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    The Biomedical Use of Silk: Past, Present, Future
    (Weinheim : Wiley-VCH, 2019) Holland, Chris; Numata, Keiji; Rnjak-Kovacina, Jelena; Seib, F. Philipp
    Humans have long appreciated silk for its lustrous appeal and remarkable physical properties, yet as the mysteries of silk are unraveled, it becomes clear that this outstanding biopolymer is more than a high-tech fiber. This progress report provides a critical but detailed insight into the biomedical use of silk. This journey begins with a historical perspective of silk and its uses, including the long-standing desire to reverse engineer silk. Selected silk structure–function relationships are then examined to appreciate past and current silk challenges. From this, biocompatibility and biodegradation are reviewed with a specific focus of silk performance in humans. The current clinical uses of silk (e.g., sutures, surgical meshes, and fabrics) are discussed, as well as clinical trials (e.g., wound healing, tissue engineering) and emerging biomedical applications of silk across selected formats, such as silk solution, films, scaffolds, electrospun materials, hydrogels, and particles. The journey finishes with a look at the roadmap of next-generation recombinant silks, especially the development pipeline of this new industry for clinical use. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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    Ultrathin 2D Titanium Carbide MXene (Ti3C2Tx) Nanoflakes Activate WNT/HIF-1α-Mediated Metabolism Reprogramming for Periodontal Regeneration
    (Weinheim : Wiley-VCH, 2021) Cui, Di; Kong, Na; Ding, Liang; Guo, Yachong; Yang, Wenrong; Yan, Fuhua
    Periodontal defect regeneration in severe periodontitis relies on the differentiation and proliferation of periodontal ligament cells (PDLCs). Recently, an emerging 2D nanomaterial, MXene (Ti3C2Tx), has gained more and more attention due to the extensive antibacterial and anticancer activity, while its potential biomedical application on tissue regeneration remains unclear. Through a combination of experimental and multiscale simulation schemes, Ti3C2Tx has exhibited satisfactory biocompatibility and induced distinguish osteogenic differentiation of human PDLCs (hPDLCs), with upregulated osteogenesis-related genes. Ti3C2Tx manages to activate the Wnt/β-catenin signaling pathway by enhancing the Wnt-Frizzled complex binding, thus stabilizing HIF-1α and altering metabolic reprogramming into glycolysis. In vivo, hPDLCs pretreated by Ti3C2Tx display excellent performance in new bone formation and osteoclast inhibition with enhanced RUNX2, HIF-1α, and β-catenin in an experimental rat model of periodontal fenestration defects, indicating that this material has high efficiency of periodontal regeneration promotion. It is demonstrated in this work that Ti3C2Tx has highly efficient therapeutic effects in osteogenic differentiation and periodontal defect repairment. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
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    Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic-co-glycolic acid), and Silica Nanoparticles
    (Weinheim : Wiley-VCH, 2017) Saborano, Raquel; Wongpinyochit, Thidarat; Totten, John D.; Johnston, Blair F.; Seib, F. Philipp; Duarte, Iola F.
    Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications. 1H NMR analysis of cell extracts and culture media is used to quantify the changes in the intracellular and extracellular metabolomes of macrophages in response to nanoparticle exposure. Increased glycolytic activity, an altered tricarboxylic acid cycle, and reduced ATP generation are consistent with a proinflammatory phenotype. Furthermore, amino acids possibly arising from autophagy, the creatine kinase/phosphocreatine system, and a few osmolytes and antioxidants emerge as important players in the metabolic reprogramming of macrophages exposed to nanoparticles. This metabolic signature is a common response to all nanoparticles tested; however, the direction and magnitude of some variations are clearly nanoparticle specific, indicating material-induced biological specificity. Overall, metabolic reprogramming of macrophages can be achieved with nanoparticle treatments, modulated through the choice of the material, and monitored using 1H NMR metabolomics.
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    Poly(2-alkyl-2-oxazoline)-Heparin Hydrogels—Expanding the Physicochemical Parameter Space of Biohybrid Materials
    (Weinheim : Wiley-VCH, 2021) Hahn, Dominik; Sonntag, Jannick M.; Lück, Steffen; Maitz, Manfred F.; Freudenberg, Uwe; Jordan, Rainer; Werner, Carsten
    Poly(ethylene glycol) (PEG)-glycosaminoglycan (GAG) hydrogel networks are established as very versatile biomaterials. Herein, the synthetic gel component of the biohybrid materials is systematically varied by combining different poly(2-alkyl-2-oxazolines) (POx) with heparin applying a Michael-type addition crosslinking scheme: POx of gradated hydrophilicity and temperature-responsiveness provides polymer networks of distinctly different stiffness and swelling. Adjusting the mechanical properties and the GAG concentration of the gels to similar values allows for modulating the release of GAG-binding growth factors (VEGF165 and PDGF-BB) by the choice of the POx and its temperature-dependent conformation. Adsorption of fibronectin, growth of fibroblasts, and bacterial adhesion scale with the hydrophobicity of the gel-incorporated POx. In vitro hemocompatibility tests with freshly drawn human whole blood show advantages of POx-based gels compared to the PEG-based reference materials. Biohybrid POx hydrogels can therefore enable biomedical technologies requiring GAG-based materials with customized and switchable physicochemical characteristics. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.