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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    Bringing hydrogel-based craniofacial therapies to the clinic

    Trubelja, AlenKasper, F. KurtisFarach-Carson, Mary C.Harrington, Daniel A....
    20页
    查看更多>>摘要：This review explores the evolution of the use of hydrogels for craniofacial soft tissue engineering, ranging in complexity from acellular injectable fillers to fabricated, cell-laden constructs with complex compositions and architectures. Addressing both in situ and ex vivo approaches, tissue restoration secondary to trauma or tumor resection is discussed. Beginning with relatively simple epithelia of oral mucosa and gingiva, then moving to more functional units like vocal cords or soft tissues with multilayer branched structures, such as salivary glands, various approaches are presented toward the design of function-driven architectures, inspired by native tissue organization. Multiple tissue replacement paradigms are presented here, including the application of hydrogels as structural materials and as delivery platforms for cells and/or therapeutics. A practical hierarchy is proposed for hydrogel systems in craniofacial applications, based on their material and cellular complexity, spatial order, and biological cargo(s). This hierarchy reflects the regulatory complexity dictated by the Food and Drug Administration (FDA) in the United States prior to commercialization of these systems for use in humans. The wide array of available biofabrication methods, ranging from simple syringe extrusion of a biomaterial to light-based spatial patterning for complex architectures, is considered within the history of FDA-approved commercial therapies. Lastly, the review assesses the impact of these regulatory pathways on the translational potential of promising pre-clinical technologies for craniofacial applications. Statement of significance While many commercially available hydrogel-based products are in use for the craniofacial region, most are simple formulations that either are applied topically or injected into tissue for aesthetic purposes. The academic literature previews many exciting applications that harness the versatility of hydrogels for craniofacial soft tissue engineering. One of the most exciting developments in the field is the emergence of advanced biofabrication methods to design complex hydrogel systems that can promote the functional or structural repair of tissues. To date, no clinically available hydrogel-based therapy takes full advantage of current pre-clinical advances. This review surveys the increasing complexity of the current landscape of available clinical therapies and presents a framework for future expanded use of hydrogels with an eye toward translatability and U.S. regulatory approval for craniofacial applications. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Droplet microfluidics-base d biome dical microcarriers

    Fan, QihuiYe, FangfuShao, ChangminChi, Junjie...
    13页
    查看更多>>摘要：Droplet microfluidic technology provides a new platform for controllable generation of microdroplets and droplet-derived materials. In particular, because of the ability in high-throughput production and accurate control of the size, structure, and function of these materials, droplet microfluidics presents unique advantages in the preparation of functional microcarriers, i.e., microsized liquid containers or solid particles that serve as substrates of biomolecules or cells. These microcarriers could be extensively applied in the areas of cell culture, tissue engineering, and drug delivery. In this review, we focus on the fabrication of microcarriers from droplet microfluidics, and discuss their applications in the biomedical field. We start with the basic principle of droplet microfluidics, including droplet generation regimes and its control methods. We then introduce the fabrication of biomedical microcarriers based on single, double, and multiple emulsion droplets, and emphasize the various applications of microcarriers in biomedical field, especially in 3D cell culture, drug development and biomedical detection. Finally, we conclude this review by discussing the limitations and challenges of droplet microfluidics in preparing microcarriers. Statement of significance Because of its precise control and high throughput, droplet microfluidics has been employed to generate functional microcarriers, which have been widely used in the areas of drug development, tissue engineering, and regenerative medicine. This review is significant because it emphasizes recent progress in research on droplet microfluidics in the preparation and application of biomedical microcarriers. In addition, this review suggests research directions for the future development of biomedical microcarriers based on droplet microfluidics by presenting existing shortcomings and challenges. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Fluorine-containing bio-inert polymers: Roles of intermediate water

    Koguchi, RyoheiJankova, KatjaTanaka, Masaru
    23页
    查看更多>>摘要：Fluorine-containing polymers are used not only in industrial processes but also in medical applications, because they exhibit excellent heat, weather, and chemical resistance. As these polymers are not easily degraded in our body, it is difficult to use them in applications that require antithrombotic properties, such as artificial blood vessels. The material used for medical applications should not only be stable in vivo , but it should also be inert to biomolecules such as proteins or cells. In this review, this property is defined as "bio-inert," and previous studies in this field are summarized. Bio-inert materials are less recognized as foreign substances by proteins or cells in the living body, and they must be covered at interfaces designed with the concept of intermediate water (IW). On the basis of this concept, we present here the current understanding of bio-inertness and unusual blood compatibility found in fluoropolymers used in biomedical applications. IW is the water that interacts with materials with moderate strength and has been quantified by a variety of analytical methods and simulations. For example, by using differential scanning calorimetry (DSC) measurements, IW was defined as water frozen at around-40 degrees C. To consider the role of the IW, quantification methods of the hydration state of polymers are also summarized. These investigations have been conducted independently because of the conflict between hydrophobic fluorine and bio-inert properties that require hydrophilicity. In recent years, not many materials have been developed that incorporate the good points of both aspects, and their properties have seldom been linked to the hydration state. This has been critically performed now. Furthermore, fluorine-containing polymers in medical use are reviewed. Finally, this review also describes the molecular design of the recently reported fluorine-containing bio-inert polymers for controlling their hydration state. Statement of significance A material covered with a hydration layer known as intermediate water that interacts moderately with other objects is difficult to be recognized as a foreign substance and exhibits bio-inert properties. Fluoropolymers show high durability, but conflict with bio-inert characteristics requiring hydrophilicity as these research studies have been conducted independently. On the other hand, materials that combine the advantages of both hydrophobic and hydrophilic features have been developed recently. Here, we summarize the molecular architecture and analysis methods that control intermediate water and provide a guideline for designing novel fluorine-containing bio-inert materials. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Nanotraps based on multifunctional materials for trapping and enrichment

    Xu, WenxinXu, NaZhang, ManyueWang, Yan...
    16页
    查看更多>>摘要：Many biomarkers for early diagnosis of cancer and other diseases are difficult to detect because they of -ten exist in body fluids in very low concentrations and are masked by high-abundance proteins such as albumin and immunoglobulins. At the same time, water pollution is one of the most serious environmen-tal problems, but the existing adsorption materials have many shortcomings such as slow kinetics, small adsorption capacity and low adsorption efficiency. Nanotraps, mixed with gases or liquids, can capture and concentrate target substances, such as biomolecules, metal ions and oxoanions. Using nanotraps is a versatile sample pre-processing approach and it can improve the sensitivity of downstream analysis tech-niques. Herein, the preparations and applications of different types of nanotraps are mainly introduced. What's more, the shortcomings of using nanotraps in practical applications are also discussed. Using nan-otraps is a promising sample pre-processing technology, which is of great significance for biomarkers discovery, diseases diagnosis, sewage purification and valuable ions recovery. Statement of significance This review collates and summarizes the preparations and applications of different types of nanotraps, and discusses the shortcomings of using nanotraps in practical applications. Nanotraps, mixed with gases or liquids, can capture and concentrate target materials, such as biomolecules, metal ions and oxoan-ions. Using nanotraps is a versatile sample pre-processing approach and it can improve the sensitivity of downstream analysis techniques. During the COVID-19 pandemic, hydrogel nanotraps were successfully utilized for RT-PCR analysis with the FDA Emergency Used Authorization for COVID-19. Using nanotraps is a promising sample pre-processing technology, which is of great significance for biomarkers discovery, diseases diagnosis, sewage purification and valuable ions recovery. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    • Elsevier

    Topical gel-based biomaterials for the treatment of diabetic foot ulcers

    Liechty, Kenneth W.Krebs, Melissa D.Zgheib, CarlosBardill, James R....
    19页
    查看更多>>摘要：Diabetic foot ulcers (DFUs) are a devastating ailment for many diabetic patients with increasing prevalence and morbidity. The complex pathophysiology of DFU wound environments has made finding effective treatments difficult. Standard wound care treatments have limited efficacy in healing these types of chronic wounds. Topical biomaterial gels have been developed to implement novel treatment approaches to improve therapeutic effects and are advantageous due to their ease of application, tunability, and ability to improve therapeutic release characteristics. Here, we provide an updated, comprehensive review of novel topical biomaterial gels developed for treating chronic DFUs. This review will examine preclinical data for topical gel treatments in diabetic animal models and clinical applications, focusing on gels with protein/peptides, drug, cellular, herbal/antioxidant, and nano/microparticle approaches. Statement of significance By 2050, 1 in 3 Americans will develop diabetes, and up to 34% of diabetic patients will develop a diabetic foot ulcer (DFU) in their lifetime. Current treatments for DFUs include debridement, infection control, maintaining a moist wound environment, and pressure offloading. Despite these interventions, a large number of DFUs fail to heal and are associated with a cost that exceeds $31 billion annually. Topical biomaterials have been developed to help target specific impairments associated with DFU with the goal to improve healing. A summary of these approaches is needed to help better understand the current state of the research. This review summarizes recent research and advances in topical biomaterials treatments for DFUs. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Biofabrication of small diameter tissue-engineered vascular grafts

    Weekes, AngusBartnikowski, NicolePinto, NigelJenkins, Jason...
    20页
    查看更多>>摘要：Current clinical treatment strategies for the bypassing of small diameter ( < 6 mm) blood vessels in the management of cardiovascular disease frequently fail due to a lack of suitable autologous grafts, as well as infection, thrombosis, and intimal hyperplasia associated with synthetic grafts. The rapid advancement of 3D printing and regenerative medicine technologies enabling the manufacture of biological, tissue engineered vascular grafts (TEVGs) with the ability to integrate, remodel, and repair in vivo , promises a paradigm shift in cardiovascular disease management. This review comprehensively covers current stateof-the-art biofabrication technologies for the development of biomimetic TEVGs. Various scaffold based additive manufacturing methods used in vascular tissue engineering, including 3D printing, bioprinting, electrospinning and melt electrowriting, are discussed and assessed against the biomechanical and functional requirements of human vasculature, while the efficacy of decellularization protocols currently applied to engineered and native vessels are evaluated. Further, we provide interdisciplinary insight into the outlook of regenerative medicine for the development of vascular grafts, exploring key considerations and perspectives for the successful clinical integration of evolving technologies. It is expected that continued advancements in microscale additive manufacturing, biofabrication, tissue engineering and decellularization will culminate in the development of clinically viable, off-the-shelf TEVGs for small diameter applications in the near future. Statement of significance Current clinical strategies for the management of cardiovascular disease using small diameter vessel bypassing procedures are inadequate, with up to 75% of synthetic grafts failing within 3 years of implantation. It is this critically important clinical problem that researchers in the field of vascular tissue engineering and regenerative medicine aim to alleviate using biofabrication methods combining additive manufacturing, biomaterials science and advanced cellular biology. While many approaches facilitate the development of bioengineered constructs which mimic the structure and function of native blood vessels, several challenges must still be overcome for clinical translation of the next generation of tissue engineered vascular grafts. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Magnetic nanocomposite hydrogel with tunable stiffness for probing cellular responses to matrix stiffening

    Yan, TianhaoRao, DepengChen, YeWang, Yu...
    12页
    查看更多>>摘要：As cells have the capacity to respond to their mechanical environment, cellular biological behaviors can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are dynamic and accompanied by matrix stiffening. Herein, we developed a stiffening cell culture platform based on polyacrylamide-Fe3O4 magnetic nanocomposite hydrogel with tunable stiffness under the application of magnetic field. This platform provided a wide range of tunable stiffness (-0.3-20 kPa) covering most of human tissue elasticity with a high biocompatibility. Overall, the increased magnetic interactions between magnetic nanoparticles reduced the pore size of the hydrogel and enhanced the hydrogel stiffness, thereby facilitating the adhesion and spreading of stem cells, which was attributed to the F-actin assembly and vinculin recruitment. Such stiffening cell culture platform provides dynamic mechanical environments for probing the cellular response to matrix stiffening, and benefits studies of dynamic biological processes. Statement of significance Cellular biological behaviors can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are dynamic and accompanied by matrix stiffening. Herein, we developed a stiffening cell culture platform based on polyacrylamide/Fe3O4 magnetic nanocomposite hydrogels with a wide tunable range of stiffness under the application of magnetic field, without adversely affecting cellular behaviors. Such matrix stiffening caused by enhanced magnetic interaction between magnetic nanoparticles under the application of the magnetic field could induce the morphological variations of stem cells cultured on the hydrogels. Overall, our stiffening cell culture platform can be used not only to probe the cellular response to matrix stiffening but also to benefit various biomedical studies. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Colloidal hydrogels made of gelatin nanoparticles exhibit fast stress relaxation at strains relevant for cell activity

    Bertsch, PascalAndree, LeaBesheli, Negar HassaniLeeuwenburgh, Sander C. G....
    9页
    查看更多>>摘要：Viscoelastic properties of hydrogels such as stress relaxation or plasticity have been recognized as important mechanical cues that dictate the migration, proliferation, and differentiation of embedded cells. Stress relaxation rates in conventional hydrogels are usually much slower than cellular processes, which impedes rapid cellularization of these elastic networks. Colloidal hydrogels assembled from nanoscale building blocks may provide increased degrees of freedom in the design of viscoelastic hydrogels with accelerated stress relaxation rates due to their strain-sensitive rheology which can be tuned via interparticle interactions. Here, we investigate the stress relaxation of colloidal hydrogels from gelatin nanoparticles in comparison to physical gelatin hydrogels and explore the particle interactions that govern stress relaxation. Colloidal and physical gelatin hydrogels exhibit comparable rheology at small deformations, but colloidal hydrogels fluidize beyond a critical strain while physical gels remain primarily elastic independent of strain. This fluidization facilitates fast exponential stress relaxation in colloidal gels at strain levels that correspond to strains exerted by cells embedded in physiological extracellular matrices (1050%). Increased attractive particle interactions result in a higher critical strain and slower stress relaxation in colloidal gels. In physical gels, stress relaxation is slower and mostly independent of strain. Hence, colloidal hydrogels offer the possibility to modulate viscoelasticity via interparticle interactions and obtain fast stress relaxation rates at strains relevant for cell activity. These beneficial features render colloidal hydrogels promising alternatives to conventional monolithic hydrogels for tissue engineering and regenerative medicine. Statement of significance In the endeavor to design biomaterials that favor cell activity, research has long focused on biochemical cues. Recently, the time-, stress-, and strain-dependent mechanical properties, i.e. viscoelasticity, of biomaterials has been recognized as important factor that dictates cell fate. We herein present the viscoelastic stress relaxation of colloidal hydrogels assembled from gelatin nanoparticles, which show a strain dependent fluidization at strains relevant for cell activity, in contrast to many commonly used monolithic hydrogels with primarily elastic behavior. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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    Spatiotemporal control of myofibroblast activation in acoustically-responsive scaffolds via ultrasound-induced matrix stiffening

    Farrell, EastonAliabouzar, MitraQuesada, CaroleBaker, Brendon M....
    11页
    查看更多>>摘要：Hydrogels are often used to study the impact of biomechanical and topographical cues on cell behavior. Conventional hydrogels are designed a priori , with characteristics that cannot be dynamically changed in an externally controlled, user-defined manner. We developed a composite hydrogel, termed an acoustically-responsive scaffold (ARS), that enables non-invasive, spatiotemporally controlled modulation of mechanical and morphological properties using focused ultrasound. An ARS consists of a phase-shift emulsion distributed in a fibrin matrix. Ultrasound non-thermally vaporizes the emulsion into bubbles, which induces localized, radial compaction and stiffening of the fibrin matrix. In this in vitro study, we investigate how this mechanism can control the differentiation of fibroblasts into myofibroblasts, a transition correlated with substrate stiffness on 2D substrates. Matrix compaction and stiffening was shown to be highly localized using confocal and atomic force microscopies, respectively. Myofibroblast phenotype, evaluated by alpha-smooth muscle actin (alpha-SMA) immunocytochemistry, significantly increased in matrix regions proximal to bubbles compared to distal regions, irrespective of the addition of exogenous transforming growth factor-beta 1 (TGF-beta 1). Introduction of the TGF-beta 1 receptor inhibitor SB431542 abrogated the proximal enhancement. This approach providing spatiotemporal control over biophysical signals and resulting cell behavior could aid in better understanding fibrotic disease progression and the development of therapeutic interventions for chronic wounds. Statement of Significance Hydrogels are used in cell culture to recapitulate both biochemical and biophysical aspects of the native extracellular matrix. Biophysical cues like stiffness can impact cell behavior. However, with conventional hydrogels, there is a limited ability to actively modulate stiffness after polymerization. We have developed an ultrasound-based method of spatiotemporally-controlling mechanical and morphological properties within a composite hydrogel, termed an acoustically-responsive scaffold (ARS). Upon exposure to ultrasound, bubbles are non-thermally generated within the fibrin matrix of an ARS, thereby locally compacting and stiffening the matrix. We demonstrate how ARSs control the differentiation of fibroblasts into myofibroblasts in 2D. This approach could assist with the study of fibrosis and the development of therapies for chronic wounds. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

    Vitale, MattiaLigorio, CosimoMcAvan, BethanHodson, Nigel W....
    11页
    查看更多>>摘要：Hydrogels are water-swollen networks with great potential for tissue engineering applications. However, their use in bone regeneration is often hampered due to a lack of materials' mineralization and poor mechanical properties. Moreover, most studies are focused on osteoblasts (OBs) for bone formation, while osteoclasts (OCs), cells involved in bone resorption, are often overlooked. Yet, the role of OCs is pivotal for bone homeostasis and aberrant OC activity has been reported in several pathological diseases, such as osteoporosis and bone cancer. For these reasons, the aim of this work is to develop customised, reinforced hydrogels to be used as material platform to study cell function, cell-material interactions and ultimately to provide a substrate for OC differentiation and culture. Here, Fmoc-based RGD-functionalised peptide hydrogels have been modified with hydroxyapatite nanopowder (Hap) as nanofiller, to create nanocomposite hydrogels. Atomic force microscopy showed that Hap nanoparticles decorate the peptide nanofibres with a repeating pattern, resulting in stiffer hydrogels with improved mechanical properties compared to Hap-and RGD-free controls. Furthermore, these nanocomposites supported adhesion of Raw 264.7 macrophages and their differentiation in 2D to mature OCs, as defined by the adoption of a typical OC morphology (presence of an actin ring, multinucleation, and ruffled plasma membrane). Finally, after 7 days of culture OCs showed an increased expression of TRAP, a typical OC differentiation marker. Collectively, the results suggest that the Hap/Fmoc-RGD hydrogel has a potential for bone tissue engineering, as a 2D model to study impairment or upregulation of OC differentiation. Statement of significance Altered osteoclasts (OC) function is one of the major cause of bone fracture in the most commonly skeletal disorders (e.g. osteoporosis). Peptide hydrogels can be used as a platform to mimic the bone microenvironment and provide a tool to assess OC differentiation and function. Moreover, hydrogels can incorporate different nanofillers to yield hybrid biomaterials with enhanced mechanical properties and improved cytocompatibility. Herein, Fmoc-based RGD-functionalised peptide hydrogels were decorated with hydroxyapatite (Hap) nanoparticles to generate a hydrogel with improved rheological properties. Furthermore, they are able to support osteoclastogenesis of Raw264.7 cells in vitro as confirmed by morphology changes and expression of OC-markers. Therefore, this Hap-decorated hydrogel can be used as a template to successfully differentiate OC and potentially study OC dysfunction. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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