found within these microcapsules. Overall, our outcomes demonstrate that alginate-gelatin microcapsules represent a simple, yet very accurate tumor-like model, enabling us to mimic the most relevant malignant hints described in vivo, suggesting that confinement and mechanical stress need to be considered when studying pathogenicity and drug resistance of cancer cells in vitro. Statement of significance: In this work, we analyzed the reliability of alginate-gelatin microcapsules as an artificial tumor model. These scaffolds are characterized by their composition, elastic properties, and their ability to restrict cell migration, proliferation, and release from confinement. Our results demonstrate four novel outcomes: (i) studying cell migration and proliferation in 3D enabled discrimination between malignant and non-pathogenic cells, (ii) studying the cell morphology of cancer aggregates entrapped in alginate-gelatin microcapsules enabled determination of malignancy degree in vitro, (iii) determination that confinement and mechanical stress, instead of hypoxia, are required to generate clones resistant to anticancer drugs (i.e. cisplatin), and (iv) evidence that resistance to anticancer drugs could be due to the presence of polynucleated cells localized inside polymer-based artificial tumors.
      原文链接:
    • NSTL
    • Elsevier

    Bovine serum albumin-based biomimetic gene complexes with specificity facilitate rapid re-endothelialization for anti-restenosis

    Yang F.Jiang H.Feng Y.Gai W....
    21页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Re-endothelialization is a critical problem to inhibit postoperative restenosis, and gene delivery exhibits great potential in rapid endothelialization. Unfortunately, the therapeutic effect is enormously limited by inefficient specificity, poor biocompatibility and in vivo stability owing largely to the complicated in vivo environment. Herein, we developed a series of platelet membrane (PM) cloaked gene complexes based on natural bovine serum albumin (BSA) and polyethyleneimine (PEI). The gene complexes aimed to accelerate re-endothelialization for anti-restenosis via pcDNA3.1-VEGF165 (VEGF) plasmid delivery. Based on BSA and PM coating, these gene complexes exhibited good biocompatibility, stability with serum and robust homing to endothelium-injured site inherited from platelets. Besides, they enhanced the expression of VEGF protein by their high internalization and nucleus accumulation efficiency, and also substantially promoted migration and proliferation of vascular endothelial cells. The biological properties were further optimized via altering PEI and PM content. Finally, rapid recovery of endothelium in a carotid artery injured mouse model (79% re-endothelialization compared with model group) was achieved through two weeks’ treatment by the PM cloaked gene complexes. High level of expressed VEGF in vivo was also realized by the gene complexes. Moreover, neointimal hyperplasia (IH) was significantly inhibited by the gene complexes according to in vivo study. The results verified the great potential of the PM cloaked gene complexes in re-endothelialization for anti-restenosis. Statement of significance: Rapid re-endothelialization is a major challenge to inhibit postoperative restenosis. Herein, a series of biodegradable and biocompatible platelet membrane (PM) cloaked gene complexes were designed to accelerate re-endothelialization for anti-restenosis via pcDNA3.1-VEGF165 (VEGF) plasmid delivery. The PM cloaked gene complexes provided high VEGF expression in vascular endothelial cells (VECs), rapid migration and proliferation of VECs and robust homing to endothelium-injured site. In a carotid artery injured mouse model, PM cloaked gene complexes significantly promoted VEGF expression in vivo, accelerated re-endothelialization and inhibited neointimal hyperplasia due to their good biocompatibility and superior specificity. Overall, the optimized PM cloaked gene complexes overcomes multiple obstacles in gene delivery for re-endothelialization and can be a promising candidate for gene delivery and therapy of postoperative restenosis.
      原文链接:
    • NSTL
    • Elsevier

    Regulating the bacterial oxygen microenvironment via a perfluorocarbon-conjugated bacteriochlorin for enhanced photodynamic antibacterial efficacy

    Wu M.Chen C.Liu Z.Tian J....
    11页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Photodynamic therapy (PDT) has attracted considerable attention, since it could effectively kill bacteria and prevent the development of multi-drug resistance. However, PDT currently suffers from oxygen limitation and hypoxia is a prominent feature of pathological states encountered in inflammation, wounds, and bacterial infections. Herein, an oxygen-tunable nanoplatform based on perfluorocarbon-conjugated tetrafluorophenyl bacteriochlorin (FBC-F) was designed for effective antimicrobial therapy. The introduction of fluorine atoms can not only increase the reactive oxygen species (ROS) production capacity of FBC-F by facilitating the intersystem crossing (ISC) process of FBC photosensitizers, but also make FBC-F deliver more oxygen into the treatment sites benefiting from the outstanding oxygen-dissolving capability of perfluorocarbon. As a consequence, the FBC-F nanoplatform was able to efficiently generate singlet oxygens for type II PDT, as well as superoxide anions and hydroxyl radicals for type I PDT, and significantly improve antibacterial efficacy in vitro. In vivo experiments further proved that the FBC-F with a powerful antibacterial capability could well promote wound healing and destroy biofilm. Thus, this FBC-F nanoplatform may open a new path in photodynamic antibacterial therapy. Statement of significance: Photodynamic therapy is a promising antibacterial treatment, but its efficacy is severely compromised by hypoxia. To overcome such a limitation, we constructed an oxygen-regulated nanoplatform (FBC-F) by attaching perfluorocarbons (PFC) to the NIR photosensitizer (FBC). As an analogue of bacteriochlorin, FBC could generate 1O2 through energy transfer, as well as O2?· and ·OH through electron transfer for synergistic type I and type II photodynamic antibacterial therapy. Benefiting from the oxygen-dissolving capability of PFC, FBC-F could efficiently deliver more oxygen into the treatment site and alleviate the hypoxic environment. As a consequence, FBC-F could effectively generate large amounts of reactive oxygen species to achieve improved antibacterial efficacy and provide a promising approach for eliminating biofilms.
      原文链接:
    • NSTL
    • Elsevier

    Tumor-acidity and bioorthogonal chemistry-mediated construction and deconstruction of drug depots for ferroptosis under normoxia and hypoxia

    Zhou J.Wang K.Jiang M.Li J....
    11页
    查看更多>>摘要：? 2022Mounting evidence shows that tumor hypoxia stress promotes tumor invasion and metastasis and induces therapeutic resistance. Oxygen-independent Fenton reaction, which refers to the iron-catalyzed conversion of endogenous hydrogen peroxide (H2O2) to hydroxyl radical (·OH), has been designed for ferroptosis therapy. Nevertheless, the treatment efficiency is compromised by limited H2O2 content and limited tumor retention and penetration of nanoparticles. Herein, we designed a tumor-acidity and bioorthogonal chemistry mediated construction and deconstruction of drug depots for tumor ferroptosis under normoxia and hypoxia. Briefly, the dendritic poly(amidoamine) (PAMAM, G4) was modified using cinnamaldehyde (CA) to deplete GSH and increase H2O2 levels, and ferrocene (Ferr) served as Fenton reaction catalyst to generate PFC. Subsequently, PFC was modified with maleic acid amide with slow pH-response rate and poly(2-azepane ethyl methacrylate) (PAEMA) with rapid pH-response rate, accompanied with highly efficient bioorthogonal chemistry to construct and deconstruct drug depots for enhanced tumor retention and penetration. The small-sized PFC potentially induced H2O2 self-supplied ferroptosis under normoxia and hypoxia. In sum, this work utilizes two tumoral acidity-responsive groups with different response rates and highly efficient bioorthogonal click chemistry, which paves a way for ferroptosis and provides a general drug delivery strategy with enhanced tumor retention and penetration. Statement of significance: Oxygen independent Fenton reaction refers to the conversion of endogenous H2O2 to ·OH which has been designed for ferroptosis therapy. Nevertheless, limited H2O2 level and abundant GSH in tumor cells could both compromise the treatment efficiency. Herein, we developed a tumor-acidity and bioorthogonal chemistry mediated construction and deconstruction of drug depots, which elevate the intracellular H2O2 level and deplete GSH for tumor ferroptosis under normoxia and hypoxia microenvironment. This work utilizes two tumoral acidity response groups with different response rates and highly efficient bioorthogonal click reactions, which paves a way for tumor cell ferroptosis and provides a general drug delivery strategy for enhanced tumor accumulation and penetration.
      原文链接:
    • NSTL
    • Elsevier