Trismus in head and neck cancer: translation and validation of the Chinese version of the Gothenburg Trismus Questionnaire-2 (C-GTQ-2).

OBJECTIVES: Trismus, marked by restricted mouth opening, significantly affects patients with temporomandibular disorder (TMD) and head and neck cancer (HNC). Despite its prevalence, specialized questionnaires for trismus assessment are scarce. This study aims to fill this gap by translating and validating the Gothenburg Trismus Questionnaire version 2 (GTQ-2) into Chinese (C-GTQ-2), enhancing the evaluation of trismus in HNC and TMD patients. MATERIALS AND METHODS: The study involved 78 HNC patients, 75 TMD patients, and a control group of 150 individuals without trismus symptoms. Participants were asked to complete the C-GTQ-2 and other health-related quality of life (HRQL) instruments. A subset of 30 individuals retook the questionnaire within two weeks to assess test-retest reliability. RESULTS: The C-GTQ-2 demonstrated remarkable reliability, with Cronbach's alpha values exceeding 0.70 in three of the four domains, indicating high internal consistency. The instrument also showcased high intra-class correlations in the test-retest, affirming its reliability. Furthermore, it exhibited strong convergent validity, aligning well with other HRQL instruments, and effectively discriminated between patients with and without trismus, establishing its discriminant validity. CONCLUSIONS: The C-GTQ-2 emerges as a valid and reliable tool for assessing trismus in HNC and TMD patients, promising to significantly enhance both clinical and research approaches to managing trismus-related complications in the Chinese-speaking demographic. CLINICAL RELEVANCE: C-GTQ-2 proves effective for trismus assessment in head and neck cancer and temporomandibular disorder patients, offering enhanced clinical and research utility.

Anti-Colorectal Cancer Effects of Fucoidan Complex-Based Functional Beverage Through Retarding Proliferation, Cell Cycle and Epithelial-Mesenchymal Transition Signaling Pathways.

BACKGROUND: Fucus vesiculosus-derived fucoidan, a multifunctional bioactive polysaccharide sourced from marine organisms, exhibits a wide range of therapeutic properties, including its anti-tumor effects. While previous research has reported on its anti-cancer potential, limited studies have explored its synergistic capabilities when combined with other natural bioactive ingredients. In this current study, we present the development of an integrative functional beverage, denoted as VMW-FC, which is composed of a fucoidan complex (FC) along with a blend of various herbal components, including vegetables (V), mulberries and fruits (M), and spelt wheat (W). OBJECTIVE: Colorectal cancer (CRC) remains a significant cause of mortality, particularly in metastatic cases. Therefore, the urgent need for novel alternative medicines that comprehensively inhibit CRC persists. In this investigation, we assess the impact of VMW-FC on CRC cell proliferation, cell cycle dynamics, metastasis, in vivo tumorigenesis, and potential side effects. METHODS: Cell growth was assessed using MTT and colony formation assays, while metastatic potential was evaluated through wound healing and transwell migration assays. The underlying signaling mechanisms were elucidated through qPCR and western blot analysis. In vivo tumor formation and potential side effects were evaluated using a subcutaneous tumor-bearing NOD/SCID mouse model. RESULTS: Our findings demonstrate that VMW-FC significantly impedes CRC proliferation and migration in a dose- and time-dependent manner. Furthermore, it induces sub-G1 cell cycle arrest and an increase in apoptotic cell populations, as confirmed through flow-cytometric analysis. Notably, VMW-FC also suppresses xenograft tumor growth in NOD/SCID mice without causing renal or hepatic toxicity. CONCLUSION: The integrative herbal concoction VMW-FC presents a promising approach for inhibiting CRC by slowing proliferation and migration, inducing cell cycle arrest and apoptosis, and suppressing markers associated with proliferation (Ki-67, PCNA, and CDKs) and epithelial-mesenchymal transition (EMT) (Vimentin, N-cadherin, and ß-catenin).

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Exploring Possible Diagnostic Precancerous Biomarkers for Oral Submucous Fibrosis: A Narrative Review.

Oral submucous fibrosis (OSF) stands as a progressive oral ailment, designated as a potentially malignant disorder. OSF has gained widespread recognition as a significant precursor to malignant transformation. In the pursuit of dependable, straightforward, and non-invasive diagnostic measures for the early detection of oral malignant progression, research has delved into potential diagnostic biomarkers of OSF. This comprehensive review delves into current investigations that explore the correlation between various biomarkers and OSF. The molecular biomarkers of OSF are categorized based on cytology and sampling methods. Moreover, this review encompasses pertinent studies detailing how these biomarkers are acquired and processed. Within this scope, we scrutinize four potential biomarkers that hold the promise of facilitating the development of diagnostic tools for detecting early-stage OSF.

Revisiting best practice guidelines and patient care workflow for managing the risk of medication-related osteonecrosis of the jaw: comparative summary and case studies.

OBJECTIVE: Patients taking antiresorptive medications in dental clinics are at risk of medication-related osteonecrosis of the jaw (MRONJ), which poses daily challenges for their clinicians. This paper aimed to summarize and revisit the three most recognized practice guidelines for the management and prevention of MRONJ, which were proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), and presented by the Journal of Bone and Mineral Research (JBMR) and the Journal of Clinical Oncology (JCO). Results and case studies: The AAOMS position paper focused on risk stratification by different medications, management decision trees, risk factors, pathophysiology, and disease staging. The JBMR international consensus presented eight focused questions, which were addressed by systematic reviews. The JCO clinical practice guideline presented six clinical questions, and each concluded with practical recommendations. Practical information was summarized and converted into an adoptable patient care workflow for clinicians to follow and apply in daily practice. Three case studies presented were treated following these guidelines. Each patient underwent advanced surgeries including alveoloplasty, tooth extraction, implant placement, and particulate bone grafting. Some of the considerations not fully informed were discussed and illustrated in each step of the patient care workflow, which included specifics for risk communication, updates on the use of antibiotics, biomarkers, and drug holidays. CONCLUSION AND PRACTICAL IMPLICATIONS: Structured risk communication with official informed consent documentation should be considered before initiating invasive treatments. Disease control phase with home care therapy should be provided prior to staged reconstructive therapy. Drug holidays and antibiotics coverage can be customized based on individual conditions and related procedures with interprofessional coordination.

CX3CL1 induces cell migration and invasion through ICAM-1 expression in oral squamous cell carcinoma cells.

Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C-X3-C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1-induced cell motility is upregulated through intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre-treated with CX3CR1 monoclonal antibody (mAb) and small-interfering RNA (siRNA). The CX3CL1-CX3CR1 axis activates promoted PLCß/PKCα/c-Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein-1 (AP-1) activity. The CX3CR1 mAb and PLCß, PKCα, c-Src inhibitors reduced CX3CL1-induced c-Jun phosphorylation, c-Jun translocation into the nucleus and c-Jun binding to the ICAM-1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM-1 expression through the CX3CR1 and the PLCß/PKCα/c-Src signal pathway, suggesting that CX3CL1-CX3CR1-mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.

AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway.

BACKGROUND: Despite the advancement in chemotherapeutic drugs for colon cancer treatment, it is still a life-threatening disease worldwide due to drug resistance. Therefore, an urgently needed to develop novel drugs for colon cancer therapies. AGA is a combination of traditional Chinese medicine Antler's extract (A), Ganoderma lucidum (G), and Antrodia camphorata (A); it contains a lot of biomolecules like polysaccharides, fatty acids, and triterpenoids that are known to exerting anti-oxidative, anti-inflammatory, anti-microbial and anti-tumor activities in oral cancer. In this study, we investigate AGA anti-proliferative, anti-metastatic and apoptotic activity to explore its anti-cancer activity against colon cancer cells and its underlying mechanism. METHOD: Here, in-vitro studies were performed to determine the antiproliferative activity of AGA through MTT and colony formation assays. Wound healing and transwell migration assay were used to evaluate the metastasis. Flow cytometry and protein expression were used to investigate the involved molecular mechanism by evaluating the cell cycle and apoptosis. The in-vivo anti-cancerous activity of AGA was assessed by xenograft mice model of colon cancer cells. RESULTS: We found that AGA significantly inhibited the proliferative capacity and metastasis of colon cancer cells in-vitro. In addition, AGA induced cell cycle arrest in the sub-G1 phase through upregulating p21 and downregulating CDK2, CDK6 in SW620, and CDK4 in SW480 and HT29, respectively. Annexin-v assay indicated that colon cancer cells had entered early and late apoptosis after treatment with AGA. Furthermore, a mechanistic protein expressions study revealed that AGA in p53-dependent and independent regulated the apoptosis of colon cancer by downregulating the p53 protein expression in SW620 and SW480 cells but upregulating in a dose-dependent manner in HT29 cells and increasing the expression of Bax and caspase-9 to inhibit the colon cancer cells. In vivo study, we found that AGA significantly reduced the xenograft tumor growth in NOD/SCID mice with no adverse effect on the kidney and liver. CONCLUSION: Collectively, AGA has the potential to inhibit colon cancer through inhibiting proliferation, migration, and cell cycle kinase by upregulating p21 protein expression and promoting the apoptotic protein in a p53-dependent and independent manner.

Interleukin-11/gp130 upregulates MMP-13 expression and cell migration in OSCC by activating PI3K/Akt and AP-1 signaling.

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.

Platelet-Derived Biomaterials Inhibit Nicotine-Induced Intervertebral Disc Degeneration Through Regulating IGF-1/AKT/IRS-1 Signaling Axis.

Apart from aging process, adult intervertebral disc (IVD) undergoes various degenerative processes. However, the nicotine has not been well identified as a contributing etiology. According to a few studies, nicotine ingestion through smoking, air or clothing may significantly accumulate in active as well as passive smokers. Since nicotine has been demonstrated to adversely impact various physiological processes, such as sympathetic nervous system, leading to impaired vasculature and cellular apoptosis, we aimed to investigate whether nicotine could induce IVD degeneration. In particular, we evaluated dose-dependent impact of nicotine in vitro to simulate its chronic accumulation, which was later treated by platelet-derived biomaterials (PDB). Further, during in vivo studies, mice were subcutaneously administered with nicotine to examine IVD-associated pathologic changes. The results revealed that nicotine could significantly reduce chondrocytes and chondrogenic indicators (Sox, Col II and aggrecan). Mice with nicotine treatment also exhibited malformed IVD structure with decreased Col II as well as proteoglycans, which was significantly increased after PDB administration for 4 weeks. Mechanistically, PDB significantly restored the levels of IGF-1 signaling proteins, particularly pIGF-1 R, pAKT, and IRS-1, modulating ECM synthesis by chondrocytes. Conclusively, the PDB impart reparative and tissue regenerative processes by inhibiting nicotine-initiated IVD degeneration, through regulating IGF-1/AKT/IRS-1 signaling axis.

The Novel Herbal Cocktail AGA Alleviates Oral Cancer through Inducing Apoptosis, Inhibited Migration and Promotion of Cell Cycle Arrest at SubG1 Phase.

Traditional Chinese medicines Antler's extract (A) and Ganoderma lucidum (G) and Antrodia Camphorata (A) have been known to individually contain a plethora of bioactive factors including triterpenoids, polysaccharides etc., exerting various curative impacts such as anti-inflammatory, anti-oxidative, anti-atherosclerotic and anti-viral activities. However, their combinatorial therapeutic efficacy for oral cancer has not been investigated. Hence, we synthesized a robust cocktail called AGA and investigated its anti-oral cancer potential in vitro and in vivo. An MTT assay revealed the IC50 of AGA to be about 15 mg at 72 h. Therefore, 10 mg and 20 mg doses were selected to study the effect of AGA. The AGA significantly inhibited proliferation of oral cancer cells (HSC3, SAS, and OECM-1) in a dose- and time-dependent manner. AGA retarded cell cycle regulators (CDK4, CDK6, cyclin A, B1, D1 and E2) and apoptosis inhibitory protein Bcl-2, but enhanced pro-apoptotic protein Bax and a higher percentage of cells in Sub-G1 phase. Mechanistically, AGA suppressed all EMT markers; consequently, it decreased the migration ability of cancer cells. AGA significantly reduced xenograft tumor growth in nude mice with no adverse events in liver and renal toxicity. Conclusively, AGA strongly inhibited oral cancer through inducing apoptosis and inhibiting the migration and promotion of cell cycle arrest at subG1 phase, which may be mediated primarily via cocktail-contained triterpenoids and polysaccharides.

Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer.

Recent reports have indicated the role of highly expressed methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) enzyme in cancers, showing poor survival; however, detailed mechanistic insight of metabolic functions of MTHFD2 have not been well-defined. Therefore, we aimed to examine the metabolic functions and cellular reprograming potential of MTHFD2 in lung cancer (LCa). In this study, we initially confirmed the expression levels of MTHFD2 in LCa not only in tissue and OncomineTM database, but also at molecular levels. Further, we reprogrammed metabolic activities in these cells through MTHFD2 gene knockdown via lentiviral transduction, and assessed their viability, transformation and self-renewal ability. In vivo tumorigenicity was also evaluated in NOD/SCID mice. Results showed that MTHFD2 was highly expressed in stage-dependent LCa tissues as well in cell lines, A549, H1299 and H441. Cellular viability, transformation and self-renewal abilities were significantly inhibited in MTHFD2-knockdown LCa cell lines. These cells also showed suppressed tumor-initiating ability and reduced tumor size compared to vector controls. Under low oxygen tension, MTHFD2-knockdown groups showed no significant increase in sphere formation, and hence the stemness. Conclusively, the suppressed levels of MTHFD2 is essential for cellular metabolic reprogramming leading to inhibited LCa growth and tumor aggressiveness.

Amelioration of Nicotine-Induced Osteoarthritis by Platelet-Derived Biomaterials Through Modulating IGF-1/AKT/IRS-1 Signaling Axis.

Besides inhalation, a few studies have indicated that the uptake of nicotine through air or clothing may be a significant pathway of its exposure among passive smokers. Nicotine is well known to exert various physiological impacts, including stimulating sympathetic nervous system, causing vascular disturbances, and inducing cell death. Therefore, we aimed to establish whether exposure of nicotine could induce articular cartilage degeneration in a mouse model of osteoarthritis (OA). We specifically assessed dose-dependent effect of nicotine in vitro to mimic its accumulation. Further, during the in vivo studies, mice subcutaneously administered with nicotine was examined for OA-associated pathologic changes. We found that nicotine significantly suppressed chondrocytes and chondrogenic markers (Sox, Col II, and aggrecan). Nicotine-treated mice also showed altered knee joint ultrastructure with reduced Col II and proteoglycans. After corroborating nicotine-induced OA characteristics, we treated this pathologic condition through employing platelet-derived biomaterial (PDB)-based regenerative therapy. The PDB significantly suppressed OA-like pathophysiological characteristics by 4 weeks. The mechanistic insight underlying this therapy demonstrated that PDB significantly restored levels of insulin-like growth factor 1 (IGF-1) signaling pathway proteins, especially pIGF-1 R, pAKT, and IRS-1, regulating extracellular matrix synthesis by chondrocytes. Taken together, the PDB exerts regenerative and reparative activities in nicotine-mediated initiation and progression of OA, through modulating IGF-1/AKT/IRS-1 signaling axis.

Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest.

Cancer pathogenesis results from genetic alteration-induced high or low transcriptional programs, which become highly dependent on regulators of gene expression. However, their role in progressive regulation of non-small-cell lung cancer (NSCLC) and how these dependencies may offer opportunities for novel therapeutic options remain to be understood. Previously, we identified forkhead box F1 (FOXF1) as a reprogramming mediator which leads to stemnesss when mesenchymal stem cells fuse with lung cancer cells, and we now examine its effect on lung cancer through establishing lowly and highly expressing FOXF1 NSCLC engineered cell lines. Higher expression of FOXF1 was enabled in cell lines through lentiviral transduction, and their viability, proliferation, and anchorage-dependent growth was assessed. Flow cytometry and Western blot were used to analyze cellular percentage in cell-cycle phases and levels of cellular cyclins, respectively. In mice, tumorigenic behavior of FOXF1 was investigated. We found that FOXF1 was downregulated in lung cancer tissues and cancer cell lines. Cell proliferation and ability of migration, anchorage-independent growth, and transformation were inhibited in H441-FOXF1H and H1299-FOXF1H, with upregulated tumor suppressor p21 and suppressed cellular cyclins, leading to cell-cycle arrest at the gap 1 (G1) phase. H441-FOXF1H and H1299-FOXF1H injected mice showed reduced tumor size. Conclusively, highly expressing FOXF1 inhibited NSCLC growth via activating tumor suppressor p21 and G1 cell-cycle arrest, thus offering a potentially novel therapeutic strategy for lung cancer.

Effect of Hydroxyapatite Formation on Titanium Surface with Bone Morphogenetic Protein-2 Loading through Electrochemical Deposition on MG-63 Cells.

Calcium phosphate ceramics used in dentistry and orthopedics are some of the most valuable biomaterials, owing to their excellent osteoconduction, osteoinduction, and osseointegration. Osteoconduction and osteoinduction are critical targets for bone regeneration, and osseointegration is essential for any dental implantations. In this study, a hydroxyapatite (HAp) hybrid coating layer with the sequential release of bone morphogenetic protein 2 (BMP-2) was deposited onto an etched titanium substrate by electrochemical deposition. The resulting release of BMP-2 from Ti⁻HAp was assessed by immersing samples in a simulated buffer fluid solution. Through coculture, human osteosarcoma cell proliferation and alkaline phosphatase activity were assessed. The characteristics and effect on cell proliferation of the hybrid coatings were investigated for their functionality through X-ray diffraction (XRD) and cell proliferation assays. Findings revealed that -0.8 V vs. Ag/AgCl (3 M KCl) exhibited the optimal HAp properties and a successfully coated HAp layer. XRD confirmed the crystallinity of the deposited HAp on the titanium surface. Ti-0.8 V Ti⁻HAp co-coating BMP sample exhibited the highest cell proliferation efficiency and was more favorable for cell growth. A successful biocompatible hybrid coating with optimized redox voltage enhanced the osseointegration process. The findings suggest that this technique could have promising clinical applications to enhance the healing times and success rates of dental implantation.

Targeting LncRNA HOTAIR suppresses cancer stemness and metastasis in oral carcinomas stem cells through modulation of EMT.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, such as cell growth, apoptosis and tumorigenesis. However, the functional roles of lncRNAs and mechanistic analysis of their interplays with oncogenic pathways in oral cancer remain largely unknown. In the current study, we examined the significance of lncRNA HOTAIR (HOX transcript antisense RNA) in tumor progression of oral squamous cell carcinomas (OSCC). We found the expression of HOTAIR was upregulated in tumor tissues, especially in the metastatic samples. And it was also observed in metastatic OSCC cell lines. Silence of HOTAIR in oral carcinomas stem cells (OCSC) significantly inhibited their cancer stemness, invasiveness and tumourigenicity in xenotransplantation models. By contrast, overexpression of HOTAIR in OSCC enhanced their metastatic potential and epithelial-mesenchymal transition (EMT) characteristics. And we showed that the expression of HOTAIR was positively related to mesenchymal markers and inversely correlated with epithelial marker in clinical samples. Moreover, Kaplan-Meier survival analysis suggested that high level of HOTAIR was a strong predictor of poor survival in OSCC patients. Collectively, our data demonstrated that HOTAIR-mediated cancer stemness and metastasis are associated with the regulation of EMT and HOTAIR may serve as a therapeutic target in OSCC.

Mechanism and Clinical Properties of StemBios Cell Therapy: Induction of Early Osseointegration in Novel Dental Implants.

PURPOSE: To examine early bone tissue healing in dental implants incorporating StemBios cell therapy. MATERIALS AND METHODS: SLAffinity samples were examined by scanning electron microscopy and atomic force microscopy. The clinical trial comprised 11 patients, who each received a dental implant in the mandible. Only one of these 11 patients received StemBios cell therapy in combination with the dental implant. The patients continued to be observed over a 4-month period after implantation using computed tomography and resonance frequency analysis. RESULTS: It was found that StemBios cell therapy promoted bone tissue healing in the case of the treated dental implant. The data indicated that stress altered more smoothly and declined faster in the patient who received the StemBios cell therapy than those without StemBios cell therapy over 4 months. CONCLUSION: A dental implant with SLAffinity surface treatment, in combination with StemBios cell therapy, significantly promoted bone tissue healing, especially at early osseointegration compared with that of implants without StemBios cell therapy when monitored over a 4-month period.

A common glycan structure on immunoglobulin G for enhancement of effector functions.

Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.

Nano-textured fluidic biochip as biological filter for selective survival of neuronal cells.

This is an innovative study to engineer biological filter to evaluate the effect of template surface structure and physiochemical properties that can be used for wide variety of applications in biological, health care as well as environmental protection. Specifically, planar silicon (Si) wafer and arrayed Si nano-tips (SiNT) templates were fabricated and coated with gold for various lengths of time to study the effect of surface charge, surface roughness, and hydrophilicity on biological activity of rat pheochromocytoma cell lines PC12. The initial growth and proliferation of PC12 cells on Si and SiNT templates showed an antipathy for the ultra-sharp SiNTs templates. In contrast, the same cells demonstrated a preferable adherence to and proliferation on planar Si templates, resulting in higher cell densities by three orders of magnitude than those on SiNT templates. It is hypothesized that SiNTs array does generate nano-fluidic effect such that the effective contact region for aqueous solution on SiNTs is lower than that on planar Si templates, thus decreasing adsorbable area for cell viability and survival. Moreover, the effect of the gold coating on cell number density was analyzed in terms of the surface roughness, zeta potential and wetting properties of the templates. It was determined that surface charge, as measured by the zeta potential, strongly correlated with the trend observed in the surface cell density, whereas no such correlation was observed for surface roughness or wetting properties in the ranges of our experiment conditions.

Controlled surface morphology and hydrophilicity of polycaprolactone toward selective differentiation of mesenchymal stem cells to neural like cells.

Differentiation of mesenchymal stem cells (MSCs) into neuron cells has great potential in therapy of damaged nerve tissue. It has been shown that three-dimensional biomaterials have great ability to up regulate the expression of neuronal proteins. In this study, O2 plasma technology was used to enhance hydrophilicity of poly (ε-caprolactone) (PCL) toward selective differentiation of MSCs into neural cells. Random and aligned PCL nanofibers scaffolds were fabricated by electrospinning method and their physicochemical and mechanical properties were carried out by scanning electron microscope (SEM), contact angle, and tensile measurements. Contact angle studies of PCL and plasma treated PCL (p-PCL) nanofibers revealed significant change on the surface properties PCL nanofibers from the view point of hydrophilicity. Physiochemical studies revealed that p-PCL nanofibers were extremely hydrophilic compared with untreated PCL nanofibers which were highly hydrophobic and nonabsorbent to water. Differentiation of MSCs were carried out by inducing growth factors including basic fibroblast growth factor, nerve growth factor, and brain derived growth factor, NT3, 3-isobutyl-1-methylxanthine (IBMX) in Dulbecco's modified Eagle's medium/F12 media. Differentiated MSCs on nanofibrous scaffold were examined by immunofluorescence assay and was found to express the neuronal proteins; ß-tubulin III and Map2, on day 15 after cell culture. The real-time polymerase chain reaction (RT-PCR) analysis showed that p-PCL nanofibrous scaffold could upregulate expression of Map-2 and downregulate expression of Nestin genes in nerve cells differentiated from MSCs. This study indicates that mesenchymal stem cell cultured on nanofibrous scaffold have potential differentiation to neuronal cells on and could apply in nerve tissue repair.

Effect of recombinant human bone morphogenetic protein-2 and Ling Zhi-8 on osteogenesis: a comparative study using a rabbit sinus model.

PURPOSE: This study evaluated the osteogenetic capability of Ling Zhi-8 (LZ-8; a protein purified from traditional Chinese medicine [lingzhi]) compared with recombinant human bone morphogenic protein-2 (rhBMP-2) in a standardized bony defect using a rabbit sinus model. MATERIALS AND METHODS: Twelve male New Zealand white rabbits (18 to 24 weeks old, 3.3 to 3.8 kg) were included in the study. Implants of normal saline 0.1 mg, rhBMP-2 0.1 mg, and LZ-8 0.1 mg were each mixed with a uniform biodegradable polyurethane-based material (Nasopore). The implants were inserted in a standardized bony defect of the nasal bone created by a 2.5-mm trephine bur. The rabbits were sacrificed at 1, 2, 4, and 8 weeks postoperatively. Volume computerized tomographic and histomorphometric examinations were used to evaluate the quantity and quality of regenerated bone. RESULTS: At postoperative week 4, radiography showed that the new bone volume was significantly larger in the rhBMP-2 group compared with the LZ-8 group (P = .041) and the control group (P = .015). Histomorphometrically, better wound healing of the rhBMP-2 group was found during the healing phase compared with the other 2 groups. CONCLUSION: The biomaterial implants using rhBMP-2 and LZ-8 had good biocompatibility and osteogenetic capabilities in the rabbit sinus model. Bone healing in rhBMP-2-treated defects was excellent and showed a significant difference compared with LZ-8. However, LZ-8-treated defects also exhibited bone regeneration, and this traditional Chinese medicine may possess osteogenic potential. Further investigations of the mechanism and application of this protein in osteogenesis are needed.