Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Recent Advances in Polymer Microneedles for Drug Transdermal Delivery: Design Strategies and Applications.

In recent years, transdermal drug delivery based on microneedles (MNs) technology has received extensive attention, which offers a safer and painless alternative to hypodermic needle injections. They can pierce the stratum corneum and deliver drugs to the epidermis and dermis-structures of skin, showing prominent properties such as minimally invasiveness, bypassing first-pass metabolism, and can be self-administered. A range of materials has been used to fabricate MNs, such as silicon, metal, glass, and polymers. Among them, polymer MNs have gained increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. MN products have recently become available on the market, and some of them are under evaluation for efficacy and safety. This paper focuses on the current state of polymer MNs in drug transdermal delivery. The materials and methods for the fabrication of polymer MNs and their drug administration are described. The recent progress of polymer MNs for treatment of cancer, vaccine delivery, blood glucose regulation, androgenetic alopecia, obesity, tissue healing, myocardial infarction, and gout are reviewed. The challenges of MNs technology are summarized and the future development trend of MNs is also prospected.

Treatment of Multiple Odontogenic Keratocysts Involving Chinese Patients.

PURPOSE: The optimal treatment of odontogenic keratocysts (OKCs) remains a matter of debate in reported studies. The present study aimed to estimate the postoperative recurrence rates of multiple OKCs (MOKCs) in Chinese patients. MATERIALS AND METHODS: A retrospective cohort study of histologically confirmed MOKCs treated from 2003 to 2017 using enucleation, marsupialization alone, enucleation and peripheral ostectomy, or marsupialization followed by secondary enucleation was performed. Patients with MOKCs who had undergone follow-up for 12 or more months with panoramic radiographs and radiographs of the chest and skull available from the first visit and had been treated by the same team using the same treatment protocol were included in the study. Patients were excluded if the lesion had been treated previously, they had a solitary OKC, or their medical records were not available for review. The treatment methods, recurrence rate, and interval to recurrence were evaluated. The Kaplan-Meier method was used to estimate the survival rate and median time to recurrence. Univariate analysis was used to identify the risk factors associated with recurrence. Significant differences were determined at an α level of 5%. RESULTS: The sample included 81 patients with MOKCs; 21 (25.6%) were male and 60 (74.07%) were female. The age range was 7 to 63 years (mean ± standard deviation, 18.4 ± 4). The overall recurrence rate was 26.63%, with an overall recurrence-free interval of 26.85 months. The average length of follow-up was 55.68 months. No association was found between the treatment method used and the risk of recurrence (P = .178). Although the interval to recurrence was not affected by any of the study variables, the average interval to the recurrence of MOKCs involving the maxilla was short compared with that of MOKCs involving the mandible. CONCLUSIONS: The surgical treatment method did not influence the risk of recurrence in patients with MOKCs, and the interval to recurrence was not associated with any of the study variables.

Glomus tumor in the floor of the mouth: a case report and review of the literature.

BACKGROUND: Glomus tumors are rare benign neoplasms that usually occur in the upper and lower extremities. Oral cavity involvement is exceptionally rare, with only a few cases reported to date. CASE PRESENTATION: A 24-year-old woman with complaints of swelling in the left floor of her mouth for 6 months was referred to our institution. Her swallowing function was slightly affected; however, she did not have pain or tongue paralysis. Enhanced computed tomography revealed a 2.8 × 1.8 × 2.1 cm-sized well-defined, solid, heterogeneous nodule above the mylohyoid muscle. The mandible appeared to be uninvolved. The patient underwent surgery via an intraoral approach; histopathological examination revealed a glomus tumor. The patient has had no evidence of recurrence over 4 years of follow-up. CONCLUSIONS: Glomus tumors should be considered when patients present with painless nodules in the floor of the mouth.

Integration of metformin-loaded MIL-100(Fe) into hydrogel microneedles for prolonged regulation of blood glucose levels.

The transdermal drug delivery based on microneedles (MNs) provides a suitable and painless self-administration for diabetic patients. In this work, the hydrogel-forming MNs were firstly fabricated using poly(vinyl alcohol) (PVA) and chitosan (CS) as matrix. A hypoglycemic drug, metformin (Met), had been loaded into MIL-100(Fe). Then, both of free Met and Met-loaded MIL-100(Fe) were integrated into hydrogel-forming MNs for regulation of blood glucose levels (BGLs) on diabetic rats. After penetrated into the skin, the free Met could be firstly released from MNs. Due to the absorption of interstitial fluid and subsequent release of loaded Met from MIL-100(Fe), leading to a sustainable and long-term drug release behaviors. A notable hypoglycemic effect and low risk of hypoglycemia could be obtained on diabetic rat modelsin vivo. The as-fabricated hydrogel-forming MNs expected to become a new type of transdermal drug delivery platform for transdermal delivery of high-dose drugs to form a long-term hypoglycemic effect.

Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings.

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.

Genipin crosslinked quaternary ammonium chitosan hydrogels for wound dressings.

Bacterial infection can lead to various complications, such as inflammations on surrounding tissues, which can prolong wound healing and thus represent a significant clinical and public healthcare problem. Herein, a report on the fabrication of a novel genipin/quaternized chitosan (CS) hydrogel for wound dressing is presented. The hydrogel was prepared by mixing quaternized CS and genipin under 35 °C bath. The hydrogels showed porous structure (250-500 µm) and mechanical properties (3000-6000 Pa). In addition, the hydrogels displayed self-healing ability and adhesion performance on different substrates. Genipin crosslinked quaternized CS hydrogels showed antibacterial activities againstE. coliandS. aureus. The CCK-8 and fluorescent images confirmed the cytocompatibility of hydrogels by seeding with NIH-3T3 cells. The present study showed that the prepared hydrogel has the potential to be used as wound dressing.

Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.

Transdermal delivery of allopurinol to acute hyperuricemic mice via polymer microneedles for the regulation of serum uric acid levels.

Allopurinol (AP) is widely used to treat hyperuricemia which may cause severe side effects upon oral administration. Alternative means for the treatment of hyperuricemia are demanded to simultaneously facilitate drug absorption, patient compliance, and fewer side effects. In this study, a new polymer microneedle (MN) system was developed for the transdermal delivery of AP to acute hyperuricemic mice. This study aims to achieve the controllable regulation of serum uric acid (SUA) levels with fewer side effects compared with oral administration. The matrix of polymer MNs consisted of polyvinylpyrrolidone (PVP) and polycaprolactone (PCL), in which the rapid dissolution of PVP offers a rapid dissolution of AP into the blood and the biodegradability of PCL resulting in a sustainable drug release behavior. An in vivo study demonstrated that the AP-loaded MN system can effectively reduce the SUA levels as oral administration with lower side effects, which will be conducive to reducing the adverse reactions and improving the bioavailability of AP. This MN-mediated strategy can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia and improvement of patient compliance.

A retrospective study of the malignant change of odontogenic keratocyst.

The odontogenic keratocyst (OKC) is a common cystic lesion of the maxilla and mandible. Squamous cell carcinoma (SCC) arising from OKC or dysplasia occurring in OKC is rare. This study aimed to explore the incidence and clinical features of the dysplasia and malignant transformation of OKC. In this study, 544 patients diagnosed with OKC were collected. Among them, 3 patients were diagnosed as SCC arising from OKC, and 12 patients were diagnosed as OKC with dysplasia. The incidence was calculated. Clinical features were analyzed by chi-square test. In addition, a representative case reconstructing mandible with vascularized fibula flap under general anesthesia was reported. And cases reported before were reviewed. The incidence of the dysplasia and malignant transformation of OKC, which are highly associated with the clinical features of swelling and chronic inflammation, is about 2.76%. But the relevance between the dysplasia and malignant transformation and age, gender together with pain is not statistically high. All in all, the clinical features of swelling and chronic inflammation can be considered as characteristics of the dysplasia and malignant transformation of OKC. Although the pain isn't statistically relevant, it may be a dangerous clew. Also, combined with earlier literatures, the dysplasia and malignant transformation of OKC shows unique features of radiographs and histopathology.

Myofascial iliac crest flap for reconstruction of combined oral mucosa-mandibular defects: A single-centre experience.

BACKGROUND: Deep circumflex iliac artery (DCIA) myofascial iliac crest flap has been used for combined oral mucosa-mandibular defects reconstruction. The bone component of this composite flap can reconstruct the mandible with superior contour match, and the muscle fascia which used for repairing the oral mucosa defect will transform into an oral mucosa-like appearance. To explore its scope of clinical application and how the fascia transformed into oral mucosa will give surgeons flexibility to reconstruct the combined oral mucosa-mandibular defects. METHODS: A retrospective review of 18 patients who received combined oral mucosa-mandibular defects reconstruction with DCIA myofascial iliac crest flaps from Dec 2016 to Dec 2020 was performed. The characteristics of the mandibular defects and the flaps were recorded. The postoperative dynamic changes of one graft's fascia were observed from serial photographs. RESULTS: All myofascial iliac crest flaps survived successfully. The bone grafts were from 4.0 to 9.5 cm (mean 7.6 ± 1.5 cm) in length and from 2.0 to 3.5 cm (mean 2.7 ± 0.4 cm) in height. The sizes of fascia were from 13.5 to 48.0 cm2 (mean 27.2 ± 9.4 cm2). The grafted fascia firstly changed into a yellow pseudomembrane-like appearance, and then experienced muscle oedema before finally transformed into an oral mucosa-like appearance at about 60 days after operation. CONCLUSION: Myofascial iliac crest flap is a good option for reconstruction of combined oral mucosa-mandibular defects because of its excellent bone and oral mucosa matches.

Design of 3D polycaprolactone/ε-polylysine-modified chitosan fibrous scaffolds with incorporation of bioactive factors for accelerating wound healing.

Electrospun nanofibrous scaffolds show great application potentials for wound healing owing to their effective simulation of extracellular matrix (ECM). Three-dimensional (3D) nanofibrous dressings exhibit relatively high specific surface areas, better mimicry of native ECM, adjustable hydrophilicity and breathability, good histocompatibility, enhanced wound healing, and reduced inflammation. In the present work, we designed the 3D polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) nanofibrous scaffolds by an electrospinning and gas foaming process. Then, gelatin and heparin (Gel/Hep) were assembled onto the surface of PCL/PCS nanofibers by electrostatic adsorption, and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into Gel/Hep layer to form a multifunctional 3D nanofibrous scaffold (PCL/PCS@Gel/Hep+VEGF) for accelerating wound healing. The as-fabricated 3D PCL/PCS@GEL/Hep+VEGF nanofibrous scaffold showed excellent antibacterial ability, hemocompatibility and biocompatibility in vitro and wound healing ability in vivo. Immunological analysis showed that the as-fabricated nanofibrous scaffold inhibited inflammation at the wound sites while promoting angiogenesis during the wound healing process. STATEMENT OF SIGNIFICANCE: The electrospun 3D fibrous scaffolds using polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) have been fabricated as backbone for mimicking the extracellular matrix (ECM). Gelatin and heparin (Gel/Hep) were wrapped onto the surface of PCL/PCS fibers by electrostatic adsorption and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into surface Gel/Hep layer to form multifunctional 3D fibrous scaffolds. The as-fabricated multifunctional 3D fibrous scaffolds with good antibacterial ability and biocompatibility have been used as dressings for accelerating wound healing by inhibiting inflammation at the wound sites while promoting angiogenesis during the wound healing process.

Micromechanical model for the ferromagnetic shape memory alloy-epoxy resin composite considering variant reorientation and magneto-mechanical coupling.

The mechanical and magnetic properties of Ferromagnetic Shape Memory Alloy-Epoxy Resin (FSMA-ER) composite which is a new kind of functional composite material are investigated in this work. Based on the Mori-Tanaka method and equivalent inclusion theory of the micromechanics, a micromechanical constitutive model in the form of tensor for this new composite is established, which considers the interaction between different variants in FSMA, as well as the interaction between FSMA and epoxy resin. The mechanical and magnetic behavior of the FSMA-ER composite under complex loads can be well described by this model. Numerical results show that the FSMA-ER composite exhibits a good pseudoelastic property due to the reorientation of different variants in FSMA. Several other particular features of this new composite are also observed through the numerical results, which can content many special requirements in the actual applications. This research not only displays the particular mechanical and magnetic behavior of the FSMA-ER composite but also provides a base for the design of this kind of material.

Management of mandibular odontogenic keratocyst through radical resection: Report of 35 cases.

The present study reported the clinical outcomes of 35 patients with mandibular odontogenic keratocysts (OKCs) following treatment by radical resection and immediate defect reconstruction. Amongst 565 patients with OKCs that were treated between April 2003 and May 2015, 35 patients underwent segmental or marginal mandibulectomy. The use of radical resection was based on clinical and/or radiographic evidence of size, cortical perforation and subsequent soft tissue involvement, and on the history of previous recurrence of the same lesion. Recurrence, justifications of the main major factor for resection, and functional and cosmetic results of the patients following mandibular reconstruction were systematically evaluated. There were 26 OKCs in the mandibular molar-ramus region, eight in the mandibular anterior-premolar region and one in the mandibular molar-ramus and anterior-molar regions. Among the 35 patients, 20 had primary OKCs and 15 had recurrent OKCs. A total of 31 patients underwent segmental mandibulectomy, of which 28 were immediately reconstructed with a vascularized flap, whereas four patients underwent marginal mandibulectomy. The functional and cosmetic outcomes of patients were evaluated as satisfactory. The length of the follow-up period ranged from 2 to 17 years following operation (average, 5.82 years). Recurrence was identified in one patient who had been treated with marginal mandibulectomy. In conclusion, the findings from the present study suggested that radical resection may be recommended for patients with OKCs and locally aggressive features. Immediate mandibular reconstruction with a vascularized flap may be a crucial part of this aggressive treatment method that may reduce OKCs-associated morbidity.

Brown tumor of multiple facial bones associated with primary hyperparathyroidism: A clinical case report.

RATIONALE: Only 4.5% of brown tumors involve facial bones; of these, solitary bone involvement is usual. Brown tumors of multiple facial bones are extremely rare. Here, we report the case of a brown tumor of multiple facial bones initially misdiagnosed as an odontogenic cyst. PATIENT CONCERNS: A pregnant 26-year-old woman was referred to our hospital with painful swelling of multiple facial bones, anemia, urinary calculi, marasmus, and a history of multiple bone fractures. Laboratory examination revealed an elevated serum calcium level of 3.09 mmol/L (normal range: 2.0-2.8 mmol/L) and a low phosphorus level of 0.62 mmol/L (normal range: 0.81-1.65 mmol/L). The serum alkaline phosphatase concentration was 397 IU/L (normal range: 24-82 IU/L) and parathyroid hormone level was 267 pg/mL (normal range: 14-72 pg/mL). Cone beam computed tomography revealed multiple ossifying fibromas of the maxilla and mandible. Incisional biopsy revealed abundant spindle cells with areas of hemorrhage and haphazardly arranged diffuse multinucleated giant cells. DIAGNOSES: The patient was diagnosed with primary hyperparathyroidism (HPT). INTERVENTIONS: She was treated by parathyroidectomy. OUTCOMES: The multiple osteitis fibrosa cystica gradually resolved as bone re-mineralized. The patient has been followed up for 2 years without evidence of tumor recurrence. LESSONS: As multiple osteolytic lesions of facial bones can be caused by primary HPT, serum calcium and parathyroid hormone assays should be performed routinely when investigating these lesions.

An investigation on the biotribocorrosion behaviour of CoCrMo alloy grafted with polyelectrolyte brush.

Surface grafting of polyelectrolyte brush, such as 3-sulfopropyl methacrylate potassium salt (SPMK), on hip implant materials has been reported to reduce the wear of the orthopaedic bearing surface. However, the biotribocorrosion behaviour of the SPMK brush has not been taken into consideration in previous research. In the present study, SPMK was grafted on Co28Cr6Mo alloy through photo-induced polymerization, and the biotribocorrosion behaviour was investigated by a series of frictional-electrochemical tests using a universal materials tester combined with an electrochemical measurement (three-electrode) system. Co28Cr6Mo disk and polyethylene (PE) pin were used as the contact pair, and the lubricants were 0.9% saline solution (NaCl) and 0.9% saline solution coupled with 25% bovine serum albumin (BSA). The results showed that SPMK was successfully grafted on Co28Cr6Mo alloy, which was confirmed by the comparison of Raman spectroscopy and static contact angle of the samples before and after surface modification. The greatly reduced electrochemical parameters such as corrosion current and pitting potential indicated that the corrosion rate of Co28Cr6Mo alloy was significantly reduced following SPMK grafting. Additionally, the frictional-electrochemical coupled measurement performed under reciprocating sliding demonstrated that the lowest corrosion current was obtained for the SPMK-grafted Co28Cr6Mo disk, with 0.9% NaCl coupled with 25% BSA as the electrolyte. It is indicated from the present study that SPMK polyelectrolyte brush can greatly improve the anti-biotribocorrosion properties of Co28Cr6Mo alloy, and thus has potential application on surface modification of hip implant materials.

Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery.

A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N-methyldiethanolamine (MDEA) and N-butyldiethanolamine (BDEA), respectively. The chemical structure, molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by (1)H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro. It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively.

Layer-by-layer supramolecular assemblies based on linear and star-shaped poly(glycerol methacrylate)s for doxorubicin delivery.

Hollow microcapsules, composed of pH responsive polyelectrolytes via a layer-by-layer (LBL) adsorption technique, were prepared. Linear or star-shaped poly(glycerol metha crylate)s (PGOHMAs) modified with 1,4-butanediamine and 1,2-ethanediamine (EDA) were synthesized and used as polycations. Poly(acrylic acid) was employed as polyanion and SiO2 (about 170 nm) as template. After LBL absorption, SiO2 cores were removed by HF treatment. The particle size and zeta potential were measured by dynamic light scattering, showing that the diameter of star-shaped amino-PGOHMA was larger than linear counterpart. The LBL assembly and core-etching process were evidenced by scanning electron microscope, transmission electron microscope, and energy dispersive spectrometer. The cytotoxicity experiments on human umbilical vein endothelial cells were carried out to evaluate the toxicity of LBL assembly. The star-shaped and EDA-modified PGOHMA exhibited better cell viability. The microcapsules were then used to load an anticancer drug, doxorubicin hydrochloride. High loading capacity (about 42%) and entrapment efficiency (84%) were obtained for star-shaped polymer-based microcapsules. The cumulative release rate was evaluated in vitro, showing faster release at an acidic condition compared to neutral pH. Confocal laser scanning microscopy evidenced the successful cellular uptake of DOX-loaded microparticles.