Atomic layer deposition (ALD)-constructed TaS2nanoflakes for cancer-related nucleolin detection.

Sensitive detection of nucleolin (NCL) is of great significance for the early diagnosis of cancer. In this work, as a new type of two-dimensional (2D) transition metal dichalcogenides (TMDCs), TaS2nanoflakes (NFs) were precisely constructed by atomic layer deposition (ALD) on carbon fiber paper (CFP) with high specific surface area.In situobservation showed that the nucleation and growth of TaS2nanoflakes were precisely controlled by the number of ALD cycles, thereby regulating their electrochemical properties. The electrochemical performance of TaS2NFs was observed in depth, and compared with that of traditional 2D TMDCs. Due to the high surface area and conductivity, anodic/cathodic current of ∼1570µA of TaS2NFs/CFP can be obtained. Subsequently, an electrochemical biosensor based on ALD-constructed TaS2NFs/CFP for cancer-related NCL detection was fabricated. Due to the excellent electrochemical performance of TaS2NFs/CFP, ultrasensitive detection of NCL in the linear range of 0.1 pM-10 nM with a detection limit of 0.034 pM was achieved.

Efficacy comparison of antibiotic bone cement-coated implants and external fixations for treating infected bone defects.

PURPOSE: This study aimed to investigate the clinical efficacy of antibiotic bone cement-coated implants compared with external fixations for treating infected bone defects. METHODS: We retrospectively enrolled 119 patients with infected bone defects in our hospital from January 2010 to June 2021, of which 56 were treated with antibiotic bone cement-coated implants and 63 were with external fixation. RESULTS: The pre-operative and post-operative haematological indexes were tested to assess the infection control; the post-operative CRP level in the internal fixation group was lower than that in the external fixation group. No statistical significance was found in the rate of infection recurrence, loosening and rupture of the fixation, and amputation between the two groups. Twelve patients in the external fixation group had pin tract infection. In the evaluation of the Paley score scale, bone healing aspect revealed no significant difference between the two groups, while in the limb function aspect, antibiotic cement-coated implant group showed a much better score than the external fixation group (P = 0.002). The anxiety evaluation scale result also showed lower score in the antibiotic cement implant group (P < 0.001). CONCLUSIONS: Compared with external fixation, antibiotic bone cement-coated implant had the same effect on controlling infection and was more effective in recovering limb function and mental health in the first-stage treatment of infected bone defects after debridement.

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BACKGROUND: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs. METHODS: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation. RESULTS: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres. CONCLUSIONS: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Thermal/ultrasound-triggered release of liposomes loaded with Ganoderma applanatum polysaccharide from microbubbles for enhanced tumour ablation.

The effectiveness of thermal ablation for the treatment of liver tumours is limited by the risk of incomplete ablation, which can result in residual tumours. Herein, an enhancement strategy is proposed based on the controlled release of Ganoderma applanatum polysaccharide (GAP) liposome-microbubble complexes (GLMCs) via ultrasound (US)-targeted microbubble destruction (UTMD) and sublethal hyperthermic (SH) field. GLMCs were prepared by conjugating GAP liposomes onto the surface of microbubbles via biotin-avidin linkage. In vitro, UTMD promotes the cellular uptake of liposomes and leads to apoptosis of M2-like macrophages. Secretion of arginase-1 (Arg-1) and transforming growth factor-beta (TGF-ß) by M2-like macrophages decreased. In vivo, restriction of tumour volume was observed in rabbit VX2 liver tumours after treatment with GLMCs via UTMD in GLMCs + SH + US group. The expression levels of CD68 and CD163, as markers of tumour-associated macrophages (TAMs) in the GLMCs + SH + US group were reduced in liver tumour tissue. Decreased Arg-1, TGF-ß, Ki67, and CD31 factors related to tumour cell proliferation and angiogenesis was evident on histological analysis. In conclusion, thermal/US-triggered drug release from GLMCs suppressed rabbit VX2 liver tumour growth in the SH field by inhibiting TAMs, which represents a potential approach to improve the effectiveness of thermal ablation.

A High-Performance Self-Supporting Electrochemical Biosensor to Detect Aflatoxin B1.

High-performance electrochemical biosensors for the rapid detection of aflatoxin B1 (AFB1) are urgently required in the food industry. Herein, a multi-scaled electrochemical biosensor was fabricated by assembling carboxylated polystyrene nanospheres, an aptamer and horseradish peroxidase into a free-standing carbon nanofiber/carbon felt support. The resulting electrochemical biosensor possessed an exceptional performance, owing to the unique structures as well as the synergistic effects of the components. The 3D porous carbon nanofiber/carbon felt support served as an ideal substrate, owing to the excellent conductivity and facile diffusion of the reactants. The integration of carboxylated polystyrene nanospheres with horseradish peroxidase was employed as a signal amplification probe to enhance the electrochemical responses via catalyzing the decomposition of hydrogen peroxide. With the aid of the aptamer, the prepared sensors could quantitatively detect AFB1 in wine and soy sauce samples via differential pulse voltammetry. The recovery rates of AFB1 in the samples were between 87.53% and 106.71%. The limit of detection of the biosensors was 0.016 pg mL-1. The electrochemical biosensors also had excellent sensitivity, reproducibility, specificity and stability. The synthetic strategy reported in this work could pave a new route to fabricate high-performance electrochemical biosensors for the detection of mycotoxins.

Low-molecular-weight supramolecular adhesives based on non-covalent self-assembly of a small molecular gelator.

Currently developed adhesives are overwhelmingly polymeric in nature. Herein, we highlight for the first time the potential of supramolecular eutectogels assembled from small molecules as robust low-molecular-weight (LMW) supramolecular adhesives in air, water and organic solvents, and under low temperatures. These supramolecular eutectogels were produced from commercial alkyl trimethyl ammonium bromide (CnTAB) in emerging deep eutectic solvents (DESs), which demonstrated rapid (∼2 min), robust, and tunable adhesion to both hydrophilic and hydrophobic surfaces at room temperature in air. Moreover, high adhesion performance was maintained even in liquid nitrogen (-196 °C), underwater, and in organic solvents. A study of the structure-property relationship of these adhesives and molecular dynamics (MD) simulations further clarified the assembly and adhesion mechanism of the C12TAB molecules in DESs. Compared with traditional polymer adhesives and several existing examples of LMW supramolecular adhesives with solvent-free dry network structures, the spontaneous self-assembly of LMW gelators in versatile DESs provides a new strategy for the facile construction of high-strength supramolecular adhesives with gel network structures for a diverse range of harsh environments.

Analysis of the epidemiological status, microbiology, treatment methods and financial burden of hematogenous osteomyelitis based on 259 patients in Northwest China.

Background: The incidence of hematogenous osteomyelitis is on the rise, and the prognosis is poor. There has been no large-scale epidemiological analysis of hematogenous osteomyelitis in the world, and the treatment method is still controversial. Methods: A retrospective case study method was used to collect and analyze clinical data obtained from patients with hematogenous osteomyelitis in a tertiary hospital in Northwest China from January 1, 2011, to December 31, 2020. The aim of this study was to investigate the epidemiological status, microbiological characteristics, treatment and financial burden of hematogenous osteomyelitis in Northwest China to explore the therapeutic effects of different treatment methods, elucidate the epidemiological characteristics of hematogenous osteomyelitis and to provide a basis for the choice of treatment. Results: We included 259 patients with hematogenous osteomyelitis, including 96 patients with acute hematogenous osteomyelitis and 163 patients with chronic hematogenous osteomyelitis. The cause of the disease was not obvious in most patients, the sex ratio of males to females was 1.98, and the three most common infected sites were the tibia, femur and phalanx. Regarding preoperative serum inflammatory markers, the rate of positivity for ESR was the highest at 67.58%. Among pathogenic microorganisms, Staphylococcus aureus was the most common. Regarding the financial burden, the median total cost per patient was 25,754 RMB, and medications accounted for the largest proportion of the main costs. Conclusions: The most common pathogen associated with HO infection was MSSA. Oxacillin has good PK and PD and is recommended as the first-line drug. Some blood-borne bone infections may lead to complications, such as pulmonary infection through bacteremia, which requires early detection to avoid a missed diagnosis. Regarding surgical intervention, debridement plus absorbable calcium sulfate bone cement and calcium sulfate calcium phosphate bone cement exclusion have achieved good therapeutic effects, but they are worthy of further in-depth research. Regarding the financial burden, the median total cost per patient was 25,754 RMB. The financial burden of blood-borne osteomyelitis was lower than that of traumatic osteomyelitis. Among the main costs, drugs accounted for the largest proportion.

Bone substitute biomedical material of multi-(amino acid) copolymer: in vitro degradation and biocompatibility.

Degradable polymers with good mechanical strength as bone repair biomaterials have been paid more attention in biomedical application. In this study, a multi-(amino acid) copolymer consisting of 6-aminocaproic acid and five natural amino acids was prepared by a reaction of acid-catalyzed condensation. The results revealed that the copolymer could be slowly degradable in Tris-HCl solution, and lost its initial weight of 31.9 wt% after immersion for 12 weeks, and the changes of pH value of Tris-HCl solution were in range from 6.9 to 7.4 during soaking. The compressive strength of the copolymer decreased from 107 to 68 MPa after immersion for 12 weeks. The proliferation and differentiation of MG-63 cells on the copolymer significantly increased with time, and the cells with normal phenotype extended and spread well on the copolymer surfaces. When the copolymer was implanted in muscle and bone defects of femoral cortex of dogs for 12 weeks, the histological evaluation confirmed that the copolymer exhibited excellent biocompatibility and more effective osteogenesis in vivo. When implanted into cortical bone defects of dogs, the copolymer could be combined directly with the natural bone without fibrous capsule tissue between implants and host bone. The results indicated that the multi-(amino acid) copolymer with sufficient strength, good biocompatibility and osteoconductivity had clinical potential for load-bearing bone repair or substitution.

Cobalt-Iron Double Ion-Bovine Serum Albumin Chelation-Assisted Thermo-Sensitive Surface-Imprinted Nanocage with High Specificity.

To develop multifunctional protein imprinted materials, a cobalt-iron double ion-BSA directional chelation-assisted thermo-sensitive surface-imprinted hollow nanocage (Co-Fe@CBMA-MIPs) with excellent specificity is developed on the surface of ZIF-67@Co-Fe in this study by synergizing the advantages of surface imprinting, metal ion chelation, anti-protein adsorption segments, and thermo-sensitive components. Beyond previous research, well-designed multifunctional protein-imprinted materials possess high binding capacity, fast adsorption kinetics, and outstanding selectivity. When the adsorption is carried out at 32 °C, the adsorption capacity of Co-Fe@CBMA-MIPs for BSA reaches 520.35 mg/g within 50 min. The imprinting factor is 8.55. The selectivity factors of Co-Fe@CBMA-MIPs for HSA, Bhb, OVA, and Lyz are 3.72, 6.09, 4.10, and 8.41, respectively. More significantly, Co-Fe@CBMA-MIPs could specifically recognize BSA from mixed proteins and actual samples and exhibit excellent repeated use stability. Based on the above advantages, the development of this research provides an effective means to improve the recognition specificity of molecularly imprinted polymers.

Smart Titanium Coating Composed of Antibiotic Conjugated Peptides as an Infection-Responsive Antibacterial Agent.

Antibacterial coating is rapidly emerging as a pivotal strategy for mitigating spread of bacterial pathogens. However, many challenges still need to be overcome in order to develop a smart coating that can achieve on-demand antibacterial effects. In this study, a Staphylococcus aureus (S. aureus) sensitive peptide sequence is designed, and an antibiotic is then conjugated with this tailor-made peptide. The antibiotic-peptide conjugate is then linked to the surface of a titanium implant, where the peptide can be recognized and cleaved by an enzyme secreted by S. aureus. This allows for the release of antibiotics in the presence of S. aureus, thus achieving delivery of an antibacterial specifically when an infection occurs.

Combined cortisol and melatonin measurements with detailed parameter analysis can assess the circadian rhythms in bipolar disorder patients.

OBJECTIVES: Bipolar disorder (BD) is a common chronic mental illness. The circadian clock disorder shows a significant correlation with the pathogenesis, phenotype and recurrence of BD. We aim to evaluate non-invasive methods that can comprehensively assess the circadian rhythmicity in BD patients. METHODS: We non-invasively collected salivary samples and oral epithelial cells from recruited subjects. Then the levels of cortisol and melatonin in saliva were measured and the circadian clock gene expressions (PER2 and BMAL1) of epithelial cells were analyzed. Due to the disease characteristics of the manic patients who were difficult to cooperate with the protocol, only one patient at manic episode was recruited. Besides, 11 patients at the depressive episode, 15 healthy controls and four patients at recovery stage were recruited. RESULTS: Our results exhibited that the peak phase of cortisol level mainly manifested around 8:00 a.m., and the maximal melatonin level reached around 5:00 a.m. The phase of cortisol in patients with depression did not change significantly, but the level of cortisol decreased significantly, while the phase of melatonin level moved forward about 2.5 hr. Furthermore, the levels and phases of cortisol and melatonin in recovery patients tended to be similar to those of healthy controls. CONCLUSIONS: With detailed parameter analysis, the combined detection of melatonin and cortisol can better judge the biological clock disorder of bipolar patients. The circadian rhythms of patients at the recovery stage tend to be normal. The clock gene expression examination needs strict quality control and more investigations before being applied to assess human circadian rhythms.

Custom-Made Antibiotic Cement-Coated Nail for the Treatment of Infected Bone Defect.

BACKGROUND: Longbone infected bone defect remains a great challenge due to multiple surgeries, long-term treatment duration, and uncertain prognosis. Treatment principles include eradication/debridement, stabilization, and antibiotic administration. An antibiotic cement-coated nail has shown great prospects due to both local antibiotic elution and stabilization of bone defects. However, the current fabrication technique remains to be improved. METHODS: For the first time, we described a new method for custom-made cement-coated nail fabrication based on a 3D printing technique. A retrospective study of 19 consecutive patients with long bone infected bone defects from one medical center was conducted who met the inclusion and exclusion criteria from November 2016 to May 2020. The treatment involved thorough debridement, custom-made antibiotic cement-coated nail filling, and culture-specific systemic antibiotic treatment guided by a multidisciplinary team. Clinical and radiographic examinations (X-ray and CT scans) were used to evaluate bony union. Clinical and laboratory examinations were used to evaluate the infection control. The SF-36 score was used to evaluate patients' quality of life pre- and postoperatively. RESULTS: The mean follow-up was 98.8 weeks (ranging from 40 to 192). All cases achieved infection control, 3 cases achieved bone healing after one-stage operation, and 12 cases achieved bone healing after a two-stage bone graft procedure. At the last follow-up, none of the 19 patients had infection recurrence or 1 case had failure of the protective plate. The pre- and postoperative SF-36 score showed that there were statistical differences in all the 9 aspects. CONCLUSIONS: The precise custom-made antibiotic cement-coated intramedullary nail through the 3D printing technique used in this study is an effective strategy for the treatment of infected bone defects of long bone. This technique may help to increase the infection control rate and promote bone healing.

A novel possible strategy based on self-assembly approach to achieve complete periodontal regeneration.

Limitations of current regeneration modalities underscore the importance of restoring the three-dimensional (3D) microenvironment of periodontal development, which is able to elicit the intrinsic capacity of mesenchymal stem cells to proceed to engage in a redevelopment-like program. With increased attention for the potential therapeutic applications of periodontal ligament stem cells (PDLSCs) in periodontal regeneration, it has been proposed that bone marrow mesenchymal stem cells (BMMSCs) are very likely another cell source of physiological repair of periodontal tissues. With this in mind, enlightened from the research targeting the fabrication of laminar structures such as liver and kidney with heterotypic stratification of cell sheets, we proposed a novel possible strategy based on self-assembly approach, which is akin to the physiological phenomenon that occurs during organogenesis, to enhance complete reconstruction of functional complex periodontium-organ systems. We assumed that in this strategy, using the intrinsic capacity of monodispersed cells to self-assemble into a microtissue such as a 3D spheroid, bilayered cell pellet constructs comprising calcified bone-forming cell pellets (i.e., BMMSCs) and cementum/PDL-forming cell pellets (i.e., PDLSCs) would be fabricated in vitro in a tissue-mimicking way and then implanted into periodontal defects. We hypothesize that this novel strategy might open new options to reconstruct extended periodontal defects and then achieve the ultimate goal of predictable and complete regeneration of the periodontium.

Comprehensive and sequential management of an impacted maxillary central incisor with severe crown-root dilacerations.

Tooth dilaceration refers to a dental anomaly characterized by an abrupt deviation in the longitudinal axis of tooth. Crown-root dilaceration is diagnosed in teeth with sharp angles at the cement-enamel junction. The greater the bending degree is, the less chance there is for successful teeth preservation and relocation. In this report, a clinical case of an impacted maxillary central incisor with severe crown-root dilacerations was described by means of an operative evaluation using three-dimensional dental computed tomography and a multidisciplinary approach that included surgical, orthodontic, endodontic, prosthetic and periodontal therapy.

Effects of inorganic ions and natural organic matter on the aggregation of nanoplastics.

The aggregation of nanoplastics (NPs) is a key issue in understanding the dynamic nature of NPs in the environment. The aggregation of NPs under various environmental conditions has not yet been studied. We investigated the influences of inorganic ions and natural organic matter (NOM) on polystyrene (PS) NPs aggregation in solutions. Results showed that PS NPs remained stable in wide ionic strength solutions of NaCl (1-100 mM) and CaCl2 (0.1-15 mM), and only in low ionic strength FeCl3 solutions (0.01 mM). However, obvious PS NPs aggregation was observed in FeCl3 solutions with an increase in ionic strength (0.1 and 1 mM). Moreover, NOM had a negligible effect on PS NPs aggregation in all ionic strengths of NaCl and CaCl2 solutions and in low ionic strength FeCl3 solutions (0.01 mM). However, NOM reduced PS NPs aggregation in an intermediate ionic strength FeCl3 (0.1 mM) solution and increased aggregation in a high ionic strength FeCl3 (1 mM) solution. Based on the theoretical analysis of interaction forces among PS NPs, the Derjaguin-Landau-Verwey-Overbeek force was a contributor governing PS NPs aggregation either in the absence or presence of NOM. In addition, other factors, including electrostatic heterogeneity of PS NPs surfaces, steric repulsion induced by NOM, and clusters formed via bridging effect in the presence of NOM also contributed to altered PS NPs aggregation under selected conditions. The PS NPs-NOM clusters were directly observed using a cryogenic scanning electron microscope.

Age-associated microbiome shows the giant panda lives on hemicelluloses, not on cellulose.

The giant panda feeds almost exclusively on bamboo, a diet highly enriched in lignin and cellulose, but is characterized by a digestive tract similar to carnivores. It is still large unknown if and how the giant panda gut microbiota contributes to lignin and cellulose degradation. Here we show the giant pandas' gut microbiota does not significantly contribute to cellulose and lignin degradation. We found that no operational taxonomic unit had a nearest neighbor identified as a cellulolytic species or strain with a significant higher abundance in juvenile than cubs, a very low abundance of putative lignin and cellulose genes existed in part of analyzing samples but a significant higher abundance of genes involved in starch and hemicellulose degradation in juveniles than cubs. Moreover, a significant lower abundance of putative cellulolytic genes and a significant higher abundance of putative α-amylase and hemicellulase gene families were present in giant pandas than in omnivores or herbivores.

Enhanced antitumor immunity of nanoliposome-encapsulated heat shock protein 70 peptide complex derived from dendritic tumor fusion cells.

Tumor-derived heat shock proteins peptide complex (HSP.PC-Tu) has been regarded as a promising antitumor agent. However, inadequate immunogenicity and low bioavailability limit the clinical uses of this agent. In a previous study, we first produced an improved HSP70.PC-based vaccine purified from dendritic cell (DC)-tumor fusion cells (HSP70.PC-Fc) which had increased immunogenicity due to enhanced antigenic tumor peptides compared to HSP70.PC-Tu. In order to increase the bioavailability of HSP70.PC-Fc, the peptide complex was encapsulated with nanoliposomes (NL-HSP70.PC-Fc) in this study. After encapsulation, the tumor immunogenicity was observed using various assays. It was demonstrated that the NL-HSP70.PC-Fc has acceptable stability. The in vivo antitumor immune response was increased with regard to T-cell activation, CTL response and tumor therapy efficiency compared to that of HSP70.PC-Fc. In addition, it was shown that DC maturation was improved by NL-HSP70.PC-Fc, which added to the antitumor immunity. The results obtained for NL-HSP70.PC-Fc, which improved immunogenicity and increases the bioavailability of HSP70.PC, may represent superior heat shock proteins (HSPs)-based tumor vaccines. Such vaccines deserve further investigation and may provide a preclinical rationale to translate findings into early phase trials for patients with breast tumors.

pHlash: a new genetically encoded and ratiometric luminescence sensor of intracellular pH.

We report the development of a genetically encodable and ratiometic pH probe named "pHlash" that utilizes Bioluminescence Resonance Energy Transfer (BRET) rather than fluorescence excitation. The pHlash sensor-composed of a donor luciferase that is genetically fused to a Venus fluorophore-exhibits pH dependence of its spectral emission in vitro. When expressed in either yeast or mammalian cells, pHlash reports basal pH and cytosolic acidification in vivo. Its spectral ratio response is H(+) specific; neither Ca(++), Mg(++), Na(+), nor K(+) changes the spectral form of its luminescence emission. Moreover, it can be used to image pH in single cells. This is the first BRET-based sensor of H(+) ions, and it should allow the approximation of pH in cytosolic and organellar compartments in applications where current pH probes are inadequate.

Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid.

Herein a photon-manipulated mesoporous release system was constructed based on azobenzene-modified nucleic acids. In this system, the azobenzene-incorporated DNA double strands were immobilized at the pore mouth of mesoporous silica nanoparticles. The photoisomerization of azobenzene induced dehybridization/hybridization switch of complementary DNA, causing uncapping/capping of pore gates of mesoporous silica. This nanoplatform permits holding of guest molecules within the nanopores under visible light but releases them when light wavelength turns to the UV range. These DNA/mesoporous silica hybrid nanostructures were exploited as carriers for the cancer cell chemotherapy drug doxorubicin (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is light-wavelength-sensitive. Switching of the light from visible to the UV range uncapped the pores, causing the release of DOX from the mesoporous silica nanospheres and an obvious cytotoxic effect on cancer cells. We envision that this photocontrolled drug release system could find potential applications in cancer therapy.

Tissue engineering of cementum/periodontal-ligament complex using a novel three-dimensional pellet cultivation system for human periodontal ligament stem cells.

Limitations of conventional regeneration modalities underscore the necessity of recapitulating development for periodontal tissue engineering. In this study, we proposed a novel three-dimensional pellet cultivation system for periodontal ligament stem cells (PDLSCs) to recreate the biological microenvironment similar to those of a regenerative milieu. Monodispersed human PDLSCs were cultured in medium with ascorbic acid and conditioned medium from developing apical tooth germ cells and were subsequently harvested from culture plate as a contiguous cell sheet with abundant extracellular matrix. The detached cell-matrix membrane spontaneously contracted to produce a single-cell pellet. The PDLSCs embedded within this cell-matrix complex exhibited several phenotypic characteristics of cementoblast lineages, as indicated by upregulated alkaline phosphatase activity, accelerated mineralization, and the expression of bone sialoprotein and osteocalcin genes. When this PDLSC pellets were transplanted into immunocompromised mice, a regular aligned cementum/PDL-like complex was formed. These results suggest that the combination of apical tooth germ cell-conditioned medium and endogenous extracellular matrix could maximally mimic the microenvironment of root/periodontal tissue development and enhance the reconstruction of physiological architecture of a cementum/PDL-like complex in a tissue-mimicking way; on the other hand, such PDLSC pellet may also be a promising alternative to promote periodontal defect repair for future clinical applications.