A bioswitchable delivery system for microRNA therapeutics based on a tetrahedral DNA nanostructure.

As microRNAs (miRNA) regulate almost all physiopathological activities in the human body, miRNA therapeutics that deliver miRNA regulators have attracted considerable attention in the field of nucleic acid drug development. The use of tetrahedral DNA nanostructures to deliver miRNA regulators is promising because of their simple fabrication, enhanced cell entry, effective tissue penetration, biocompatibility and functional editability. This protocol extension builds on our previous protocol for the use of tetrahedral DNA nanostructures and was designed to establish an updated bioswitchable delivery system (BDS) for achieving controlled cargo loading and release. A ribonuclease H-sensitive sequence is designed as a bioswitchable apparatus for the targeted release of the miRNA regulator. The functional sequence of the miRNA regulator and minimal secondary structure formation tendency during annealing are two key points in cargo design. We provide two BDS design strategies; BDS-A comprises an intact DNA tetrahedron with the RNA cargo hanging outside, offering the merits of lower cost, simplicity, and more direct structural design. In the BDS-B design, the RNA regulators are embedded into the DNA tetrahedron, which is beneficial for dermal tissue permeation applications. Following sequence design in Oligo 7 and Tiamat, the BDS assembly is completed and then ribonuclease H achieves controlled release of the miRNA regulator by triggering the bioswitchable apparatus. This is verified via polyacrylamide and agarose gel electrophoresis or fluorophore modifications. Both BDSs show promising cellular membrane permeability, tissue permeability and target inhibition in vitro and in vivo. The assembly and characterization of the BDS can be completed in 4 d, and the validation time for biostability and biological applications will depend on the specific use.

A Bioswitchable MiRNA Delivery System: Tetrahedral Framework DNA-Based miRNA Delivery System for Applications in Wound Healing.

The human body's primary line of defense, the skin, is especially prone to harm. Although microRNA (miRNA)-based therapies have attracted increasing attention for skin wound healing, their applications remain limited owing to a range of issues. Tetrahedral framework DNA (tFNA), a nanomaterial possessing nucleic acid characteristics, exhibits an excellent biocompatibility, in addition to anti-inflammatory and transdermal delivery capabilities, and can accelerate skin wound healing. Due to its potential to exert synergistic action with therapeutic miRNA, tFNA has been considered an ideal vehicle for miRNA therapy. The design and synthesis of a bioswitchable miRNA delivery system (BiRDS) is reported, which contains three miRNAs as well as a nucleic acid core to maximize the loading capacity while preserving the characteristics of tFNA. A high stability, excellent permeability of cells as well as tissues and good biological compatibility are demonstrated. By selectively inhibiting heparin-binding epidermal growth factor (HB-EGF), the BiRDS can inhibit the NF-κB pathway while simultaneously controlling the PTEN/Akt pathway. As a result, the BiRDS helps wound healing go through the inflammation to the proliferative phase. This study demonstrates the advantages of the BiRDS in miRNA-based therapy and provides new research ideas for the treatment of skin-related diseases.

DNA framework signal amplification platform-based high-throughput systemic immune monitoring.

Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of immune cells. However, conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing, especially in mass health screenings, because of time-consuming, technical-sensitive and high-cost features. However, the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring technology. To address this bottleneck, we constructed a generally applicable DNA framework signal amplification platform (DSAP) based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells, including CD4+, CD8+ T-lymphocytes, and monocytes (down to 1/100 µl). Based on this advanced detection platform, we present a novel high-throughput immune-cell phenotyping system, DSAP, achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and cost. As a proof-of-concept, DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients (AUC > 0.97) within 30 min, which can be applied in HIV infection monitoring and screening. Therefore, we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

A Novel Bioswitchable miRNA Mimic Delivery System: Therapeutic Strategies Upgraded from Tetrahedral Framework Nucleic Acid System for Fibrotic Disease Treatment and Pyroptosis Pathway Inhibition.

There has been considerable interest in gene vectors and their role in regulating cellular activities and treating diseases since the advent of nucleic acid drugs. MicroRNA (miR) therapeutic strategies are research hotspots as they regulate gene expression post-transcriptionally and treat a range of diseases. An original tetrahedral framework nucleic acid (tFNA) analog, a bioswitchable miR inhibitor delivery system (BiRDS) carrying miR inhibitors, is previously established; however, it remains unknown whether BiRDS can be equipped with miR mimics. Taking advantage of the transport capacity of tetrahedral framework nucleic acid (tFNA) and upgrading it further, the treatment outcomes of a traditional tFNA and BiRDS at different concentrations on TGF-ß- and bleomycin-induced fibrosis simultaneously in vitro and in vivo are compared. An upgraded traditional tFNA is designed by successfully synthesizing a novel BiRDS, carrying a miR mimic, miR-27a, for treating skin fibrosis and inhibiting the pyroptosis pathway, which exhibits stability and biocompatibility. BiRDS has three times higher efficiency in delivering miRNAs than the conventional tFNA with sticky ends. Moreover, BiRDS is more potent against fibrosis and pyroptosis-related diseases than tFNAs. These findings indicate that the BiRDS can be applied as a drug delivery system for disease treatment.

The CNN model aided the study of the clinical value hidden in the implant images.

PURPOSE: This article aims to construct a new method to evaluate radiographic image identification results based on artificial intelligence, which can complement the limited vision of researchers when studying the effect of various factors on clinical implantation outcomes. METHODS: We constructed a convolutional neural network (CNN) model using the clinical implant radiographic images. Moreover, we used gradient-weighted class activation mapping (Grad-CAM) to obtain thermal maps to present identification differences before performing statistical analyses. Subsequently, to verify whether these differences presented by the Grad-CAM algorithm would be of value to clinical practices, we measured the bone thickness around the identified sites. Finally, we analyzed the influence of the implant type on the implantation according to the measurement results. RESULTS: The thermal maps showed that the sites with significant differences between Straumann BL and Bicon implants as identified by the CNN model were mainly the thread and neck area. (2) The heights of the mesial, distal, buccal, and lingual bone of the Bicon implant post-op were greater than those of Straumann BL (P < 0.05). (3) Between the first and second stages of surgery, the amount of bone thickness variation at the buccal and lingual sides of the Bicon implant platform was greater than that of the Straumann BL implant (P < 0.05). CONCLUSION: According to the results of this study, we found that the identified-neck-area of the Bicon implant was placed deeper than the Straumann BL implant, and there was more bone resorption on the buccal and lingual sides at the Bicon implant platform between the first and second stages of surgery. In summary, this study proves that using the CNN classification model can identify differences that complement our limited vision.

Tetrahedral framework nucleic acid loaded with glabridin: A transdermal delivery system applicated to anti-hyperpigmentation.

Topical application of tyrosinase inhibitors, such as hydroquinone and arbutin, is the most common clinical treatment for hyperpigmentation. Glabridin (Gla) is a natural isoflavone that inhibits tyrosinase activity, free radical scavenging, and antioxidation. However, its water solubility is poor, and it cannot pass through the human skin barrier alone. Tetrahedral framework nucleic acid (tFNA), a new type of DNA biomaterial, can penetrate cells and tissues and can be used as carriers to deliver small-molecule drugs, polypeptides, and oligonucleotides. This study aimed to develop a compound drug system using tFNA as the carrier to transport Gla and deliver it through the skin to treat pigmentation. Furthermore, we aimed to explore whether tFNA-Gla can effectively alleviate the hyperpigmentation caused by increased melanin production and determine whether tFNA-Gla exerts substantial synergistic effects during treatment. Our results showed that the developed system successfully treated pigmentation by inhibiting regulatory proteins related to melanin production. Furthermore, our findings showed that the system was effective in treating epidermal and superficial dermal diseases. The tFNA-based transdermal drug delivery system can thus develop into novel, effective options for non-invasive drug delivery through the skin barrier.

The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores.

Increasing evidence has suggested that the HIV-1 capsid enters the nucleus in a largely assembled, intact form. However, not much is known about how the cone-shaped capsid interacts with the nucleoporins (NUPs) in the nuclear pore for crossing the nuclear pore complex. Here, we elucidate how NUP153 binds HIV-1 capsid by engaging the assembled capsid protein (CA) lattice. A bipartite motif containing both canonical and noncanonical interaction modules was identified at the C-terminal tail region of NUP153. The canonical cargo-targeting phenylalanine-glycine (FG) motif engaged the CA hexamer. By contrast, a previously unidentified triple-arginine (RRR) motif in NUP153 targeted HIV-1 capsid at the CA tri-hexamer interface in the capsid. HIV-1 infection studies indicated that both FG- and RRR-motifs were important for the nuclear import of HIV-1 cores. Moreover, the presence of NUP153 stabilized tubular CA assemblies in vitro. Our results provide molecular-level mechanistic evidence that NUP153 contributes to the entry of the intact capsid into the nucleus.

Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels.

Delivering the virus genome into the host nucleus through the nuclear pore complex (NPC) is pivotal in human immunodeficiency virus 1 (HIV-1) infection. The mechanism of this process remains mysterious owing to the NPC complexity and the labyrinth of molecular interactions involved. Here we built a suite of NPC mimics-DNA-origami-corralled nucleoporins with programmable arrangements-to model HIV-1 nuclear entry. Using this system, we determined that multiple cytoplasm-facing Nup358 molecules provide avid binding for capsid docking to the NPC. The nucleoplasm-facing Nup153 preferentially attaches to high-curvature regions of the capsid, positioning it for tip-leading NPC insertion. Differential capsid binding strengths of Nup358 and Nup153 constitute an affinity gradient that drives capsid penetration. Nup62 in the NPC central channel forms a barrier that viruses must overcome during nuclear import. Our study thus provides a wealth of mechanistic insight and a transformative toolset for elucidating how viruses like HIV-1 enter the nucleus.

Liver-Targeted Delivery of Small Interfering RNA of C-C Chemokine Receptor 2 with Tetrahedral Framework Nucleic Acid Attenuates Liver Cirrhosis.

Liver cirrhosis is the end stage of chronic liver diseases without approved clinical drugs. In this study, a new strategy that uses a C-C chemokine receptor 2 (CCR2) small interfering RNA silencing (siCcr2)-based therapy by loading multivalent siCcr2 with tetrahedron framework DNA nanostructure (tFNA) vehicle (tFNA-siCcr2) was established to attenuate liver fibrosis. tFNA-siCcr2 was successfully synthesized without changing the physiochemical properties of tFNA. Compared to the naked siCcr2 molecule, the tFNA-siCcr2 complex altered the accumulation from the kidney to the liver after the intraperitoneal injection. The tFNA-siCcr2 complex also prolonged hepatic retention and mainly colocalized within macrophages and endothelial cells. tFNA-siCcr2 efficiently silenced CCR2 and significantly ameliorated liver fibrosis in prevention and treatment interventions. Single-cell RNA sequencing followed by experimental validation suggested that tFNA-siCcr2 can restore the immune cell landscape and construct an antifibrotic niche by inhibiting profibrotic macrophage and neutrophil accumulation in the murine fibrotic liver. Molecularly, the tFNA-siCcr2 complex reduced inflammatory mediator production by inactivating the NF-κB signaling pathway. In conclusion, the tFNA-based liver-targeted tFNA-siCcr2 delivery complex efficiently ameliorated liver fibrosis by restoring the immune cell landscape and constructing an antifibrotic niche, which makes the tFNA-siCcr2 complex a potential therapeutic candidate for the clinical treatment of liver cirrhosis.

Tetrahedral Framework Nucleic Acids: A Novel Strategy for Antibiotic Treating Drug-Resistant Infections.

Antibiotic multiresistance (AMR) has emerged as a major threat to human health as millions of people die from AMR-related problems every year. As has been witnessed during the global COVID-19 pandemic, the significantly increased demand for antibiotics has aggravated the issue of AMR. Therefore, there is an urgent need to find ways to alleviate it. Tetrahedral framework nucleic acids (tFNAs) are novel nanomaterials that are often used as drug delivery platforms because of their structural diversity. This study formed a tFNAs-antibiotic compound (TAC) which has a strong growth inhibitory effect on Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro owing to the increased absorption of antibiotics by bacteria and improved drug movement across cell membranes. We established a mouse model of systemic peritonitis and local wound infections. The TAC exhibited good biosafety and improved the survival rate of severely infected mice, promoting the healing of local infections. In addition to the better transport of antibiotics to the target, the TAC may also enhance immunity by regulating the differentiation of M1 and M2 macrophages, providing a new option for the treatment of infections.

A dynamic DNA tetrahedron framework for active targeting.

An active targeting strategy-enabled DNA tetrahedron delivery vehicle could facilitate stable drug encapsulation and stimuli-responsive on-demand release, building a universal platform for different drug delivery requirements. Owing to the excellent biocompatible nature, programmability and remarkable cell and tissue permeability, the tetrahedral DNA nanostructure (TDN) has proven its value in the delivery of various bioactive molecules. We previously described this as a static multifunctional complex in our earlier protocol. However, static structures and passive targeting behavior might introduce off-target effects under complicated biological conditions. Therefore, in this Protocol Extension, we present a major update of the TDN delivery vehicle enabling an active targeting strategy to be used for stimuli-sensitive conformation changes and on-site cargo release, which could avoid drawbacks, including complex and time-consuming fabrication processes and undetermined cell penetration ability of other DNA-based delivery vehicles. Upon exquisite design of TDN size based on cargo type, one-pot annealing is applied to fabricate the Tiamat-designed TDN exoskeleton. Then the design of the dynamic DNA apparatus can be based on the target and environmental stimuli, including DNA strand hybridization-based and pH-sensitive DNA apparatus, and careful titration of strand lengths and mismatches is achieved using polyacrylamide and agarose gel electrophoresis, or fluorophore modifications. Finally, cargo loading strategies are designed, including site and stand titration and cargo encapsulation verification. The dynamic structures show promising targetability and effectiveness in antitumor and anti-inflammatory treatment in vitro and in vivo. Assembly and characterization in the lab takes ~5 d, and the timing for the verification of biostability and biological applications depends on the uses.

Functionalized DNA-Origami-Protein Nanopores Generate Large Transmembrane Channels with Programmable Size-Selectivity.

The DNA-origami technique has enabled the engineering of transmembrane nanopores with programmable size and functionality, showing promise in building biosensors and synthetic cells. However, it remains challenging to build large (>10 nm), functionalizable nanopores that spontaneously perforate lipid membranes. Here, we take advantage of pneumolysin (PLY), a bacterial toxin that potently forms wide ring-like channels on cell membranes, to construct hybrid DNA-protein nanopores. This PLY-DNA-origami complex, in which a DNA-origami ring corrals up to 48 copies of PLY, targets the cholesterol-rich membranes of liposomes and red blood cells, readily forming uniformly sized pores with an average inner diameter of ∼22 nm. Such hybrid nanopores facilitate the exchange of macromolecules between perforated liposomes and their environment, with the exchange rate negatively correlating with the macromolecule size (diameters of gyration: 8-22 nm). Additionally, the DNA ring can be decorated with intrinsically disordered nucleoporins to further restrict the diffusion of traversing molecules, highlighting the programmability of the hybrid nanopores. PLY-DNA pores provide an enabling biophysical tool for studying the cross-membrane translocation of ultralarge molecules and open new opportunities for analytical chemistry, synthetic biology, and nanomedicine.

A minimally invasive method for titanium mesh fixation with resorbable sutures in guided bone regeneration: A retrospective study.

OBJECTIVES: Titanium mesh has become a mainstream choice for guided bone regeneration (GBR) owing to its excellent space maintenance. However, the traditional fixation method using titanium screws impacts surgery efficiency and increases patient trauma. We report a novel method of fixing a titanium mesh using resorbable sutures. We assessed the feasibility of resorbable sutures for fixing a titanium mesh and whether it can serve as a stable, universal, and minimally invasive fixation method for a broader application of titanium meshes. METHODS: Patients undergoing GBR with a digital titanium mesh fixed using titanium screws (TS group) and resorbable sutures (RS group) were observed at different time points. The stability of the fixation methods was evaluated on parameters such as titanium mesh spatial displacement, bone augmentation, and bone resorption. RESULTS: A total of 36 patients were included in this study. The exposure rate of the titanium mesh in the TS group was 16.67%, while no exposure was noted in the RS group. There was no significant difference in the parameters of titanium mesh spatial displacement, bone augmentation, and bone resorption between the two groups (p > 0.05). CONCLUSION: The use of resorbable sutures for fixing a titanium mesh can achieve similar results to traditional fixation using titanium screws. Although this new fixation method can improve the efficiency of the surgery and reduce the risk of complications, the long-term clinical effects require further follow-up investigation.

A Tetrahedral Framework DNA-Based Bioswitchable miRNA Inhibitor Delivery System: Application to Skin Anti-Aging.

MicroRNA (miR)-based therapy shows strong potential; however, structural limitations pose a challenge in fully exploiting its biomedical functionality. Tetrahedral framework DNA (tFNA) has proven to be an ideal vehicle for miR therapy. Inspired by the ancient Chinese myth "Sun and Immortal Birds," a novel bioswitchable miR inhibitor delivery system (BiRDS) is designed with three miR inhibitors (the three immortal birds) and a nucleic acid core (the central sun). The BiRDS fuses miR inhibitors within the framework, maximizing their loading capacity, while allowing the system to retain the characteristics of small-sized tFNA and avoiding uncertainty associated with RNA exposure in traditional loading protocols. The RNase H-responsive sequence at the tail of each "immortal bird" enables the BiRDS to transform from a 3D to a 2D structure upon entering cells, promoting the delivery of miR inhibitors. To confirm the application potential, the BiRDS is used to deliver the miR-31 inhibitor, with antiaging effects on hair follicle stem cells, into a skin aging model. Superior skin penetration ability and RNA delivery are observed with significant anti-aging effects. These findings demonstrate the capability and editability of the BiRDS to improve the stability and delivery efficacy of miRs for future innovations.

A Lysosome-Activated Tetrahedral Nanobox for Encapsulated siRNA Delivery.

Tetrahedral framework nucleic acids (tFNAs) have attracted extensive attention as drug nanocarriers because of their excellent cellular uptake. However, for oligonucleotide cargos, tFNA mainly acts as a static delivery platform generated via sticky-ended ligation. Here, inspired by the original stable space inside the tetrahedral scaffold, a dynamic lysosome-activated tFNA nanobox is fabricated for completely encapsulating a short interfering RNA (siRNA) of interest. The closed tetrahedral structure endows cargo siRNA with greater resistance against RNase and serum and enables solid integration with the vehicle during delivery. Moreover, the pH-responsive switch of nanobox allows the controlled release of siRNA upon entry into lysosomes at cell culture temperature. Based on protective loading and active unloading, an excellent silencing effect on the target tumor necrosis factor alpha (TNFα) gene is achieved in in vitro and in vivo experiments. Conclusively, the nanobox offers a dynamic pH-sensitive confinement delivery system for siRNA and can be an extendable strategy for other small RNA.

Prospects and challenges of dynamic DNA nanostructures in biomedical applications.

The physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and pH. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal particles. However, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications, including their use as DNA aptamers, ion concentration/pH-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.

Therapeutic Effects of Self-Assembled Tetrahedral Framework Nucleic Acids on Liver Regeneration in Acute Liver Failure.

Liver failure is a serious disease that is characterized by global hepatocyte necrosis. Hepatocyte proliferation and liver regeneration are critically important for the success of treatments for liver disease. Tetrahedral framework nucleic acids (TFNAs), which are widely used antioxidants and anti-inflammatory nanomaterials, activate multiple proliferation and prosurvival pathways. Therefore, the effects of a TFNA on hepatocyte proliferation and liver regeneration in mouse livers injured by 70% partial hepatectomy (PHx), acetaminophen overdose, and carbon tetrachloride were explored in this study. The TFNA, which was successfully self-assembled from four specifically designed ssDNAs, entered the body quickly and was taken up effectively by hepatocytes in the liver and could eventually be cleared by the kidneys. The TFNA promoted hepatocyte proliferation in vitro by activating the Notch and Wnt signaling pathways. In the three in vivo mouse models of liver injury, the TFNA attenuated the injuries and enhanced liver regeneration by regulating the cell cycle and the P53 signaling pathway. Therefore, by promoting hepatocyte proliferation and enhancing liver regeneration, the TFNA shows potential as an effective therapeutic agent for treating acute liver injury induced by 70% PHx and other factors, thereby preventing the progression to acute liver failure and reducing the associated mortality rate.

Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis.

Gouty arthritis is a very familiar inflammatory arthritis. Controlling inflammation is the key to preventing gouty arthritis. However, colchicine, the most highly represented drug used in clinical practice, has strict contraindications owing to some severe side effects. Curcumin (Cur), a natural anti-inflammatory drug, has demonstrated good safety and efficacy. However, the rapid degradation, poor aqueous solubility, and low bioavailability of Cur limit its therapeutic effect. To strengthen the effectiveness and bioavailability of Cur. Cur loaded tetrahedral framework nucleic acids (Cur-TFNAs) were synthesized to deliver Cur. Compared with free Cur, Cur-TFNAs exhibit a preferable drug stability, good biocompatibility (CCK-8 assay), ease of uptake (immunofluorescence), and higher tissue utilization (in vivo biodistribution). Most importantly, Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression. Therefore, we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.

Functionalizing Framework Nucleic-Acid-Based Nanostructures for Biomedical Application.

Strategies for functionalizing diverse tetrahedral framework nucleic acids (tFNAs) have been extensively explored since the first successful fabrication of tFNA by Turberfield. One-pot annealing of at least four DNA single strands is the most common method to prepare tFNA, as it optimizes the cost, yield, and speed of assembly. Herein, the focus is on four key merits of tFNAs and their potential for biomedical applications. The natural ability of tFNA to scavenge reactive oxygen species, along with remarkable enhancement in cellular endocytosis and tissue permeability based on its appropriate size and geometry, promotes cell-material interactions to direct or probe cell behavior, especially to treat inflammatory and degenerative diseases. Moreover, the structural programmability of tFNA enables the development of static tFNA-based nanomaterials via engineering of functional oligonucleotides or therapeutic molecules, and dynamic tFNAs via attachment of stimuli-responsive DNA apparatuses, leading to potential applications in targeted therapies, tissue regeneration, antitumor strategies, and antibacterial treatment. Although there are impressive performance and significant progress, the challenges and prospects of functionalizing tFNA-based nanostructures are still indicated in this review.

Hard tissue stability after guided bone regeneration: a comparison between digital titanium mesh and resorbable membrane.

Guided bone regeneration (GBR) uses resorbable and non-resorbable membranes as biological barriers. This study compared the differences in hard tissue stability between GBR using evidence-based digital titanium mesh and resorbable collagen membranes during implant placement. A total of 40 patients (65 implant sites) were enrolled and divided into two groups: resorbable membrane and digital titanium mesh groups. The alveolar bone was analyzed at two- and three-dimensional levels using cone-beam computed tomography and by reconstructing and superimposing the hard tissues at four time points: preoperatively, postoperatively, before second-stage surgery, and 1 year after loading. The use of digital titanium mesh showed less alveolar bone resorption in vertical and horizontal directions two-dimensionally before the second-stage surgery and 1 year after loading. Regarding volumetric stability, the percentage of resorption after 6 months of healing with resorbable membrane coverage reached 37.5%. However, it was only 23.4% with titanium mesh. Although postoperative bone volume was greater at all labial sites with resorbable membrane than with digital titanium mesh, after substantial bone resorption within 1 year of loading, the labial bone thickness at the upper part of implants was thinner with resorbable membrane than with digital titanium mesh. Furthermore, digital titanium meshes made according to ideal bone arch contour reduced soft tissue irritation, and the exposure rate was only 10%. Therefore, although both resorbable membrane and digital titanium mesh in GBR were able to successfully reconstruct the bone defect, digital titanium meshes were better at maintaining the hard tissue volume in the osteogenic space.