Successful regeneration of large segmental bone defects remains a major challenge in clinical orthopedics, thus it is of important significance to fabricate a suitable alternative material to stimulate bone regeneration. Due to their excellent biocompatibility, sufficient mechanical strength, and similar structure and composition of natural bone, the mineralized collagen scaffolds (MCSs) have been increasingly used as bone substitutes via tissue engineering approaches. Herein, we thoroughly summarize the state of the art of MCSs as tissue-engineered scaffolds for acceleration of bone repair, including their fabrication methods, critical factors for osteogenesis regulation, current opportunities and challenges in the future. First, the current fabrication methods for MCSs, mainly including direct mineral composite, in-situ mineralization and 3D printing techniques, have been proposed to improve their biomimetic physical structures in this review. Meanwhile, three aspects of physical (mechanics and morphology), biological (cells and growth factors) and chemical (composition and cross-linking) cues are described as the critical factors for regulating the osteogenic feature of MCSs. Finally, the opportunities and challenges associated with MCSs as bone tissue-engineered scaffolds are also discussed to point out the future directions for building the next generation of MCSs that should be endowed with satisfactorily mimetic structures and appropriately biological characters for bone regeneration.

Periodic fluid shear stress plays a dominant role in promoting the preparation of highly oriented HIM of collagen fibers.

Collagen is the critical organic component of bone matrix, which is the template for bone biomineralization. Phosphorylation modification of collagen plays an important role in the process of biomineralization in vivo, but its mechanism on in vitro biomimetic mineralization of bone matrix remains unclear at the molecular level. Sodium tripolyphosphate is used to phosphorylate collagen in this study and new phosphate groups appear on collagen fibrils after phosphorylation modification. The chelating amount of calcium is improved linearly with increasing the phosphorylation degree of collagen fibrils, which demonstrates that the introduced phosphate groups serve as new nucleation sites and participate in the formation of apatite minerals inside the collagen fibers. Stabilized nanosized amorphous calcium phosphate by polyacrylic acid can also permeate into collagen fibers and further transform into another layer of hydroxyapatite minerals. Both layers of apatite minerals eventually induce the formation of hierarchical intrafibrillar mineralization structure within the phosphorylated collagen fibers. The present research enriches the previous biomineralization mechanism of bone matrix, provides a facile strategy for biomimetic mineralization of collagen, and offers the basis for future investigation of the advanced bone substitute materials. K E Y W O R D Sapatite, bone matrix, collagen, hierarchical intrafibrillar mineralization, phosphorylation

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Intrafibrillar mineralization of collagen under a 1.5 Pa FSS environment versus the serious extrafibrillar mineralization of collagen under no FSS.

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The bone matrix plays an indispensable role in the human body, and its unique biomechanical and mechanobiological properties have received much attention. The bone matrix has unique mechanical anisotropy and exhibits both strong toughness and high strength. These mechanical properties are closely associated with human life activities and correspond to the function of bone in the human body. None of the mechanical properties exhibited by the bone matrix is independent of its composition and structure. Studies on the biomechanics of the bone matrix can provide a reference for the preparation of more applicable bone substitute implants, bone biomimetic materials and scaffolds for bone tissue repair in humans, as well as for biomimetic applications in other fields. In providing mechanical support to the human body, bone is constantly exposed to mechanical stimuli. Through the study of the mechanobiology of the bone matrix, the response mechanism of the bone matrix to its surrounding mechanical environment can be elucidated and used for the health maintenance of bone tissue and defect regeneration. This paper summarizes the biomechanical properties of the bone matrix and their biological significance, discusses the compositional and structural basis by which the bone matrix is capable of exhibiting these mechanical properties, and studies the effects of mechanical stimuli, especially fluid shear stress, on the components of the bone matrix, cells and their interactions. The problems that occur with regard to the biomechanics and mechanobiology of the bone matrix and the corresponding challenges that may need to be faced in the future are also described.

Poly(N-isopropylacrylamide) (PNIPAM) based electrically conductive hydrogels (PNIPAM-ECHs) have been extensively studied in recent decades due to their thermal-responsive (leading to the volume change of hydrogels) and electrically conductive performance. The incorporation of conductive components into the PNIPAM hydrogel network makes it become conductive hydrogel, and as a result, the PNIPAM hydrogel could become sensitive to an electrical signal, greatly expanding its application. In addition, conductive components usually bring new stimuli-responsive properties of PNIPAM-based hydrogels, such as near-infrared light and stress/strain responsive properties. PNIPAM-ECHs display a wide range of applications in human motion detection, actuators, controlled drug release, wound dressings, etc. To summarize recent research advances and achievements related to PNIPAM-ECHs, this manuscript first reviews the design and structure of representative PNIPAM-ECHs according to their conductive components. Then, the applications of PNIPAM-ECHs have been classified and discussed. Finally, the remaining problems related to PNIPAM-ECHs have been summarized and a future research direction is proposed which is to fabricate PNIPAM-ECHs with integrated multifunctionality.