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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    Concepts and clinical aspects of active implants for the treatment of bone fractures

    Braun, Benedikt J.Pohlemann, TimGanse, BergitaOrth, Marcel...
    9页
    查看更多>>摘要:Nonunion is a complication of long bone fractures that leads to disability, morbidity and high costs. Early detection is difficult and treatment through external stimulation and revision surgery is often a lengthy process. Therefore, alternative diagnostic and therapeutic options are currently being explored, including the use of external and internal sensors. Apart from monitoring fracture stiffness and displacement directly at the fracture site, it would be desirable if an implant could also vary its stiffness and apply an intervention to promote healing, if needed. This could be achieved either by a predetermined protocol, by remote control, or even by processing data and triggering the intervention itself (self-regulated 'intelligent' or 'smart' implant). So-called active or smart materials like shape memory alloys (SMA) have opened up opportunities to build active implants. For example, implants could stimulate fracture healing by active shortening and lengthening via SMA actuator wires; by emitting pulses, waves, or electromagnetic fields. However, it remains undefined which modes of application, forces, frequencies, force directions, time durations and periods, or other stimuli such implants should ideally deliver for the best result. The present paper reviews the literature on active implants and interventions for nonunion, discusses possible mechanisms of active implants and points out where further research and development are needed to build an active implant that applies the most ideal intervention.

    The interactions between DNA nanostructures and cells: A critical overview from a cell biology perspective

    Frtus, AdamSmolkova, BarboraUzhytchak, MariiaLunova, Mariia...
    13页
    查看更多>>摘要:DNA nanotechnology has yielded remarkable advances in composite materials with diverse applications in biomedicine. The specificity and predictability of building 3D structures at the nanometer scale make DNA nanotechnology a promising tool for uses in biosensing, drug delivery, cell modulation, and bioimag-ing. However, for successful translation of DNA nanostructures to real-world applications, it is crucial to understand how they interact with living cells, and the consequences of such interactions. In this review, we summarize the current state of knowledge on the interactions of DNA nanostructures with cells. We identify key challenges, from a cell biology perspective, that influence progress towards the clinical trans -lation of DNA nanostructures. We close by providing an outlook on what questions must be addressed to accelerate the clinical translation of DNA nanostructures.Statement of significance Self-assembled DNA nanostructures (DNs) offers unique opportunities to overcome persistent challenges in the nanobiotechnology field. However, the interactions between engineered DNs and living cells are still not well defined. Critical systematization of current cellular models and biological responses trig-gered by DNs is a crucial foundation for the successful clinical translation of DNA nanostructures. More -over, such an analysis will identify the pitfalls and challenges that are present in the field, and provide a basis for overcoming those challenges. (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

    Patient-derived Tumour Organoids: A Bridge between Cancer Biology and Personalised Therapy

    Wu, WenceLi, XiaoyangYu, Shengji
    14页
    查看更多>>摘要:Patient-derived tumour organoids (PDOs) have revolutionised our understanding of cancer biology and the applications of personalised therapies. These advancements are principally ascribed to the ability of PDOs to consistently recapitulate and maintain the genomic, proteomic and morphological characteristics of parental tumours. Given these characteristics, PDOs (and their extended biobanks) are a representative preclinical model eminently suited to translate relevant scientific findings into personalized therapies rapidly. Here, we summarise recent advancements in PDOs from the perspective of cancer biology and clinical applications, focusing on the current challenges and opportunities of reconstructing and standar-dising more sophisticated PDO models.Statement of Significance Patient-derived tumour organoids (PDOs), three-dimensional (3D) self-assembled organotypic structures, have revolutionised our understanding of cancer biology and the applications of personalised therapies. These advancements are principally ascribed to the ability of PDOs to consistently recapitulate and main-tain the genomic, proteomic and morphological characteristics of parental tumours. Given these charac-teristics, PDOs (and their extended biobanks) are a representative preclinical model eminently suited to translate relevant scientific findings into personalized therapies rapidly. (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

    ZIF-8 modified multifunctional injectable photopolymerizable GelMA hydrogel for the treatment of periodontitis

    Cheng, ZhiqiangJia, WenyuanJiao, KunWang, Shaoru...
    12页
    查看更多>>摘要:Periodontitis is a chronic inflammatory disease caused by plaque that leads to alveolar bone resorption. In the treatment of periodontitis, it is necessary to reduce the bacterial load and promote alveolar bone regeneration. In this study, zeolitic imidazolate framework-8 (ZIF-8) is used in the treatment of periodontitis, and an injectable photopolymerizable ZIF-8/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z) is constructed. We confirm that ZIF-8 nanoparticles are successfully loaded into GelMA, which demonstrates fluidity and photopolymerizability. GelMA-Z continuously releases Zn2+ and shows good cytocompatibility. In vitro, GelMA-Z can effectively upregulate the expression of osteogenesis-related genes and proteins, increase alkaline phosphatase activity, promote extracellular matrix mineralization by rat bone mesenchymal stem cells, and exert an obvious antibacterial effect against Porphyromonas gingivalis. In vivo, GelMA-Z reduces the bacterial load, relieves inflammation and promotes alveolar bone regeneration in a rat model. The above results show that GelMA-Z has potential prospects in the treatment of periodontitis. Statement of significance Various methods have been explored for the treatment of periodontitis. However, current regiments have difficulty achieving ideal alveolar bone regeneration. In this study, we constructed a zeolitic imidazolate framework-8 (ZIF-8)/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z). (1) The injectable and photopolymerizable GelMA-Z showed biocompatibility in vitro and in vivo. (2) GelMA-Z continually released zinc ions to promote the osteogenic differentiation of bone mesenchymal stem cells and kill bacteria in vitro. (3) In a rat model, the GelMA-Z pregel solution was used to fill the periodontal pocket and then crosslinked by UV exposure. GelMA-Z can stably remain in the periodontal pocket to reduce the bacterial load, relieve inflammation and promote alveolar bone regeneration. In conclusion, GelMA-Z has great potential for use in the treatment of periodontitis, especially in promoting alveolar bone regeneration. (C) 2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc.

    An all-in-one CO gas therapy-based hydrogel dressing with sustained insulin release, anti-oxidative stress, antibacterial, and anti-inflammatory capabilities for infected diabetic wounds

    Chen, JunpengChen, DongfanChen, JialeShen, Tianxi...
    17页
    查看更多>>摘要:To effectively treat diabetic wounds, the development of versatile medical dressings that can long-term regulate blood glucose and highly effective anti-oxidative stress, antibacterial and anti-inflammatory are critical. Here, an all-in-one CO gas-therapy-based versatile hydrogel dressing (ICOQF) was developed via the dynamic Schiff base reaction between the amino groups on quaternized chitosan (QCS) and the aldehyde groups on benzaldehyde-terminated F108 (F108-CHO) micelles. CORM-401 (an oxidant-sensitive COreleasing molecules) was encapsulated in the hydrophobic core of F108-CHO micelles and insulin was loaded in the three-dimensional network structure of ICOQF. The dynamic Schiff base bonds not only endowed ICOQF with good tissue adhesion, injectability and self-healing, but also gave it sustained and controllable insulin release ability. In addition, ICOQF could quickly generate CO in inflamed wound tissue by consuming reactive oxygen species. The generated CO could effectively anti-oxidative stress by activating the expression of heme oxygenase; antibacterial by inducing the rupture of bacterial cell membranes and mitochondrial dysfunction and inhibiting the synthesis of adenosine triphosphate; and anti-inflammatory by inhibiting the proliferation of activated macrophages and promoting the polarization of the M1 phenotype to the M2 phenotype. Due to these outstanding properties, ICOQF significantly promoted the healing of STZ-induced MRSA -infected diabetic wounds accompanied by good biocompatibility. This study clearly shows that ICOQF is a versatile hydrogel dressing with great application potential for the management of diabetic wounds.

    Designer self-assembling peptide nanofibers induce biomineralization of lidocaine for slow-release and prolonged analgesia

    Gong, DeyingHe, LiuZhang, WenshengQiu, Feng...
    14页
    查看更多>>摘要:The burst release of small molecular water-soluble drugs is a major problem when pursuing their long-acting formulations. Although various types of carrier materials have been developed for tackling this problem, it is still a big challenge to prevent water-soluble small molecules from fast release and diffu-sion. In this study, a biomineralization strategy based upon a self-assembling peptide is proposed for the slow release of lidocaine, a classic anesthetic with high solubility and a very small molecular weight. A bolaamphiphilic peptide was designed to self-assemble and produce negatively charged nanofibers, which were used as the template to absorb positively charged lidocaine molecules through an electrostatic in-teraction. The biomineralization of lidocaine was then induced by adjusting the pH, which lead to the formation of lidocaine microcrystals with a homogenous size. The microcrystals were incorporated into a hyaluronic acid hydrogel to form an injectable formulation. This formulation slowly released lidocaine and generate a prolonged anesthetic and analgesic effect in rodent models. Due to the constrained local and plasma lidocaine concentration, as well as the biocompatibility and biodegradability of the peptide materials, this formulation also showed considerable safety. These results suggest that nanofiber assisted biomineralization can provide a potential strategy for the fabrication of long-acting formulations for small molecular water-soluble drugs.Statement of significance Long-acting formulations are highly pursued to achieve stronger therapeutic effect, or to avoid repeated administration of drugs, especially through painful injection. Using carrier materials to slow down the release of bioactive molecules is a common strategy to reach this goal. However, for many water-soluble small molecular drugs currently used in clinic, it is notoriously difficult to slow down their release and diffusion. This study proposes a novel strategy based on a controllable mineralization process using self-assembling peptide nanofibers as the template. Taking lidocaine as an example, we showed how peptide-drug microcrystals with well-controlled size and shape could be obtained, which exhibit significantly prolonged anesthetic and analgesic effect. As a proof-of-concept study, this work proposes a promising strategy to control the release of water-soluble small molecular drugs. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

    Hotmelt tissue adhesive with supramolecularly-controlled sol-gel transition for preventing postoperative abdominal adhesion

    Nishiguchi, AkihiroIchimaru, HiroakiIto, ShimaNagasaka, Kazuhiro...
    14页
    查看更多>>摘要:Postoperative adhesion is a serious and frequent complication, but there is currently no reliable anti adhesive barrier available due to low tissue adhesiveness, undesirable chemical reactions, and poor operability. To overcome these problems, we report a single-syringe hotmelt tissue adhesive that dissolves upon warming over 40 degrees C and coheres at 37 degrees C as a postoperative barrier. Tendon-derived gelatin was conjugated with the ureidopyrimidinone unit to supramolecularly control the sol-gel transition behavior. This functionalization improved bulk mechanical strength, tissue-adhesive properties, and stability under physiological conditions through the augmentation of intermolecular hydrogen bonding by ureidopyrimidinone unit. This biocompatible adhesive prevented postoperative adhesion between cecum and abdominal wall in adhesion models of rats. This hotmelt tissue adhesive has enormous potential to prevent postoperative complications and may contribute to minimally invasive surgery.Statement of significance There is a strong need to develop medical tissue adhesives with high biocompatibility, tissue adhesiveness, and operatability to prevent postoperative complications. In this report, single syringe, hotmelt-type tissue adhesive was developed by controlling sol-gel transition behavior of gelatin through supramolecular approach. The functionalization of gelatin with quadruple hydrogen bonding improved key features necessary for anti-adhesive barrier including bulk mechanical strength, tissue adhesive property, stability under physiological conditions, and anti-adhesive property. The hotmelt tissue adhesive can be used for a sealant, hemostatic reagent, and wound dressing to prevent postoperative complications including delayed bleeding, perforation, and inflammation and contribute to minimally invasive surgery. (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

    Articular cartilage reconstruction with TGF-? 1-simulating self-assembling peptide hydrogel-based composite scaffold

    Ye, WeilongYang, ZhenCao, FuyangLi, Hao...
    13页
    查看更多>>摘要:Transforming growth factor- fi (TGF- fi) is an important inducing factor for the differentiation of mesenchymal stem cells and the secretion of collagen II, but the inaccessibility and instability limit its application in clinical practice. In this study, the TGF- fi1-simulating peptide LIANAK (CM) was connected with the self-assembling peptide Ac-(RADA) 4 -CONH 2 (RAD) to obtain the functionalized self-assembling peptide Ac-(RADA) 4 -GG-LIANAK-CONH 2 (RAD-CM). The results indicated that the CM-functionalized RAD hydrogel contributed to the enhanced expressions of chondrogenic genes and extracellular matrix deposition. The self-assembling peptides were then combined with decellularized cartilage extracellular matrix (DCM) to construct a composite scaffold for articular cartilage repair. The CM-functionalized composite scaffold RAD/RAD-CM/DCM (R/C/D) exhibited good bioactivity and structural stability and exhibited satisfactory performance in promoting neocartilage restoration and the reconstruction of the osteochondral unit. This study provides a promising strategy for in situ cartilage regeneration via the stable presentation of TGF- fi1-simulating peptide.

    An injectable and biodegradable hydrogel incorporated with photoregulated NO generators to heal MRSA-infected wounds

    Hu, YanlingWang, WenjunCai, YuTu, Yuexing...
    12页
    查看更多>>摘要:The development of degradable hydrogel fillers with high antibacterial activity and wound-healing property is urgently needed for the treatment of infected wounds. Herein, an injectable, degradable, photoactivated antibacterial hydrogel (MPDA-BNN6@Gel) was developed by incorporating BNN6-loaded mesoporous polydopamine nanoparticles (MPDA-BNN6 NPs) into a fibrin-based hydrogel. After administration, MPDA-BNN6@Gel created local hyperthermia and released large quantities of NO gas to treat methicillinresistant Staphylococcus aureus infection under the stimulation of an 808 nm laser. Experiments confirmed that the bacteria were eradicated through irreversible damage to the cell membrane, genetic metabolism, and material energy. Furthermore, in the absence of laser irradition, the fibrin and small amount of NO that originated from MPDA-BNN6@Gel promoted wound healing in vivo . This work indicates that MPDABNN6@Gel is a promising alternative for the treatment of infected wounds and provides a facile tactic to design a photoregulated bactericidal hydrogel for accelerating infected wound healing.Statement of Significance The development of a degradable hydrogel with high antibacterial activity and wound-healing property is an urgent need for the treatment of infected wounds. Herein, an injectable, degradable, and photo activated antibacterial hydrogel (MPDA-BNN6@Gel) has been developed by incorporating BNN6-loaded mesoporous polydopamine nanoparticles (MPDA-BNN6 NPs) into a fibrin-based hydrogel. After administration of MPDA-BNN6@Gel, the MPDA-BNN6@Gel could generate local hyperthermia and release large quantities of NO gas to treat the methicillin-resistant Staphylococcus aureus infection under the irradiation of 808 nm laser. Furthermore, in the absence of a laser, the fibrin and a small amount of NO originating from MPDA-BNN6@Gel could promote wound healing in vivo . (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

    Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing

    Chen, JueyingHe, JiahuiYang, YutongQiao, Lipeng...
    12页
    查看更多>>摘要:The development of compressible, stretchable and self-healing hydrogel dressings with good adhesive, antibacterial and angiogenesis properties is needed to promote the regeneration of diabetic wounds in clinical applications. In this work, a series of self-healing, adhesive and antibacterial hydrogels based on gelatin methacrylate (GelMA), adenine acrylate (AA), and CuCl2 were designed through covalent bonding, coordination complexation of Cu2+ and carboxyl groups and hydrogen bonding to promote diabetic wound healing. These hydrogels exhibit efficient self-healing properties, remarkable fatigue resistance, and good adhesive properties due to the hydrogen bond and the metal-ligand coordination provided by the Cu2+ and the carboxyl group. The GelMA/AA/Cu1.0 hydrogel (containing 1.0 mg/mL Cu2+) with well-balanced biocompatibility and antibacterial properties exhibited efficient hemostatic performance in a mouse liver trauma model and significantly promoted the healing process in a full-thickness skin diabetic wound model. The immunohistochemistry results showed that the GelMA/AA/Cu1.0 hydrogel can promote regular epithelialization and collagen deposition when compared to the Tegaderm (TM) Film, GelMA hydrogel, and GelMA/AA/Cu0 hydrogel. The immunofluorescence results confirmed that the GelMA/AA/Cu1.0 hydrogel can reduce the expression of proinflammatory factors and promote angiogenesis. In conclusion, the GelMA/AA/Cu hydrogel is an effective wound dressing to promote the healing process of diabetic skin wounds. Statement of significance Diabetic wounds exhibit an extremely high risk of bacterial infection and poor angiogenesis in a high-sugar environment, hindering their healing process. Hydrogel wound dressings are a promising wound care material that need to have stable and long-lasting adhesive properties, avoid shedding, provide lasting protection to wounds, antibacterial properties and promote angiogenesis. In this study, a series of self-healing, adhesive, and antibacterial hydrogels based on gelatin methacrylate (GelMA), acrylated adenine (AA), and CuCl2 were designed and synthesized via free radical polymerization, hydrogen bond, and ionic bond to promote diabetic wound healing. Overall, GelMA/AA/Cu hydrogels are promising materials to promote diabetic wound healing. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.