Enhancing wound healing and adhesion through dopamine-assisted gelatin-silica hybrid dressings.

Gelatin, widely employed in hydrogel dressings, faces limitations when used in high fluid environments, hindering effective material adhesion to wound sites and subsequently reducing treatment efficacy. The rapid degradation of conventional hydrogels often results in breakdown before complete wound healing. Thus, there is a pressing need for the development of durable adhesive wound dressings. In this study, 3-glycidoxypropyltrimethoxysilane (GPTMS) was utilized as a coupling agent to create gelatin-silica hybrid (G-H) dressings through the sol-gel method. The coupling reaction established covalent bonds between gelatin and silica networks, enhancing structural stability. Dopamine (DP) was introduced to this hybrid (G-H-D) dressing to further boost adhesiveness. The efficacy of the dressings for wound management was assessed through in-vitro and in-vivo tests, along with ex-vivo bioadhesion testing on pig skin. Tensile bioadhesion tests demonstrated that the G-H-D material exhibited approximately 2.5 times greater adhesion to soft tissue in wet conditions compared to pure gelatin. Moreover, in-vitro and in-vivo wound healing experiments revealed a significant increase in wound healing rates. Consequently, this material shows promise as a viable option for use as a moist wound dressing.

Theranostic doxorubicin encapsulated FeAu alloy@metal-organic framework nanostructures enable magnetic hyperthermia and medical imaging in oral carcinoma.

Metal-organic frameworks (MOFs) have emerged as attractive candidates in cancer theranostics due to their ability to envelop magnetic nanoparticles, resulting in reduced cytotoxicity and high porosity, enabling chemodrug encapsulation. Here, FeAu alloy nanoparticles (FeAu NPs) are synthesized and coated with MIL-100(Fe) MOFs to fabricate FeAu@MOF nanostructures. We encapsulated Doxorubicin within the nanostructures and evaluated the suitability of this platform for medical imaging and cancer theranostics. FeAu@MOF nanostructures (FeAu@MIL-100(Fe)) exhibited superparamagnetism, magnetic hyperthermia behavior and displayed DOX encapsulation and release efficiency of 69.95 % and 97.19 %, respectively, when stimulated with alternating magnetic field (AMF). In-vitro experiments showed that AMF-induced hyperthermia resulted in 90 % HSC-3 oral squamous carcinoma cell death, indicating application in cancer theranostics. Finally, in an in-vivo mouse model, FeAu@MOF nanostructures improved image contrast, reduced tumor volume by 30-fold and tumor weight by 10-fold, which translated to enhancement in cumulative survival, highlighting the prospect of this platform for oral cancer treatment.

Study of polymethylmethacrylate/tricalcium silicate composite cement for orthopedic application.

BACKGROUND: Among orthopedic surgery materials, poly (methyl methacrylate) (PMMA) is most commonly used for its excellent mechanical properties and rapid self-setting time. However, PMMA bone cement has been reported to cause thermal necrosis and to have poor bioactivity, which must be improved. In contrast, tricalcium silicate (TCS), the most significant component of Portland Cement and the most effective bone cement material, might not always meet the needs of the cement due to its poor mechanical properties and elevated pH levels during hydration. We hypothesize that the benefits of both PMMA and TCS can be harnessed by mixing them together in different proportions. This would represent a better solution for the issues faced when using them alone. METHODS: We, therefore, prepared a novel organic-inorganic PMMA/TCS composite bone cement mixing PMMA and different amounts of TCS and tested its effect on the biophysical properties. RESULTS: The addition of 30% TCS reduced the exothermic temperature and pH variation during cement setting and hydration processes. However, the mechanical and handling properties of the bioactive PMMA/TCS composite were not affected. The in vitro study also revealed that the composite materials had higher cell viability than pure PMMA and TCS. Also, the in vivo study on animals indicated that the composite materials were more capable of forming bone, which further reinforced the biocompatibility of the proposed PMMA/TCS bone cement. CONCLUSION: By combining the advantages of each component, it could be possible to construct a more effective composite bone cement material. This would meet the needs of implantation material for orthopedic surgeries or a possible bone filler.

Assessing Suitability of Co@Au Core/Shell Nanoparticle Geometry for Improved Theranostics in Colon Carcinoma.

The interactions between cells and nanomaterials at the nanoscale play a pivotal role in controlling cellular behavior and ample evidence links cell intercommunication to nanomaterial size. However, little is known about the effect of nanomaterial geometry on cell behavior. To elucidate this and to extend the application in cancer theranostics, we have engineered core-shell cobalt-gold nanoparticles with spherical (Co@Au NPs) and elliptical morphology (Co@Au NEs). Our results show that owing to superparamagnetism, Co@Au NPs can generate hyperthermia upon magnetic field stimulation. In contrast, due to the geometric difference, Co@Au NEs can be optically excited to generate hyperthermia upon photostimulation and elevate the medium temperature to 45 °C. Both nanomaterial geometries can be employed as prospective contrast agents; however, at identical concentration, Co@Au NPs exhibited 4-fold higher cytotoxicity to L929 fibroblasts as compared to Co@Au NEs, confirming the effect of nanomaterial geometry on cell fate. Furthermore, photostimulation-generated hyperthermia prompted detachment of anti-cancer drug, Methotrexate (MTX), from Co@Au NEs-MTX complex and which triggered 90% decrease in SW620 colon carcinoma cell viability, confirming their application in cancer theranostics. The geometry-based perturbation of cell fate can have a profound impact on our understanding of interactions at nano-bio interface which can be exploited for engineering materials with optimized geometries for superior theranostic applications.

Polyelectrolyte multilayer composite coating on 316 L stainless steel for controlled release of dual growth factors accelerating restoration of bone defects.

A composite coating of polyelectrolyte multilayers (PEMs) consisting of collagen, a chitosan barrier, and poly-γ-glutamic acid was fabricated using a spin coating technique to investigate and overcome the limited osseointegration capacity of 316 L stainless steel (316 L SS). To further enhance the biocompatibility, bone morphogenetic protein 2 (BMP-2) and basic fibroblast growth factor-2 (FGF-2) were loaded separately as dual growth factors, allowing for progressive drug release following the natural process of bone regeneration. The first burst release of FGF-2 triggered the proliferation of surrounding cells, and the subsequent release of BMP-2 stimulated their differentiation. The microstructure, surface potential, hardness, reduced Young's modulus, and wettability were assessed using scanning electron microscopy, nanoindentation, and water contact angle. The formation of apatite layers after immersion in simulated body fluid confirmed the bioactivity of this PEM. PEMs loaded with BMP-2 and FGF-2 showed a long sustained release of growth factors for up to 48 days. The biological properties were studied in vitro with rat bone mesenchymal stem cells (rBMSCs) and in vivo using a rat critical-sized calvarial defect model. PEMs loaded with growth factors further stimulated the proliferation and osteogenic differentiation of rBMSCs and the histology results indicated that new bone tissues could directly grow onto the PEMs. These findings suggest that PEM composite coating possesses significant potential for surface modification and long-term drug release of metallic implants to assist with bone restoration.

Oral Cancer Theranostic Application of FeAu Bimetallic Nanoparticles Conjugated with MMP-1 Antibody.

Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron-gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.

Perceived pain for orthodontic patients with conventional brackets or self-ligating brackets over 1 month period: A single-center, randomized controlled clinical trial.

BACKGROUND/PURPOSE: The objective of this 2-arm parallel trial was to test the superiority of self-ligating brackets (SLB) over conventional brackets (CB) in terms of perceived pain for orthodontic patients. METHODS: Patients about to undergo treatment were included to fixed appliance placed with CB or SLB. Eligibility criteria included malocclusion patients whose age between 12 to 40 years and suitable for orthodontic fixed appliance treatment. The main outcome was pain intensity measured by visual analog scale (VAS) with all patients followed at 4 h, 24 h, 3 days, 1 week and 1 month. Randomization was accomplished with a computer-generated list of random numbers. Blinding was applicable for outcome assessment only. Data were analyzed using multi-level nonlinear mixed effect model, Friedman's test and Wilcoxon signed rank test with the Bonferroni correction for multiple tests. RESULTS: Eight-eight patients were randomized in a 1:1 ratio to either SLB or CB. All patients completed the study, and none were lost to follow-up. There were no drop-outs after randomization. Baseline characteristics were similar between groups. The is no statistical significant difference in pain intensity between CB and SLB at 4 h, 24 h, 3 days, 1 week and 1 month. Data were analyzed on an intention-to-treat basis. No serious harm was observed. CONCLUSION: The results of this study indicated no evidence that the pain intensity differs between CB and SLB at 4 h, 24 h, 3 days, 1 week and 1 month.

Gamma-poly glutamate/gelatin composite hydrogels crosslinked by proanthocyanidins for wound healing.

A novel multifunctional poly(γ-glutamic acid) (γ-PGA)/gelatin hydrogel has been developed and used as a wound dressing. An ideal wound dressing should effectively provide a moist environment, absorb wound exudates and protect the wound from foreign microbes. Water soluble γ-PGA salts of sodium and calcium forms were chosen for their good biocompatibility, biodegradability and water absorption capacity. Oligomeric proanthocyanidins (OPCs), naturally occurring plant metabolites and potent antioxidants, were investigated as a non-toxic crosslinking agent in this study. The effects of hydrogels on the degree of crosslinking, swelling, in vitro degradation, mechanical properties and radical scavenging activity were systemically evaluated. A cell viability assay demonstrated that these OPCs crosslinked γ-PGA/gelatin (PGO) hydrogels were not cytotoxic to L929 fibroblasts. Dermal irritation and skin sensitization tests were examined using a guinea pig model; the hydrogels were considered to be neither allergic nor a dermal sensitizer in guinea pigs. Lastly, an in vivo wound healing model in rats was used to study the effects of the hydrogels on wound healing for 21 days. PGO hydrogels formed by both Na and Ca salts could accelerate wound contraction and re-epithelialization, in which Na-PGO hydrogel was significantly better than the untreated control group. The findings suggest that PGO hydrogels are promising wound dressing materials for the treatment for wound healing.

Effect of oral appliance on circulating leukocyte telomere length and SIRT1 in obstructive sleep apnea.

OBJECTIVES: The increased cardiovascular risk seen in patients with obstructive sleep apnea (OSA) may be due to combination of oxidative stress, systemic inflammation and damage to leukocyte telomere length (LTL) seen with aging. Another molecule, Sirtuin 1 (SIRT1), a histone/protein deacetylase, regulates endothelial nitric oxide synthase and is involved in different aspects of cardiovascular disease, aging and stress resistance. The aim of this study was to evaluate the effects of mandibular advancement device (MAD) on the circulating LTL and SIRT1 protein level in peripheral blood mononuclear cells (PBMCs) in patients with OSA. MATERIALS AND METHODS: Forty patients with moderately severe to severe OSA who desired MAD and 20 healthy controls were prospectively enrolled. The LTL was measured by quantitative polymerase chain reaction while SIRT1 protein levels in PBMC was assessed using a Sirtuin 1 ELISA Kit. All study subjects underwent baseline sleep study, with OSA patients having repeat testing at 3 months after MAD. RESULTS: Compared to healthy subjects, patients with OSA at baseline had lower LTL and SIRT1 protein levels in PBMC. After 3 months of MAD, 24 OSA patients, designated as MAD responders, median (range) LTL increased from (0.556 [0.393-0.748]) to (0.708 [0.533-0.893]) and SIRT1 protein levels in PBMC increased from 0.58 ± 0.23 pg/µg of total protein to 0.95 ± 0.26 pg/µg of total protein. For the 16 MAD unresponsive patients, LTL and SIRT1 protein levels remained low. CONCLUSIONS: Successful treatment of OSA with MAD can restore LTL and SIRT1 protein levels in PBMC. CLINICAL RELEVANCE: LTL and SIRT1 protein levels in PBMC can be improved following effective treatment of OSA using MAD.

Effect of oral appliance on endothelial function in sleep apnea.

OBJECTIVES: This study evaluated the effects of mandibular advancement device (MAD) on serum levels of nitric oxide derivatives and endothelial function by endothelium-dependent flow-mediated dilation (FMD) in obstructive sleep apnea syndrome (OSAS). METHODS: Thirty patients with moderately severe-to-severe OSAS who desired MAD and 15 healthy controls were prospectively enrolled. FMD was measured by high-resolution B-mode ultrasonography, while serum NO x level from peripheral blood samples was measured by ELISA. All subjects participated in the sleep studies, which were repeated 2 months after MAD in OSAS patients. RESULTS: Serum NO x level and FMD were lower in patients with OSAS than in controls prior to MAD. Serum NO x levels in 19 of 30 patients with OSAS, the designated MAD responders, increased from 11.8 ± 5.8 µM pre-MAD to 22.7 ± 4.9 µM post-MAD. The FMD increased from 5.9 ± 4.6 pre-MAD to 10.5 ± 4.8 post-MAD. For the 11 unresponsive patients, serum NO x and FMD remained impaired after MAD. CONCLUSIONS: Successful treatment of OSAS with MAD can restore serum levels of NO x and FMD. CLINICAL RELEVANCE: Endothelial function can be improved following effective treatment of OSAS using MAD.

Temporomandibular joint structural derangement and general joint hypermobility.

AIM: To explore the relationship between general joint hypermobility (GJH) and displacement of the temporomandibular joint (TMJ) disc as evident from magnetic resonance imaging (MRI). METHODS: Fifth finger extension, thumb apposition, elbow extension, knee extension, trunk flexion, and ankle dorsiflexion were measured in 66 young female patients with MRI-evident TMJ internal derangement (ID) and in 30 age-matched female controls. The Beighton score of each subject was measured quantitatively. The possible association between TMJ ID and mobility of a single joint or index of GJH, ie, the Beighton score, were assessed with one-way ANOVA with post-hoc Bonferroni and chi-square test, respectively. Correlations of the mobility of every measured joint were also explored. RESULTS: Very few of the TMJ ID patients and control subjects were diagnosed with GJH according to the Beighton score. The Beighton score did not differentiate between subjects with and without TMJ ID. Subjects with TMJ ID, especially patients with MRI-evident disc displacement without reduction, seemed to have a stiffer trunk than controls, but this may not be of clinical relevance. The mobilities of paired joints were significantly correlated; however, the mobilities of different anatomical joints seemed to be independent. CONCLUSION: Based on the Beighton score, GJH does not seem to be a reliable indicator of the presence of TMJ ID.

Low bone mineral density and temporomandibular joint derangement in young females.

AIMS: To analyze the bone mineral density (BMD) in a group of young female patients with a disc displacement in at least 1 temporomandibular joint (TMJ) as well as in a group of age-matched young females with a normal condyle-disc relationship. METHODS: Fifty-six young female patients with anterior disc displacement based on magnetic resonance imaging (MRI) and 40 age- and gender-matched controls with asymptomatic TMJs were recruited for this study. Subjects between 18 and 30 years were recruited. Based on the MRI findings, 10 of the 40 subjects in the control group also had anterior disc displacement. In all, 16 subjects had an anterior disc displacement with reduction (DDwR), 50 had an anterior disc displacement without reduction (DDw/oR), and 30 had a normal condyle-disc relationship. BMD was measured in the lumbar area by means of dual-energy x-ray absorptiometry. The relationship between the 3 types of condyle-disc relationship and BMD was then analyzed. RESULTS: Patients with a DDw/oR had a significantly lower mean BMD value in the lumbar area than the subjects with a normal condyle-disc relationship (P < .05, analysis of variance, post-hoc with Bonferroni test). Twenty-two (44%) of 50 patients with DDw/oR had osteopenia. CONCLUSION: Low BMD is often associated with DDw/oR in young Taiwanese female patients.

Magnetic resonance images of the temporomandibular joints of patients with acquired open bite.

OBJECTIVES: Acquired anterior open bites were reported as the consequence of condylar collapse, which was associated with inflammatory TMJ disorders. However, we have seen such malocclusion patients whose condylar changes seemed to be related to TMJ degeneration associated with internal derangement. The aims of this study were to review the clinical history and to study the TMJ MRI of these patients. STUDY DESIGN: TMJ MRIs of patients, who had presented acquired anterior open bite at first visit, were retrieved from the image database for the analysis. Clinical histories focused on internal derangement were collected retrospectively. The soft tissue and hard tissue changes disclosed by MRI were also studied. RESULTS: All patients had experienced common signs/symptoms of TMJ internal derangement. All affected TMJs had anteriorly displaced disks and degenerative changes. Horizontally destructed condylar forms were seen significantly more frequently in these patients. CONCLUSION: TMJ degeneration associated with displaced disks might be a cause leading to the development of acquired anterior open bite.