Cytokine release by human bone marrow stromal cells isolated from osteoarthritic and diabetic osteoarthritic patients in vitro.

OBJECTIVES: Primary Osteoarthritis (OA) is a disease of progressive joints degeneration due to idiopathic causes. Recent evidence showed a positive relationship between OA and metabolic syndrome. This pilot study aimed to assess the baseline level of pro and anti-inflammatory cytokines in OA patients with or without Diabetic Mellitus (DM) and assess the effect of hydrogen peroxide (H2O2) in cytokine production. METHODS: Patients with primary hip and knee OA were recruited, and 3 mL of bone marrow was harvested during joint replacement surgery. Bone marrow stromal cells (BMSC) was isolated and cultured in a culture flask for three passages. Later experiment was then sub-cultured in a well plate labeled as the control group and H2O2 (0.1 mM) treated group. ProcartaPlex® Multiplex Immunoassay was performed to measure cytokine levels produced by the BMSC at 0 h, as well as 72 h. RESULTS: Cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-1ß generally exhibited higher cytokine levels in subjects with DM than in nonDM subjects at 0 and 72 h. For IL-17, its expression was similar in nonDM and DM groups at 0 and 72 h. Cytokine IL-10 showed no significant difference in both the groups while DM and nonDM groups treated with H2O2 showed decreased IL-4 levels compared to control groups at 72 h. Bone marrow cells from DM-OA are more vulnerable to chemical insult and are associated with higher levels of proinflammatory cytokines production and lower IL-4 level production. CONCLUSIONS: This study provides a clue that management of OA with co-morbidity like DM needs future studies.

Typical response of CD14++CD16- monocyte to knee synovial derived mediators as a key target to overcome the onset and progression of osteoarthritis.

Objective: Synovitis with increased infiltration of immune cells is observed in osteoarthritis (OA). Given the inflammatory condition of synovitis, we explored the protein profile of OA synovium (OAS) and its effect on circulating monocytes activation, migration, and functional commitments. Methods: Knee-synovium was acquired from end-stage OA (N = 8) and trauma patients (Trauma baseline control: TBC; N = 8) for characterization using H&E histology, IHC (iNOS), LCMS-QTOF, and MALDI-imaging. Response of peripheral blood monocytes to OAS conditioned-media (OACM) was observed using transwell (n = 6). The migrated cells were captured in SEM, quantified using phase-contrast microphotographs, and their activation receptors (CCR2, CXCR2, CX3CR1, and CD11b), pro-inflammatory genes, and phagocytic potential were studied using flow cytometry, gene expression array/qPCR, and latex beads (LB) phagocytosis assay, respectively. Results: The Venn diagram displayed 119 typical proteins in OAS, while 55 proteins in TBCS. The STRING protein network analysis indicated distinctive links between proteins and gene ontology (GO) and revealed proteins associated with leukocyte-mediated immunity in OAS as compared to TBC. The MALDI-imaging showed typical localized proteins at 2234.97, 2522.61, 2627.21, 3329.50, and 3539.69 m/z and IHC confirmed pro-inflammatory iNOS expression in OA synovium. CD14++CD16- classical monocytes significantly migrated in OACM and expressed CCR2, CXCR2, and CD11b receptors, TNFRSF11A, MAPK1, S100A8, HSPB1, ITGAL, NFATC1, IL13RA1, CD93, IL-1ß, TNF-α, and MYD88 genes and increased LB uptake as compared to SFM. Conclusion: Our findings suggest that the differential protein profile of OA synovium and the classical monocytes migrated, activated, and functionally committed in response to these mediators could be of therapeutic advantage.

Potential Use of 3D CORAGRAF-Loaded PDGF-BB in PLGA Microsphere Seeded Mesenchymal Stromal Cells in Enhancing the Repair of Calvaria Critical-Size Bone Defect in Rat Model.

Our previous study evidenced that the 3D CORAGRAF loaded with PLGA microsphere constitutes PDGF-BB can support cell attachment and proliferation and can induce an osteogenic commitment of mesenchymal stromal cells in the in vitro condition. However, how this construct can perform in pathophysiological conditions in terms of repairing critical bone defects is yet to be understood. A study was therefore conducted to investigate the regeneration potential of calvaria critical-size defects using CORAGRAF + PLGA with PDGF-BB + mesenchymal stromal cells (MSCs) in a rat model. A 5 mm critical bone defect was created on calvaria of 40 male Sprague-Dawley rats. CORAGRAF incorporated either with or without PDGF-BB and seeded with rat bone-marrow-derived MSCs was implanted at the defect region. The bone regeneration potential of implanted constructs was assessed using micro-CT imaging and histological staining in weeks 4 and 8. The micro-CT images indicated a significant closure of defects in the cranial bone of the rats treated with 3D CORAGRAF + PLGA with PDGF-BB + MSCs on week 4 and 8 post-implantation. This finding, further supported with the histology outcome where the rat cranial defect treated with CORAGRAF + PLGA with PDGF-BB + MSCs indicated neo-bony ingrowth with organized and mature bone-like morphology as compared with other groups. The previous in vitro results substantiated with our pre-clinical findings demonstrate that the combination of CORAGRAF + PLGA with PDGF-BB + MSCs could be an ideal construct to support bone regeneration in critical bone defects. Hence, this construct can be further investigated for its safety and efficacy in large animal models, or it can be skipped to human trial prior for commercialization.

Calcium-Silicate-Incorporated Gellan-Chitosan Induced Osteogenic Differentiation in Mesenchymal Stromal Cells.

Gellan-chitosan (GC) incorporated with CS: 0% (GC-0 CS), 10% (GC-10 CS), 20% (GC-20 CS) or 40% (GC-40 CS) w/w was prepared using freeze-drying method to investigate its physicochemical, biocompatible, and osteoinductive properties in human bone-marrow mesenchymal stromal cells (hBMSCs). The composition of different groups was reflected in physicochemical analyses performed using BET, FTIR, and XRD. The SEM micrographs revealed excellent hBMSCs attachment in GC-40 CS. The Alamar Blue assay indicated an increased proliferation and viability of seeded hBMSCs in all groups on day 21 as compared with day 0. The hBMSCs seeded in GC-40 CS indicated osteogenic differentiation based on an amplified alkaline-phosphatase release on day 7 and 14 as compared with day 0. These cells supported bone mineralization on GC-40 CS based on Alizarin-Red assay on day 21 as compared with day 7 and increased their osteogenic gene expression (RUNX2, ALP, BGLAP, BMP, and Osteonectin) on day 21. The GC-40 CS-seeded hBMSCs initiated their osteogenic differentiation on day 7 as compared with counterparts based on an increased expression of type-1 collagen and BMP2 in immunocytochemistry analysis. In conclusion, the incorporation of 40% (w/w) calcium silicate in gellan-chitosan showed osteoinduction potential in hBMSCs, making it a potential biomaterial to treat critical bone defects.

Unleashing frugal innovation in private higher education institutions via intellectual capital and Information technology capability: a systematic literature review.

Background: Given the persistent challenges to the higher education business model, private higher education institutions (PHEIs) are exploring myriad ways to increase enrolment and income, while aggressively managing spending. Many PHEIs are facing financial distress and struggling because of decreasing budgets and declining revenue. Thus, carving unique strategies that direct the institution to focus on its core competencies, making additional budget cuts without compromising quality, developing new revenue streams, embracing new technology, and offering affordable programs, will ultimately lead to financial success. Frugal innovation (FI) can shed light on these challenges. Methods: This paper presents a systematic literature review to investigate and analyse prior research that focused on FI within the sphere of intellectual capital (IC) and information technology capabilities (ITC) research, and their relationships in PHEIs. Transfield's five phases were employed to extract journal articles published over a thirty-year period (1990 to 2020) from major online databases using keyword searches. Although an initial search generated 76,025 papers, the search for IC and FI yielded 41 papers, and finally only two papers were selected as they clearly related IC with FI. Results: There was a research gap in the literature published from 1990 to 2020 regarding IC applications to achieve FI. This work revealed that IC and ITC research for FI in PHEI remain insufficiently explored.   Conclusions: Further research is required on the evaluation model of IC, ITC and FI, methodologies, empirical analysis, and the development of measurement metrics. A limitation to this study is the number of keywords selected.

Enhancing innovative delivery in schools using design thinking.

The pandemic has created challenges in all sectors of the economy and education. Traditional teaching approaches seem futile in the new context, thus the need to constantly reinvent the delivery to meet the fast-paced changes in the education domain. Hence, Design Thinking (DT) is an alternative approach that might be useful in the given context. DT is known to be a human-centric approach to innovative problem-solving processes. DT could be employed in the delivery process to develop twenty-first-century skills and enhance creativity and innovation, in an attempt to identify alternative solutions. The study explores the role of design thinking (DT) in the form of empathy, thinking process, gamified lessons and curriculum enhancement, which leads to innovative delivery among teachers. It enhances and facilitates innovative content delivery by leveraging creativity. The study targeted 131 teachers, whereby 61 are primary school teachers and 70 are secondary school teachers. A questionnaire constituting of 23 close-ended questions using the 5-point Likert scale was used to collect data. Data was analyzed using SmartPLS to establish relationships between DT and Innovative Delivery in schools. The data was further analyzed to seek co-relations between the DT steps and the successful transformation of content delivery by teachers. The study established a framework for the application of design thinking for teachers as the primary support in developing activities for their students. The study showed that thinking process, gamifying lessons and curriculum enhancement have positive significance in innovative delivery, whereas empathy did not show a significant positive relationship. The outcome of this study will help fill the gap towards creating an interesting method of delivery in schools and constantly innovating the method to suit the evolving generation. This insight is crucial for the Ministry of Education and policymakers to enhance teachers' ability to innovatively deliver content to students.

A comparative study on in vitro osteogenic priming potential of electron spun scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for tissue engineering application.

A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds.

Knowledge management systems in support of disasters management: A two decade review.

Humans are increasingly being challenged with numerous forms of man-made and natural emergency situations. Emergencies cannot be prevented, but they can be better managed. The successful management of emergency situations requires proper planning, guided response, and well-coordinated efforts across the emergency management life cycle. Literature suggests that emergency management efforts benefit from well-integrated knowledge-based emergency management information systems (EMIS). This study presents a systematic review of papers pertaining to the application of knowledge-driven systems in support of emergency management that have been published in the last two decades. Our review presents two major findings. First, only limited work has been done in three EMIS-knowledge management system (KMS) subdomains: (i) definition, (ii) use, and (iii) methods. Second, only limited research has been done in embedding roles in KM systems. We highlight role alignment to the 12 fundamental roles, as called for by Turoff et al. (2004), in the context of creating dynamic systems in aid of emergency management efforts. We believe that these two findings warrant the attention of the research community.

Disaster preparedness: an investigation on motivation and barriers.

This article presents a preliminary investigation on the motivations for and the barriers that hinder preparedness toward disasters in a community. Survey questionnaires were distributed to local individuals in the nine districts of Selangor state in Malaysia. A total of 402 usable questionnaires were analyzed. The initial findings revealed that community members are motivated for disaster preparedness mainly for family safety reason. However, generally they do not know how to be prepared. This article concludes by highlighting the importance of knowledge and information in community preparedness. This research is limited to one state in Malaysia. However, the chosen state has a large effect on the Malaysian gross domestic product; hence, lack of preparedness poses a critical risk to its large population. This study on motivation and barriers for disaster preparedness is intended to increase the effectiveness of community readiness as a whole toward major disasters such as landslide and flood. The result of this study is valuable to the scientific community within the disaster management domain, the government agencies for policy and strategy formulations, and the local community to preempt, deal with, and ultimately survive disasters. This research aims to ensure that the community is continuously prepared and able to meet the evolving needs of the individual citizen as the nation strives toward promoting a knowledgeable society.

Mechanical and functional assessment of the wrist affected by rheumatoid arthritis: A finite element analysis.

Understanding the pathomechanics involved in rheumatoid arthritis (RA) of the wrist provides valuable information, which will invariably allow various therapeutic possibilities to be explored. The computational modelling of this disease permits the appropriate simulation to be conducted seamlessly. A study that underpins the fundamental concept that produces the biomechanical changes in a rheumatoid wrist was thus conducted through the use of finite element method. The RA model was constructed from computed tomography datasets, taking into account three major characteristics: synovial proliferation, cartilage destruction and ligamentous laxity. As control, a healthy wrist joint model was developed in parallel and compared. Cartilage was modelled based on the shape of the articulation while the ligaments were modelled with linear spring elements. A load-controlled analysis was performed simulating physiological hand grip loading conditions. The results demonstrated that the diseased model produced abnormal wrist extension and stress distribution as compared to the healthy wrist model. Due to the weakening of the ligaments, destruction of the cartilage and lower bone density, the altered biomechanical stresses were particularly evident at the radioscaphoid and capitolunate articulations which correlate to clinical findings. These results demonstrate the robust finding of the developed RA wrist model, which accurately predicted the pathological process.