Self-reporting scaffolds for in situ monitoring for regenerative medicine and tissue engineering applications

This thesis describes the development and utilisation of a self-reporting scaffold to improve current monitoring methods of the cellular microenvironment. In vitro tissue models hold a lot of promise for regenerative medicine and tissue engineering. However, many models lack the ability to non-invasively monitor in situ cellular responses in a physiologically relevant environment. By development of electrospun self-reporting scaffolds and incorporation of flow culture conditions, this limitation can be overcome. Electrospun matrices have been shown to mimic the structural architecture of the native extracellular matrix, whilst flow conditions have been shown to regulate cellular processes, and enhance mass transport and nutrient exchange throughout polymeric scaffolds. Here we show the development of optically transparent self-reporting electrospun scaffolds that incorporate ratiometric pH-sensitive nanosensors and respond to biological and mechanical cues of the native extracellular matrix through exposure to shear stress. Optically transparent self-reporting scaffolds were fabricated by directly electrospinning pH responsive, ratiometric nanosensors within a gelatin biopolymer matrix. The sensors consist of a porous polyacrylamide matrix which encapsulates pH-sensitive fluorophores that exhibit an additive fluorescent response across the full physiological range between pH 3-8, and a pH-insensitive reference fluorophore. The self-reporting scaffold was able to support cell growth whilst being able to simultaneously monitor local pH changes in real time. A Quasi-Vivo® bioreactor system was also used to generate a flow of cell culture medium and expose cell-seeded scaffolds to a continual shear stress. This novel diagnostic scaffold and the use of flow conditions can help simulate enhance the understanding of in vitro conditions, and generate advanced simulations in vivo to facilitate tissue engineering and regenerative medicine applications

New generation of bioreactors that advance extracellular matrix modelling and tissue engineering

Bioreactors hold a lot of promise for tissue engineering and regenerative medicine applications. They have multiple uses including cell cultivation for therapeutic production and for in vitro organ modelling to provide a more physiologically relevant environment for cultures compared to conventional static conditions. Bioreactors are often used in combination with scaffolds as the nutrient flow can enhance oxygen and diffusion throughout the 3D constructs to prevent the formation of necrotic cores. A variety of scaffolds have been fabricated to achieve a structural architecture that mimic native extracellular matrix. Future developments of in vitro models will incorporate the ability to non-invasively monitor the cellular microenvironment to enhance the understanding of in vitro conditions. This review details current advancements in bioreactor and scaffold systems and provides insight on how in vitro models can be augmented for future biomedical applications

Self-reporting scaffolds for in situ monitoring for regenerative medicine and tissue engineering applications

This thesis describes the development and utilisation of a self-reporting scaffold to improve current monitoring methods of the cellular microenvironment. In vitro tissue models hold a lot of promise for regenerative medicine and tissue engineering. However, many models lack the ability to non-invasively monitor in situ cellular responses in a physiologically relevant environment. By development of electrospun self-reporting scaffolds and incorporation of flow culture conditions, this limitation can be overcome. Electrospun matrices have been shown to mimic the structural architecture of the native extracellular matrix, whilst flow conditions have been shown to regulate cellular processes, and enhance mass transport and nutrient exchange throughout polymeric scaffolds. Here we show the development of optically transparent self-reporting electrospun scaffolds that incorporate ratiometric pH-sensitive nanosensors and respond to biological and mechanical cues of the native extracellular matrix through exposure to shear stress. Optically transparent self-reporting scaffolds were fabricated by directly electrospinning pH responsive, ratiometric nanosensors within a gelatin biopolymer matrix. The sensors consist of a porous polyacrylamide matrix which encapsulates pH-sensitive fluorophores that exhibit an additive fluorescent response across the full physiological range between pH 3-8, and a pH-insensitive reference fluorophore. The self-reporting scaffold was able to support cell growth whilst being able to simultaneously monitor local pH changes in real time. A Quasi-Vivo® bioreactor system was also used to generate a flow of cell culture medium and expose cell-seeded scaffolds to a continual shear stress. This novel diagnostic scaffold and the use of flow conditions can help simulate enhance the understanding of in vitro conditions, and generate advanced simulations in vivo to facilitate tissue engineering and regenerative medicine applications

Rise of Decentralised Finance | Reimagining Financial Regulation

Based on decentralised ledger technology (DLT), decentralised finance (DeFi) involves the provision of financial services without reliance on centralised intermediaries (such as banks). While DeFi seeks to complement existing financial services, its reliance on crypto asset speculation and arbitrage coupled with instances of security, operational and governance failures, may pose risks to consumers and the financial system. Therefore, the proliferation of such markets without any regulatory oversight requires immediate consideration. While existing literature focuses on the innovation potential of DeFi, there is little discussion about the legal implications of DeFi. This article seeks to address this gap in the literature and recommends possible regulatory approaches. The article highlights that DeFi will challenge traditional financial regulations designed for centralised systems where identifying the subject of regulatory obligations is straightforward. Further, participants in a DeFi system can be spread across multiple jurisdictions, challenging the determination of the relevant jurisdiction whose law will apply. As the DeFi market is still evolving, this article argues that regulatory focus must be on specific aspects. This includes regulatory clarity for cryptoassets, regulating gatekeepers of the DeFi ecosystem i.e., service providers (like exchanges, wallets, custodians), and issuance of regulatory guidance on the applicability of existing laws to DLT systems. These regulatory approaches must be supplemented with measures such as designing internationally well-recognised standards for DeFi services, harnessing technology (“Regtech” and “Suptech”) for better supervision and compliance and leveraging existing regulatory sandboxes for a cost-benefit analysis of such innovations and determining regulatory responses

Plausible role of Arq Ajīb in combating COVID-19: A multi-faceted review

The current pandemic caused by SARS-CoV-2 has led to a massive change in every aspect of our lives. It has grossly affected the healthcare system, business and world trade, disruption of movement and supply of essential goods and has crippled the global economy. Although few vaccines have been approved for the control of disease, targeted therapy options for this virulent disease still remain limited and elusive. Exhaustive search for potent therapeutic candidate is in progress, for which herbal armory are also being explored. Medicinal plants and their products play a vital role in alleviating various diseases and have been reported to exhibit a wide range of biological activities. Plant-based drugs with antiviral, anti-inflammatory and immunomodulotry activities were hypothetically considered as potential drugs to prevent and mitigate the prevailing situation caused by SARS-CoV-2. Arq Ajīb ‘a Unani formulation’ presents compelling approach in treating numerous diseases. The ingredients of Arq Ajīb and their phytocompounds have been reported for wide-ranging pharmaco-biological activities including antiviral, anti-inflammatory, immunomodulotry, anti-allergic, antitussive and bronchodilatory activities. Scientific data available on the formulation ingredients and their phytocompounds indicates that the formulation may have a significant role in augmenting the immune status of individual, protecting them from infection and providing symptomatic relief to patients affected with COVID-19. Hence, it may be considered as a potential drug for the development of novel therapeutic candidate for SARS-CoV-2 infection. This multi-faceted review highlights the therapeutic significance and pharmacological actions of Arq Ajīb and its ingredients to demonstrate the plausible role of the formulation in combating COVID-19. Keywords: Arq Ajīb, COVID-19, Pudina, Ajwain, Camphor, Unani formulatio

Entrepreneurial competencies and SMEs’ growth: the mediating role of network competence

Purpose The purpose of this paper is twofold. First, to examine the influence of two dimensions of entrepreneurial competencies, namely, strategic competency and ethical competency on the growth of small and medium enterprises (SMEs); and second, to explore the role of network competence as a mediator among these understudied variables. Design/methodology/approach: The data for this study were collected from wholesale and retail-based SMEs in Malaysia through a standard structured questionnaire. PLS–SEM approach was utilised to analyse the data. Findings: Although the findings did not reveal a direct effect of strategic and ethical competencies of entrepreneurs on SMEs’ growth, these competences, however, were found to be influential in driving their growth when network competence was used as a mediator. Originality/value: The existence of a mediation effect between strategic and ethical competencies and SMEs’ growth via network competence has provided insights which add new knowledge to the extant entrepreneurship and SMEs’ performance literature

Composition-based view of the firm as a promising approach to studying small businesses

Paper aims Extant Literature based on the resource-based view (RBV) of the firm suggests that it can be used to study organizations of all types and sizes. In essence, the RBV argues that firms that possess rare, non-imitable, valuable, unique, and non-substitutable resources will outperform firms that do not possess such resources. This study questions the applicability of this assumption to smaller businesses, which are likely to have common resources readily available in the market rather than rare, non-imitable, non-substitutable, unique, or valuable resources. The purpose of this study is to discuss whether the composition-based view (CBV) of the firm offers a more promising approach than the RBV to studying small businesses. Originality This study is one of the first to tentatively suggest a change in theoretical approach when studying small businesses. Research method A structured critical review approach is taken. Main findings The findings reveal that the CBV offers a more promising and appropriate theoretical framework than the RBV for research on small businesses, whereas the RBV is better suited to research on larger firms. Implications for theory and practice Future studies can use RBV and CBV to study large and small businesses, respectively.Systematic review</p

Inclusive and equitable language for skin colour in the British Journal of Dermatology: acknowledging our past and laying the foundations to move forward

The field of dermatology must recognize that the language we use to describe skin colour has been profoundly affected by misconstruction and misattribution of skin colour naming with human group names, phenotype, phototype and Western racialization. The use of one term for a ‘race’ of people is an abnegation of the past 150 years of scientific progress.1 Skin colour nomenclature is a field of rapidly evolving research driven by multiple disciplines, in particular anthropology. While there is understandable urgency that cannot be ignored, it is important to avoid creating a multitude of new scales or terms that might add to the confusion. With the BJD’s commitment to global health and equity, we must acknowledge this challenge. A 2022 publication in the BJD by Singh et al. states, ‘As the sociomedical drivers of dermatological racial health disparities are increasingly discussed, morphological fluency must be met with fluency in cultural safety and anti-oppression.’2 Since its publication there has been further recognition of the issue from national academies, additional publications and meetings. We in the skin biology and dermatology community need to recognize that many skin colour terms still in use are pejorative, racist and ambiguous. Outdated, confusing terms prevent clarity and undermine the accuracy of dermatological research

Effectiveness and survival of methotrexate versus adalimumab in patients with moderate-to-severe psoriasis: a cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

BackgroundMost information on the comparative effectiveness and survival of methotrexate (MTX) and adalimumab (ADA) in the treatment of psoriasis is from randomized control trials and may not translate to the everyday clinical setting.ObjectivesTo determine the real-world effectiveness and survival of MTX and ADA in patients with moderate-to-severe psoriasis registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).MethodsEligible patients were registered in BADBIR, ≥ 16 years of age and receiving a first course of MTX or ADA between September 2007 and December 2021, with ≥ 6 months of follow-up. Effectiveness was defined as achieving an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 reported ≥ 13 weeks after the treatment start date until the stop date. The average treatment effect (ATE) was estimated using inverse probability of treatment weighting with propensity score, including baseline covariates. ATE results were presented as risk ratios (RR). A flexible parametric model was used to estimate adjusted standardized average survival, defined as treatment discontinuation associated with ineffectiveness or the occurrence of adverse events (AEs) at 6, 12 and 24 months. Restricted mean survival time (RMST) at 2 years of treatment exposure was calculated.ResultsIn total, 6575 patients (median age 44 years; 44% female) were analysed; 2659 (40.4%) were prescribed MTX and 3916 (59.5%) ADA. The proportion of patients achieving PASI ≤ 2 was higher in the ADA cohort (77.4%) than in the MTX cohort (37.4%). ADA was more effective than MTX [RR 2.20, 95% confidence interval (CI) 1.98–2.45]. Overall survival associated with ineffectiveness or AEs was lower in the MTX cohort than in the ADA cohort at 6 months [survival estimate 69.7 (95% CI 67.9–71.5) vs. 90.6 (95% CI 89.8–91.4)], 1 year [survival estimate 52.5 (95% CI 50.4–54.8) vs. 80.6 (95% CI 79.5–81.8)] and 2 years [survival estimate 34.8 (95% CI 32.5–37.2) vs. 68.6 (95% CI 67.2–70.0)]. The difference in RMST (years) overall, or when stratified by ineffectiveness and AEs, was 0.53 (95% CI 0.49–0.58), 0.37 (95% CI 0.33–0.42) and 0.29 (95% CI 0.25–0.33), respectively.ConclusionsPatients on ADA were twice as likely to be clear or nearly clear of psoriasis and were less likely to discontinue their medication than patients on MTX. Findings from this real-world cohort provide important information to aid clinicians managing patients with psoriasis