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  1. The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery. 
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  2. Abstract

    Load‐bearing soft tissues are soft but strong, strong yet tough. These properties can only be replicated in synthetic hydrogels, which do not have the biocomplexity required by many biomedical applications. By contrast, natural hydrogels, although retaining the native complexity, are weak and fragile. Here a thermomechanical casting method is presented to achieve the mechanical capabilities of synthetic materials in biopolymer hydrogels. The thermomechanical cast and chemically crosslinked biopolymer chains form a short‐range disordered but long‐range ordered structure in water. Upon stretch, the disordered structure transforms to a hierarchically ordered structure. This disorder‐order transformation resembles the synergy of the disordered elastin and ordered collagen in load‐bearing soft tissues. As entropy drives a reverse order‐disorder transformation, the hydrogels can resist repeated cycles of loads without deterioration in mechanical properties. Gelatin hydrogels produced by this method combine tissue‐like tunable mechanical properties that outperform the gelatin prepared by synthetic approaches, and in vivo biocomplexity beyond current natural systems. Unlike polymer engineering approaches, which rely on specific crosslinks provided by special polymers, this strategy utilizes the entropy of swollen chains and is generalizable to many other biopolymers. It could thus significantly accelerate translational success of biomaterials.

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  3. 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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