Cranial suture lineage and contributions to repair of the mouse skull.

The cranial sutures are proposed to be a stem cell niche, harbouring skeletal stem cells that are directly involved in development, homeostasis and healing. Like the craniofacial bones, the sutures are formed from both mesoderm and neural crest. During cranial bone repair, neural crest cells have been proposed to be key players; however, neural crest contributions to adult sutures are not well defined, and the relative importance of suture proximity is unclear. Here, we use genetic approaches to re-examine the neural crest-mesoderm boundaries in the adult mouse skull. These are combined with calvarial wounding experiments suggesting that suture proximity improves the efficiency of cranial repair. Furthermore, we demonstrate that Gli1+ and Axin2+ skeletal stem cells are present in all calvarial sutures examined. We propose that the position of the defect determines the availability of neural crest-derived progenitors, which appear to be a key element in the repair of calvarial defects.

Green endoscopy: British Society of Gastroenterology (BSG), Joint Accreditation Group (JAG) and Centre for Sustainable Health (CSH) joint consensus on practical measures for environmental sustainability in endoscopy.

GI endoscopy is highly resource-intensive with a significant contribution to greenhouse gas (GHG) emissions and waste generation. Sustainable endoscopy in the context of climate change is now the focus of mainstream discussions between endoscopy providers, units and professional societies. In addition to broader global challenges, there are some specific measures relevant to endoscopy units and their practices, which could significantly reduce environmental impact. Awareness of these issues and guidance on practical interventions to mitigate the carbon footprint of GI endoscopy are lacking. In this consensus, we discuss practical measures to reduce the impact of endoscopy on the environment applicable to endoscopy units and practitioners. Adoption of these measures will facilitate and promote new practices and the evolution of a more sustainable specialty.

Lower gastrointestinal polypectomy competencies in the United Kingdom: a retrospective analysis of Directly Observed Polypectomy Skills (DOPyS).

BACKGROUND: Polypectomy is often the most hazardous part of colonoscopy. There is significant variability in polypectomy training and assessment internationally. DOPyS (Directly Observed Polypectomy Skills) is a validated assessment tool and is used to demonstrate polypectomy competency in the UK. This study aimed to describe the learning curve for polypectomy competency in UK trainees. METHODS: Retrospective DOPyS data (January 2009 to September 2015) were obtained from the UK Joint Advisory Group (JAG) for intestinal endoscopy training system (JETS) national database. The number of lower gastrointestinal (LGI) procedures, overall cecal intubation rate (CIR), procedure intensity, and time in days to the first DOPyS assessment were recorded, and time to JAG certification was calculated. RESULTS: 4965 DOPyS assessments from 336 trainees were analyzed. Within the study period, 124 and 53 trainees achieved provisional and full colonoscopy certification, respectively. Trainees started formative assessment of polypectomy after > 130 LGI procedures and with a CIR of > 70 %. Within 3 years from the first DOPyS assessment, 94 % of trainees achieved provisional certification, and 50 % full certification. Higher procedure intensity at baseline DOPyS assessment was associated with a higher likelihood of obtaining certification sooner. CONCLUSION: There is a significant variation in time to competency, and this potentially reflects the time necessary to acquire polypectomy skills. There is a need to start polypectomy training earlier, once sufficient skills, such as tip control, have been achieved to shorten the time to competency. Overall, the CIR could be used as a guide for such technical skills. Increasing exposure to training lists also potentially reduces the time to polypectomy competency.

Endoscopic cuff-assisted colonoscopy versus cap-assisted colonoscopy in adenoma detection: randomized tandem study-DEtection in Tandem Endocuff Cap Trial (DETECT).

BACKGROUND AND AIMS: Adenoma miss rate during colonoscopy is directly linked to risk of postcolonoscopy colorectal cancer. One of the reasons for missed adenomas is poor visualization of proximal folds during standard colonoscopy withdrawal. Disposable distal attachments such as the plastic cap and Endocuff (Arc Medical Design, Leeds, UK) that hold back folds appear to improve adenoma detection. The primary aim of this study was to compare adenoma detection rates between Endocuff-assisted colonoscopy (EAC) and cap-assisted colonoscopy (CAC). METHODS: This is a randomized, single-center, tandem colonoscopy trial performed by the same endoscopists on the same day, first with Endocuff Vision (Arc Medical Design, Leeds, UK) followed by cap or vice versa. All procedures were performed by 3 experienced gastroenterology fellows. RESULTS: One hundred fifty-four patients were recruited. Seventy-eight (50.6%) had CAC as their first procedure. Mean patient age was 61 years (male-to-female ratio, 1:1). Adenoma detection rate was significantly higher for EAC when compared to CAC (53% vs 26%, P = .001). Polyp miss rate was significantly lower in EAC (8.4%) compared with CAC (26.1%, P < .001) as was adenoma miss rate (EAC vs CAC, 6%, vs 19%; P = .002) and diminutive adenoma (<5 mm) miss rate in the EAC group (1.8% vs 19.6%, P < .001). However, there was no significant differences in the miss rates for small adenomas (5-9 mm) (3.7% vs 2.9%, P = .69) or adenomas 10 mm or larger (1.6% vs 2.6%, P = .98 ). The mean number of adenomas per procedure was significantly higher with EAC compared with CAC (1.5 vs .8, P < .001). Cecal intubation time was significantly shorter with EAC than CAC (median 6 vs 7 minutes, P = .01). Conversely, withdrawal time (median 10 vs 8 minutes, P = .01) was significantly longer in EAC. CONCLUSIONS: This randomized, tandem study demonstrates that EAC has a significantly higher adenoma detection rate and lower adenoma miss rate than CAC. Although insertion times were shorter with EAC, procedures were slightly more uncomfortable, and the cuff had to be removed in a small number of cases. (Clinical trial registration number: NCT03254498.).

Catalytic dissociation of tris(dimethylamino)silane on hot tungsten and tantalum filament surfaces.

The dissociation of tris(dimethylamino)silane (TrDMAS) on hot tungsten and tantalum surfaces was studied under collision-free conditions. The products from the hot-wire decomposition of TrDMAS were monitored using a 10.5 eV vacuum ultraviolet laser single-photon ionization in tandem with time-of-flight mass spectrometry. Formation of a methyl radical and N-methyl methyleneimine (NMMI) was detected. A transition from a surface reaction rate-limiting regime at filament temperatures lower than 1800-2000 °C to mass transport regime at higher temperatures (>1800-2000 °C) was observed for the formation of both products. In the surface reaction regime, the Arrhenius behavior was followed in two separate temperature regions with different activation energies. It was found that low temperatures (900-1300 °C) favor the production of the methyl radical and high temperatures (1400-2000 °C) favor the production of NMMI with lower activation energies. A theoretical investigation using ab initio calculations of the concerted and stepwise formation of NMMI along with the homolytic cleavages of N-CH3 and Si-H in the gas phase has shown that the concerted pathway to form NMMI is the most energetically favorable one of all four routes with an activation barrier of 328 kJ mol-1. The lower activation energy values determined experimentally for the formation of NMMI and ˙CH3 as compared to those obtained from theoretical calculations indicate that the dissociation of TrDMAS, an N-containing organosilicon molecule, on the W and Ta surfaces is a catalytic cracking process.

Mesenteric Infarction: Clinical Outcomes After Restoration of Bowel Continuity.

INTRODUCTION: Patients who have a bowel resection for mesenteric infarction may require parenteral nutrition (PN). This study primarily aimed to determine the aetiological factors for a mesenteric infarction and the effects of restoring bowel continuity on the long-term PN requirements. METHODS: A retrospective review of data on patients treated for mesenteric infarction from 2000 to 2010. RESULTS: A total of 113 patients (61 women, median age 54 years) were identified. Seventy-four (65%) had a superior mesenteric artery thromboembolism, 25 (22%) had a superior mesenteric vein thrombosis, and 4 (3%) had superior mesenteric artery stricture or spasm. Patients younger than 60 years most commonly had a clotting abnormality (n = 23/46, 50%), whereas older patients had a cardiological risk factor (n = 11/17, 65%). All patients with a jejunostomy required long-term PN. Fifty-seven (49%) patients had restoration of bowel continuity (colon brought into circuit). After this, PN was stopped within 1 year in 20 (35%), within 2 years in 29 (50%) patients and within 5 years in 44 (77%) patients (P = 0.001). CONCLUSIONS: A thrombotic tendency is the main etiological factor in most patients younger than 60 years. An anastomosis of the remaining jejunum to the colon can allow PN to be stopped.

Stimuli-responsive dynamic hydrogels: design, properties and tissue engineering applications.

The field of tissue engineering and regenerative medicine has been evolving at a rapid pace with numerous novel and interesting biomaterials being reported. Hydrogels have come a long way in this regard and have been proven to be an excellent choice for tissue regeneration. This could be due to their innate properties such as water retention, and ability to carry and deliver a multitude of therapeutic and regenerative elements to aid in better outcomes. Over the past few decades, hydrogels have been developed into an active and attractive system that can respond to various stimuli, thereby presenting a wider control over the delivery of the therapeutic agents to the intended site in a spatiotemporal manner. Researchers have developed hydrogels that respond dynamically to a multitude of external as well as internal stimuli such as mechanics, thermal energy, light, electric field, ultrasonics, tissue pH, and enzyme levels, to name a few. This review gives a brief overview of the recent developments in such hydrogel systems which respond dynamically to various stimuli, some of the interesting fabrication strategies, and their application in cardiac, bone, and neural tissue engineering.

Strategies for targeted gene delivery using lipid nanoparticles and cell-derived nanovesicles.

Gene therapy is a promising approach for the treatment of many diseases. However, the effective delivery of the cargo without degradation in vivo is one of the major hurdles. With the advent of lipid nanoparticles (LNPs) and cell-derived nanovesicles (CDNs), gene delivery holds a very promising future. The targeting of these nanosystems is a prerequisite for effective transfection with minimal side-effects. In this review, we highlight the emerging strategies utilized for the effective targeting of LNPs and CDNs, and we summarize the preparation methodologies for LNPs and CDNs. We have also highlighted the non-ligand targeting of LNPs toward certain organs based on their composition. It is highly expected that continuing the developments in the targeting approaches of LNPs and CDNs for the delivery system will further promote them in clinical translation.

Trends in mechanobiology guided tissue engineering and tools to study cell-substrate interactions: a brief review.

Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, the subsequent downstream responses at the cellular, nuclear and epigenetic levels and the outcomes are beginning to get unraveled more recently. There have been various instances where researchers have established the underlying connection between the cellular mechanosignalling pathways and cellular physiology, cellular differentiation, and also tissue pathology. It has been now accepted that mechanosignalling, alone or in combination with classical pathways, could play a significant role in fate determination, development, and organization of cells and tissues. Furthermore, as mechanobiology is gaining traction, so do the various techniques to ponder and gain insights into the still unraveled pathways. This review would briefly discuss some of the interesting works wherein it has been shown that specific alteration of the mechanical properties of the substrates would lead to fate determination of stem cells into various differentiated cells such as osteoblasts, adipocytes, tenocytes, cardiomyocytes, and neurons, and how these properties are being utilized for the development of organoids. This review would also cover various techniques that have been developed and employed to explore the effects of mechanosignalling, including imaging of mechanosensing proteins, atomic force microscopy (AFM), quartz crystal microbalance with dissipation measurements (QCMD), traction force microscopy (TFM), microdevice arrays, Spatio-temporal image analysis, optical tweezer force measurements, mechanoscanning ion conductance microscopy (mSICM), acoustofluidic interferometric device (AID) and so forth. This review would provide insights to the researchers who work on exploiting various mechanical properties of substrates to control the cellular and tissue functions for tissue engineering and regenerative applications, and also will shed light on the advancements of various techniques that could be utilized to unravel the unknown in the field of cellular mechanobiology.

JAG consensus statements for training and certification in colonoscopy.

Introduction: In the UK, endoscopy certification is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for colonoscopy training and certification. Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted between 2019 and 2020 with multisociety expert representation. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on colonoscopy training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer reviewed by JAG and relevant stakeholders for incorporation into the updated colonoscopy certification pathway. Results: In total, 45 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (20), assessment of competence (8) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (1) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, unassisted caecal intubation rate >90%, rectal retroversion >90%, polyp detection rate >15%+, polyp retrieval rate >90%, patient comfort <10% with moderate-severe discomfort); (2) minimum procedure count 280+; (3) performing 15+ procedures over the preceding 3 months; (4) attendance of the JAG Basic Skills in Colonoscopy course; (5) terminal ileal intubation rates of 60%+ in inflammatory bowel disease; (6) satisfying requirements for formative direct observation of procedure skills (DOPS) and direct observation of polypectomy skills (Size, Morphology, Site, Access (SMSA) level 2); (7) evidence of reflective practice as documented on the JAG Endoscopy Training System reflection tool; (8) successful performance in summative DOPS. Conclusion: The UK standards for training and certification in colonoscopy have been updated, culminating in a single-stage certification process with emphasis on polypectomy competency (SMSA Level 2+). These standards are intended to support training, improve standards of colonoscopy and polypectomy, and provide support to the newly independent practitioner.

JAG consensus statements for training and certification in flexible sigmoidoscopy.

Introduction: Joint Advisory Group (JAG) certification in endoscopy is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update standards for training and certification in flexible sigmoidoscopy (FS). Methods: A modified Delphi process was conducted between 2019 and 2020 with multisociety representation from experts and trainees. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on FS training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer-reviewed by national stakeholders for incorporation into the JAG FS certification pathway. Results: In total, 41 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (17), assessment of competence (7) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (A) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, rectal retroversion >90%, polyp retrieval rate >90%, patient comfort <10% with moderate-severe discomfort); (B) minimum procedure count ≥175; (C) performing 15+ procedures over the preceding 3 months; (D) attendance of the JAG Basic Skills in Lower gastrointestinal Endoscopy course; (E) satisfying requirements for formative direct observation of procedural skill (DOPS) and direct observation of polypectomy skill (SMSA level 1); (F) evidence of reflective practice as documented on the JAG Endoscopy Training System reflection tool and (G) successful performance in summative DOPS. Conclusion: The UK standards for training and certification in FS have been updated to support training, uphold standards in FS and polypectomy, and provide support to the newly independent practitioner.

A brief review of mRNA therapeutics and delivery for bone tissue engineering.

The therapeutics for bone tissue regeneration requires constant advancements owing to the steady increase in the number of patients suffering from bone-related disorders, and also to find efficient and cost-effective treatment modalities. One of the major advancements in the field of therapeutics is the development of mRNAs. mRNAs, which have been extensively tested for the vaccines, could be very well utilized as a potential inducer for bone regeneration. The ability of mRNAs to enter the cells and instruct the cellular machinery to produce the required native proteins such as BMP or VEGF is a great way to avoid the issues faced with growth factor deliveries such as the production cost, loss of biological function etc. However, there have been a few hurdles for using mRNAs as an effective therapeutic agent, such as proper dosing, tolerating the degradation by RNases, improving the half-life, controlling the spatio-temporal release and reducing the off-target effects. This brief review discusses the various developments in the field of mRNA therapeutics especially for bone tissue engineering, how nano-formulations are being developed to effectively deliver the mRNAs into the cells by evading the immune responses, how researchers have developed certain strategies to increase the half-life, to successfully deliver the mRNAs to specific bone defect area and bring about effective bone regeneration.

Comparative evaluation of efficacy of three different denture cleansing methods in reducing Candida albicans count in removable partial denture wearers: A randomized controlled trial.

Aims: The study aims to find out the best possible method of cleaning the removable partial denture (RPD) by evaluating the Candida count limiting ability in RPD users using three different cleaning methods. Settings and Design: The present study is randomized controlled trial. Three groups were formed with 20 participants in each. The groups were Group 1 RPD cleansing done using sterile saline and denture brush (negative control group), Group 2 RPD cleansing done using soap and denture brush and Group 3 RPD cleansing done using denture cleansing tablet and denture brush. Materials and Methods: A baseline data and 15 days' postinsertion data of Candida count was recorded using swab collection, from the RPDs given. The swab was collected, cultured, and incubated using standard methods. Once Candida was identified using Sabouraud's dextrose agar, Candida albicans was further confirmed using germ tube test and cornmeal agar. Statistical Analysis Used: The analysis was done using SPSS software (IBM Corp. Released 2010. IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp.). Paired t-test, was used to compare the number of colonies pre and postintervention. The difference between the groups was analyzed using one-way analysis of variance (ANOVA) and Tukey's post hoc analysis. Results: The comparison of baseline data and postintervention data within each group using paired t test demonstrated statistically significant values; P = 0.046 and 0.000 in Group 2 and 3 respectively. The difference between the Candida colonies in three different groups after the intervention (15 Days) was analyzed using analysis of variance and found to be statistically significant with P = 0.004. Tukey's post hoc analysis was used to analyze the difference between the groups. It was concurred that there was a statistically significant difference between all three groups, but the difference in the mean was highest between the Group 1 and 3 (1210.99). Conclusion: Within the limitations of the study, it is concluded that the use of denture cleansers and brush on a daily basis would actively reduce the number of C. albicans colony formation in RPD and thereby improve the overall health of denture wearer.

Correlating the trends of COVID-19 spread and air quality during lockdowns in Tier-I and Tier-II cities of India-lessons learnt and futuristic strategies.

The present study focuses on the impact of early imposed lockdowns and following unlocking phases on the status of air quality in six Tier-I and nine Tier-II cities of India as compared to the pre-lockdown measures. Furthermore, the study highlights the possible correlation of air quality index (AQI) with the initial trend of COVID-19 issues including the vaccination cases. Based on the statistical data analysis, we observed that the long-term averages for representing the short-term pre-lockdown conditions can impose a healing effect to the observed anomalies in air pollution data. However, the reduction in air pollution during the imposed lockdown series was only a phenomenal consequence, and the trends started reversing during the later phases of partial unlocking, where the correlation showed reversing trends. Being a yearly averaged parameter, the marginal reductions in the exceedance factor (EF) alone could not dictate air quality compared to the AQI. As there is incoherent variability in the pollutant distributions among the cities during various phases of the study, the trend analysis served as a preferable criterion to choose the preferred sources of variations. Based on the results, the correlation analysis revealed that air quality expressed in terms of AQI can act as an important precursor to estimate the critical phase of COVID-19 spread and the effectiveness of various control measures taken during each phase. Based on our proposed ranking, Kolkata and Patna are ranked first in the Tier-I and Tier-II cities respectively according to their responsiveness to the various institutionalized restrictions in terms of air quality parameters.

Addition of lactoferrin and substance P in a chitin/PLGA-CaSO4 hydrogel for regeneration of calvarial bone defects.

Calcium-based injectable hydrogels with various bioactive active molecules possess a great potential for bone regeneration. Herein, we have synthesized a chitin-PLGA-calcium sulfate hydrogel (CSG) containing bioactive molecules - lactoferrin (LF) and substance P (SP). SEM and XRD analysis revealed that CS crystal growth was altered with the addition of LF. Rheological measurements indicated that the injectability of the hydrogels was maintained after the addition of LF, however, there was a reduction in storage modulus after LF addition. The addition of LF increased stem cell proliferation whereas, SP enhanced the cell migration. Osteogenic gene expression revealed that LF concentration at 25 µg/mg of CSG was optimal for a favourable outcome. To this optimized LF containing CSG, SP was incorporated and 0.05 µg/mg was found to be most effective (CSG-L3S2) in vitro studies. Further, the µ-CT and histological studies confirmed that CSG-L3S2 showed enhanced bone regeneration compared to the controls in critical-sized calvarial defect of mice. Thus the results indicate that a combination of the chemotactic agent (SP), pleiotropic growth protein (LF), and CS in the chitin-PLGA hydrogel could be a promising approach for non-load bearing bone defects.

Sulfonated Polyrotaxane Surfaces with Basic Fibroblast Growth Factor Alter the Osteogenic Potential of Human Mesenchymal Stem Cells in Short-Term Culture.

Human mesenchymal stem cells (hMSCs) are prone to senescence and lose their differentiation potential when expanded under nonfavorable conditions. This leads to the underutilization of hMSCs in clinical situations such as bone regeneration. The use of growth factors and small molecules as supplements and changing the physical properties of the cell culture surface have been explored to maintain the self-renewal and differentiation potential of hMSCs during the in vitro expansion phase. Here, we have explored the effect of polyrotaxanes (PRXs) with different molecular mobilities along with either soluble or immobilized fibroblast growth factor 2 (FGF2) in the maintenance of the osteogenic differentiation potential of hMSCs during in vitro expansion. We found that a less expanded shape of the hMSCs was associated with highly mobile PRX surfaces, and less mobile PRX surfaces led to flattened cell morphology. The presence of FGF2 induced further expansion of the cell shape and size. The immobilization of FGF2 helped to improve the yield of hMSCs on highly mobile surfaces by promoting cell attachment to the surfaces. hMSCs cultured on highly mobile PRX surfaces exhibited poor actin cytoskeletal organization and retention of the transcriptional regulator, yes-associated protein (YAP), in cytoplasm in contrast to the hMSCs on less mobile PRX surfaces. When the hMSCs that proliferated under these conditions were collected and subjected to osteogenic differentiation on tissue culture polystyrene (TCPS) surfaces, we found that only the hMSCs cultured on highly mobile PRXs with FGF2 in both soluble and immobilized forms showed mineralization indicative of osteogenic differentiation. Further, we found that hMSCs cultured on highly mobile PRX surfaces expressed higher levels of stemness marker genes, Nanog and Oct4. These results indicate that culturing hMSCs on PRX surfaces with different molecular mobilities even for a short period of time (4 days) was sufficient to cause a drastic change in the osteogenic potential. From these results, it is suggested that apart from the use of supplements such as FGF2 in its freely soluble or immobilized form, the consideration of proper molecular mobility of the substrates could enable us to design better culture conditions for the hMSCs with osteogenic potential.

Effect of oral environment and prescribed fluoride mouthwashes on different types of TMA wires - An in-vivo study.

OBJECTIVE: The aim of this study was to investigate the effect of intraoral conditions and fluoride mouthwashes on mechanical properties and surface characteristics of different types of titanium molybdenum alloy (TMA) wires. MATERIALS AND METHODS: Three types of TMA wires of dimension 0.017" × 0.025" [1. Standard TMA (TMA), 2. ion-implanted, low-friction TMA (LF) and 3. Colored, Honey Dew TMA (HD)] were tested in three conditions as three groups; A) Control (as received), B) No fluoride (following intraoral use without fluoride) and C) Fluoride (following intraoral use with fluoride rinses). Surface roughness was evaluated using 3D Optical Profilometer. Three point bending tests were done to evaluate load deflection characteristics (LDR), ultimate tensile strength (UTS), and Young's modulus (E). Statistical evaluation was done using one-way analysis of variance (ANOVA), Bonferroni multiple comparison, and paired t-tests. RESULTS: Control group TMA exhibited significantly higher surface roughness, peak height, and LDR as well as lower UTS and E when compared to LF and HD (P < 0.001). In nonfluoride group, the surface roughness and LDR increased significantly for all three types of wires (P < 0.001). The UTS and E showed a significant decrease (P < 0.001). Additional use of fluoride mouthwashes (fluoride group) further increased surface roughness and LDR and decreased the UTS and E (P < 0.001). CONCLUSION: The ion-implanted LF/HD varieties had better surface smoothness, lower LDR, higher UTS, and higher E than standard TMA in the control group, pointing towards a better efficiency of these wires. Intraoral conditions significantly increased surface roughness and deteriorated mechanical properties of all types of TMA wires. With the use of daily fluoride mouthwashes, the deterioration was much worse.

The improvement of calvarial bone healing by durable nanogel-crosslinked materials.

Different approaches have been developed to improve the scaffold properties that provide structural support and biological interaction to achieve the desired environment for tissue regeneration. We previously reported that addition of human fibroblast growth factor 18 (hFGF18) to acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogel-crosslinked (NanoClik) hydrogels that contain human bone morphogenetic protein 2 (hBMP2) stabilized bone healing in mouse calvarial defect model. In this study, we evaluated the use of disc-shaped dried nanogel-crosslinked gel as carriers of growth factors in order to seek possible clinical application in future. Both conventionally-dried NanoClik disc and nanogel-crosslinked porous (NanoCliP) disc made by freeze-drying that contained the growth factors induced bone healing but not as much as with NanoClik hydrogel application but addition of RGD peptides (RGD-NanoCliP disc) improved the healing. All type of discs showed the same biphasic ovalbumin-Alexa Fluor 488 protein release profile in vitro, an initial burst followed by a gradual sustained release more than one week, which was confirmed in vivo. Histological analysis showed remarkable new bone formation with more calcification in RGD-NanoCliP disc with the growth factors and the osteogenesis appeared to begin in the dura mater in contact with the disc. These observations suggest: (1) the fitness of the durable discs to the bone defect is a critical factor for bone healing, which is supplemented by addition of RGD peptides, (2) the porosity is suitable for osteoblast recruitment, (3) growth factor release pattern of the CHPOA nanogel based gels is ideal for bone healing.

Role of fibroblast growth factors in bone regeneration.

Bone is a metabolically active organ that undergoes continuous remodeling throughout life. However, many complex skeletal defects such as large traumatic bone defects or extensive bone loss after tumor resection may cause failure of bone healing. Effective therapies for these conditions typically employ combinations of cells, scaffolds, and bioactive factors. In this review, we pay attention to one of the three factors required for regeneration of bone, bioactive factors, especially the fibroblast growth factor (FGF) family. This family is composed of 22 members and associated with various biological functions including skeletal formation. Based on the phenotypes of genetically modified mice and spatio-temporal expression levels during bone fracture healing, FGF2, FGF9, and FGF18 are regarded as possible candidates useful for bone regeneration. The role of these candidate FGFs in bone regeneration is also discussed in this review.

Parallelization of multicategory support vector machines (PMC-SVM) for classifying microarray data.

BACKGROUND: Multicategory Support Vector Machines (MC-SVM) are powerful classification systems with excellent performance in a variety of data classification problems. Since the process of generating models in traditional multicategory support vector machines for large datasets is very computationally intensive, there is a need to improve the performance using high performance computing techniques. RESULTS: In this paper, Parallel Multicategory Support Vector Machines (PMC-SVM) have been developed based on the sequential minimum optimization-type decomposition method for support vector machines (SMO-SVM). It was implemented in parallel using MPI and C++ libraries and executed on both shared memory supercomputer and Linux cluster for multicategory classification of microarray data. PMC-SVM has been analyzed and evaluated using four microarray datasets with multiple diagnostic categories, such as different cancer types and normal tissue types. CONCLUSION: The experiments show that the PMC-SVM can significantly improve the performance of classification of microarray data without loss of accuracy, compared with previous work.