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1.
Smart and Functionalized Development of Nucleic Acid-Based Hydrogels: Assembly Strategies, Recent Advances, and Challenges.
Zhang, Y, Zhu, L, Tian, J, Zhu, L, Ma, X, He, X, Huang, K, Ren, F, Xu, W
Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2021;(14):2100216
Abstract
Nucleic acid-based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new-generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid-based hydrogels. Also, recent advances in the design of multifunctional and stimuli-responsive nucleic acid-based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined.
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Autotolerant ceruloplasmin based biocathodes for implanted biological power sources.
Aleksejeva, O, Sokolov, AV, Marquez, I, Gustafsson, A, Bushnev, S, Eriksson, H, Ljunggren, L, Shleev, S
Bioelectrochemistry (Amsterdam, Netherlands). 2021;:107794
Abstract
High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and also biocathodes in biological power sources. In comparison to fungal and plant blue multicopper oxidases, e.g. Myrothecium verrucaria bilirubin oxidase and Rhus vernicifera laccase, respectively, the inflammatory response to HCp in human blood is significantly reduced. Partial purification of HCp allowed to preserve the native conformation of the enzyme and its biocatalytic activity. Therefore, electrochemical studies were carried out with the partially purified enzyme immobilised on nanostructured graphite electrodes at physiological pH and temperature. Amperometric investigations revealed low reductive current densities, i.e. about 1.65 µA cm-2 in oxygenated electrolyte and in the absence of any mediator, demonstrating nevertheless direct electron transfer based O2 bioelectroreduction by HCp for the first time. The reductive current density obtained in the mediated system was about 12 µA cm-2. Even though the inflammatory response of HCp is diminished in human blood, inadequate bioelectrocatalytic performance hinders its use as a cathodic bioelement in a biofuel cell.
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Biological Factors, Metals, and Biomaterials Regulating Osteogenesis through Autophagy.
di Giacomo, V, Cataldi, A, Sancilio, S
International journal of molecular sciences. 2020;(8)
Abstract
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. This review provides a revision of the literature on all the exogen factors that can modulate osteogenesis through autophagy regulation. Metal ion exposition, mechanical stimuli, and biological factors, including hormones, nutrients, and metabolic conditions, were taken into consideration for their ability to tune osteogenic differentiation through autophagy. In addition, an exhaustive overview of biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is provided as well. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for finely tailoring innovative therapeutic treatments and designing novel biomaterials.
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Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine.
Su, Y, Liu, C, Fang, H, Zhang, D
Microbial cell factories. 2020;(1):173
Abstract
Due to its clear inherited backgrounds as well as simple and diverse genetic manipulation systems, Bacillus subtilis is the key Gram-positive model bacterium for studies on physiology and metabolism. Furthermore, due to its highly efficient protein secretion system and adaptable metabolism, it has been widely used as a cell factory for microbial production of chemicals, enzymes, and antimicrobial materials for industry, agriculture, and medicine. In this mini-review, we first summarize the basic genetic manipulation tools and expression systems for this bacterium, including traditional methods and novel engineering systems. Secondly, we briefly introduce its applications in the production of chemicals and enzymes, and summarize its advantages, mainly focusing on some noteworthy products and recent progress in the engineering of B. subtilis. Finally, this review also covers applications such as microbial additives and antimicrobials, as well as biofilm systems and spore formation. We hope to provide an overview for novice researchers in this area, offering them a better understanding of B. subtilis and its applications.
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5.
Biodegradable Polymers for Gene-Delivery Applications.
Chen, CK, Huang, PK, Law, WC, Chu, CH, Chen, NT, Lo, LW
International journal of nanomedicine. 2020;:2131-2150
Abstract
Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral- and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given.
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Electrospinning Piezoelectric Fibers for Biocompatible Devices.
Azimi, B, Milazzo, M, Lazzeri, A, Berrettini, S, Uddin, MJ, Qin, Z, Buehler, MJ, Danti, S
Advanced healthcare materials. 2020;(1):e1901287
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Abstract
The field of nanotechnology has been gaining great success due to its potential in developing new generations of nanoscale materials with unprecedented properties and enhanced biological responses. This is particularly exciting using nanofibers, as their mechanical and topographic characteristics can approach those found in naturally occurring biological materials. Electrospinning is a key technique to manufacture ultrafine fibers and fiber meshes with multifunctional features, such as piezoelectricity, to be available on a smaller length scale, thus comparable to subcellular scale, which makes their use increasingly appealing for biomedical applications. These include biocompatible fiber-based devices as smart scaffolds, biosensors, energy harvesters, and nanogenerators for the human body. This paper provides a comprehensive review of current studies focused on the fabrication of ultrafine polymeric and ceramic piezoelectric fibers specifically designed for, or with the potential to be translated toward, biomedical applications. It provides an applicative and technical overview of the biocompatible piezoelectric fibers, with actual and potential applications, an understanding of the electrospinning process, and the properties of nanostructured fibrous materials, including the available modeling approaches. Ultimately, this review aims at enabling a future vision on the impact of these nanomaterials as stimuli-responsive devices in the human body.
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Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.
Gómez-Barrena, E, Rosset, P, Gebhard, F, Hernigou, P, Baldini, N, Rouard, H, Sensebé, L, Gonzalo-Daganzo, RM, Giordano, R, Padilla-Eguiluz, N, et al
Biomaterials. 2019;:100-108
Abstract
BACKGROUND ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. METHODS Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. FINDINGS With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). INTERPRETATION Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. FUNDING EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).
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Development, Characterization and In Vitro Biological Properties of Scaffolds Fabricated From Calcium Phosphate Nanoparticles.
Morejón, L, Delgado, JA, Antunes Ribeiro, A, Varella de Oliveira, M, Mendizábal, E, García, I, Alfonso, A, Poh, P, van Griensven, M, Balmayor, ER
International journal of molecular sciences. 2019;(7)
Abstract
Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We aimed to fabricate biocompatible 3D-scaffolds featuring macro- and microporous calcium phosphates with high pore interconnection. Nanoparticles of hydroxyapatite (HA) and calcium deficient hydroxyapatite (CDHA) were synthesized by wet chemical precipitation. Scaffolds were produced from them by the replication polymeric foam technique. Solid content and sintering temperature were varied. Nanoparticles and scaffolds were characterized regarding morphology, chemical and mineral composition, porosity and mechanical properties. Biocompatibility, cell attachment and distribution were evaluated in vitro with human adipose mesenchymal stem cells. Scaffolds with total porosity of 71%-87%, pores in the range of 280-550 µm and connectivity density up to 43 mm-3 were obtained. Smaller pore sizes were obtained at higher sintering temperature. High solid content resulted in a decrease of total porosity but increased interconnectivity. Scaffolds 50HA/50β-TCP featured superior interconnectivity and mechanical properties. They were bioactive and biocompatible. High HA solid content (40 wt.%) in the HA pure scaffolds was negative for cell viability and proliferation, while in the 50HA/50β-TCP composite scaffolds it resulted more biocompatible.
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9.
Protein-Engineered Functional Materials.
Wang, Y, Katyal, P, Montclare, JK
Advanced healthcare materials. 2019;(11):e1801374
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Abstract
Proteins are versatile macromolecules that can perform a variety of functions. In the past three decades, they have been commonly used as building blocks to generate a range of biomaterials. Owing to their flexibility, proteins can either be used alone or in combination with other functional molecules. Advances in synthetic and chemical biology have enabled new protein fusions as well as the integration of new functional groups leading to biomaterials with emergent properties. This review discusses protein-engineered materials from the perspectives of domain-based designs as well as physical and chemical approaches for crosslinked materials, with special emphasis on the creation of hydrogels. Engineered proteins that organize or template metal ions, bear noncanonical amino acids (NCAAs), and their potential applications, are also reviewed.
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10.
Demineralized Bone Matrix Carriers and their Clinical Applications: An Overview.
Zhang, H, Yang, L, Yang, XG, Wang, F, Feng, JT, Hua, KC, Li, Q, Hu, YC
Orthopaedic surgery. 2019;(5):725-737
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Abstract
Reconstruction of massive bone defects is challenging for orthopaedic clinicians, especially in cases of severe trauma and resection of tumors in various locales. Autologous iliac crest bone graft (ICBG) is the "gold standard" for bone grafting. However, the limited availability and complications at donor sites resulted in seeking other options like allografts and bone graft substitutes. Demineralized bone matrix (DBM) is a form of allograft using acidic solution to remove mineral components, while leaving much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates, and some trace cell debris. It is an osteoconductive and osteoinductive biomaterial and is approved as a medical device for use in bone defects and spinal fusion. To pack consistently into the defect sites and stay firmly in the filling parts, DBM products have various forms combined with biocompatible viscous carriers, including sponges, strips, injectable putty, paste, and paste infused with chips. The present review aims to summarize the properties of various kind of viscous carriers and their clinical use combined with DBM in commercially available products. Given DBM'mercially available products. Given DBM;s long clinical track record and commercial accessibility in standard forms, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopaedic repair and regenerative medicine contexts are attractive.