The visionary idea that RNA adopts nonbiological roles in today's nanomaterial world has been nothing short of phenomenal. These RNA molecules have ample chemical functionality and self-assemble to form distinct nanostructures in response to external stimuli. They may be combined with inorganic materials to produce nanomachines that carry cargo to a target site in a controlled manner and respond dynamically to environmental changes. Comparable to biological cells, programmed RNA nanomachines have the potential to replicate bone healing in vitro. Here, an RNA-biomineral nanomachine is developed, which accomplishes intrafibrillar and extrafibrillar mineralization of collagen scaffolds to mimic bone formation in vitro. Molecular dynamics simulation indicates that noncovalent hydrogen bonding provides the energy source that initiates self-assembly of these nanomachines. Incorporation of the RNA-biomineral nanomachines into collagen scaffolds in vivo creates an osteoinductive microenvironment within a bone defect that is conducive to rapid biomineralization and osteogenesis. Addition of RNA-degrading enzymes into RNA-biomineral nanomachines further creates a stop signal that inhibits unwarranted bone formation in tissues. The potential of RNA in building functional nanostructures has been underestimated in the past. The concept of RNA-biomineral nanomachines participating in physiological processes may transform the nanoscopic world of life science.
Abstract For the past two decades, the function of intrabony nerves on bone has been a subject of intense research, while the function of bone on intrabony nerves is still hidden in the corner. In the present review, the possible crosstalk between bone and intrabony peripheral nerves will be comprehensively analyzed. Peripheral nerves participate in bone development and repair via a host of signals generated through the secretion of neurotransmitters, neuropeptides, axon guidance factors and neurotrophins, with additional contribution from nerve‐resident cells. In return, bone contributes to this microenvironmental rendezvous by housing the nerves within its internal milieu to provide mechanical support and a protective shelf. A large ensemble of chemical, mechanical, and electrical cues works in harmony with bone marrow stromal cells in the regulation of intrabony nerves. The crosstalk between bone and nerves is not limited to the physiological state, but also involved in various bone diseases including osteoporosis, osteoarthritis, heterotopic ossification, psychological stress‐related bone abnormalities, and bone related tumors. This crosstalk may be harnessed in the design of tissue engineering scaffolds for repair of bone defects or be targeted for treatment of diseases related to bone and peripheral nerves.
Although deoxyribonucleic acid (DNA) is the genetic coding for the very essence of life, these macromolecules or components thereof are not necessarily lost after a cell dies. There appears to be a link between extracellular DNA and biomineralization. Here the authors demonstrate that extracellular DNA functions as an initiator of collagen intrafibrillar mineralization. This is confirmed with in vitro and in vivo biological mineralization models. Because of their polyanionic property, extracellular DNA molecules are capable of stabilizing supersaturated calcium phosphate solution and mineralizing 2D and 3D collagen matrices completely as early as 24 h. The effectiveness of extracellular DNA in biomineralization of collagen is attributed to the relatively stable formation of amorphous liquid droplets triggered by attraction of DNA to the collagen fibrils via hydrogen bonding. These findings suggest that extracellular DNA is biomimetically significant for fabricating inorganic-organic hybrid materials for tissue engineering. DNA-induced collagen intrafibrillar mineralization provides a clue to the pathogenesis of ectopic mineralization in different body tissues. The use of DNase for targeting extracellular DNA at destined tissue sites provides a potential solution for treatment of diseases associated with ectopic mineralization.
Bilateral communication between bone and nerves is crucial for optimal repair of large bone defects as well as repair of peripheral nerves within the skeleton. However, simultaneous regeneration of bone and nerves is an issue that has long been overlooked in prior literature. Incongruous or even contradictory requirements or regeneration environments for bone and nerves make simultaneous regeneration of multiple tissues challenging. The present review commences with introducing natural crosstalk between bone and nerves, highlighting the rationale for simultaneous regeneration of bone and nerves. These issues will pave the way for the development of inspirational materials design concepts that capitalize on the principles of osteoconduction, osteoinduction, neuroconduction, neuroinduction, and neuroattraction. Potential strategies based on selection of appropriate scaffolds, acellular biological factors and architectural design will be addressed.
To improve osseointegration and enhance the success rate of implanted biomaterials, the surface modification technology of bone implants has developed rapidly. Intensive research on osteoimmunomodulation has shown that the surfaces of implants should possess favorable osteoimmunomodulation to facilitate osteogenesis.A novel, green and efficient phase-transited lysozyme (PTL) technique was used to prime titanium discs with a positive charge. In addition, sodium hyaluronate (HA) and self-assembled type I collagen containing aspirin (ASA) nanoparticles were decorated on PTL-primed Ti discs via electrostatic interaction.The behaviors of bone marrow stromal cells (BMSCs) on the Ti disc surfaces containing ASA were analyzed in different conditioned media (CM) generated by macrophages. Additionally, the secretion of inflammation-related cytokines of macrophages on the surfaces of different Ti discs was investigated in in vitro experiments, which showed that the Ti surface containing ASA not only supported the migration, proliferation and differentiation of BMSCs but also reduced the inflammatory response of macrophages compared with Ti discs without surface modification. After implantation in vivo, the ASA-modified implant can significantly contribute to bone formation around the implant, which mirrors the evaluation in vitro.This study highlights the significant effects of appropriate surface characteristics on the regulation of osteogenesis and osteoimmunomodulation around an implant. Implant modification with ASA potentially provides superior strategies for the surface modification of biomaterials.
Abstract Objective To investigate the significant role of fibrocytes in pathogenesis of fibrous epulis. Material Human epulis specimens and human peripheral blood mononuclear cells (PBMCs) were used in this study. Methods Different subtypes of human fibrous epulides and normal gingival tissue specimens were collected for histological and immunofluorescence analyses. Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human PBMCs were subsequently isolated from peripheral blood to identify the factor that trigger fibrocyte differentiation in vitro . Results We demonstrated the presence of circulation-derived fibrocytes in fibrous epulides. These fibrocytes differentiate into myofibroblasts or osteoblasts under the local inflammatory environment in fibrous epulides. TGF-β1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner. The TGF-β1 along with a high calcium and phosphorus extracellular environment stimulates the fibrocytes to differentiate into osteoblasts. The fibrocytes-derived myofibroblasts and osteoblasts are responsible for the fibrogenesis and osteogenesis of fibrous epulides, respectively. The persistent local inflammatory environment drived the differentiation of circulation-derived fibrocytes and drived the recurrence of fibrous epulides. Conclusions Fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the recurrence of fibrous epulides.
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