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Metallic magnesium is a promising high-capacity anode material for energy storage technologies beyond lithium-ion batteries. However, most reported Mg metal anodes are only cyclable under shallow cycling (≤1 mAh cm

This research aims to investigate how price, service quality, and perceived value affect customer satisfaction among consumers of Telekom Malaysia broadband. This quantitative research distributed an online questionnaire to collect data from 271 current or former customers of Telekom Malaysia Broadband. The findings concluded that service quality and perceived value have significant positive relationships with customer satisfaction, whereas price possesses a significant negative relationship with customer satisfaction. The findings contribute to the continuous improvement on customer satisfaction among consumers of Telekom Malaysia broadband and other telecommunication providers by improving price, service quality, and perceived value.

Supplementary Literature from Genetic Alterations in the Tyrosine Kinase Transcriptome of Human Cancer Cell Lines

Supplementary Tables 1-14 from Genetic Alterations in the Tyrosine Kinase Transcriptome of Human Cancer Cell Lines

Protein tyrosine kinases (PTKs) play a critical role in the manifestation of cancer cell properties, and respective signaling mechanisms have been studied extensively on immortalized tumor cells. To characterize and analyze commonly used cancer cell lines with regard to variations in the primary structure of all expressed PTKs, we conducted a cDNA-based sequence analysis of the entire tyrosine kinase transcriptome of 254 established tumor cell lines. The profiles of cell line intrinsic PTK transcript alterations and the evaluation of 155 identified polymorphisms and 234 somatic mutations are made available in a database designated “Tykiva” (tyrosine kinome variant). Tissue distribution analysis and/or the localization within defined protein domains indicate functional relevance of several genetic alterations. The cysteine replacement of the highly conserved Y367 residue in fibroblast growth factor receptor 4 or the Q26X nonsense mutation in the tumor-suppressor kinase CSK are examples, and may contribute to cell line–specific signaling characteristics and tumor progression. Moreover, known variants, such as epidermal growth factor receptor G719S, that were shown to mediate anticancer drug sensitivity could be detected in other than the previously reported tumor types. Our data therefore provide extensive system information for the design and interpretation of cell line–based cancer research, and may stimulate further investigations into broader clinical applications of current cancer therapeutics. [Cancer Res 2007;67(23):11368–76]

Supplementary Text from Genetic Alterations in the Tyrosine Kinase Transcriptome of Human Cancer Cell Lines

A major challenge hindering the practical adoption of room-temperature sodium-sulfur batteries (NaSBs) is polysulfide dissolution and shuttling, which results in irreversible capacity decay and low Coulombic efficiencies. In this work, we demonstrate for the first time NaSBs using a ferrocene-derived amorphous sulfurized cyclopentadienyl composite (SCC) cathode. Polysulfide dissolution is eliminated via covalent bonding between the insoluble short-chain sulfur species and carbon backbone. Control experiments with a metal-free composite analogue determined that the iron species in the SCC does not have a significant role in polysulfide anchoring. Instead, the superior electrochemical performance is attributed to sulfur covalently bonded to carbon and the uniform nanoparticulate morphology of the SCC composite. In the carbonate-based electrolyte, a discharge capacity of 795 mAh g

Room-temperature sodium-sulfur batteries have potential in stationary applications, but challenges such as loss of active sulfur and low electrical conductivity must be solved. Nitrogen-doped nanocarbon host cathodes have been employed in metal-sulfur batteries: polar interactions mitigate the loss of sulfur, while the conductive nanostructure addresses the low conductivity. Nevertheless, these two properties run contrary to each other as greater nitrogen-doping of nanocarbon hosts is associated with lower conductivity. Herein, we investigate the polarity-conductivity dilemma to determine which of these properties have the stronger influence on cycling performance. Lower carbonization temperatures produce more pyridinic nitrogen and pyrrolic nitrogen, which from density functional theory calculations preferentially bind discharge products (Na2S and short-chain polysulfides). Despite its lower conductivity, the highly doped composite showed better Coulombic efficiency and stability, retaining a high capacity of 980 mAh g(S)-1 after 800 cycles. Our findings represent a paradigm shift where nitrogen-doping should be prioritized in designing shuttle-free, long-life sodium-sulfur batteries.

Introduction The current gold standard for diagnosing interstitial lung disease (ILD) involves an ILD clinic evaluation, followed by discussion in a multidisciplinary meeting (MDM). However, there is a paucity of data on the impact of ILD MDMs on the diagnosis and management of ILDs in Southeast Asia. We studied the clinical impact of the ILD service on the diagnosis and management of ILDs at a university-affiliated tertiary hospital in Singapore. Methods A single-centre retrospective review was done on 97 consecutive patients referred for evaluation to the ILD service from March 2016 to August 2017. Results Mean age of the patients was 67 ± 11 years. Gender distribution was almost equal (52% male), with a majority of never-smokers (63%). Mean forced vital capacity (FVC) was 1.81 ± 0.66 L (66% ± 20% predicted). The three commonest referral diagnoses were ILD of uncertain classification (n = 38, 39%), connective tissue disease-associated ILD (CTD-ILD) (n = 24, 25%) and idiopathic pulmonary fibrosis (IPF) (n = 16, 17%). Following evaluation by the ILD service, there was a change of diagnosis in 60 (62%) patients and a change of management in 71 (73%) patients. The majority of consensus MDM diagnoses were IPF (n = 35, 36%), CTD-ILD (n = 30, 30%) and others (n = 15, 15%). There was a significant prognostic separation between the IPF and non-IPF diagnoses made following evaluation by the ILD service. Conclusion The ILD service allowed for more precise subtyping of various ILDs. This is particularly useful for IPF patients, who can benefit from antifibrotic therapies.

Tooth loss greatly affects a person's quality of life and many turn to dental implants to replace lost teeth. The success of a dental implant depends on the amount of alveolar bone supporting the implant, and thus, bone augmentation is often necessary to preserve or build up bone volume in the alveolar ridge. Bone can be augmented with autogenous bone, allografts, or xenografts, but the limitations of such natural bone grafts prompt researchers to develop synthetic scaffolds supplemented with cells and/or bioactive agents as alternative bone grafts. The translation of these combination scaffolds from the laboratory to the clinic requires reliable experimental models that can simulate the clinical conditions in human patients. In this article, we describe the use of a porcine alveolar defect model as a platform to evaluate the efficacy of a novel combination of a three-dimensional-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold and adipose-derived mesenchymal stem cells (AD-MSCs) in lateral alveolar augmentation. The surgical protocol for the defect creation and regenerative surgery, as well as analytical methods to determine the extent of tissue regeneration, are described and discussed.

The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses.

Calcium imaging with protein-based indicators is widely used to follow neural activity in intact nervous systems. The popular GCaMP indicators are based on the calcium-binding protein calmodulin and the RS20 peptide. These sensors report neural activity at timescales much slower than electrical signaling, limited by their biophysical properties and trade-offs between sensitivity and speed. We used large-scale screening and structure-guided mutagenesis to develop and optimize several fast and sensitive GCaMP-type indicators. The resulting ‘jGCaMP8’ sensors, based on calmodulin and a fragment of endothelial nitric oxide synthase, have ultra-fast kinetics (rise times, 2 ms) and still feature the highest sensitivity for neural activity reported for any protein-based sensor. jGCaMP8 sensors will allow tracking of larger populations of neurons on timescales relevant to neural computation.

The COVID-19 pandemic has rerouted the healthcare ecosystem by accelerating digital health, and rapid adoption of eHealth is partly influenced by eHealth literacy (eHL). This study aims to examine patients' eHL in relation to their "technology readiness"-an innate attitude that is underexplored in clinical research. A total of 276 adult inpatients with hypertension, diabetes mellitus, and coronary heart disease were surveyed cross-sectionally in 2019 using self-reported questionnaires: eHealth Literacy Scale and Technology Readiness Index (2.0). The study found moderate eHL (mean, 27.38) and moderate technology readiness (mean, 3.03) among patients. The hierarchical regression model shows that lower eHL scores were associated with patients of minor ethnicity (Malaysian Chinese), with an unemployed status, and having >1 cardiovascular risk (β = -0.136 to -0.215, R2 = 0.283, Ps < .005). Technology readiness is a strong determinant of eHL (ΔR2 = 0.295, P < .001) with its subdomains (optimism, innovativeness, and discomfort) significantly influencing eHL (|β| = 0.28-0.40, Ps < .001), except for the insecurity subdomain. Deployment of eHealth interventions that incorporate assessment of patients' eHL and technology readiness will enable targeted strategies, especially in resource-limited settings hit hard by the pandemic crisis.

International audience; MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B–related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair. The cellular mechanisms regulating MR1 cell surface expression are critical to its function and MAIT cell recognition, yet they are poorly defined. Here, we report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that mediates low affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction controls the kinetics of MR1 internalization from the cell surface and minimizes recycling. We propose MR1 uses AP2 endocytosis to define the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system.

Purpose Severe peripheral neuropathy is a common dose-limiting toxicity of taxane chemotherapy, with no effective treatment. Frozen gloves have shown to reduce the severity of neuropathy in several studies but comes with the incidence of undesired side effects such as cold intolerance and frostbite in extreme cases. A device with thermoregulatory features which can safely deliver tolerable amounts of cooling while ensuring efficacy is required to overcome the deficiencies of frozen gloves. The role of continuous-flow cooling in prevention of neurotoxicity caused by paclitaxel has been previously described. This study hypothesized that cryocompression (addition of dynamic pressure to cooling) may allow for delivery of lower temperatures with similar tolerance and potentially improve efficacy. Method A proof-of-concept study was conducted in cancer patients receiving taxane chemotherapy. Each subject underwent four-limb cryocompression with each chemotherapy infusion (three hours) for a maximum of 12 cycles. Cryocompression was administered at 16 °C and cyclic pressure (5–15 mmHg). Skin surface temperature and tolerance scores were recorded. Neuropathy was assessed using clinician-graded peripheral sensory neuropathy scores, total neuropathy score (TNS) and nerve conduction studies (NCS) conducted before (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). Results were retrospectively compared with patients who underwent paclitaxel chemotherapy along with continuous-flow cooling and controls with no hypothermia. Results In total, 13 patients underwent 142 cycles of cryocompression concomitant with chemotherapy. Limb hypothermia was well tolerated, and only 1 out of 13 patients required an intra-cycle temperature increase, with no early termination of cryocompression in any subject. Mean skin temperature reduction of 3.8 ± 1.7 °C was achieved. Cryocompression demonstrated significantly greater skin temperature reductions compared to continuous-flow cooling and control (p < 0.0001). None of the patients experienced severe neuropathy (clinician-assessed neuropathy scores of grade 2 or higher). NCS analysis showed preservation of motor amplitudes at NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4%, p = 0.004; below fibula head stimulation: 12.7 ± 25.6%, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3%, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes. Conclusion When compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.

The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B(2) synthesis to activate mucosal-associated invariant T (MAIT) cells. Key aspects of this evolutionarily conserved pathway remain uncharacterized, including where MR1 acquires ligands and what accessory proteins assist ligand binding. We answer these questions by using a fluorophore-labeled stable MR1 antigen analog, a conformation-specific MR1 mAb, proteomic analysis, and a genome-wide CRISPR/Cas9 library screen. We show that the endoplasmic reticulum (ER) contains a pool of two unliganded MR1 conformers stabilized via interactions with chaperones tapasin and tapasin-related protein. This pool is the primary source of MR1 molecules for the presentation of exogenous metabolite antigens to MAIT cells. Deletion of these chaperones reduces the ER-resident MR1 pool and hampers antigen presentation and MAIT cell activation. The MR1 antigen-presentation pathway thus co-opts ER chaperones to fulfill its unique ability to present exogenous metabolite antigens captured within the ER.

The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.

Skin ageing is associated with a decrease in collagen and delayed wound healing. The previous study has shown that supplementation of growth factors can enhance the production of extracellular matrix (ECM) and efficiency of wound healing. This study aimed to produce a Dermal Fibroblast Conditioned Medium (DFCM) and evaluate its potential on in vitro skin wound healing and anti-ageing properties. DFCM were obtained by culturing confluent human dermal fibroblasts (n=3) in keratinocyte-specific medium (DFCM-KM), fibroblast-specific medium (DFCM-FM) and fibroblast-specific medium with growth supplements (DFCM-GM). Protein concentration was determined by Bicinchoninic Acid (BCA) assay. To evaluate the wound healing and anti-ageing properties, human dermal fibroblasts were supplemented with three different DFCM. Fibroblasts cultured with F12:DMEM+10%FBS was used as a control. The growth rate of fibroblasts was evaluated by culturing cells until day 4. Migration rate was evaluated at 12 h after seeding. In vitro healing rate was evaluated via scratch assay. Anti-ageing potential of DFCM was evaluated via RT2 Profiler PCR Array. Concentration of total protein was found to be significantly higher in DFCM-GM (2914.79±150.67mg/mL) compared to DFCM-KM and DFCM-FM. Out of the tested 12 anti-ageing genes, fibroblasts supplemented with DFCM-GM demonstrated a significantly higher expression of WRN compared to other conditions. In conclusion, DFCM-GM contains more proteins and found superior in modulating wound healing and anti-ageing properties.

The ensuing COVID-19 pandemic poses unprecedented and daunting challenges to the routine delivery of oncological and supportive care to patients with breast cancer. Considerations include the infective risk of patients who are inherently immunosuppressed from their malignancy and therapies, long-term oncological outcomes from the treatment decisions undertaken during this extraordinary period, and diverted healthcare resources to support a coordinated whole-of-society outbreak response. In this review, we chronicle the repercussions of the COVID-19 outbreak on breast cancer management in Singapore and describe our approach to triaging and prioritising care of breast tumours. We further propose adaptations to established clinical processes and practices across the different specialties involved in breast oncology, with references to the relevant evidence base or expert consensus guidelines. These recommendations have been developed within the unique context of Singapore’s public healthcare sector. They can serve as a resource to guide breast cancer management for future contingencies in this city-state, while certain elements therein may be extrapolatable to other medical systems during this global public health emergency.

PURPOSE. The TRK pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse effects (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial. METHODS. Patients with advanced or unresectable solid tumors treated with a TRK inhibitor were retrospectively identified in a search of clinical databases. Among these patients, the frequency, severity, duration, and management outcomes of AEs including weight gain, dizziness or ataxia, and withdrawal pain were characterized. RESULTS. Ninety-six patients with 15 unique cancer histologies treated with a TRK inhibitor were identified. Weight gain was observed in 53% (95% CI, 43%-62%) of patients and increased with time on TRK inhibition. Pharmacologic intervention, most commonly with GLP-1 analogs or metformin, appeared to result in stabilization or loss of weight. Dizziness, with or without ataxia, was observed in 41% (95% CI, 31%-51%) of patients with a median time to onset of 2 weeks (range, 3 days to 16 months). TRK inhibitor dose reduction was the most effective intervention for dizziness. Pain upon temporary or permanent TRK inhibitor discontinuation was observed in 35% (95% CI, 24%-46%) of patients; this was more common with longer TRK inhibitor use. TRK inhibitor re-initiation was the most effective intervention for withdrawal pain. CONCLUSIONS. TRK inhibition-related AEs including weight gain, dizziness, and withdrawal pain occur in a substantial proportion of patients receiving TRK inhibitors. This safety profile is unique relative to other anticancer therapies and warrants careful monitoring. These on-target toxicities are manageable with pharmacologic intervention and dose modification.

In this pilot study, we aim to investigate the clinical efficacy of a novel polycaprolactone-tricalcium phosphate (PCL-TCP) membrane for guided bone regeneration (GBR) in an in vivo model. Eight rabbits, each with two surgically created calvarial defects were reconstructed using a bovine particulate bone substitute, then covered with a mechanical barrier using a PCL-TCP or collagen membrane, or left uncovered without any membrane. The rabbits were sacrificed at 1 and 2 months and the reconstructed defects were harvested for histology and histomorphometry evaluations. Results showed no statistical significance in percentage bone area fraction (BAF%) between the PCL-TCP and collagen membranes at 1 and 2 months. The BAF% of the PCL-TCP membrane group was statistically higher at 2 months compared to 1 month (p .05). We postulate that this is attributed to the greater stiffness and slower degradation of PCL-TCP. We conclude that the novel PCL-TCP membrane is as effective as the commercially available collagen membrane as a mechanical barrier for GBR, with good handling characteristics. Future work should explore variations in PCL-TCP composition to further improve its usability and rate of desired degradation.

Cells respond to physiological mechanical stresses especially during early fetal development. Adopting a biomimetic approach, it is necessary to develop bioreactor systems to explore the effects of physiologically relevant mechanical strains and shear stresses for functional tissue growth and development. This study introduces a multimodal bioreactor system that allows application of cyclic compressive strains on premature bone grafts that are cultured under biaxial rotation (chamber rotation about 2 axes) conditions for bone tissue engineering. The bioreactor is integrated with sensors for dissolved oxygen levels and pH that allow real‐time, non‐invasive monitoring of the culture parameters. Mesenchymal stem cells‐seeded polycaprolactone–β‐tricalcium phosphate scaffolds were cultured in this bioreactor over 2 weeks in 4 different modes—static, cyclic compression, biaxial rotation, and multimodal (combination of cyclic compression and biaxial rotation). The multimodal culture resulted in 1.8‐fold higher cellular proliferation in comparison with the static controls within the first week. Two weeks of culture in the multimodal bioreactor utilizing the combined effects of optimal fluid flow conditions and cyclic compression led to the upregulation of osteogenic genes alkaline phosphatase (3.2‐fold), osteonectin (2.4‐fold), osteocalcin (10‐fold), and collagen type 1 α1 (2‐fold) in comparison with static cultures. We report for the first time, the independent and combined effects of mechanical stimulation and biaxial rotation for bone tissue engineering using a bioreactor platform with non‐invasive sensing modalities. The demonstrated results show leaning towards the futuristic vision of using a physiologically relevant bioreactor system for generation of autologous bone grafts for clinical implantation. MOE (Min. of Education, S’pore)

Theory and clinical practicum in mental health are an important component for students in most nursing curriculum. Some studies have shown that knowledge and confidence in caring for people with mental illness improve after mental health clinical placements while others had contrasting results. Our study examined the relationship between clinical placement, confidence and stigma surrounding mental illness. We undertook a cross-sectional, descriptive correlational study in a sample of 144 undergraduate nursing students in Singapore who had completed their theoretical and clinical practicum in mental health using the Clinical Placement Survey Clinical Confidence Scale and Social Distance Scale. Descriptive, correlations and multiple regression were used to analyse the data. The results showed the mean scores for the social distance scale, clinical confidence scale and clinical placement survey were 19.92 out of 35, 49.29 out of 80 and 103.43 out of 154 respectively. Attitudes toward clinical placement experiences were significantly correlated with both stigmatising attitudes and clinical confidence of which, intentions of working in mental health settings were specifically significantly associated with stigmatising attitudes and attitudes toward clinical placement experiences, with emphasis on greater sense of preparedness, lesser perceived anxiety and greater preference for a future career in mental health nursing. This study highlighted the need to improve current mental health clinical placements to better build nursing students' confidence in caring for mentally ill patients. The interest toward specialising in mental health nursing is still lacking in nursing undergraduate students despite mental health clinical placements.

Cells need a home to proliferate and remodel; biomimicry of the microarchitecture and microenvironment is important, and with 10 years of history in more than 20,000 clinical applications of 3D printed medical grade polycaprolactone scaffolds, we present the lessons learnt and project the future.

There have been growing interests in the rise of public GAP standards in Southeast Asia that have been implemented by the governments in the region. This paper investigates the local implementation of Malaysian public GAP standard called MyGAP by examining its effectiveness in raising the awareness and improving the land use practices of participant small-scale farmers toward better food safety and quality assurance. For this objective, 19 MyGAP certified and 57 uncertified durian farms in the state of Pahang, Malaysia were surveyed. The research found that while certified farm managers showed much better understanding of the basic intent of the policy than uncertified farms, their interests in and assessment of the merits from the scheme concentrate in economic realms rather than related to the original policy goal of food safety and quality assurance. As regards land use practices, certified farms showed much better performance than uncertified farms in record keeping and pesticide management. A set of circumstantial evidence seems to suggest, however, that certified farms' better pesticide management is more likely due to the certification screening of already-well-performing farmers than due to improved practices ex post facto. The observed significant discrepancy in the recent MyGAP adoption rates between durian in Pahang State and crop nationwide makes it difficult for us to determine the degree to which MyGAP's existing level of stringency in compliance led to such pre-screening determinism.

This work investigated the antimicrobial activity of Ag octahedral nanoparticle containing polycaprolactone scaffolds (Ag–PCL) that is fabricated via cryomilling. The fabricated composite scaffolds exhibited localized antibacterial activity with no adverse effects on viability and osteogenic differentiation of human fetal mesenchymal stem cells (hfMSCs). Compared to plain PCL scaffolds, the Ag–PCL scaffolds significantly reduce bacteria survival to 32.2% over a 4 hour incubation.

Application of dynamic mechanical loads on bone and bone explants has been reported to enhance osteogenesis and mineralization. To date, published studies have incorporated a range of cyclic strains on 3D scaffolds and platforms to demonstrate the effect of mechanical loading on osteogenesis. However, most of the loading parameters used in these studies do not emulate the in vivo loading conditions. In addition, the scaffolds/platforms are not representative of the native osteoinductive environment of bone tissue and hence may not be entirely accurate to study the in vivo mechanical loading. We hypothesized that biomimicry of physiological loading will potentiate accelerated osteogenesis in bone grafts. In this study, we present a compression bioreactor system that applies cyclic compression to cellular grafts in a controlled manner. Polycaprolactone-β Tricalcium Phosphate (PCL-TCP) scaffolds seeded with Mesenchymal Stem Cells (MSC) were cyclically compressed in bioreactor for a period of 4 weeks at 1 Hz and physiological strain value of 0.22% for 4 h per day. Gene expression studies revealed increased expressions of osteogenesis-related genes (Osteonectin and COL1A1) on day 7 of cyclic loading group relative to its static controls. Cyclic compression resulted in a 3.76-fold increase in the activity of Alkaline Phosphatase (ALP) on day 14 when compared to its static group (p

Xenografting involves the transplantation of human tissue or cells into animal models and is an important tool for regenerative medicine research. Implantation of engineered human bone tissues into animal models, for example, is performed in preclinical evaluations of product safety and efficacy. With the advent of improved experimental methodologies, these models are further being exploited to interrogate molecular mechanisms and physiological interactions in vivo. In parallel to these developments, patient-derived xenograft murine models of cancer are increasingly being studied for various applications in cancer research and therapy; it follows that xenograft models in tissue engineering may be adapted for such approaches. In this review, we first discuss the development of human bone xenograft models to recapitulate physiological states in regenerative medicine. Subsequently, we discuss the use of these techniques for applications in modeling pathological states in skeletal oncology, namely, hematopoietic malignancies, bone metastatic disease, and primary bone malignancy.