Gravity-Oriented Microfluidic Device for Biocompatible End-to-End Fabrication of Cell-Laden Microgels.

Droplet microfluidics are extensively utilized to generate monodisperse cell-laden microgels in biomedical applications. However, maintaining cell viability is still challenging due to overexposure to harsh conditions in subsequent procedures that recover the microgels from the oil phase. Here, a gravity-oriented microfluidic device for end-to-end fabrication of cell-laden microgels is reported, which integrates dispersion, gelation, and extraction into a continuous workflow. This innovative on-chip extraction, driven by native buoyancy and kinetically facilitated by pseudosurfactant, exhibits 100% retrieval efficiency for microgels with a wide range of sizes and stiffnesses. The viability of encapsulated cells is perfectly maintained at ≈98% with minimal variations within and between batches. The end-to-end fabrication remarkably enhances the biocompatibility and practicality of microfluidics-based cell encapsulation and is promising to be compatible with various applications ranging from single-cell analysis to clinical therapy.

Moisture-Adaptive Contractile Biopolymer-Derived Fibers for Wound Healing Promotion.

The advancement in thermosensitive active hydrogels has opened promising opportunities to dynamic full-thickness skin wound healing. However, conventional hydrogels lack breathability to avoid wound infection and cannot adapt to wounds with different shapes due to the isotropic contraction. Herein, a moisture-adaptive fiber that rapidly absorbs wound tissue fluid and produces a large lengthwise contractile force during the drying process is reported. The incorporation of hydroxyl-rich silica nanoparticles in the sodium alginate/gelatin composite fiber greatly improves the hydrophilicity, toughness, and axial contraction performance of the fiber. This fiber exhibits a dynamic contractile behavior as a function of humidity, generating ≈15% maximum contraction strain or ≈24 MPa maximum isometric contractile stress. The textile knitted by the fibers features excellent breathability and generates adaptive contraction in the target direction during the natural desorption of tissue fluid from the wounds. In vivo animal experiments further demonstrate the advantages of the textiles over traditional dressings in accelerating wound healing.

Effect of tissue adhesives in repairing perineal trauma during childbirth: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To investigate the effect of tissue adhesives on perineal wound healing and pain relief in women with perineal trauma during childbirth. BACKGROUND: Due to the high incidence and severe consequences of perineal trauma during childbirth, tissue adhesives are recommended as an alternative to conventional sutures to repair perineal trauma. Although many original studies have explored the effect of tissue adhesives on perineal wound healing and pain relief in women with perineal trauma during childbirth, these studies have differed in participants, interventions and outcomes. Therefore, the effect of tissue adhesives on wound healing and pain relief in perineal trauma during childbirth is inconclusive. DESIGN: A systematic review and meta-analysis based on PRISMA 2020. METHODS: A systematic and comprehensive literature search was conducted. Eight electronic databases, three clinical trial registers, and grey literature were searched from inception to 28th April 2021 and reference lists were also retrieved. Randomised controlled trials (RCTs) involving women with first- or second-degree perineal lacerations or women who underwent episiotomy were included. The intervention was the use of tissue adhesives alone or in combination with sutures. For the outcome indicators of perineal wound healing and pain relief, subgroup analyses based on the extent of perineal trauma and measurement time points were conducted, respectively. RESULTS: A total of 14 RCTs involving 2264 participants were included in this research. The results indicated that for first-degree lacerations, the incidence of wound complications was significantly higher in the tissue adhesives group. In contrast, for episiotomy, the effect of the combination of tissue adhesives and sutures was comparable to that of sutures exclusively. The pooled results revealed that tissue adhesives exerted a positive effect on relieving immediate and short-term perineal pain, but no significant difference was found in the effect of long-term pain relief. Moreover, this review also supported the effect of tissue adhesives in shortening intraoperative repair time and improving clinician-maternal satisfaction. CONCLUSIONS: The existing evidence illustrates that tissue adhesives effectively promote perineal wound healing and relieve immediate and short-term pain. However, for first-degree lacerations, the increased occurrence of wound complications must be prudently considered when applying tissue adhesives alone, whereas, for episiotomy, the combination of tissue adhesives and sutures may be a promising repair alternative. Future studies are encouraged to adopt long-term effect, adverse effect, and cost-effect analysis as important outcome indicators to comprehensively validate the applicability and generalisability of tissue adhesives. RELEVANCE TO CLINICAL PRACTICE: For first-degree perineal lacerations, we do not recommend using tissue adhesives alone to repair the wound, given the increased wound complications. While for episiotomy, the combination of tissue adhesives and sutures may be a promising alternative to the use of sutures exclusively. Additionally, the adverse effect and long-term effect of using tissue adhesives alone to repair perineal trauma should be further clarified.

Liposome-Embedded Cu2-xAgxS Nanoparticle-Mediated Photothermal Immunoassay for Daily Monitoring of cTnI Protein Using a Portable Thermal Imager.

Functional photothermal nanomaterials have gained widespread attention in the field of precise cancer therapy and early disease diagnosis due to their unique photothermal conversion properties. However, the relatively narrow temperature response range and the outputable accuracy of commercial thermometers limit the accurate detection of biomarkers. Herein, we designed a liposome-embedded Cu2-xAgxS amplification-based photothermal sensor for the accurate determination of cardiac troponin I (cTnI) in health monitoring and point-of-care testing (POCT). The combinable 3D-printing detecting device monitored and visualized target signal changes in the testing system under the excitation of near-infrared (NIR) light, which was recorded and evaluated for possible pathogenicity by a smartphone. Notably, we predicted the potentially efficient thermal conversion efficiency of Cu2-xAgxS from the structure and charge density distribution, calculated by the first-principles and density functional theory (DFT), which provided a theoretical basis for the construction of novel photothermal materials, and the experimental results proved the correctness of the theoretical projections. Under optimal conditions, the photothermal immunoassay showed a dynamic linear range of 0.02-10 ng mL-1 with a detection limit of 11.2 pg mL-1. This work instructively introduces promising theoretical research and provides new insights for the development of sensitive portable photothermal biosensors.

A MSALL quantitative method for the determination of Poloxamer 188 in rat plasma by UHPLC-Q-TOF/MS and its application to pharmacokinetic study.

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, an MSALL quantitative method for the determination of PL188 in rat plasma by UHPLC-Q-TOF/MS was developed and validated. PL188 was analyzed on PLRP-S reversed-phase column (50 × 4.6 mm, 8 µm, 1,000 Å) with mobile phase 0.1% formic acid-water and 0.1% formic acid in acetonitrile-isopropanol (2:3, v/v). The liner range was 0.1-10.0 µg/ml. A pharmacokinetic study was performed on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: half-life was 2.0 ± 1.1 h, volume of distribution was 5.1 ± 3.2 L/kg, area under the concentration-time curve was 3.0 ± 0.6 µg/L h and clearance was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188.

Michael Polyaddition Approach Towards Sulfur Enriched Nonaromatic Polymers with Fluorescence-Phosphorescence Dual Emission.

Nonaromatic photoluminescent polymers have attracted great attention due to their intriguing photophysical properties and promising implications in optoelectronic and biological areas. The luminescence from these nonconventional luminophores can be well rationalized by the clustering-triggered emission mechanism. Sulfur, although as an n-electron-rich element with big radius, is not been widely utilized in construction of nonconventional luminophores despite of its potential competitiveness in nonaromatic photoluminescent polymers. Herein, the "click" type Michael polyaddition is utilized to construct sulfur-bearing nonconventional luminophores, and two sulfur enriched nonaromatic poly(thioether sulfone)s (PES) are obtained, which demonstrate fluorescence-phosphorescence dual emission. More investigations concerning the monomer of bis(vinylsulfonyl)methane are further proceeded to support acquired results. Finally, the application of explosive detection by the prepared PES is also conducted.

Ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry method for quantifying polymer poloxamer 124 and its application to pharmacokinetic study.

Poloxamer is a commonly used pharmaceutical excipient. It is a high molecular polymer formed using polypropylene oxide and polyethylene oxide units. Specifically, poloxamer 124 is one of the smaller molecular weight in the poloxamer series; however, its pharmacokinetic behaviors in vivo are still unclear. In this study, a method for quantifying poloxamer 124 in rat plasma through ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was developed. The intravenous dosage of PL124 was 10 mg/kg. Plasma was collected at different times. The calibration curve was linear in the range of 0.1-5 µg/mL for the poloxamer 124 (r ≥ 0.9956) with the lower limit of quantitation of 0.1 µg/ml. The relative standard deviation of the intraday and interday precisions was below 8.0%, and the relative error of the accuracy was within ±12.0%. The extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of poloxamer 124 in rats. Results indicated that poloxamer 124 could be rapidly absorbed and eliminated through caudal vein injection. This study is helpful for the further study of poloxamer 124.

Ferritin-Based Nanocomposite Hydrogel Promotes Tumor Penetration and Enhances Cancer Chemoimmunotherapy.

Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug-loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin-based nanocomposite hydrogel is constructed to facilitate tumor penetration and improve cancer chemoimmunotherapy. Specifically, doxorubicin-loaded human ferritin (Dox@HFn) and oxidized dextran (Dex-CHO) are used to construct the injectable hydrogel (Dox@HFn Gel) through the formation of pH-sensitive Schiff-base bonds. After peritumoral injection, the Dox@HFn Gel is retained locally for up to three weeks, and released intact Dox@HFn gradually, which can not only facilitate tumor penetration through active transcytosis but also induce immunogenic cell death (ICD) to tumor cells to generate an antitumor immune response. Combining with anti-programmed death-1 antibody (αPD-1), Dox@HFn Gel induces remarkable regression of orthotopic 4T1 breast tumors, further elicits a strong systemic anti-tumor immune response to effectively suppress tumor recurrence and lung metastasis of 4T1 tumors after surgical resection. Besides, the combination of Dox@HFn GelL with anti-CD47 antibody (αCD47) inhibits postsurgical tumor recurrence of aggressive orthotopic glioblastoma tumor model and significantly extends mice survival. This work sheds light on the construction of local hydrogels to potentiate antitumor immune response for improved cancer therapy.

3D embedded bioprinting of large-scale intestine with complex structural organization and blood capillaries.

Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.

Functionalized sampling swabs array-based portable ATP bioluminescence sensor with on-site enrichment and high specificity for live Salmonella detection.

Live food-borne pathogens, featured with rapid proliferative capacity and high pathogenicity, pose an emerging food safety and public health crisis. The high-sensitivity detection of pathogens is particularly imperative yet remains challenging. This work developed a functionalized nylon swab array with enhanced affinity for Salmonella typhimurium (S.T.) for high-specificity ATP bioluminescence-based S.T. detection. In brief, the nylon swabs (NyS) were turned to N-methylation nylon (NyS-OH) by reacting with formaldehyde, and NyS-OH were further converted to NyS-CA by reacting with carboxylic groups of citric acid (CA) and EDC/NHS solution, for altering the NyS surface energy to favor biomodification. The antibody-immobilized nylon swab (MNyS-Ab) was ready for S.T.-specific adsorption. Three prepared MNyS-Ab were installed on a stirrer to form an MNyS-Ab array, allowing for on-site enrichment of S.T. through absorptive extraction. The enriched S.T. was quantified by measuring the bioluminescence of ATP released from cell lysis utilizing a portable ATP bioluminescence sensor. The bioassay demonstrated a detectable range of 102-107 CFU mL-1 with a detection limit (LOD) of 8 CFU/mL within 35 min. The signal of single MNyS-Ab swabs was 500 times stronger than the direct detection of 106 CFU/mL S.T. The MNyS-Ab array exhibited a 100-fold increase in extraction level compared to a single MNyS. This combination of a portable bioluminescent sensor and modified nylon swab array offers a novel strategy for point-of-care testing of live S.T. strains. It holds promise for high-sensitivity measurements of other pathogens and viruses.

Characterization of airborne microplastics at different workplaces of the poly(ethylene:propylene:diene) (EPDM) rubber industry.

Microplastics (MPs) as an emerging air pollutant have received widespread attention, but research on airborne MPs at occupational sites is still limited, especially in the rubber industry. Hence, indoor air samples were collected from three production workshops and an office of a rubber factory producing automotive parts to analyze the characteristics of airborne MPs in different workplaces of this industry. We found MP contamination in all air samples from the rubber industry, and the airborne MPs at all sites mainly showed small-sized (< 100 µm) and fragmented characteristics. The abundance and source of MPs at various locations is primarily related to the manufacturing process and raw materials of the workshop. The abundance of MPs in the air was higher in workplaces where production activities are involved than in office (360 ± 61 n/m3), of which the highest abundance of airborne MPs was in the post-processing workshop (559 ± 184 n/m3). In terms of types, a total of 40 polymer types were identified. The post-processing workshop has the largest proportion of injection-molded plastic ABS, the extrusion workshop has a greater proportion of EPDM rubber than the other locations, and the refining workshop has more MPs used as adhesives, such as aromatic hydrocarbon resin (AHCR).

Development and Characterization of Complementary Polymer Network Bioinks for 3D Bioprinting of Soft Tissue Constructs.

The development of 3D bioprinting has been hindered by a narrow "biofabrication window" with a limited variety of feasible bioinks which are compatible with both high printability and well cytocompatibility. Herein, a generalizable strategy using complementary polymer network (CPN) bioinks is developed in the current study, to address the conflict between the printability and cytocompatibility of bioinks in extrusion 3D bioprinting, especially for the manufacture of soft tissue constructs. In this strategy, CPN bioinks are formed though mixing two interpenetrated polymer networks, one of which is a photocrosslinkable polymer network, and the other is a dynamic polymer network crosslinked by reversible covalent linkage, thereby endowed with well reversible thixotropy. Compatible with well printability, shape fidelity, and cytocompatibility, the utilization of CPN bioinks provides a viable solution for extrusion 3D bioprinting of photocrosslinkable biomaterials at a low concentration, thus suitable for soft tissue construct fabrication. Briefly, this study is testified to be a successful attempt to extend the bioink diversity within the "biofabrication window," and offers a novel insight into designing more feasible bioinks based on their special rheological properties, for further tissue engineering and biomedicine application.

Au-Pt nanozyme-based multifunctional hydrogel dressing for diabetic wound healing.

Diabetic chronic wound healing is a critical clinical challenge due to the particularity of wound microenvironment, including hyperglycemia, excessive oxidative stress, hypoxia, and bacterial infection. Herein, we developed a multifunctional self-healing hydrogel dressing (defined as OHCN) to regulate the complex microenvironment of wound for accelerative diabetic wound repair. The OHCN hydrogel dressing was constructed by integrating Au-Pt alloy nanoparticles into a hydrogel (OHC) that formed through Schiff-base reaction between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS). The dynamic cross-linking of OHA and antibacterial CMCS imparted the OHCN hydrogel dressing with excellent antibacterial and self-healing properties. Meanwhile, Au-Pt alloy nanoparticles endowed the OHCN hydrogel dressing with the functions of lowering blood glucose, alleviating oxidative damage, and providing O2 by simulating glucose oxidase and catalase. Through a synergistic combination of OHC hydrogel and Au-Pt alloy nanoparticles, the resulted OHCN hydrogel dressing significantly ameliorated the pathological microenvironment and accelerated the healing rate of diabetic wound. The proposed nanozyme-decorated multifunctional hydrogel offers an efficient strategy for the improved management of diabetic chronic wound.

Microbiota dysbiosis in odontogenic rhinosinusitis and its association with anaerobic bacteria.

Odontogenic rhinosinusitis is a subtype of rhinosinusitis associated with dental infection or dental procedures and has special bacteriologic features. Previous research on the bacteriologic features of odontogenic rhinosinusitis has mainly used culture-dependent methods. The variation of microbiota between odontogenic and nonodontogenic rhinosinusitis as well as the interplay between the involved bacteria have not been explored. Therefore, we enrolled eight odontogenic rhinosinusitis cases and twenty nonodontogenic rhinosinusitis cases to analyze bacterial microbiota through 16S rRNA sequencing. Significant differences were revealed by the Shannon diversity index (Wilcoxon test p = 0.0003) and PERMANOVA test based on weighted UniFrac distance (Wilcoxon test p = 0.001) between odontogenic and nonodontogenic samples. Anaerobic bacteria such as Porphyromonas, Fusobacterium, and Prevotella were significantly dominant in the odontogenic rhinosinusitis group. Remarkably, a correlation between different bacteria was also revealed by Pearson's correlation. Staphylococcus was highly positively associated with Corynebacterium, whereas Fusobacterium was highly negatively correlated with Prophyromonas. According to our results, the microbiota in odontogenic rhinosinusitis, predominantly anaerobic bacteria, was significantly different from that in nonodontogenic rhinosinusitis, and the interplay between specific bacteria may a major cause of this subtype of rhinosinusitis.

A UHPLC-Q-TOF/MS method for the determination of poloxamer 124 and its application in a tissue distribution study in rats.

Poloxamers are commonly used pharmaceutical excipients. They are high molecular weight polymers formed from polypropylene oxide (PPO) and polyethylene oxide (PEO). However, PL124, a low molecular weight example in the poloxamer family, has rarely been reported, and there is no research into its tissue distribution in the body after administration. In this study, rat tissue samples were quantitatively studied via UHPLC-Q-TOF/MS after the intravenous administration of 10 mg kg-1 PL124. The quantitative method showed good sensitivity and selectivity. The linear range of PL124 was 0.1-5 µg mL-1 and the LLOQ was 0.1 µg mL-1. The relative error in terms of the accuracy was no higher than 13.9%, and the relative standard deviation in terms of the precision was no higher than 9.6%. The extraction recovery, matrix effect, and stability results of the established method were also satisfactory. The research showed that PL124 can be quickly distributed to large amounts of tissue, and tissue with higher levels of blood flow has higher concentrations. PL124 could be rapidly eliminated in 4 h from most organs, except the heart and liver. This study can be helpful for the further analysis of PL124.

Graphene-coated copper-doped ZnO quantum dots for sensitive photoelectrochemical bioanalysis of thrombin triggered by DNA nanoflowers.

This work reports a photoelectrochemical (PEC) biosensing platform for the sensitive and specific screening of thrombin by using graphene oxide-coated copper-doped zinc oxide quantum dots (Cu0.3Zn0.7O-GO QDs) as the photoactive materials and glucose oxidase-encapsulated DNA nanoflowers (GOx-DFs) for signal amplification. Interestingly, the coated graphene oxide nanosheets on the surface of the Cu0.3Zn0.7O QDs could cause the charge to transfer rapidly and ameliorate the photocorrosion. The doped copper into the quantum dots could enhance the absorption of visible light by tuning the band gap of ZnO QDs, therefore increasing the photocurrent under visible irradiation. Upon addition of target thrombin, a sandwiched reaction was carried out between thrombin aptamer and GOx-DFs, accompanying the formation of nanocomposites with the magnetic microparticles (MMPs)/thrombin/GOx-DFs. Followed by magnetic separation, the carried GOx oxidized glucose to H2O2, thus resulting in the increasing photocurrent of the Cu0.3Zn0.7O-GO QD-modified electrode. Under optimum conditions, the developed PEC biosensing platform exhibited good analytical performance with a linear range of 50-10 000 fM thrombin and a limit of detection of 29 fM. Impressively, our strategy offers a new horizon in developing bridge-connected graphene-coated nanomaterials and novel signal amplification strategy for the development of PEC biosensors.

Improved oral delivery of insulin by PLGA nanoparticles coated with 5ß-cholanic acid conjugated glycol chitosan.

Oral insulin has been regarded as the best alternative to insulin injection in therapy of diabetes because of its convenience and painlessness. However, several obstacles in the gastrointestinal tract, such as gastric acid and enzyme, greatly reduce the bioavailability of oral insulin. Herein, we report design and preparation of poly (d, l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with 5ß-cholanic acid modified glycol chitosan (GC-CA) (GC-CA@PLGA NPs) to improve the oral delivery of insulin. The GC-CA@PLGA NPs with the size of (302.73 ± 5.13 nm) and zeta potential of (25.03 ± 0.31 mV) were synthesized using the double-emulsion method. The insulin-loading capacity and encapsulation efficiency were determined to be 5.77 ± 0.58% and 51.99 ± 5.27%, respectively. Compared with GC-modified PLGA NPs (GC@PLGA NPs) and bare PLGA NPs, the GC-CA@PLGA NPs showed excellent stability and uptake by Caco-2 cells after simulated gastric acid digestion. Further experiment suggests good biocompatibility of GC-CA@PLGA NPs, including hemolysis and cytotoxicity. Inin vivoexperiment, the insulin loaded in the GC-CA@PLGA NPs exhibited a long-term and stable release profile for lowering blood glucose and presented 30.43% bioavailability in oral administration. In brief, we have developed an efficient and safe drug delivery system, GC-CA@PLGA NPs, for significantly improved oral administration of insulin, which may find potential application in the treatment of diabetes.

[Research progress in pulpless posterior tooth restored with ceramic onlay].

Minimal invasive restoration is a common technique in the restoration of pulpless posterior teeth. The development of bonding techniques and ceramic materials in recent years has increased the use of high-strength ceramic onlay in the restoration of endodontically treated posterior teeth because of its minimal invasiveness, improved aesthetics, and low requirement of mechanical retention. This study conducts a retrospective analysis on the material, tooth preparation, bonding, and clinical considerations of ceramic onlay in endodontically treated posterior tooth.

[Three-year retrospective clinical evaluation of pulp-less molars with defects of varying degree repaired by cast ceramic onlays of three marginal types].

OBJECTIVE: This study aimed to evaluate the clinical effect of pulp-less molars with defects of different degrees repaired by cast ceramic onlays of three marginal types. METHODS: A total of 165 endodontically treated molars of 105 patients were included in this study and were divided into three kinds of defect (mild, moderate, severe) according to the number of remaining axial walls. Each defect was divided into three groups according to the shape of edge to edge, bevel edge, and concave shoulder. After tooth preparation, the casting of ceramic onlays was performed. Treatment follow-up was done for the evaluation of the success and survival rates of three groups under the same defect. RESULTS: The average follow-up was 925.44 days. Under the mild defect, the success and survival rates of the edge to edge onlays were respectively 100% and 100%; bevel edge onlays, 100% and 100%; and concave shoulder onlays, 94.4% and 100%. Under the moderate defect, the success and survival rates of the edge to edge onlays were respectively 96.0% and 100%; bevel edge onlays, 80.0% and 93.3%; and concave shoulder onlays, 95.2% and 95.2%. Under the severe defect, the success and survival rates of the edge to edge onlays were respectively 95.2% and 100%; bevel edge onlays, 73.7% and 89.5%; and concave shoulder onlays, 73.3% and 80.0%. Under different defects, the success or survival rates of the three kinds of onlays had no significant difference (P>0.05). CONCLUSIONS: The edge to edge type is the most preferable way of onlay tooth preparation and can achieve good clinical results in the mild, middle, and severe tooth defection with root canal treatment.