Treatment outcomes of permanent teeth with uncomplicated and complicated crown fractures and factors associated with pulp survival: A retrospective study.

BACKGROUND: Crown fracture is the most common injury in permanent teeth. This study aimed to evaluate the treatment outcomes of permanent teeth with uncomplicated and complicated crown fractures and to investigate potential factors. MATERIALS AND METHODS: This retrospective study included patients who experienced crown fractures in permanent teeth from 2018 to 2021 with at least 12 months of follow-up. All complicated crown fractured teeth were treated with pulpotomy, while for teeth with uncomplicated crown fractures, three treatments (restoration, indirect pulp capping, or pulpotomy) were employed. The chi-square test was used to compare the prognosis of teeth with uncomplicated and complicated crown fractures. Potential factors associated with pulp survival including gender, interval, root development, enamel infraction, mobility, concomitant luxation injury, treatment, and coronal restoration were identified via Cox regression analysis. RESULTS: A total of 307 teeth from 220 children (average age = 9.3 ± 1.4 years; age range, 6-14 years) with a median follow-up of 23 months were included, and 82.1% of all teeth had immature roots. Complicated crown fractured teeth (93.6%, 102/109) had a significantly higher success rate compared with uncomplicated crown fractured teeth (85.4%, 169/198) (p < .05). Pulpotomy (96.9%) had the highest success rate of all treatments for uncomplicated crown fractures, followed by only restoration (85.0%) and indirect pulp capping (76.9%). The success rate of teeth that received pulpotomy was significantly higher than those treated by indirect pulp capping (p < .05). In uncomplicated crown fractures, teeth with Class II mobility were more vulnerable to failure than teeth without abnormal mobility (HR = 34.83; 95% CI, 9.59-126.56; p < .05); teeth that received pulpotomy were less prone to failure than teeth that received indirect pulp capping (HR = 13.53; 95% CI, 1.58-115.72; p < .05). CONCLUSION: Crown fractures treated with conservative pulp treatments had a relatively highly favorable prognosis. The prognosis of uncomplicated crown fractured teeth was impacted by the severity of periodontal injury and treatment strategies. Accurate diagnosis and identification of micro-exposures are important. Dentists should take multiple risk factors into account and select optimal treatment strategies.

Recent Advances in Cyclodextrin-Based Light-Responsive Supramolecular Systems.

Cyclodextrins (CDs), one of the host molecules in supramolecular chemistry, can host guest molecules to form inclusion complexes via non-covalent and reversible host-guest interactions. CD-based light-responsive supramolecular systems are typically constructed using CDs and guest molecules with light-responsive moieties, including azobenzene, arylazopyrazole, o-nitrobenzyl ester, pyrenylmethyl ester, coumarin, and anthracene. To date, numerous efforts have been reported on the topic of CD-based light-responsive supramolecular systems, but these have not yet been highlighted in a separated review. This review summarizes the efforts reported over the past ten years. The main text of this review is divided into five sections (vesicles, micelles, gels, capturers, and nanovalves) according to the formation of self-assemblies. This feature article aims to afford a comprehensive understanding of the light-responsive moieties used in the construction of CD-based light-responsive supramolecular systems and to provide a helpful guide for the further design of CD-based light-responsive supramolecular systems.

Interlayer-crosslinked micelles prepared from star-shaped copolymers via click chemistry for sustained drug release.

To balance the stability and the particle size of polymeric micelles, star-shaped copolymers Hx-yne-N3-PEG containing both alkynyl and azido groups were synthesized from hyperbranched 2,2-bismethylolpropionic acid polyester (H20 with 16 hydroxyl, H30 with 32 hydroxyl, H40 with 64 hydroxyl) to develop interlayer-crosslinked micelles by click chemistry. The results of dynamic light scattering indicate that the crosslinking could enhance the stability of polymeric micelles. The crosslinked micelles are regular nanosized (approximately 20 nm) spheres observed by a transmission electron microscope. The crosslinked micelles have better drug loading capacity and more sustained drug release behavior than the un-crosslinked micelles.

A Functionalized Cyclic Lactide Monomer for Synthesis of Water-Soluble Poly(Lactic Acid) and Amphiphilic Diblock Poly(Lactic Acid).

Biodegradable and bioabsorbable poly(lactic acid)s are one of the most important biomedical materials. However, it is difficult to introduce the functional groups into poly(lactic acid)s in order to improve their hydrophilicity and degradation rate. Here the authors describe the synthesis of functionalized cyclic lactide monomer 3,6-bis(benzyloxymethyl)-1,4-dioxane-2,5-dione (BnLA) using an advanced synthetic route. Water-soluble hydroxyl-functionalized homopoly(lactic acid) (P(OH)LA) is synthesized via ring-opening polymerization (ROP) of BnLA, followed by a hydrogenolytic deprotection reaction. Amphiphilic diblock poly(lactic acid) (P(OH)LA-PLA) is synthesized via ROP of DL-lactide using PBnLA as an initiator, followed by a hydrogenolytic deprotection reaction. P(OH)LA-PLA is able to form polymeric micelles with the diameter of sub-100 nm.

Click Chemistry in Functional Aliphatic Polycarbonates.

Click chemistry, one of the most important methods in conjugation, plays an extremely significant role in the synthesis of functional aliphatic polycarbonates, which are a group of biodegradable polymers containing carbonate bonds in their main chains. To date, more than 75 articles have been reported on the topic of click chemistry in functional aliphatic polycarbonates. However, these efforts have not yet been highlighted. Six categories of click reactions (alkyne-azide reaction, thiol-ene reaction, Michael addition, epoxy-amine/thiol reaction, Diels-Alder reaction, and imine formation) that have been afforded for further post-polymerization modification of polycarbonates are reviewed. Through this review, a comprehensive understanding of functional aliphatic polycarbonates aims to afford insight on the design of polycarbonates for further post-polymerization modification via click chemistry and the expectation of the practical application.

UV-Responsive Supramolecular Vesicles with Double Hydrophobic Chains.

In order to improve the stability of polymeric vesicles, supramolecular vesicles are developed via self-assembly of the inclusion of γ-cyclodextrin (γ-CD) and 1-pyrenemethyl palmitate (Py-pal). The inclusion has one hydrophilic head and double hydrophobic tails, which looks like the phospholipid. From the transmission electron microscopy (TEM) image, it can be observed that the average diameter of supramolecular vesicles is approximately 55 nm and there is a huge cavity in supramolecular vesicles. Due to the photo-breakable ester of Py-pal, supramolecular vesicles are broken under UV irradiation. Supramolecular vesicles are used as UV-responsive drug carriers to release the hydrophilic drug such as doxorubicin hydrochloride (DOX•HCl).

In Vitro Modeling as a Tool for Testing Therapeutics for Spinal Muscular Atrophy and IGHMBP2-Related Disorders.

Spinal Muscular Atrophy (SMA) is the leading genetic cause of infant mortality. The most common form of SMA is caused by mutations in the SMN1 gene, located on 5q (SMA). On the other hand, mutations in IGHMBP2 lead to a large disease spectrum with no clear genotype-phenotype correlation, which includes Spinal Muscular Atrophy with Muscular Distress type 1 (SMARD1), an extremely rare form of SMA, and Charcot-Marie-Tooth 2S (CMT2S). We optimized a patient-derived in vitro model system that allows us to expand research on disease pathogenesis and gene function, as well as test the response to the AAV gene therapies we have translated to the clinic. We generated and characterized induced neurons (iN) from SMA and SMARD1/CMT2S patient cell lines. After establishing the lines, we treated the generated neurons with AAV9-mediated gene therapy (AAV9.SMN (Zolgensma) for SMA and AAV9.IGHMBP2 for IGHMBP2 disorders (NCT05152823)) to evaluate the response to treatment. The iNs of both diseases show a characteristic short neurite length and defects in neuronal conversion, which have been reported in the literature before with iPSC modeling. SMA iNs respond to treatment with AAV9.SMN in vitro, showing a partial rescue of the morphology phenotype. For SMARD1/CMT2S iNs, we were able to observe an improvement in the neurite length of neurons after the restoration of IGHMBP2 in all disease cell lines, albeit to a variable extent, with some lines showing better responses to treatment than others. Moreover, this protocol allowed us to classify a variant of uncertain significance on IGHMBP2 on a suspected SMARD1/CMT2S patient. This study will further the understanding of SMA, and SMARD1/CMT2S disease in particular, in the context of variable patient mutations, and might further the development of new treatments, which are urgently needed.

A water-soluble polycarbonate with dimethylamino pendant groups prepared by enzyme-catalyzed ring-opening polymerization.

A water-soluble polycarbonate with dimethylamino pendant groups, poly(2-dimethylaminotrimethylene carbonate) (PDMATC), is synthesized and characterized. First, the six-membered carbonate monomer, 2-dimethylaminotrimethylene carbonate (DMATC), is prepared via the cyclization reaction of 2-(dimethylamino)propane-1,3-diol with triphosgene in the presence of triethylamine. Although the attempted ring-opening polymerization (ROP) of DMATC with Sn(Oct)(2) as a catalyst fails, the ROP of DMATC is successfully carried out with Novozym-435 as a catalyst to give water-soluble aliphatic polycarbonate PDMATC with low cytotoxicity and good degradability.

Gradient adhesion modification of polyacrylamide/alginate-calcium tough hydrogels.

Strong hydrogel adhesion requires the synergy of adhesion and cohesion. Gradient adhesive-tough hydrogels can balance adhesion and cohesion, however, their construction is still a challenging task. Here, we used ethylenediaminetetraacetic acid (EDTA) on-side coordination-induced diffusion chelating Ca2+ to form an adhesive surface in a polyacrylamide/alginate-calcium (PAAm/Alg-Ca2+) tough hydrogel as a facile method for the construction of gradient adhesive-tough hydrogels. The adhesion energy of a gradient adhesive-tough hydrogel to skin is increased by 128% compared with PAAm/Alg-Ca2+ tough hydrogels and the elongation at break is two times higher than that of PAAm/Alg hydrogels. In addition, gradient adhesive-tough hydrogels also exhibit wide linear sensitivity (the gauge factor (GF) = 0.196 (0% < ε < 400%); GF = 0.260 (400% < ε < 650%)) as a wearable strain sensor to monitor human motions. This work provides a versatile strategy for the design of gradient adhesive-tough hydrogels and also provides a practical model for the development of wearable strain sensors.

Advances in non-covalent crosslinked polymer micelles for biomedical applications.

As a drug delivery system, crosslinked polymer micelles can reduce the drug release in advance in the blood circulation, improve the stability of polymer micelles, effectively deliver drugs to the treatment site, further improve the bioavailability of drugs and reduce the side effects. Among them, non-covalent crosslinked polymer micelles have the advantages of sensitive response to external stimuli, self-healing after damage, and no need to use chemicals for crosslinking. This review mainly introduces the research progress of polymer micelles crosslinked by hydrogen bonding, dipole interaction, hydrophobic interaction, host-guest interaction, π-π stacking, and metal coordination reported in recent years, and summarizes the applications of these micelles in biomedical fields such as drug delivery, gene transfection, and imaging.

Adhesive and tough hydrogels: from structural design to applications.

In recent years, multifunctional hydrogels have garnered great interest. Usually, there is a contradiction between the toughness and interface adhesion of traditional hydrogels. In engineering and medical applications, hydrogels need to have good adhesive properties and toughness. The design of functional hydrogels with strong adhesion and high toughness is key to their application. In this review, the research progress of adhesive and tough hydrogels in recent years is outlined. Specifically, the structural design (such as integrated, layered, and gradient structures) and applications (such as cartilage repair, drug delivery, strain sensors, tissue adhesives, soft actuators, and supercapacitors) of adhesive and tough hydrogels are classified and discussed, providing new insights on their design and development.

Nanocomposite adhesive hydrogels: from design to application.

With the rapid development of hydrogels, hydrogel adhesion has attracted increasing attention in the last decade, but strong adhesion remains a challenge due to the large amount of water in hydrogels. The factors that affect hydrogel adhesion mainly include chemistries of bonds, topologies of connection, and mechanisms of energy dissipation. Strategies such as surface modification, surface initiation, bulk modification, bridging polymers, topological adhesion, and the use of nanocomposites have been developed to achieve strong hydrogel adhesion. In nanocomposite hydrogels, nanoparticles interlink with polymer chains to form strong bonds, which lower adhesion energy and offer energy dissipation, thus enhancing the adhesion. This review emphatically outlines nanocomposite adhesive hydrogels from design to application and provides useful understanding for the design and further development of nanocomposite adhesive hydrogels.

MicroRNA Delivery with Bioreducible Polyethylenimine as a Non-Viral Vector for Breast Cancer Gene Therapy.

Polyethylenimines (PEIs) are outstanding macromolecules belonging to the polycations used in gene transfection. The transfection efficiency and cytotoxicity of PEIs increase with the increase in their molecular weight. To break up the correlation between transfection efficiency and cytotoxicity for non-viral gene delivery, disulfide cross-linked polyethylenimine (PEI-SS) has been widely employed as highly efficient gene vectors for DNA/siRNA delivery in numerous efforts. In this work, PEI-SS is described as a non-viral vector for miRNA delivery for the first time. PEI-SS is synthesized via cross-linking using disulfide bonds as the cross-linker from low molecular weight PEI. PEI-SS can efficiently bind anti-miR-155 to form the polyplex with nano-sized spherical structures in the size range of 10-100 nm. The polyplex is degraded by glutathione (GSH, a reducing agent) in cancer cells. Anti-miR-155 is then released to efficiently inhibit tumor growth.

Nanofibrous Spongy Microspheres To Distinctly Release miRNA and Growth Factors To Enrich Regulatory T Cells and Rescue Periodontal Bone Loss.

In addition to T cells' roles in immune response and autoimmune diseases, certain types of T cells, called regulatory T cells (Tregs), play important roles in microenvironment modulation for resolution and tissue regeneration. However, there are currently few options available other than introducing more Tregs or immunosuppressive drugs to locally enrich Tregs. Herein, poly(l-lactic acid) (PLLA) nanofibrous spongy microspheres (NF-SMS), PLLA/polyethylene glycol (PEG) co-functionalized mesoporous silica nanoparticles (MSN), and poly(lactic acid- co-glycolic acid) microspheres (PLGA MS) are integrated into one multibiologic delivery vehicle for in situ Treg manipulation, where the MSNs and PLGA MS were utilized to distinctly release IL-2/TGF-ß and miR-10a to locally recruit T cells and stimulate their differentiation into Tregs, while PLLA NF-SMS serve as an injectable scaffold for the adhesion and proliferation of these Tregs. In a mouse model of periodontitis, the injectable and biomolecule-delivering PLLA NF-SMS lead to Treg enrichment, expansion, and Treg-mediated immune therapy against bone loss. This system can potentially be utilized in a wide variety of other immune and regenerative therapies.

Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.

MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a 'double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3ß to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.

Phenylboronic acid-functionalized polymeric micelles with a HepG2 cell targetability.

Phenylboronic acid-functionalized amphiphilic block copolymer Pluronic-PMCC-BA was synthesized via ring-opening polymerization of 5-methyl-5-benzyloxycarbonyl-1,3-dioxan-2-one (MBC) with fumaric acid as a catalyst followed by the deprotection of carboxyl groups by catalyzed hydrogenation and the condensation of 3-aminophenylboronic acid with the copolymer side groups. Pluronic-PMCC-BA can form stable micelle solution by self-assembly in water. The phenylboronic acid groups are located at the shell of micelle as proved by (1)H NMR. The diameter of drug-free micelles is approximate 60 nm. Nano-spheres with narrow size distribution could be observed in the TEM image. MTT assay results show that Pluronic-PMCC-BA exhibits slight cytotoxicity when the polymer concentration is higher than 25 µg mL(-1). The toxicities of DOX@Pluronic-PMCC and DOX@Pluronic-PMCC-BA to COS7, HeLa, and HepG2 cell lines are similar with those of free DOX. Interestingly, phenylboronic acid groups located at the surface of Pluronic-PMCC-BA micelles can recognize HepG2 cells and promote the drug uptake of the cells, which are observed by confocal laser scanning microscopy (CLSM). The results imply that Pluronic-PMCC-BA would be a promising material for targeted drug delivery to the cancer cells.

Garcinia xanthones as orally active antitumor agents.

Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D7.4, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.

Phenylboronic-acid-modified amphiphilic polyether as a neutral gene vector.

A phenylboronic-acid-modified amphiphilic block polyether is prepared via reaction of polyglycidol-block-poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide)-block-polyglycidol (Pluronic-PG) with 2-(N,N-dimethylaminomethyl)-5-aminomethyl phenylboronic acid using phosgene as a coupling reagent. The boronic-acid-modified non-cationic polymer binds plasmid pGL3 effectively, forms sub-µm polymer/DNA complex particles, and greatly facilitates the cell uptake of the plasmid. The efficiency of the polymer as a gene vector is evaluated in vitro by transfection of pGL3 to HeLa, COS-7 and HepG2 cells. Pluronic-PG-BA enhances the transfection efficiency by 100 to 1000 times compared with Pluronic-PG. The presence of serum does not significantly affect the transfection efficiency.