Biomimetic Self-Maturation Mineralization System for Enamel Repair.

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.

Polyphosphate-crosslinked collagen scaffolds for hemostasis and alveolar bone regeneration after tooth extraction.

Post-extraction bleeding and alveolar bone resorption are the two frequently encountered complications after tooth extraction that result in poor healing and rehabilitation difficulties. The present study covalently bonded polyphosphate onto a collagen scaffold (P-CS) by crosslinking. The P-CS demonstrated improved hemostatic property in a healthy rat model and an anticoagulant-treated rat model. This improvement is attributed to the increase in hydrophilicity, increased thrombin generation, platelet activation and stimulation of the intrinsic coagulation pathway. In addition, the P-CS promoted the in-situ bone regeneration and alveolar ridge preservation in a rat alveolar bone defect model. The promotion is attributed to enhanced osteogenic differentiation of bone marrow stromal cells. Osteogenesis was improved by both polyphosphate and blood clots. Taken together, P-CS possesses favorable hemostasis and alveolar ridge preservation capability. It may be used as an effective treatment option for post-extraction bleeding and alveolar bone loss. Statement of significance: Collagen scaffold is commonly used for the treatment of post-extraction bleeding and alveolar bone loss after tooth extraction. However, its application is hampered by insufficient hemostatic and osteoinductive property. Crosslinking polyphosphate with collagen produces a modified collagen scaffold that possesses improved hemostatic performance and augmented bone regeneration potential.

Silicified collagen scaffold induces semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration.

Sensory nerves promote osteogenesis through the release of neuropeptides. However, the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive. The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats. The wound sites were accompanied by extensive nerve innervation and angiogenesis. Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model. Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A (Sema3A) and semaphorin 4D (Sema4D) in the dorsal root ganglion (DRG), as detected by the upregulation of signaling molecules. Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells. These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies. Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model, whereas overexpression of Sema3A promoted the silicon-induced phenomena. Activation of "mechanistic target of rapamycin" (mTOR) pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds. These findings support the role of silicon in inducing Sema3A production by sensory nerves, which, in turn, stimulates osteogenesis and angiogenesis. Taken together, silicon has therapeutic potential in orthopedic rehabilitation.

Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization.

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.

Neuroprotective effect of methylprednisolone combined with placenta-derived mesenchymal stem cell in rabbit model of spinal cord injury.

The aim of this study was to assess the ability of the combination treatment of methylprednisolone (MP) and placenta-derived mesenchymal stem cells (PDMSCs) in a rabbit model of spinal cord injury (SCI). Rabbits were randomly divided into four groups: group 1 (control), group 2 (MP), group 3 (PDMSCs) and group 4 (MP + PDMSCs). In all groups, the spinal cord injury model was created by the weight drop method. Levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined by kit. Histopathological examination was also performed. Neurological evaluation was carried out with the Tarlov scoring system. The results showed both MP and PDMSCs had neuroprotective effects, and combining the administration of MP with PDMSCs was shown a significant effect on the recovery of neurological function. Therefore, the combined use of MP and PDMSCs can be used as a potential therapeutic method for SCI.

[Characteristics of nitrogen and phosphorus removal and control of membrane fouling in MBR and SMBR].

To improve the efficiency and running stability of wastewater advanced treatment, a sequencing membrane bioreactor (SMBR) and a traditional membrane bioreactor (MBR) were used to investigate the characteristics of nitrogen and phosphorus removal, and the effect of anoxic time on treatment systems and membrane fouling. Simultaneously, molecular biology techniques were applied to analyze the composition of microbial community and the structure of suspended sludge. The results showed that SMBR had higher efficiency in removing TN than MBR, which indicated that intermittent aeration could enhance the ability of nitrogen removal. SMBR and MBR had a similar removal efficiency of NH4(+)-N, TP, COD, and turbidity with the removal rates of 94%, 78%, 80%, and 97%, respectively. Extension of SMBR anoxic time had no effect on COD, NH4(+) -N removal but decreased TN and TP removal rate, dropping from 61% and 74% to 46% and 52%, respectively. Intermittent aeration and powder activated carbon (PAC) could both mitigate membrane fouling. The analysis on microbial community indicated that there was no difference in the composition and structure of microbial community between SMBR and MBR. Nitrospira and Dechloromonas were both highly abundant functional groups, which provided the basis for highly efficient control of bioreactors.

Inositol-requiring protein 1α signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy.

Accumulating evidence suggests that repeated seizures could induce endoplasmic reticulum (ER) stress. Inositol-requiring protein 1α (IRE1α) is a vital pro-apoptotic molecule in ER stress, but it remains unclear whether the signaling pathway mediated by IRE1α is involved in human temporal lobe epilepsy. In this report, we investigated IRE1α-mediated ER stress pro-apoptotic signaling pathway in resected anterior temporal neocortex from 32 patients with intractable mesial temporal lobe epilepsy by immunofluorescence and western blot analysis. Our results indicate that chronic epilepsy induces ER stress, and IRE1α-mediated ER stress apoptotic signaling pathway is involved in brain damage after repeated seizures, which may provide a new therapeutic target to prevent brain damage caused by epilepsy.

[PAH sources in road runoff system in Beijing].

In this study, road runoff, rainwater, ground sediment and roadside tree water samples were collected from three types of roads in Beijing in 2006. The samples were analyzed for polycyclic aromatic hydrocarbons (PAHs). The average PAH concentrations in each media in May-June were generally higher than those in July-August. Factor analysis indicated that PAHs in road runoff were mainly from ground sediment, and rainwater and roadside tree water also had certain influence to road runoff. Multiple regression analysis indicated that PAHs in ground sediment and road runoff mainly come from vehicular emission at the vehicle way and branch road, and at the bicycle way, the contributions of vehicular emission and coal combustion were equal. PAHs in rain were mainly from coal/oil combustion, and PAHs in roadside tree water were dominated by vehicular emission source.

[Concentration characteristics and influencing factors of atmospheric polycyclic aromatic hydrocarbons in TSP in the southeastern suburb of Beijing, China].

ATSP samples were collected at three sampling sites in the southeastern suburb of Beijing from March, 2005 to January, 2006. The samples were analyzed for TSP and sixteen PAHs. The concentrations and seasonal changes of TSP and sixteen PAHs were illustrated. Concentrations of sigma 16PAHs range from 0.29 - 1 184.48 ng/m3, and the average value is 239.44 ng/m3. Partial correlation analysis was applied to investigate the influence of meteorological parameters (temperature, wind speed, air pressure and relative humidity) and air pollution indexes (SO2, NO2 and PM10) on PAHs concentrations. Finally, quantitative estimation equations between PAHs and meteorological parameters and air pollution indexes were put forward by applying stepwise linear regression method, and the equations are sigma 16PAHs = 572.56 - 23.18 t and sigma 16PAHs = 5.99 SO2, respectively. Concentration of PAHs could be estimated using temperature or API of SO2.