RESUMO
Enamel repair is crucial for restoring tooth function and halting dental caries. However, contemporary research often overlooks the retention of organic residues within the repair layer, which hinders the growth of dense crystals and compromises the properties of the repaired enamel. During the maturation of natural enamel, the organic matrix undergoes enzymatic processing to facilitate further crystal growth, resulting in a highly mineralized tissue. Inspired by this process, a biomimetic self-maturation mineralization system is developed, comprising ribonucleic acid-stabilized amorphous calcium phosphate (RNA-ACP) and ribonuclease (RNase). The RNA-ACP induces initial mineralization in the form of epitaxial crystal growth, while the RNase present in saliva automatically triggers a biomimetic self-maturation process. The mechanistic study further indicates that RNA degradation prompts conformational rearrangement of the RNA-ACP, effectively excluding the organic matter introduced earlier. This exclusion process promotes lateral crystal growth, resulting in the generation of denser enamel-like apatite crystals that are devoid of organic residues. This strategy of eliminating organic residues from enamel crystals enhances the mechanical and physiochemical properties of the repaired enamel. The present study introduces a conceptual biomimetic mineralization strategy for effective enamel repair in clinical practice and offers potential insights into the mechanisms of biomineral formation.
Assuntos
Biomimética , Fosfatos de Cálcio , Cárie Dentária , Humanos , RNA , Ribonucleases , Esmalte DentárioRESUMO
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.
Assuntos
Osso e Ossos , Colágeno , Nanotecnologia , Biomineralização , Osso e Ossos/metabolismo , Colágeno/química , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Osteogênese , CicatrizaçãoRESUMO
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.