Application of an Antibacterial Coating Layer via Amine-Terminated Hyperbranched Zirconium-Polysiloxane for Stainless Steel Orthodontic Brackets.

The massive growth of various microorganisms on the orthodontic bracket can form plaques and cause diseases. A novel amine-terminated hyperbranched zirconium-polysiloxane (HPZP) antimicrobial coating was developed for an orthodontic stainless steel tank (SST). After synthesizing HPZP and HPZP-Ag coatings, their structures were characterized by nuclear magnetic resonance spectroscopy, scanning electron microscopy, thickness measurement, contact angle detection, mechanical stability testing, and corrosion testing. The cell toxicity of the two coatings to human gingival fibroblasts (hGFs) and human oral keratinocytes (hOKs) was detected by cell counting kit eight assays, and SST, HPZP@SST, and HPZP-Ag@SST were cocultured with Staphylococcus aureus, Escherichia coli, and Streptococcus mutans for 24 hr to detect the antibacterial properties of the coatings, respectively. The results show that the coatings are about 10 µm, and the water contact angle of HPZP coating is significantly higher than that of HPZP-Ag coating (P < 0.01). Both coatings can be uniformly and densely distributed on SST and have good mechanical stability and corrosion resistance. The cell counting test showed that HPZP coating and HPZP-Ag coating were less toxic to cells compared with SST, and the toxicity of HPZP-Ag coating was greater than that of HPZP coating, with the cell survival rate greater than 80% after 72 hr cocultured with hGFs and hOKs. The antibacterial test showed that the number of bacteria on the surface of different materials was ranked from small to large: HPZP@SST < HPZP-Ag@SST < SST and 800 µg/mL HPZP@SST showed a better bactericidal ability than 400 µg/mL after cocultured with S. aureus, E. coli, and S. mutans, respectively (all P < 0.05). The results showed that HPZP coating had a better effect than HPZP-Ag coating, with effective antibacterial and biocompatible properties, which had the potential to be applied in orthodontic process management.

CHN nanocomposites and nanocoating resist enamel white spot lesions by enhancing remineralization and antibacterial activity.

Enamel white spot lesions (WSLs) are usually caused by the dissolution of minerals (mainly calcium and phosphate) on the tooth surface due to the acidic environment in the oral cavity. Without timely intervention, WSLs may lead to white spots or a sense of transparency on the tooth surface, and even the formation of dental caries (tooth decay) in severe cases. The key to preventing and treating WSLs is inhibiting the activity of acid-producing bacteria and promoting the remineralization of demineralized enamel. In this study, the network structure formed by sodium tripolyphosphate (TPP) cross-linked chitosan was used to stabilize calcium phosphate, and the multifunctional nanocomposite was constructed by integrating antibacterial components of traditional Chinese medicine, honokiol nanoparticles (HK-NPs) and sodium fluoride to achieve the purpose of resisting cariogenic bacteria and remineralizing with sustained release of calcium and phosphate ions. Notably, we enhanced the remineralization effect of nanocomposites with the help of functional nanocoatings inspired by the mussel biomimetic coating. The experimental results show that the synergistic remineralization effect of nanocomposite and nanocoating is better than that of a single strategy. This multi-prong treatment strategy provides the theoretical and experimental basis for the clinical prevention and treatment of WSLs.

A hydrogel-based first-aid tissue adhesive with effective hemostasis and anti-bacteria for trauma emergency management.

BACKGROUND: Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management. METHODS: We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively. RESULTS: Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®). CONCLUSIONS: Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment.

Hypoxia mitigation by manganese-doped carbon dots for synergistic photodynamic therapy of oral squamous cell carcinoma.

Photodynamic therapy (PDT) is widely used for cancer treatment due to its non-invasive and precise effectiveness, however, hypoxia in the tumor microenvironment greatly limits the efficacy of photodynamic therapy. Compared with conventional photosensitizers, carbon dots (CDs) have great potential. Therefore, developing a water-soluble, low-toxicity photosensitizer based on CDs is particularly important, especially one that can enhance the photodynamic efficacy using the tumor microenvironment to produce oxygen. Herein, manganese-doped carbon dot (Mn-CDs, ∼2.7 nm) nanoenzymes with excellent biocompatibility were prepared by a solvothermal method using ethylenediaminetetraacetic acid manganese disodium salt hydrate and o-phenylenediamine as precursors. TEM, AFM, HR-TEM, XRD, XPS, FT-IR, ζ potential, DLS, UV-Vis, and PL spectra were used to characterize the Mn-CDs. Cancer resistance was assessed using the CCK-8 kit, calcein AM versus propidium iodide (PI) kit, and the Annexin V-FITC/PI cell apoptosis assay kit. The obtained Mn-CDs have excellent near-infrared emission properties, stability, and efficient 1O2 generation. Notably, the manganese doping renders CDs with catalase (CAT)-like activity, which leads to the decomposition of acidic H2O2 in situ to generate O2, enhancing the PDT efficacy against OSCC-9 cells under 635 nm (300 mW·cm-2) irradiation. Thus, this work provides a simple and feasible method for the development of water-soluble photosensitizers with oxygen production, presenting good biosafety for PDT in hypoxic tumors.

Microneedle patches containing mesoporous polydopamine nanoparticles loaded with triamcinolone acetonide for the treatment of oral mucositis.

Oral mucositis (OM) is the most common disease of the oral mucosa, which affects people's daily production and life. Triamcinolone ointment is the common clinical drug for OM treatment. However, the hydrophobic properties of triamcinolone acetonide (TA) and the complex microenvironment of the oral cavity led to its low bioavailability and unstable therapeutic effects on ulcer wounds. Herein, dissolving microneedle patches (MNs) composed of mesoporous polydopamine nanoparticles (MPDA) loaded with TA (TA@MPDA), sodium hyaluronic acid (HA), and Bletilla striata polysaccharide (BSP) are prepared as the transmucosal delivery system. The prepared TA@MPDA-HA/BSP MNs exhibit well-arranged microarrays, high mechanical strength and fast solubility (<3 min) properties. In addition, the hybrid structure improves the biocompatibility of TA@MPDA and expedites oral ulcer healing in the SD rat model through the synergistic anti-inflammatory and pro-healing effects of microneedle ingredients (hormones, MPDA and Chinese herbs extracts), with 90% less amount of TA compared with Ning Zhi Zhu®. TA@MPDA-HA/BSP MNs are shown to be their great potential as novel ulcer dressings for OM management.

Applications of photothermally mediated nanohybrids for white spot lesions in orthodontics.

In orthodontic treatment, cariogenic bacteria in the oral cavity are the main cause of enamel white spot lesions (WSLs). Therefore, to effectively prevent and treat WSLs, it is crucial to inhibit the cariogenic bacterial activity while promoting the remineralization of demineralized tooth enamel. However, fluoride preparations commonly used for the prevention and treatment of WSLs can induce dental fluorosis if ingested in excess, and their remineralization effect is limited by the residual hydroxyapatite (HAp) content and salivary Ca2+ and PO43- levels. In this study, we propose a strategy (CMCS/ACP@PDA) for antibacterial and remineralization of WSLs by a nanohybrid of carboxymethyl chitosan (CMCS)-stabilized amorphous calcium phosphate (ACP) loaded polydopamine nanoparticles (PDA NPs) based on biomimetic remineralization techniques and biocompatible near-infrared (NIR) photoactivation therapy. The nanohybrid utilizes the excellent photothermal conversion ability of polydopamine for antimicrobial purposes, while CMCS with its own positive and negative charges (-NH3+ and -COO-) acts as a biomimetic mineralizing agent to stabilize ACP, supplemented with abundant Ca2+ and PO43- for remineralization of demineralized enamel. The results showed that CMCS/ACP@PDA could effectively inhibit the adhesion of cariogenic Streptococcus mutants (S. mutants) with high bactericidal rates. In addition, the remineralization of demineralized enamel by nanohybrid was more effective after 7 days of in vitro mineralization. This study provides a theoretical and experimental basis for the use of CMCS/ACP@PDA nanohybrid materials as potential materials against WSLs.

Betamethasone-loaded dissolvable microneedle patch for oral ulcer treatment.

Oral inflammatory disease (OID) is among the most common oral lesions, affecting people's quality of life and even leading to oral cancer. Oral ulcers are the most common OID. However, the pain and fear caused by the localized injection of hormones hinder the clinical treatment of oral ulcers. To address this problem, soluble hyaluronic acid (HA) microneedle patches (BSP-BDP@HAMN) containing betamethasone 21-phosphate sodium (BSP) and betamethasone 17,21-dipropionate (BDP) were fabricated for potential application in oral ulcers. BSP-BDP@HAMNs had the sufficient mechanical strength to penetrate the rat tongue abdomen mucosa with an insertion depth of approximately 207 ± 3 µm. The rapidly solubilized HA microneedle carrier released BSP and BDP into the ulcer base within 3 min of entering the mucosa. Cellular assays have shown that BDP@HAMNs have wound healing-promoting and anti-inflammatory effects. Compared with topical injections and creams, BSP-BDP@HAMNs not only penetrated the ulcer surface painlessly but also worked deep in the ulcer for a long time. In conclusion, the proposed BSP-BDP@HAMN patch can improve the comfort and efficacy of oral ulcer treatment, thus providing a new prospect for oral ulcer treatment.

Injectable and Self-Healing Probiotics-Loaded Hydrogel for Promoting Superbacteria-Infected Wound Healing.

Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with Lactobacillus rhamnosus (HPF@L.rha) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed HPF@L.rha exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria (Pseudomonas aeruginosa) effect was greatly increased in a dose-dependent fashion. Additionally, in vitro evaluation shows that the prepared HPF@L.rha containing appropriate probiotic concentrations (less than 1 × 107 CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, in vivo the hydrogel combined with probiotics significantly inhibits P. aeruginosa infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.

Lidocaine-Loaded Hyaluronic Acid Adhesive Microneedle Patch for Oral Mucosal Topical Anesthesia.

The pain and fear caused by direct local injection of anesthetic or the poor experience with surface anesthetic cream increase the difficulty of clinical treatment for oral diseases. To address this problem, a hyaluronic acid microneedle patch (Li-HAMNs) that consists of fast-dissolving lidocaine hydrochloride (LDC)-loaded tips and a wet-adhesive backing layer made of polyvinyl alcohol (PVA)/carboxymethylcellulose sodium (CMC-Na) was fabricated to explore its potential use in dental topical anesthesia. Li-HAMNs could puncture the stratum corneum with an insertion depth of about 279 µm in the isolated porcine oral mucosal. The fast-dissolving tips could release LDC to improve the patients' convenience and compliance. Importantly, the backing layer, which has good adhesion ability and water-absorbing properties, could surmount the contraction and extension of oral masticatory muscles and the saliva scour. In the tail flick test, the topical anesthesia efficacy of the Li-HAMNs group was much better than clinical lidocaine cream (EMLA cream, LDC, 1.2 mg) in spite of a relatively lower LDC dose with Li-HAMNs (LDC, 0.5 mg). It is believed that the proposed adhesive microneedle patch could enhance transmucosal delivery of anesthetics and thus open a new chapter in the painless treatment of oral diseases.

Carboxymethyl chitosan-based hydrogels containing fibroblast growth factors for triggering diabetic wound healing.

Triggering the repair process of diabetic wounds is a huge clinical challenge due to microbial infection, the reduced migration and proliferation of fibroblasts, decreased angiogenesis and collagen formation caused by the long-term negative stimulation of high blood glucose levels. Herein, bio-multifunctional benzaldehyde-terminated 4-arm PEG (4-arm-PEG-CHO)/carboxymethyl chitosan (CMCS)/basic fibroblast growth factor (bFGF) hydrogels (BP/CS-bFGF) are prepared via the dynamic Schiff base reaction for diabetic wound treatment. BP/CS-bFGF hydrogel dressing shows strong wet-tissue adhesion, self-mending, and antibacterial property. Biological assessments display that the BP/CS-bFGF hydrogel has excellent biocompatibility and fast hemostasis capacity. Importantly, BP/CS-bFGF hydrogel dressing significantly accelerates full-thickness diabetic wound repair by increasing the production of Ki67, promotes the generation of epithelialization and collagen, induces the formation of hair follicles, and enhances neovascularization by upregulating the production of CD31 and CD34. Thus, our work demonstrates that BP/CS-bFGF hydrogel dressing displays great potential for diabetic chronic wound management.

Injectable Self-Healing First-Aid Tissue Adhesives with Outstanding Hemostatic and Antibacterial Performances for Trauma Emergency Care.

Soft-tissue trauma emergency caused by natural disasters and traffic accidents is highly prevalent, which can result in massive bleeding, pathogen infection, and even death. Although numerous tissue adhesives can bind to tissue surfaces and cover wounds, most of them still have several deficiencies, including long gelation time, poor adhesive strength, and anti-infection, making them inappropriate for use as first-aid bandages. Herein, injectable and self-healing four-arm-PEG-CHO/polyethyleneimine (PEI) tissue adhesives as liquid first-aid supplies are developed via the dynamic Schiff base reaction for trauma emergency. It is found that the prepared hydrogel adhesives exhibit short and controlled gelation time (9∼88 s), strong adhesive strength, and excellent antibacterial ability. Their hemostatic and antimicrobial performances can be tailored by the mass ratio of four-arm-PEG-CHO/PEI. Moreover, in vitro biological assays display that the developed tissue adhesives possess satisfactory cyto/hemocompatibility. Importantly, in vivo the designed adhesives show fast hemostatic capacity and excellent anti-infection as compared to commercial Prontosan gel. Thus, this work indicates that the four-arm-PEG-CHO/PEI first-aid tissue adhesives display great potential for wound emergency management.

Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing.

Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing.

Nanomedicine for the Diagnosis and Therapy of COVID-19.

The coronavirus disease-2019 (COVID-19) pandemics caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading around the world due to its high infection rate, long incubation period, as well as lack of effective diagnosis and therapy or vaccines, which is tearing global health systems apart. It is an urgent demand for point-of-care diagnosis and effective treatment to prevent the spread of COVID-19. Currently, based on the rapid development of functional materials with unique physicochemical features through advanced fabrication and chemical modification, nanomaterials provide an emerging tool to detect SARS-CoV-2, inhibit the interplay in the virus and host cell interface, and enhance host immune response. In our manuscript, we summarized recent advances of nanomaterials for the diagnosis and therapy of COVID-19. The limitation, current challenges, and perspectives for the nano-diagnosis and nano-therapy of COVID-19 are proposed. The review is expected to enable researchers to understand the effect of nanomaterials for the diagnosis and therapy of COVID-19 and may catalyze breakthroughs in this area.

Preparation of Fucoidan-Based Electrospun Nanofibers and Their Interaction With Endothelial Cells.

Sulfated polysaccharide fucoidan (FD) is widely applied in biomedical applications owing to its outstanding bioactivities. In addition to the biochemical features, the architecture of biomaterials plays a critical role in tissue repair and regeneration. Particularly, nanofibers have elicited great interest due to their extracellular matrix-like structure, high specific surface area, and favorable biological properties. Herein, chitosan-modified FD/ultra-high molecular weight polyethylene oxide (UHMWPEO) nanofibers are developed via green electrospinning and electrostatic interaction for studying their interaction with endothelial cells. The appropriate solvent is screened to dissolve FD. The electrospinnability of FD/UHMWPEO aqueous solutions is greatly dependent on the weight ratios of FD/UHMWPEO. The incorporation of UHMWPEO significantly improves the electrospinnability of solution and thermo-stability of nanofibers. Also, it is found that there is good miscibility or no phase separation in FD/UHMWPEO solutions. In vitro biological experiments show that the chitosan-modified FD/UHMWPEO nanofibers greatly facilitate the adhesion of endothelial cells and inhibit the attachment of monocytes. Thus, the designed FD-based nanofibers are promising bio-scaffolds in building tissue-engineered blood vessels.

Preparation of triamcinolone acetonide-loaded chitosan/fucoidan hydrogel and its potential application as an oral mucosa patch.

Oral inflammatory diseases (OIDs) are among the most common lesions in the oral cavity, affecting the quality of human life and even causing oral cancer. However, most of the current oral mucosa patches still have some limitations, particularly instant, poor mechanical strength and conformability, low adhesion to tissue, and foreign body sensation. Herein, triamcinolone acetonide (TA)-loaded chitosan/fucoidan (CF) composite hydrogels were prepared via chemical crosslinking. The macro/microscopic morphologies and (bio)physicochemical properties of composite hydrogels were investigated. Incorporating fucoidan in chitosan hydrogels greatly enhanced their swelling behavior, mechanical strength, and adhesion properties. Further, the addition of TA in CF hydrogels improved their elastic feature, inhibited inflammatory response, and promoted the formation of mature and well-organized collagen fibers. The developed composite hydrogels displayed not only good antibacterial properties but also good cytocompatibility and histocompatibility. Thus, the designed hydrogels allow the development of oral mucosa patches as a potential treatment for OIDs.

Marine polysaccharide-based composite hydrogels containing fucoidan: Preparation, physicochemical characterization, and biocompatible evaluation.

Marine polysaccharide-based hydrogels have drawn much attention for diversified biomedical applications owing to their excellent (bio)physicochemical properties. In the present work, a series of marine polysaccharide-based hydrogels composed of chitosan, alginate, or fucoidan are prepared via a facile chemical cross-linking approach in an alkali/urea aqueous system. The prepared hydrogels possess tunable microporous architecture, swelling, and biodegradable properties by changing the components and proportions of marine polysaccharides. Importantly, the developed hydrogels are mechanically robust and the maximum compressive stress is up to 28.37 ± 4.63 kPa. Furthermore, the composite hydrogels exhibit excellent cytocompatibility, blood compatibility, and histocompatibility. When implanted subcutaneously in rats, the hydrogels containing fucoidan inhibit the inflammatory response of surrounding tissue. Thus, the designed composite hydrogels are promising bio-scaffolds in biomedical applications.

A biodegradable antibacterial alginate/carboxymethyl chitosan/Kangfuxin sponges for promoting blood coagulation and full-thickness wound healing.

Conventional wound-dressing materials with structural and functional deficiencies are not effective in promoting wound healing. The development of multifunctional wound dressings is emerging as a promising strategy to accelerate blood coagulation, inhibit bacterial infection, and trigger full-thickness wound into a regenerative process. Herein, multifunctional composite sponges were developed by incorporation of traditional Chinese medicine Kangfuxin (KFX) into alginate (AG)/carboxymethyl chitosan (CMC) via green crosslinking, electrostatic interaction, and freeze-drying methods. It is demonstrated that the AG/CMC/KFX (ACK) sponges exhibit a highly interconnected and porous structure, suitable water vapor transmittance, excellent elastic properties, antibacterial behavior, cytocompatibility, and rapid hemostasis. Further, in a rat full-thickness wounds model, the ACK sponge containing 10% KFX (ACK-10) significantly facilitates wound closure compared to the AC group and ACK sponge containing 5% and 15% KFX. Thus, the multifunctional ACK-10 composite sponge has great promise for the application of full-thickness wound healing.

Biological effects on tooth root surface topographies induced by various mechanical treatments.

The cleaning and physicochemical properties on tooth root biointerfaces are pivotal for periodontal healing. Herein, this work investigated the impact of multi-treatment on the physicochemical features of tooth root surfaces and the responsive behavior of human gingival fibroblasts (hGFs). It was found that the combination of various mechanical treatments significantly affects the topographical pattern and size as well as wettability on tooth root surfaces. Furthermore, biological experiments revealed that hGF behaviors (i.e., cell adhesion, shape, spreading, arrangement, and viability) were regulated by the topography and wettability of tooth root surfaces. Also, there was no significant difference in the protein expression of NLRP3 inflammasome and IL-1ß in hGFs among tooth root surfaces under various treatments. This study provides new insights to efficiently remove the dental calculus and to understand the interaction between the tooth root interface and cell, which could guide the clinical operation and thereby is more conducive to periodontal recovery.