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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    Bone mineral organization at the mesoscale: A review of mineral ellipsoids in bone and at bone interfaces

    Micheletti C.Hurley A.Gourrier A.Palmquist A....
    13页
    查看更多>>摘要:? 2022 Acta Materialia Inc.Much debate still revolves around bone architecture, especially at the nano- and microscale. Bone is a remarkable material where high strength and toughness coexist thanks to an optimized composition of mineral and protein and their hierarchical organization across several distinct length scales. At the nanoscale, mineralized collagen fibrils act as building block units. Despite their key role in biological and mechanical functions, the mechanisms of collagen mineralization and the precise arrangement of the organic and inorganic constituents in the fibrils remains not fully elucidated. Advances in three-dimensional (3D) characterization of mineralized bone tissue by focused ion beam-scanning electron microscopy (FIB-SEM) revealed mineral-rich regions geometrically approximated as prolate ellipsoids, much larger than single collagen fibrils. These structures have yet to become prominently recognized, studied, or adopted into biomechanical models of bone. However, they closely resemble the circular to elliptical features previously identified by scanning transmission electron microscopy (STEM) in two-dimensions (2D). Herein, we review the presence of mineral ellipsoids in bone as observed with electron-based imaging techniques in both 2D and 3D with particular focus on different species, anatomical locations, and in proximity to natural and synthetic biomaterial interfaces. This review reveals that mineral ellipsoids are a ubiquitous structure in all the bones and bone-implant interfaces analyzed. This largely overlooked hierarchical level is expected to bring different perspectives to our understanding of bone mineralization and mechanical properties, in turn shedding light on structure-function relationships in bone. Statement of significance: In bone, the hierarchical organization of organic (mainly collagen type I) and inorganic (calcium-phosphate mineral) components across several length scales contributes to a unique combination of strength and toughness. However, aspects related to the collagen-mineral organization and to mineralization mechanisms remain unclear. Here, we review the presence of mineral prolate ellipsoids across a variety of species, anatomical locations, and interfaces, both natural and with synthetic biomaterials. These mineral ellipsoids represent a largely unstudied feature in the organization of bone at the mesoscale, i.e., at a level connecting nano- and microscale. Thorough understanding of their origin, development, and structure can provide valuable insights into bone architecture and mineralization, assisting the treatment of bone diseases and the design of bio-inspired materials.

    Nanomaterials in hair care and treatment

    Pereira-Silva M.Martins A.M.Sousa-Oliveira I.Ribeiro H.M....
    22页
    查看更多>>摘要:? 2022 Acta Materialia Inc.Hair care and treatment has evolved significantly through the years as new formulations are continuously being explored in an attempt to meet the demand in cosmetic and medicinal fields. While standard hair care procedures include hair washing, aimed at hair cleansing and maintenance, as well as hair dyeing and bleaching formulations for hair embellishment, modern hair treatments are mainly focused on circumventing hair loss conditions, strengthening hair follicle properties and treat hair infestations. In this regard, active compounds (ACs) included in hair cosmetic formulations include a vast array of hair cleansing and hair dye molecules, and typical hair treatments include anti-hair loss ACs (e.g. minoxidil and finasteride) and anti-lice ACs (e.g. permethrin). However, several challenges still persist, as conventional AC formulations exhibit sub-optimal performance and some may present toxicity issues, calling for an improved design of formulations regarding both efficacy and safety. More recently, nano-based strategies encompassing nanomaterials have emerged as promising tailored approaches to improve the performance of ACs incorporated into hair cosmetics and treatment formulations. The interest in using these nanomaterials is based on account of their ability to: (1) increase stability, safety and biocompatibility of ACs; (2) maximize hair affinity, contact and retention, acting as versatile biointerfaces; (3) enable the controlled release of ACs in both hair and scalp, serving as prolonged AC reservoirs; besides offering (4) hair follicle targeting features attending to the possibility of surface tunability. This review covers the breakthrough of nanomaterials for hair cosmetics and hair treatment, focusing on organic nanomaterials (polymer-based and lipid-based nanoparticles) and inorganic nanomaterials (nanosheets, nanotubes and inorganic nanoparticles), as well as their applications, highlighting their potential as innovative multifunctional nanomaterials towards maximized hair care and treatment. Statement of significance: This manuscript is focused on reviewing the nanotechnological strategies investigated for hair care and treatment so far. While conventional formulations exhibit sub-optimal performance and some may present toxicity issues, the selection of improved and suitable nanodelivery systems is of utmost relevance to ensure a proper active ingredient release in both hair and scalp, maximize hair affinity, contact and retention, and provide hair follicle targeting features, warranting stability, efficacy and safety. This innovative manuscript highlights the advantages of nanotechnology-based approaches, particularly as tunable and versatile biointerfaces, and their applications as innovative multifunctional nanomaterials towards maximized hair care and treatment.

    Interpenetrating gallol functionalized tissue adhesive hyaluronic acid hydrogel polarizes macrophages to an immunosuppressive phenotype

    Varghese O.P.Harris R.A.Oommen O.P.Samanta S....
    13页
    查看更多>>摘要:? 2022Innovative scaffold designs that modulate the local inflammatory microenvironment through favorable macrophage polarization and suppressing oxidative stress are needed for successful clinical translation of regenerative cell therapies and graft integration. We herein report derivation of a hydrazone-crosslinked gallol functionalized hyaluronic acid (HA-GA)-based hydrogel that displayed outstanding viscoelastic properties and immunomodulatory characteristics. Grafting of 6% gallol (GA) to a HA-backbone formed an interpenetrative network by promoting an additional crosslink between the gallol groups in addition to hydrazone crosslinking. This significantly enhanced the mechanical stability and displayed shear-thinning/self-healing characteristics, facilitated tissue adhesive properties to porcine tissue and also displayed radical scavenging properties, protecting encapsulated fibroblasts from peroxide challenge. The THP-1 human macrophage cell line or primary bone-marrow-derived murine macrophages cultured within HA-GA gels displayed selective polarization to a predominantly anti-inflammatory phenotype by upregulating IL4ra, IL-10, TGF-β, and TGF-βR1 expression when compared with HA-HA gels. Conversely, culturing of pro-inflammatory activated primary murine macrophages in HA-GA gels resulted in a significant reduction of pro-inflammatory TNF-α, IL-1β, SOCS3 and IL-6 marker expression, and upregulated expression of anti-inflammatory cytokines including TGF-β. Finally, when the gels were implanted subcutaneously into healthy mice, we observed infiltration of pro-inflammatory myeloid cells in HA-HA gels, while immunosuppressive phenotypes were observed within the HA-GA gels. Taken together these data suggest that HA-GA gels are an ideal injectable scaffold for viable immunotherapeutic interventions. Statement of significance: Host immune response against the implanted scaffolds that are designed to deliver stem cells or therapeutic proteins in vivo significantly limits the functional outcome. For this reason, we have designed immunomodulatory injectable scaffolds that can favorably polarize the recruited macrophages and impart antioxidant properties to suppress oxidative stress. Specifically, we have tailored a hyaluronic acid-based extracellular matrix mimetic injectable scaffold that is grafted with immunomodulatory gallol moiety. Gallol functionalization of hydrogel not only enhanced the mechanical properties of the scaffold by forming an interpenetrating network but also induced antioxidant properties, tissue adhesive properties, and polarized primary murine macrophages to immunosuppressive phenotype. We believe such immunoresponsive implants will pave the way for developing the next-generation of biomaterials for regenerative medicine applications.

    Bacteria-propelled microtubular motors for efficient penetration and targeting delivery of thrombolytic agents

    Mo C.Cao W.Li S.Zhang Z....
    11页
    查看更多>>摘要:? 2022 Acta Materialia Inc.Effective thrombolysis is critical to rapidly rebuild blood flow for thrombosis patients. Drug delivery systems have been developed to address inadequate pharmacokinetics of thrombolytic agents, but challenges still remain in the timely removal of blood clots regarding the dense fibrin networks. Herein, rod-shaped tubular micromotors were developed to achieve efficient penetration and thorough destruction of thrombi. By using electrospun fiber fragments as the template, urokinase (uPA)-loaded polydopamine (PDA) microtubes with surface decorated fucoidan (FuPDAuPA) were prepared at the aspect ratio of around 2. One E. coli Nissle 1917 (EcN) was assembled into one microtube to construct a FuPDAuPA@EcN hybrid micromotor through PDA adhesion and L-aspartate induction. The pharmacokinetic analysis indicates that the encapsulation of uPA into micromotors extends the half-life from 0.4 to 5.6 h and increases the bioavailability over 10 times. EcN-propelled motion elevates adsorption capacities of FuPDAuPA@EcN for more than four times compared with that of FuPDAuPA. The fucoidan-mediated targeting causes 2-fold higher thrombolysis capacity in vitro and over 10-fold higher uPA accumulation in thrombi in vivo. In the treatment of venous thrombi at mouse hindlimbs, intravenous administration of FuPDAuPA@EcN completely removed blood clots with almost full recovery of blood flows and apparently alleviated tail bleeding. It should be noted that FuPDAuPA@EcN treatment at a reduced uPA dose caused no significant difference in the blood flow rate compared with those of FuPDAuPA. The synergistic action of fucoidan-induced targeting and EcN-driven motion provides a prerequisite for promoting thrombolytic efficacy and reducing uPA dose and bleeding side effect. Statement of significance: The standard treatment to thrombosis patient is intravenous infusion of thrombolytic agents, but the associated bleeding complications and impairment of normal haemostasis greatly offset the therapeutic benefits. Drug delivery systems have been developed to address the limitations of inadequate pharmacokinetics of thrombolytic agents, but challenges still exist in less efficient penetration into dense networks for thorough destruction of thrombi. Up to now only few attempts have been made to construct nano-/micromotors for combating thrombosis and there is no single case that antithrombosis is assisted by bacteria or cells-propelled motors. Herein, bacteria-propelled microtubes were developed to carry urokinase for efficient penetration into blood clots and effective thrombolysis. The synergistic action of bacteria-driven motion and specific ligand-induced targeting holds a promising treatment strategy for life-threatening cardiovascular diseases such as thrombosis and atherosclerosis.

    Spatially arranged encapsulation of stem cell spheroids within hydrogels for the regulation of spheroid fusion and cell migration

    Kim S.-J.Byun H.Lee S.Kim E....
    13页
    查看更多>>摘要:? 2022Mesenchymal stem cell spheroids have been encapsulated in hydrogels for various applications because spheroids demonstrate higher cell activity than individual cells in suspension. However, there is limited information on the effect of distance between spheroids (inter-spheroid distance) on fusion or migration in a hydrogel. In this study, we developed temperature-responsive hydrogels with surface microwell patterns to culture adipose-derived stem cell (ASC) spheroids and deliver them into a Matrigel for the investigation of the effect of inter-spheroid distance on spheroid behavior. The ASC spheroids were encapsulated successfully in a Matrigel, denoted as sandwich culture, with a specific inter-spheroid distance ranging from 100 to 400 μm. Interestingly, ASCs migrated from the host spheroid and formed a bridge-like structure between spheroids, denoted as a cellular bridge, only when the inter-spheroid distance was 200 μm. Thus, we performed a sandwich culture of human umbilical vein endothelial cells (HUVECs) and ASCs in co-cultured spheroids in the Matrigel to create a homogeneous endothelial cell network in the hydrogel. The HUVECs sprouted through the ASC cellular bridge and directly interacted with the adjacent spheroid when the inter-spheroid distance was 200 μm. Similar results were obtained from an in vivo study. Thus, our study suggests the appropriate inter-spheroid distance for effective spheroid encapsulation in a hydrogel. Statement of significance: Recently, spheroid-based 3D tissue culture techniques such as spheroid encapsulation or 3D printing are being intensively investigated for various purposes. However, there is limited research regarding the effect of the inter-spheroid distance on spheroid communication. Here, we demonstrate a spatially arranged spheroid encapsulation method within a Matrigel by using a temperature-responsive hydrogel. Human adipose-derived stem cell spheroids are encapsulated with a precisely controlled inter-spheroid distance from 100 to 400 μm and show different tendencies in cell migration and spheroid fusion. Our results suggest that the inter-spheroid distance affects spheroid communication, and thus, the inter-spheroid distance needs to be considered carefully according to the purpose.

    Design of an elastic porous injectable biomaterial for tissue regeneration and volume retention

    Beduer A.Genta M.Kunz N.Verheyen C....
    12页
    查看更多>>摘要:? 2022 The AuthorsSoft tissue reconstruction currently relies on two main approaches, one involving the implantation of external biomaterials and the second one exploiting surgical autologous tissue displacement. While both methods have different advantages and disadvantages, successful long-term solutions for soft tissue repair are still limited. Specifically, volume retention over time and local tissue regeneration are the main challenges in the field. In this study the performance of a recently developed elastic porous injectable (EPI) biomaterial based on crosslinked carboxymethylcellulose is analyzed. Nearly quantitative volumetric stability, with over 90% volume retention at 6 months, is observed, and the pore space of the material is effectively colonized with autologous fibrovascular tissue. A comparative analysis with hyaluronic acid and collagen-based clinical reference materials is also performed. Mechanical stability, evidenced by a low-strain elastic storage modulus (G’) approaching 1kPa and a yield strain of several tens of percent, is required for volume retention in-vivo. Macroporosity, along with in-vivo persistence of at least several months, is instead needed for successful host tissue colonization. This study demonstrates the importance of understanding material design criteria and defines the biomaterial requirements for volume retention and tissue colonization in soft tissue regeneration. Statement of significance: We present the design of an elastic, porous, injectable (EPI) scaffold suspension capable of inducing a precisely defined, stable volume of autologous connective tissue in situ. It combines volume stability and vascularized tissue induction capacity known from bulk scaffolds with the ease of injection in shear yielding materials. By comparative study with a series of clinically established biomaterials including a wound healing matrix and dermal fillers, we establish design rules regarding rheological and compressive mechanical properties as well as degradation characteristics that rationally underpin the volume stability and tissue induction in a high-performance biomaterial. These design rules should allow to streamline the development of new colonizable injectables.

    Endothelialized microvessels fabricated by microfluidics facilitate osteogenic differentiation and promote bone repair

    Wang J.Wang H.Wang Y.Liu Z....
    14页
    查看更多>>摘要:? 2022In bone tissue engineering, vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. While various approaches have been tried to build vascular networks in bone grafts, lack of endothelialization still constitutes a major technical hurdle. In this study, we have developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. BMVs with different sizes could be readily prepared by adjusting the flow rate of microfluids. All BMVs supported perfusion and outward penetration of substances in the tube. Endothelial cells could adhere and proliferate on the inner wall of tubes. It was also found that the expression of CD31 and secretion of BMP-2 and PDGF-BB were higher in the rat umbilical vein endothelial cells (RUVECs) in BMVs than those cultured on hydrogel. When co-cultured with bone marrow mesenchymal stem cells (BMSCs), endothelialized BMVs promoted the osteogenic differentiation of BMSCs compared to those in acellular BMV group. In vivo, markedly enhanced new bone formation was achieved by endothelialized BMVs in a rat critical-sized calvarial defect model compared to those with non-endothelialized BMVs or without BMVs. Together, findings from both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering. Statement of significance: In bone tissue engineering, limited vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. In this study, we developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. Both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering.

    Core fucosylation involvement in the paracrine regulation of proteinuria-induced renal interstitial fibrosis evaluated with the use of a microfluidic chip

    Wang X.Hu X.Deng Y.Wen X....
    14页
    查看更多>>摘要:? 2022Proteinuria is a clinical manifestation of chronic kidney disease that aggravates renal interstitial fibrosis (RIF), in which injury of peritubular microvessels is an important event. However, the changes in peritubular microvessels induced by proteinuria and their molecular mechanisms remain unclear. Thus, we aimed to develop a co-culture microfluidic device that contains renal tubules and peritubular microvessels to create a proteinuria model. We found that protein overload in the renal tubule induced trans-differentiation and apoptosis of endothelial cells (ECs) and pericytes. Moreover, profiling of secreted proteins in this model revealed that a paracrine network between tubules and microvessels was activated in proteinuria-induced microvascular injury. Multiple cytokine receptors in this paracrine network were core-fucosylated. Inhibition of core fucosylation significantly reduced ligand-receptor binding ability and blocked downstream pathways, alleviating trans-differentiation and apoptosis of ECs and pericytes. Furthermore, the protective effect of genetic FUT8 deficiency on proteinuria overload-induced RIF and pericyte-myofibroblast trans-differentiation was validated in FUT8 knockout heterozygous mice. In conclusion, we constructed and used a multiple-unit integrated microfluidic device to uncover the mechanism of proteinuria-induced RIF. Furthermore, FUT8 may serve as a hub-like therapeutic target to alleviate peritubular microvascular injury in RIF. Statement of significance: In this study, we constructed a multiple-unit integrated renal tubule-vascular chip. We reproduced human proteinuria on the chip and found that multiple receptors were modified by FUT8-catalyzed core fucosylation (CF) involved in the cross-talk between renal tubules and peritubular microvessels in proteinuria-induced RIF, and inhibiting the FUT8 of receptors could block the tubule-microvessel paracrine network and reverse the damage of peritubular microvessels and renal interstitial fibrosis. This tubule-vascular chip may provide a prospective platform to facilitate future investigations into the mechanisms of kidney diseases, and target-FUT8 inhibition may be an innovative and potential therapeutic strategy for RIF induced by proteinuria.

    Titanium carbide MXene-based hybrid hydrogel for chemo-photothermal combinational treatment of localized bacterial infection

    Zheng Y.Yan Y.Lin L.He Q....
    11页
    查看更多>>摘要:? 2022With the increased emergence and threat of multi-drug resistant microorganisms, MXenes have become not only an emerging class of two-dimensional functional nanomaterials, but also potential nanomedicines (i.e., antimicrobial agents) that deserve further exploration. Very recently, Ti3C2 MXene was observed to offer a unique membrane-disruption effect and superior light-to-heat conversion efficiency, but its antibacterial property remains unsatisfactory due to poor MXene-bacteria interactions, low photothermal therapy efficiency, and occurrence of bacterial rebound in vivo. Herein, the cationic antibiotic ciprofloxacin (Cip) is combined with Ti3C2 MXene, and a hybrid hydrogel was constructed by incorporating Cip-Ti3C2 nanocomposites into the network structure of a Cip-loaded hydrogels to effectively trap and kill bacteria. We found that the Cip-Ti3C2 nanocomposites achieved an impressive in vitro bactericidal efficiency of >99.99999% (7.03 log10) for the inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by combining chemotherapy with photothermal therapy. In an MRSA-induced murine abscess model, the hybrid hydrogel simultaneously achieved high-efficiency sterilization and long-term inhibition effects, avoiding the rebound of bacteria after photothermal therapy, and thus maximized the in vivo therapeutic efficacy of Ti3C2 MXene-based systems. Overall, this work provides a strategy for efficiently combating localized bacterial infection by rationally designing MXene-based hybrid hydrogels. Statement of significance: Two-dimensional Ti3C2 MXene was recently regarded as a promising functional nanomaterial, however, its antibacterial applications are limited by the poor MXene-bacteria interactions, low photothermal therapy efficiency, and the occurrence of bacterial rebound in vivo. This work aims to construct a Ti3C2 MXene-based hybrid hydrogel for chemo-photothermal therapy and enhance the antimicrobial performance via a combination of the high-efficiency sterilization of ciprofloxacin-Ti3C2 nanocomposites with the long-term inhibition effect of ciprofloxacin hydrogel. The present study provides an example of efficient MXene-based antimicrobials to treat localized bacterial infection such as methicillin-resistant Staphylococcus aureus (MRSA)-induced skin abscess.

    Ionic interaction-driven switchable bactericidal surfaces

    Zheng S.Y.Ni Y.Zhang D.Wang S....
    12页
    查看更多>>摘要:? 2022 Elsevier LtdBacteria in the external environment inevitably invade the wound and subsequently colonize the wound surface during surgery and biomedical operations, which slows down the process of wound healing and tissue repair; this poses a significant threat to human health. Therefore, the development of an intelligent antibacterial surface has become the focus of research in the field of antimicrobial strategies, which has important social and economic significance. Here, we present a simple approach of producing an ionic interaction-driven anionic activation substratum which is then functionalized with cationic molecules through coulombic interactional immobilization. The switchable multifunctional antibacterial surface can decrease bacterial attachment and inactivate the attached microorganisms, thus overcoming the conventional challenge for antibacterial surfaces. Briefly, poly (3-sulfopropyl methacrylate potassium salt) (PSPMA) brushes were constructed by surface-initiated atom transfer radical polymerization on silicon or cotton fabric substrates, and a positive-charged component, namely lysozyme (LYZ), hexadecyl trimethyl ammonium bromide (CTAB) or chitosan (CS), was loaded on negative-charged sulfonate groups through electrostatic interactions. The resultant brush-grafted surfaces exhibited more than ~95.5% bactericidal efficacy and ~92.8% release rate after the introduction of an adequate amount of contra-ions (1.0 M; Na+ & Cl?) against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, thus achieving a regenerated surface through the cyclic process of “assembly-dissociation”. Smart cotton fabric (Fabric-PSPMA/LYZ and Fabric-PSPMA/CS) surfaces were constructed, which were found to promote wound epidermal tissue regeneration with a higher efficiency after 7-day in vivo studies. This ionic interaction-driven method used in the present work is simple and can reversibly renew antibacterial surfaces, which will help in the wider utilization of switchable antibacterial materials with a more ecologic and economic significance. Statement of significance: Smart antibacterial surfaces with renewable characteristics have attracted considerable interests over the past few years. Here, we used ionic interaction-driven force to manipulate dynamic conformational changes in PSPMA surface brushes, accompanied by highly switchable bacteria killing and bacteria releasing behaviors. Different cationic molecules were also designed for assembly/dissociation on the PSPMA-modified surfaces, and the essential parameters, including chemical structures, molecular weight, and cationic charge density, were investigated. With the refined structural combinations and the balance of bacteria killing/bacteria releasing behaviors, smart cotton fabrics (e.g., Fabric-PSPMA/lysozyme and Fabric-PSPMA/chitosan) were designed that could promote wound healing and tissue repair. These results contribute to the fundamental understanding of a switchable cationic-anionic pair design and the corresponding practical, renewable, highly antibacterial fabric.