Platelet-Drug Conjugates Engineered via One-step Fusion Approach for Metastatic and Postoperative Cancer Treatment.

The exploration of cell-based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one-step fusion process. We demonstrate doxorubicin (DOX)-encapsulated liposomes conjugated with interleukin-15 (IL-15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models.

Effect of the prosthetic index on stress distribution in Morse taper connection implant system and peri-implant bone: a 3D finite element analysis.

BACKGROUND: The combination of a prosthetic index with Morse taper connection was developed, with the purpose of making prosthetic procedures more precise. However, the presence of the index may compromise the mechanical performance of the abutment. The aim of this study is to evaluate the effect of prosthetic index on stress distribution in implant-abutment-screw system and peri-implant bone by using the 3D finite element methodology. METHODS: Two commercial dental implant systems with different implant-abutment connections were used: the Morse taper connection with platform switching (MT-PS) implant system and the internal hex connection with platform matching (IH-PM) implant system. Meanwhile, there are two different designs of Morse taper connection abutment, namely, abutments with or without index. Consequently, three different models were developed and evaluated: (1) MT-PS indexed, (2) MT-PS non-indexed, and (3) IH-PM. These models were inserted into a bone block. Vertical and oblique forces of 100 N were applied to each abutment to simulate occlusal loadings. RESULTS: For the MT-PS implant system, the maximum stress was always concentrated in the abutment neck under both vertical and oblique loading. Moreover, the maximum von Mises stress in the neck of the MT-PS abutment with index even exceed the yield strength of titanium alloy under the oblique loading. For the IH-PM implant system, however, the maximum stress was always located at the implant. Additionally, the MT-PS implant system has a significantly higher stress level in the abutment neck and a lower stress level around the peri-implant bone compared to the IH-PM implant system. The combined average maximum stress from vertical and oblique loads is 2.04 times higher in the MT-PS indexed model, and 1.82 times for the MT-PS non-indexed model than that of the IH-PM model. CONCLUSIONS: MT-PS with index will cause higher stress concentration on the abutment neck than that of without index, which is more prone to mechanical complications. Nevertheless, MT-PS decreases stress within cancellous bone and may contribute to limiting crestal bone resorption.

The influence of impaction to the third molar mineralization in northwestern Chinese population.

Age estimation by third molar mineralization has been developed for a period of time. Recent studies showed that impaction status has an influence on the rate of the third molar mineralization in Europids and male Black African populations. In this regard, the present study was conducted to determine whether the impaction status could delay the chronological process of third molar mineralization in northwestern Chinese population too. A total of 3,512 digital orthopantomograms of 1,255 male and 2,257 female northwestern Chinese subjects aged from 11 to 26 years were assessed based on the formation stages described by Demirjian et al. with two modifications. Mineralization stage and impaction status were determined for all third molars. Statistical measures were calculated at stages C-H in the male and female gender for both impacted and non-impacted third molars. It was ascertained that the mean ages with impacted third molars at stages C-H were 0.02-1.42 years higher in males and 0.04-1.52 years higher in females than those with non-impacted third molars, but statistical differences were only found at stages C, D, and E in males and stages D and E in females. The probabilities of being under 14, 16, or 18 years of age with non-impacted third molars were all higher than those with impacted third molars. The results prove that impacted third molars show significant slower mineralization than non-impacted ones at stages D and E in both males and females of northwestern Chinese population. It is recommended to consider the influence of impaction on the rate of third molar mineralization for dental age estimation.

ZnO/PUF composites with a large capacity for phosphate adsorption: adsorption behavior and mechanism studies.

Phosphate is present in all kinds of industrial wastewater; how to remove it to meet the strict total phosphorus discharge standards is a challenge. This study used a one-step foaming technique to fill polyurethane foam (PUF) with ZnO, taking advantage of PUF's excellent features like its porous network, lightweight, hydrophilicity, and abundance of binding sites to create ZnO/PUF composites with high adsorption capacity and exceptional separation properties. The adsorption isotherms, kinetics, starting pH, and matrix impacts of ZnO/PUF composites on phosphate were examined in batch studies. The results showed that the composites had good adsorption performance for phosphate with a saturated adsorption capacity of 460.25 mg/g. The quasi-secondary kinetic and Langmuir models could better describe the adsorption process, which belonged to the chemical adsorption of monomolecular layers. The composites' ability to treat phosphates in complicated waters was shown by their ability to retain a high adsorption capacity in the pH range of 3-6. In column experiments, the composite also maintains a good affinity for phosphate during dynamic adsorption. Multiple characterizations indicate that the adsorption mechanism is a combined effect of ligand exchange and electrostatic interactions. Therefore, this study provides valuable insights for practical phosphorus-containing wastewater treatment.

Tunable and fast-cured hyaluronic acid hydrogel inspired on catechol architecture for enhanced adhesion property.

Hyaluronic acid-based hydrogels have been broadly used in medical applications due to their remarkable properties such as biocompatibility, biodegradability, super hydroscopicity, non-immunogenic effect, etc. However, the inherent weak and hydrophilic polysaccharide structure of pure hyaluronic acid (HA) hydrogels has limited their potential use in muco-adhesiveness, wound dressing, and 3D printing. In this research, we developed in-situ forming of catechol-modified HA hydrogels with improved mechanical properties involving blue-light curing crosslinking reaction. The effect of catechol structure on the physicochemical properties of HA hydrogels was evaluated by varying the content (0-40 %). The as-synthesized hydrogel demonstrated rapid prototyping, excellent wetting adhesiveness, and good biocompatibility. Furthermore, an optimized hydrogel precursor solution was used as a blue light-cured bio-ink with high efficiency and good precision and successfully prototyped a microstructure that mimicked the human hepatic lobule by using DLP 3D printing method. This catechol-modified HA hydrogel with tunable physicochemical and rapid prototyping properties has excellent potential in biomedical engineering.

Evaluation of a platform-switched Morse taper connection for all-on-four or six treatment in edentulous or terminal dentition treatment: A retrospective study with 1-8 years of follow-up.

BACKGROUND: The survival rate, marginal bone loss and soft tissue health of the Ankylos implants and the balanced base abutments in all-on-four or six implant restoration of edentulous or terminal dentition patients has not been reported in the clinical research. PURPOSE: This retrospective study aimed to evaluate the Ankylos implants and the balanced base abutments in all-on-four or six implant restoration of edentulous or terminal dentition patients after 1-8 years of follow-up. MATERIALS AND METHODS: A retrospective study was conducted based on the medical records of 33 patients who received all-on-four or six treatments from April 2014 to May 2020. Four radiographic examinations [immediate postoperative (T0), definitive restorations (T1), 1-3 years after prosthetic restorations (T2), and more than 3 years after prosthetic restorations (T3)] were obtained to evaluate vertical bone height (VBH). We also calculated the survival rate and examined the condition of soft tissue with this implant system in edentulous or terminal dentition patients. Three-level linear model analyses were used to explore potential risk factors for VBH changes on the mesial and distal sides. The generalized linear model was used to analyze the influencing factors of BOP and plaque. RESULTS: A total of 218 implants were included in this study. The cumulative survival rate of the implants was 97.25% before the definitive prosthesis, 96.33% within 3 years of follow-up and 95.32% after more than 3 years of follow-up. The mean ± standard deviation (SD) bone losses of the VBH were 0.27 ± 0.05 mm (T1-T3) on the mesial side and 0.49 ± 0.06 mm (T1-T3) on the distal side. During 1-8 years of follow-up, the height and angle of the abutment (p < 0.001), the mandible implant site (p < 0.001), the length of the implant (p = 0.014 < 0.05) and age (p = 0.029 < 0.05) showed statistically significant effects on vertical mesial bone height (VMBH) and vertical distal bone height (VDBH). The risk of BOP among participants who brushed three times a day was lower than those who brushed less than three times. The plaque risk of short abutment height was higher than the long abutment. CONCLUSION: The current study showed that the Ankylos implants with the balanced base abutments in all-on-four or six implants treatment is a viable and predictable option with a high survival rate and low marginal bone loss in edentulous or terminal dentition patients. VBH around the implants was strongly associated with the mandible implant site, abutment height and angle, the length of the implant and age. Moreover, teeth-brushing times and abutment height significantly affect soft tissue health.

Biomechanical comparison of all-on-4 and all-on-5 implant-supported prostheses with alteration of anterior-posterior spread: a three-dimensional finite element analysis.

Introduction: The all-on-4 concept is widely used in clinical practice. However, the biomechanical changes following the alteration of anterior-posterior (AP) spread in all-on-4 implant-supported prostheses have not been extensively studied. Methods: Three-dimensional finite element analysis was used to compare the biomechanical behavior of all-on-4 and all-on-5 implant-supported prostheses with a change in anterior-posterior (AP) spread. A three-dimensional finite element analysis was performed on a geometrical mandible model containing 4 or 5 implants. Four different implant configurations were modeled by varying the angle of inclination of the distal implants (0°and 30°), including all-on-4a, all-on-4b, all-on-5a, and all-on-5b, and a 100 N force was successively applied to the anterior and unilateral posterior teeth to observe and analyze the differences in the biomechanical behavior of each model under the static influence at different position. Results: Adding an anterior implant to the dental arch according to the all-on-4 concept with a distal 30° tilt angle implant exhibited the best biomechanical behavior. However, when the distal implant was implanted axially, there was no significant difference between the all-on-4 and all-on-5 groups. Discussion: In the all-on-5 group, increasing the AP spread with tilted terminal implants showed better biomechanical behavior. It can be concluded that placing an additional implant in the midline of the atrophic edentulous mandible and increasing the AP spread might be beneficial in improving the biomechanical behavior of tilted distal implants.

Abutment mechanical complications of a Morse taper connection implant system: A 1- to 9-year retrospective study.

BACKGROUND: The fracture of a Morse tapered abutment connection in an osseointegrated implant is one of the most serious mechanical complications, and it is extremely hard to deal with this complication in clinical practice. PURPOSE: The aim of this study was to explore the cumulative mechanical complications focus on abutment of a platform switching Morse taper connection implant system after loading, and to perform a retrospective, approximately 1- to 9-year follow-up study to identify the predisposing factors. MATERIALS AND METHODS: A total of 495 patients with 945 fitted implants were enrolled in this study with a follow-up from January 2012 to January 2020. The data of mechanical complications of the abutment, including abutment fracture (AF) and abutment screw loosening (ASL), and possible causative factors were extracted and evaluated statistically. RESULTS: A total of 25 out of 945 (2.65%) cumulative abutment mechanical complications occurred. AF was the most common complication (n = 13, 1.38%), followed by ASL (n = 12, 1.27%). For AF, gender, type of prosthesis, abutment design, and implant diameter were identified as the causative factors. AF was mostly observed in the single crown of males in molar areas, while ASL was more likely to occur on an angled abutment than on a non-angled abutment. Moreover, the abutment with the positioning index (/X) had a higher incidence of fracture than the abutment without the positioning index (C/). CONCLUSIONS: This study shows that the Morse taper connection is a safe abutment connection. AF occurs more frequently within single crowns in molar area of males, especially with the positioning index (/X), while ASL is more likely to occur in an angled abutment.

Leveraging biomaterials for enhancing T cell immunotherapy.

The dynamic roles of T cells in the immune system to recognize and destroy the infected or mutated cells render T cell therapy a prospective treatment for a variety of diseases including cancer, autoimmune diseases, and allograft rejection. However, the clinical applications of T cell therapy remain unsatisfactory due to the tedious manufacturing process, off-target cytotoxicity, poor cell persistence, and associated adverse effects. To this end, various biomaterials have been introduced to enhance T cell therapy by facilitating proliferation, enhancing local enrichment, prolonging retention, and alleviating side effects. This review highlights the design strategies of biomaterials developed for T cell expansion, enrichment, and delivery as well as their corresponding therapeutic effects. The prospects of biomaterials for enhancing T cell immunotherapy are also discussed in this review.

Smart MSN-Drug-Delivery System for Tumor Cell Targeting and Tumor Microenvironment Release.

Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.

Polydopamine nanospheres as high-affinity signal tag towards lateral flow immunoassay for sensitive furazolidone detection.

Currently, the low sensitivity and poor binding stability of detection probe prepared via electrostatic adsorption have become the dilemmas of colloidal gold-based lateral flow immunoassays (Au-LFIAs). In this connection, polydopamine nanospheres (PDA NPs) with an eminent covalent connectivity property were introduced as a promising substitute to improve the stability of probe and sensitivity of LFIA. Whereafter, the PDA NPs-based LFIA was applied for the monitoring of furazolidone (FZD) in food samples because of the potential carcinogenic/mutagenic effects to human of its metabolite (3-amino-2-oxazolidinone, AOZ). Compared with electrostatic adsorption, the binding stability of PDA NPs-based probes was superior. And, as expected, the PDA NPs-based LFIA biosensor exhibited higher sensitivity than that of the Au-LFIA with a detection limit of 3.5 ng mL-1 for AOZ by naked-eye readout. Based on the significant enhanced binding stability and sensitivity, the PDA NPs-based LFIA is of certain spreading value for detecting other analytes.

The 3D-Printed PLGA Scaffolds Loaded with Bone Marrow-Derived Mesenchymal Stem Cells Augment the Healing of Rotator Cuff Repair in the Rabbits.

The healing of tendon-bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs-PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs-PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs-PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon-bone interface. The biomechanical analysis showed that BMSCs-PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon-bone healing in the rabbit rotator cuff repair model.

The application of BMP-12-overexpressing mesenchymal stem cells loaded 3D-printed PLGA scaffolds in rabbit rotator cuff repair.

This study investigates if the application of bone marrow-derived mesenchymal stem cells (BM-MSCs) loaded 3D-printed scaffolds could improve rotator cuff repair. The polylactic-co-glycolic acid (PLGA) scaffolds were fabricated by 3D print technology. Rabbit BM-MSCs were transfected with a recombinant adenovirus encoding bone morphogenic protein 12 (BMP-12). The effect of BM-MSCs loaded PLGA scaffolds on tendon-bone healing was assessed by biomechanical testing and histological analysis in a rabbit rotator cuff repair model. We found that the PLGA scaffolds had good biocompatible and biodegradable property. Overexpression of BMP-12 increased the mRNA and protein expression of tenogenic genes in BM-MSCs cultured with DMEM medium and seeded in PLGA scaffolds. When BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds were implanted into the injured rabbit supraspinatus tendon-bone junctions, the tendon-bone healing was improved. Our results suggest that application of BMP-12 overexpressing BM-MSCs loaded 3D-printed PLGA scaffolds promote the healing of tendon-bone interface, improve collagen organization and increase fibrocartilage in the rabbit rotor cuff repair. Rotator cuff regeneration achieved by BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds may represent a novel approach for the management of rotator cuff defect.

Circularity and self-cleavage as a strategy for the emergence of a chromosome in the RNA-based protocell.

BACKGROUND: It is now popularly accepted that an "RNA world" existed in early evolution. During division of RNA-based protocells, random distribution of individual genes (simultaneously as ribozymes) between offspring might have resulted in gene loss, especially when the number of gene types increased. Therefore, the emergence of a chromosome carrying linked genes was critical for the prosperity of the RNA world. However, there were quite a few immediate difficulties for this event to occur. For example, a chromosome would be much longer than individual genes, and thus more likely to degrade and less likely to replicate completely; the copying of the chromosome might start at middle sites and be only partial; and, without a complex transcription mechanism, the synthesis of distinct ribozymes would become problematic. RESULTS: Inspired by features of viroids, which have been suggested as "living fossils" of the RNA world, we supposed that these difficulties could have been overcome if the chromosome adopted a circular form and small, self-cleaving ribozymes (e.g. the hammer head ribozymes) resided at the sites between genes. Computer simulation using a Monte-Carlo method was conducted to investigate this hypothesis. The simulation shows that an RNA chromosome can spread (increase in quantity and be sustained) in the system if it is a circular one and its linear "transcripts" are readily broken at the sites between genes; the chromosome works as genetic material and ribozymes "coded" by it serve as functional molecules; and both circularity and self-cleavage are important for the spread of the chromosome. CONCLUSIONS: In the RNA world, circularity and self-cleavage may have been adopted as a strategy to overcome the immediate difficulties for the emergence of a chromosome (with linked genes). The strategy suggested here is very simple and likely to have been used in this early stage of evolution. By demonstrating the possibility of the emergence of an RNA chromosome, this study opens on the prospect of a prosperous RNA world, populated by RNA-based protocells with a number of genes, showing complicated functions.

[Preparation of recombinant human bone morphogenetic protein 2 decorated beta tricalcium phosphate/collagen and preliminary studies on its properties of inducing tooth formation].

OBJECTIVE: To explore a novel nanometer biomaterial which could induce the regeneration of tooth tissues intelligently, and to evaluate the feasibility of using this kind of biomaterial as the scaffold for tooth tissue engineering by investigating the role it plays in tooth tissue engineering. METHODS: The scaffold for tooth tissue engineering containing recombinant human bone morphogenetic protein 2 (rhBMP-2) was prepared by mixing nanoscale I tricalcium phosphate (beta-TCP)/collagen particles. Forty-six 8-10 weeks old specific pathogen free Sprague Dawley (SD) rats, including 34 females and 12 males, weighing 250-300 g, were involved in this study. Tooth germs were removed under a stereomicroscope from the mandible of newborn SD rat, then digested and suspended. Scanning electronic microscope (SEM), adhesion rate of cells, and MTT assay were used to evaluate the effects of the scaffold on the tooth germ cells cultured in vitro. The tissue engineered tooth germ which was constructed by tooth germ cells and scaffold was transplanted under SD rat's kidney capsule as the experimental group (n=12); the tooth germ cells (cell-control group, n=12) or scaffold without cells (material-control group, n=4) were transplanted separately as control groups. Specimens were harvested to perform general and histological observations at 4 and 8 weeks after transplantation. RESULTS: beta-TCP/collagen showed a loose and porous appearance with soft texture and excellent hydrophilicity. Tooth germ cells grew well and could attach to the scaffold tightly 3 days after coculture. The adhesion rates of tooth germ cells were 27.20% +/- 2.37%, 44.52% +/- 1.87%, and 73.81% +/- 4.15% when cocultured with scaffold for 4, 8, and 12 hours, respectively. MTT assay showed that the cell proliferation status of experimental group was similar to that of the control group, showing no significant difference (P > 0.05). Some white calcified specimens could be harvested at 4-8 weeks after transplantation. At 4 weeks after transplantation, some typical structures of dental cusp and enamel-dentin like tissues could be seen in the experimental group. Enamel-dentin like tissues also formed in some specimens of cell-control group, but they arranged irregularly. At 8 weeks after transplantation, the enamel-dentin like tissue of experimental group exhibited a mature appearance and organized structure in comparison with that at 4 weeks. And mature enamel or dentin like tissue also could be seen in cell-control group. In contrast, there was no enamel or dentin like tissue in material-control group at 4 or 8 weeks after transplantation. CONCLUSION: rhBMP-2 decorated beta-TCP/collagen scaffold has good biocompatibility and can be used as a novel nanometer biomaterial, so it is a good choice in scaffolds for tooth tissue engineering.