首页期刊导航|Acta biomaterialia
期刊信息/Journal information
Acta biomaterialia
Elsevier
Acta biomaterialia

Elsevier

1742-7061

Acta biomaterialia/Journal Acta biomaterialiaEIISTPSCI
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    Embedded bioprinting for designer 3D tissue constructs with complex structural organization

    Zeng X.Meng Z.He J.Mao M....
    22页
    查看更多>>摘要:? 2021 Acta Materialia Inc.3D bioprinting has been developed as an effective and powerful technique for the fabrication of living tissue constructs in a well-controlled manner. However, most existing 3D bioprinting strategies face substantial challenges in replicating delicate and intricate tissue-specific structural organizations using mechanically weak biomaterials such as hydrogels. Embedded bioprinting is an emerging bioprinting strategy that can directly fabricate complex structures derived from soft biomaterials within a supporting matrix, which shows great promise in printing large vascularized tissues and organs. Here, we provide a state-of-the-art review on the development of embedded bioprinting including extrusion-based and light-based processes to manufacture complex tissue constructs with biomimetic architectures. The working principles, bioinks, and supporting matrices of embedded printing processes are introduced. The effect of key processing parameters on the printing resolution, shape fidelity, and biological functions of the printed tissue constructs are discussed. Recent innovations in the processes and applications of embedded bioprinting are highlighted, such as light-based volumetric bioprinting and printing of functional vascularized organ constructs. Challenges and future perspectives with regard to translating embedded bioprinting into an effective strategy for the fabrication of functional biological constructs with biomimetic structural organizations are finally discussed. Statement of significance: It is still challenging to replicate delicate and intricate tissue-specific structural organizations using mechanically-weak hydrogels for the fabrication of functional living tissue constructs. Embedded bioprinting is an emerging 3D printing strategy that enables to produce complex tissue structures directly inside a reservoir filled with supporting matrix, which largely widens the choice of bioprinting inks to ECM-like hydrogels. Here we aim to provide a comprehensive review on various embedded bioprinting techniques mainly including extrusion-based and light-based processes. Various bioinks, supporting matrices, key processing parameters as well as their effects on the structures and biological functions of resultant living tissue constructs are discussed. We expect that it can provide an important reference and generate new insights for the bioprinting of large vascularized tissues and organs with biological functions.

    The immune microenvironment in cartilage injury and repair

    Li H.Wu J.Wang Y.Tian G....
    20页
    查看更多>>摘要:? 2021 The Author(s)The ability of articular cartilage to repair itself is limited because it lacks blood vessels, nerves, and lymph tissue. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. To date, complete regeneration of hyaline cartilage exhibiting mechanical properties remains an elusive goal, despite the many available technologies. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, mesenchymal stem cells (MSCs) undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, thereby resulting in fibrocartilage with poor mechanical qualities. All these factors suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage repair, multi-dimensional management of the joint inflammatory microenvironment in place and time is required. Therefore, this calls for elucidation of the immune microenvironment of cartilage repair after injury. This review provides a brief overview of: (1) the pathogenesis of cartilage injury; (2) immune cells in cartilage injury and repair; (3) effects of inflammatory cytokines on cartilage repair; (4) clinical strategies for treating cartilage defects; and (5) strategies for targeted immunoregulation in cartilage repair. Statement of Significance: Immune response is increasingly considered the key factor affecting cartilage repair. It has both negative and positive regulatory effects on the process of regeneration and repair. Proinflammatory factors are secreted in large numbers, and necrotic cartilage is removed. During the repair period, immune cells can secrete anti-inflammatory factors and chondrogenic cytokines, which can inhibit inflammation and promote cartilage repair. However, inflammatory factors persist, which accelerate the degradation of the cartilage matrix. Furthermore, in an inflammatory microenvironment, MSCs undergo abnormal differentiation, and chondrocytes begin to transform or dedifferentiate into fibroblast-like cells, forming fibrocartilage with poor mechanical properties. Consequently, cartilage regeneration requires multi-dimensional regulation of the joint inflammatory microenvironment in space and time to make it conducive to cartilage regeneration.

    Biomaterials via peptide assembly: Design, characterization, and application in tissue engineering

    Gray V.P.Amelung C.D.Duti I.J.Laudermilch E.G....
    33页
    查看更多>>摘要:? 2021A core challenge in biomaterials, with both fundamental significance and technological relevance, concerns the rational design of bioactive microenvironments. Designed properly, peptides can undergo supramolecular assembly into dynamic, physical hydrogels that mimic the mechanical, topological, and biochemical features of native tissue microenvironments. The relatively facile, inexpensive, and automatable preparation of peptides, coupled with low batch-to-batch variability, motivates the expanded use of assembling peptide hydrogels for biomedical applications. Integral to realizing dynamic peptide assemblies as functional biomaterials for tissue engineering is an understanding of the molecular and macroscopic features that govern assembly, morphology, and biological interactions. In this review, we first discuss the design of assembling peptides, including primary structure (sequence), secondary structure (e.g., α-helix and β-sheets), and molecular interactions that facilitate assembly into multiscale materials with desired properties. Next, we describe characterization tools for elucidating molecular structure and interactions, morphology, bulk properties, and biological functionality. Understanding of these characterization methods enables researchers to access a variety of approaches in this ever-expanding field. Finally, we discuss the biological properties and applications of peptide-based biomaterials for engineering several important tissues. By connecting molecular features and mechanisms of assembling peptides to the material and biological properties, we aim to guide the design and characterization of peptide-based biomaterials for tissue engineering and regenerative medicine. Statement of significance: Engineering peptide-based biomaterials that mimic the topological and mechanical properties of natural extracellular matrices provide excellent opportunities to direct cell behavior for regenerative medicine and tissue engineering. Here we review the molecular-scale features of assembling peptides that result in biomaterials that exhibit a variety of relevant extracellular matrix-mimetic properties and promote beneficial cell-biomaterial interactions. Aiming to inspire and guide researchers approaching this challenge from both the peptide biomaterial design and tissue engineering perspectives, we also present characterization tools for understanding the connection between peptide structure and properties and highlight the use of peptide-based biomaterials in neural, orthopedic, cardiac, muscular, and immune engineering applications.

    Physicochemical properties of nanoparticles affecting their fate and the physiological function of pulmonary surfactants

    Liu Q.Guan J.Song R.Zhang X....
    12页
    查看更多>>摘要:? 2021Pulmonary drug delivery has drawn great attention due to its targeted local lung action, reduced side effects, and ease of administration. However, inhaled nanoparticles (NPs) could adsorb different pulmonary surfactants depending on their physicochemical properties, which may impair the physiological function of the pulmonary surfactants or alter the fate of the NPs. Thus, the objective of this review is to summarize how the physicochemical properties of NPs affecting the physiological function of pulmonary surfactants and their fate. First of all, the composition and characteristics of pulmonary surfactants, methods for studying pulmonary surfactant interaction with NPs are introduced. Thereafter, the influence of physicochemical properties of NPs on hydrophobic protein adsorption and strategies to decrease the interaction of NPs with pulmonary surfactants are discussed. Finally, the influence of physicochemical properties of NPs on lipids and hydrophilic protein adsorption and consequently their fate is described. In conclusion, a better understanding of the interaction of NPs with pulmonary surfactants will promote the faster development of safe and effective nanomedicine for pulmonary drug delivery. Statement of significance: Drug delivery carriers often face complex body fluid components after entering the human body. Pulmonary surfactants diffuse at the lung gas-liquid interface, and particles inevitably interact with pulmonary surfactants after pulmonary nanomedicine delivery. This review presents an overview of how the physicochemical properties of nanoparticles affecting their fate and physiological function of pulmonary surfactants. We believe that the information included in this review can provide important guiding for the development of safe and effective pulmonary delivery nanocarriers.

    Bioactive injectable hydrogels for on demand molecule/cell delivery and for tissue regeneration in the central nervous system

    Grimaudo M.A.Krishnakumar G.S.Giusto E.Furlani F....
    14页
    查看更多>>摘要:? 2021Currently there are no potential curative therapies that can improve the central nervous system (CNS) regeneration after traumatic injuries or diseases. Indeed, the regeneration of CNS is greatly impaired by limited drug penetration across the blood brain barrier (BBB), poor drug targeting, deficient progenitor neural cells and limited proliferation of mature neural cells. To overcome these limitations, bioengineered injectable hydrogels in combination with drug and cell therapy have been proposed to mimic the complexity of the CNS microenvironment and architecture. Additionally, to enhance relevant CNS regeneration, proper biophysical and biochemical cues are needed. Recently, great efforts have been devoted to tailor stimuli-responsive hydrogels as novel carrier systems which are able to guide neural tissue regeneration. This review provides an extensive overview on the most promising injectable hydrogels for neural tissue engineering. A special emphasis is made to highlight the ability of these hydrogels to deliver bioactive compounds/cells upon the exposure to internal and external stimuli. Bioactive injectable hydrogels have a broad application in central nervous system's (CNS) regeneration. This review gives an overview of the latest pioneering approaches in CNS recovery using stimuli-responsive hydrogels for several neurodegenerative disorders. Statement of significance: This review summarizes the latest innovations on bioactive injectable hydrogels, focusing on tailoring internal/external stimuli-responsive hydrogels for the new injectable systems design, able to guide neural tissue response. The purpose is to highlight the advantages and the limitations of thermo-responsive, photo responsive, magnetic responsive, electric responsive, ultrasound responsive and enzymes-triggered injectable hydrogels in developing customizable neurotherapies. We believe that this comprehensive review will help in identifying the strengths and gaps in the existing literature and to further support the use of injectable hydrogels in stimulating CNS regeneration.

    Bacterial outer membrane vesicles as potential biological nanomaterials for antibacterial therapy

    Huang W.Meng L.Chen Y.Dong Z....
    14页
    查看更多>>摘要:? 2021Antibiotic therapy is one of the most important approaches against bacterial infections. However, the improper use of antibiotics and the emergence of drug resistance have compromised the efficacy of traditional antibiotic therapy. In this regard, it is of great importance and significance to develop more potent antimicrobial therapies, including the development of functionalized antibiotics delivery systems and antibiotics-independent antimicrobial agents. Outer membrane vesicles (OMVs), secreted by Gram-negative bacteria and with similar structure to cell-derived exosomes, are natural functional nanomaterials and known to play important roles in many bacterial life events, such as communication, biofilm formation and pathogenesis. Recently, more and more reports have demonstrated the use of OMVs as either active antibacterial agents or antibiotics delivery carriers, implying the great potentials of OMVs in antibacterial therapy. Herein, we aim to provide a comprehensive understanding of OMV and its antibacterial applications, including its biogenesis, biofunctions, isolation, purification and its potentials in killing bacteria, delivering antibiotics and developing vaccine or immunoadjuvants. In addition, the concerns in clinical use of OMVs and the possible solutions are discussed. Statement of significance: The emergence of antibiotic-resistant bacteria has led to the failure of traditional antibiotic therapy, and thus become a big threat to human beings. In this regard, developing more potent antibacterial approaches is of great importance and significance. Recently, bacterial outer membrane vesicles (OMVs), which are natural functional nanomaterials secreted by Gram-negative bacteria, have been used as active agents, drug carriers and vaccine adjuvant for antibacterial therapy. This review provides a comprehensive understanding of OMVs and summarizes the recent progress of OMVs in antibacterial applications. The concerns of OMVs in clinical use and the possible solutions are also discussed. As such, this review may guide the future works in antibacterial OMVs and appeal to both scientists and clinicians.

    The utilisation of resolvins in medicine and tissue engineering

    Blaudez F.Ivanovski S.Fournier B.Vaquette C....
    20页
    查看更多>>摘要:? 2021 Acta Materialia Inc.Recent advances in the field of regenerative medicine and biomaterial science have highlighted the importance of controlling immune cell phenotypes at the biomaterial interface. These studies have clearly indicated that a rapid resolution of the inflammatory process, mediated by a switch in the macrophage population towards a reparative phenotype, is essential for tissue regeneration to occur. While various biomaterial surfaces have been developed in order to impart immunomodulatory properties to the resulting constructs, an alternative strategy involving the use of reparative biological cues, known as resolvins, is emerging in regenerative medicine. This review reports on the mechanisms via which resolvins participate in the resolution of inflammation and describes their current utilisation in pre-clinical and clinical settings, along with their effectiveness when combined with biomaterial constructs in tissue engineering applications. Statement of significance: The resolution of the inflammatory process is necessary for achieving tissue healing and regeneration. Resolvins are lipid mediators and play a key role in the resolution of the inflammatory response and can be used in as biological cues to promote tissue regeneration. This review describes the various biological inflammatory mechanisms and pathways involving resolvins and how their action results in a pro-healing response. The use of these molecules in the clinical setting is then summarised for various applications along with their limitations. Lastly, the review focuses on the emergence resolvins in tissue engineering products including the use of a more stable form which holds greater prospect for regenerative purposes.

    Megaprosthesis anti-bacterial coatings: A comprehensive translational review

    Lex J.R.Koucheki R.Stavropoulos N.A.Michele J.D....
    13页
    查看更多>>摘要:? 2021 Acta Materialia Inc.Periprosthetic joint infections (PJI) are catastrophic complications for patients with implanted megaprostheses and pose significant challenges in the management of orthopaedic oncology patients. Despite various preventative strategies, with the increasing rate of implanted orthopaedic prostheses, the number of PJIs may be increasing. PJIs are associated with a high rate of amputation. Therefore, novel strategies to combat bacterial colonization and biofilm formation are required. A promising strategy is the utilization of anti-bacterial coatings on megaprosthetic implants. In this translational review, a brief overview of the mechanism of bacterial colonization of implants and biofilm formation will be provided, followed by a discussion and classification of major anti-bacterial coatings currently in use and development. In addition, current in vitro outcomes, clinical significance, economic importance, evolutionary perspectives, and future directions of anti-bacterial coatings will also be discussed. Megaprosthetic anti-bacterial coating strategies will help reduce infection rates following the implantation of megaprostheses and would positively impact sarcoma care. Statement of significance: This review highlights the clinical challenges and a multitude of potential solutions to combating peri-prosthetic join infections in megaprotheses using anti-bacterial coatings. Reducing infection rates following the implantation of megaprostheses would have a major impact on sarcoma care and major trauma surgeries that require reconstruction of large skeletal defects.

    Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing

    He S.Fang J.Zhong C.Ren F....
    14页
    查看更多>>摘要:? 2021 Acta Materialia Inc.Regulating cell function and tissue formation by combining gene delivery with functional scaffolds to create gene-activated matrices (GAMs) is a promising strategy for tissue engineering. However, fabrication of GAMs with low cytotoxicity, high transfection efficiency, and long-term gene delivery properties remains a challenge. In this study, a non-viral DNA delivery nanocomplex was developed by modifying poly (D, L-lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) nanoparticles with the cell-penetrating peptide KALA. Subsequently, the nanocomplex carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF) was immobilized onto a polydopamine-coated electrospun alginate nanofibrous scaffold, resulting in a GAM for enhanced skin wound healing. The nanocomplex exhibited much lower cytotoxicity and comparable or even higher transfection efficiency compared with PEI. The GAM enabled sustained gene release and long-tern transgene expression of VEGF in vitro. In an excisional full-thickness skin wound rat model, the GAM could accelerate wound closure, promote complete re-epithelization, reduce inflammatory response, and enhance neovascularization, ultimately enhancing skin wound healing. The current GAM comprising a low-toxic gene delivery nanocomplex and a biocompatible 3D nanofibrous scaffold demonstrates great potential for mediating long-term cell functions and may become a powerful tool for gene delivery in tissue engineering. Statement of significance: Gene delivery is a promising strategy in promoting tissue regeneration as an effective alternative to growth factor delivery, but the study on three-dimensional gene-activated scaffolds remains in its infancy. Herein, a biodegradable nanofibrous gene-activated matrix integrating non-viral nanoparticle vector was designed and evaluated both in vitro and in vivo. The results show that the nanoparticle vector provided high transfection efficiency with minimal cytotoxicity. After surface immobilization of the nanocomplexes carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF), the nanofibrous scaffold enabled sustained DNA release and long-term transgene expression in vitro. In a rat full-thickness skin wound model, the scaffold could accelerate wound healing. This innovative gene-activated matrix can be a promising candidate for tissue regeneration.

    Dextran sulfate-amplified extracellular matrix deposition promotes osteogenic differentiation of mesenchymal stem cells

    Wan H.-Y.Shin R.L.Y.Chen J.C.H.Assuncao M....
    15页
    查看更多>>摘要:? 2021 The AuthorsThe development of bone-like tissues in vitro that exhibit key features similar to those in vivo is needed to produce tissue models for drug screening and the study of bone physiology and disease pathogenesis. Extracellular matrix (ECM) is a predominant component of bone in vivo; however, as ECM assembly is sub-optimal in vitro, current bone tissue engineering approaches are limited by an imbalance in ECM-to-cell ratio. We amplified the deposition of osteoblastic ECM by supplementing dextran sulfate (DxS) into osteogenically induced cultures of human mesenchymal stem cells (MSCs). DxS, previously implicated to act as a macromolecular crowder, was recently demonstrated to aggregate and co-precipitate major ECM components, including collagen type I, thereby amplifying its deposition. This effect was re-confirmed for MSC cultures undergoing osteogenic induction, where DxS supplementation augmented collagen type I deposition, accompanied by extracellular osteocalcin accumulation. The resulting differentiated osteoblasts exhibited a more mature osteogenic gene expression profile, indicated by a strong upregulation of the intermediate and late osteogenic markers ALP and OCN, respectively. The associated cellular microenvironment was also enriched in bone morphogenetic protein 2 (BMP-2). Interestingly, the resulting decellularized matrices exhibited the strongest osteo-inductive effects on re-seeded MSCs, promoted cell proliferation, osteogenic marker expression and ECM calcification. Taken together, these findings suggest that DxS-mediated enhancement of osteogenic differentiation by MSCs is mediated by the amplified ECM, which is enriched in osteo-inductive factors. We have thus established a simple and reproducible approach to generate ECM-rich bone-like tissue in vitro with sequestration of osteo-inductive factors. Statement of significance: As extracellular matrix (ECM) assembly is significantly retarded in vitro, the imbalance in ECM-to-cell ratio hampers current in vitro bone tissue engineering approaches in their ability to faithfully resemble their in vivo counterpart. We addressed this limitation by leveraging a poly-electrolyte mediated co-assembly and amplified deposition of ECM during osteogenic differentiation of human mesenchymal stem cells (MSCs). The resulting pericelluar space in culture was enriched in organic and inorganic bone ECM components, as well as osteo-inductive factors, which promoted the differentiation of MSCs towards a more mature osteoblastic phenotype. These findings thus demonstrated a simple and reproducible approach to generate ECM-rich bone-like tissue in vitro with a closer recapitulation of the in vivo tissue niche.