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A study of bioprocess designs for development of the myogenic secretome as a source of bioactive extracellular vesicles
Get PDFThis thesis is submitted in partial fulfilment at the University of Wolverhampton for the degree of Doctor of Philosophy in Cell Biology.The human skeletal muscle myoblasts (HSMM) secretome decreases cytokine-induced inflammation in chondrocytes, indicating potential as therapy for arthritis. The lack of an efficient scalable workflow for the human skeletal myoblast secretome limits its development as a source of therapeutic biologics. Therefore, the principal objective of this study is to investigate approaches that could support manufacture of a bioactive human skeletal myoblast secretome at therapeutically relevant yields.
An upstream process for myogenic secreted EVs and proteins was optimised over 7-days. Analytics involved quantification of secretome yield and extracellular vesicle (EV) characterisation. Internalisation of myogenic EVs by human chondrocytes was investigated to examine bioactivity. Effects of EVs on matrix metalloproteinase-13 and nuclear factor-κB gene expression and EV ability to limit degradation of collagen II in tumour necrosis factor-α treated chondrocytes was also assessed. Potential mechanisms of action of HSMM secretome proteins were investigated by predicting their interactions with proteins involved in arthritis pathology using NetworkX, and the STRING database.
Myogenic secretome yields increased 2-fold on 75cm2 and 175cm2 surface areas compared to 25cm2 surface areas. The myogenic secretome yield on poly (lactic-co-glycolic) acid microcarriers was 3-fold greater than that produced on a 2D surface. The yield of EVs from 175cm2 and 75cm2 surface areas following SEC isolation were 4-fold and 2-fold greater respectively, compared to those achieved using precipitation. Particles within exosome size ranges (30-150 nm) were isolated at higher concentrations than microvesicle particles. Chondrocyte internalisation of 2D and 3D myogenic EVs possibly via phagocytosis, displayed heterogeneous EV distribution. The myogenic secretome may enhance collagen II expression and reduce NF-kB expression in chondrocytes. Protein - protein interaction (PPI) networks between secretome proteins and arthritis proteins were complex. Clustering using k-means demonstrated high proportions of highly weighted PPI scores, and key proteins with potential therapeutic bioactivities were identified using betweenness centrality. Taken together, this study is a basis for upstream and downstream processing of the human myogenic secretome demonstrating how this novel medicine modality may be applied as a therapeutic for arthritis.SIRC/ERD
Assessing data governance models for smart cities: Benchmarking data governance models on the basis of European urban requirements
No full text© 2025 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.scs.2025.106528Smart cities aim to improve residents’ quality of life by implementing effective services, infrastructure, and processes through information and communication technologies. However, without robust smart city data governance, much of the urban data potential remains underexploited, resulting in inefficiencies and missed opportunities for city administrations. This study addresses these challenges by establishing specific, actionable requirements for smart city data governance models, derived from expert interviews with representatives of 27 European cities. From these interviews, recurring themes emerged, such as the need for standardized data formats, clear data access guidelines, and stronger cross-departmental collaboration mechanisms. These requirements emphasize technology independence, flexibility to adapt across different urban contexts, and promoting a data-driven culture. By benchmarking existing data governance models against these newly established urban requirements, the study uncovers significant variations in their ability to address the complex, dynamic nature of smart city data systems. This study thus enhances the theoretical understanding of data governance in smart cities and provides municipal decision-makers with actionable insights for improving data governance strategies. In doing so, it directly supports the broader goals of sustainable urban development by helping improve the efficiency and effectiveness of smart city initiatives.Published versio
Speech enhancement using multisensory cooperative computing
No full textA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.This thesis investigates novel approaches for audio-visual speech enhancement (AVSE) through biologically inspired architectures, lightweight multimodal learning, and hybrid classical–deep frameworks. It advances three complementary
themes of the speech enhancement problem.
First, Multisensory Cooperative Computing (MCC) is introduced, a deep neural architecture inspired by the context-sensitive processing of two-point layer five pyramidal neurons (L5PCs). Unlike conventional point neuron models that indiscriminately process inputs, MCC adaptively filters and amplifies only contextually salient signals via a dendritic gating mechanism. Implemented on Xilinx Ultra- Scale+ MPSoC hardware, the system achieves substantial energy savings, up to 62% in semi-supervised settings and 1250× fewer energy demands per feedforward in supervised modes, by suppressing redundant synaptic activity. MCC establishes a paradigm for energy-efficient, high-capacity neuromorphic computing suited to real-time audio-visual learning.
Second, to address AVSE on resource-constrained edge devices and the challenges of real-world noise, a novel target mask, the Ideal Smoothed Mask (ISM), is proposed. ISM combines morphological and spectral filtering for robust speech separation. A transfer-learning fusion framework maps visual lip movements to speech representations with enhanced temporal modelling. Nonlinear transfer functions and a multi-objective loss incorporating mutual information strengthen cross-modal attention. The resulting system improves generalisation, reduces mask complexity, and supports real-time enhancement on constrained hardware.
Third, a lightweight AVSE framework is presented that merges classical spectral subtraction with visual speech detection. A CNN–LSTM module classifies short lip sequences into speech/no-speech labels to guide noise estimation and subtraction, overcoming the unreliability of audio-only voice activity detection (VAD) at low SNR. By isolating noise-only segments using robust lip-based cues,
the approach preserves the interpretability and efficiency of classical methods
while achieving substantial perceptual gains.
Collectively, these contributions provide a unified vision for context-aware, resource-efficient, and explainable speech enhancement, bridging deep learning with neuro-inspired design and practical deployment.EPSR
Lightweight associative memory AI models for bioacoustic event detection
No full textPaper presented at International Bioacoustics Congress (IBAC 2025), 7th-12th September 2025, Kerteminde, Denmark
Effects of paternal age and interaction with smoking, alcohol consumption and maternal age on implantation failure in women undergoing ART
No full text© 2025 The Authors, published by Springer Nature. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41598-025-03651-yIt remains unclear whether there is an independent association of paternal age with implantation failure (IF) in couples undergoing Assisted Reproductive Technology (ART) treatment. Little is known about the interactive effects of paternal age with maternal age, paternal smoking and alcohol consumption on IF. The Anhui Maternal-Child Health Cohort Study (AMCHS) interviewed 1910 infertile couples (paternal age ranged 22–57 years) to look for risk factors associated with IF. Implantation outcome was assessed using serum β-HCG between 0 and 25 IU/L 14 days post-embryo transfer. Odds ratios (ORs) for IF in relation to paternal age, and its interactions with maternal age, paternal smoking and alcohol consumption were evaluated using logistic regression models. The risk of IF (n = 735) increased with paternal age ≥ 35, while it remained similarly lower among males aged 22–34. After adjusting for socioeconomic status, paternal lifestyles and semen factors, the OR for IF was 1.50 (95%CI 1.16–1.93) at paternal age of 35- 30, paternal smoking or alcohol consumption, but not in their counterparts, respectively. Among those with a paternal age ≥ 35, each additional year of smoking was associated with a 7.0% increased risk of IF (OR = 1.07, 95% CI: 1.01–1.14); however, no such association was observed in younger paternal age groups. Significant interaction effects were observed between advanced paternal age and maternal age, as well as paternal alcohol consumption. The AMCHS had demonstrated that paternal age ≥ 35 years elevates the risk of IF, with additional impacts from advanced maternal age and paternal alcohol consumption. The findings of the AMCHS highlight the need to consider paternal and maternal ages in fertility planning and suggest that IF can be reduced by stopping paternal smoking and alcohol consumption.The National Key Research and Development Program of China Grant number: 2021YFC2700604.Accepted versio
Tailored performance of additively manufactured titanium TPMS bone scaffold
No full text© 2025 The Authors, published by Elsevier. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.bprint.2025.e00456Triply periodic minimal surfaces (TPMS), exemplified by the Schwarz geometry, provide an optimal platform for bone scaffolds due to their high surface-to-volume ratio, continuous porosity, and bone-analogous mechanical response. Here, titanium TPMS scaffolds were additively manufactured via laser powder bed fusion (L-PBF) with precise control over geometric parameters. A data-driven surrogate model, informed by experimental and numerical analyses, was developed to map the relationship between design variables and mechanical performance. The model enabled the design of scaffolds with tailored stiffness matching that of native bone, while revealing the dominant roles of wall thickness and cell size. Porosity varied from 47 % to 68 %, governed inversely by wall thickness, while elastic modulus scaled from 6 to 24 GPa, driven primarily by wall thickness and secondarily by cell size. Yield and ultimate strengths exhibited strong positive correlations with wall thickness, spanning 240–655 MPa and 320–784 MPa, respectively. This study provides a predictive framework for engineering 3D printed titanium scaffolds with targeted mechanical properties, offering a basis for next-generation load-bearing orthopaedic implants.Accepted versio
Consensus on the definition, components, timeframe and grading of composite outcome of postoperative pulmonary complication—protocol for an international mixed-method consensus study (PrECiSIOn)
No full textIntroduction Postoperative pulmonary complications (PPCs) represent a significant cause of postoperative morbidity and even mortality. However, there is a lack of consensus regarding this composite endpoint, the definition of the individual components, classification and optimal outcome measures. This study aims to refine the PPCs composite framework by evaluating its construct validity, assessing the necessity and risks of a composite measure and exploring the feasibility of differentiating severity categories. Methods A Delphi consensus process will be conducted, engaging an international multidisciplinary group of 30–40 panellists, including clinicians, researchers, patients, public representatives and health economists. Through iterative rounds, the study will seek agreement on the individual components of the PPCs composite. Additionally, consensus will establish a framework for a composite outcome measure based on a standardised severity classification, appropriate timeframes and weighted grading of PPCs. Analysis Consensus, defined by ≥75% concurrence in multiple choice questions or on Likert–scale statements, will be evaluated from round 2 onwards. Delphi rounds will be continued until all statements have reached stability of responses evaluated by χ2 tests or the Kruskal-Wallis test. Ethics and dissemination The study will be conducted in strict compliance with the principles of the Declaration of Helsinki and will adhere to ACCORD guidance for reporting. Ethics approval has been obtained for this study from the University of Wolverhampton, UK (SOABE/202425/staff/3). Informed consent will be obtained from all panellists before the commencement of the Delphi process. The results of the study will be published in a peer–reviewed journal with the authorship assigned in accordance with ICMJE requirements. Trial registration number NCT06916598 (clinicaltrials. gov).Published versio
Entrepreneurship education curriculum and entrepreneurial outcomes in the higher education sector: a Nigerian case study
No full textA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the Degree of Doctor of Philosophy.It is now known that Entrepreneurship Education (EE) not only develops and prepares students to be successful in owning and operating a business venture but also, if effectively provided, holistically develops students to master their environments, deal with the challenges and complexities of life, and other globalisation imperatives, fit well into society and the world of work, and be successful in all aspects of societal life. However, the experience in Nigeria with the compulsory EE programme has been a subject of debate. Research on EE phenomena in the country has continued to produce conflicting results, although the reality of the situation, as shown in the number of unemployed graduates and from the accounts of students, graduates, lecturers, employers, and other EE stakeholders, tend to suggest that the EE programme is poorly implemented and as a result, has failed to meet the intended goals of the programme. Unfortunately, no study appears to have been conducted that aims to unravel these questions by examining both the curriculum content and its delivery, as well as the impact thereof on the entrepreneurial outcomes of students and graduates, using a combination of three theoretical bases.
To bridge this gap in Nigeria’s EE research involved attempting to achieve the following three research objectives: To examine the nature of EE course curriculum content used by Higher Education Institutions (HEIs) in Nigeria; to examine the quality of delivery of the EE course content in Nigerian HEIs; to determine the nature of the impact of the course content of EE and its delivery in the Nigerian HEIs on the entrepreneurial outcomes of Undergraduates and Graduates. Towards achieving these objectives, the study utilised a tripartite theoretical framework – the constructivist, institutional, and human capital (HC) theories – to unravel the questions bordering on the nature of EE curriculum content, its delivery, and the impact of the curriculum content and its delivery systems on entrepreneurial outcomes of undergraduates and graduates of tertiary education institutions in Nigeria. Following the qualitative research tradition, qualitative data were collected through semi-structured interviews. Thirty-nine stakeholders of EE in Nigeria, including undergraduates, graduates, and lecturers, were selected through the purposive sampling method. Thematic analysis was adopted in the study.
The study revealed that the EE curriculum content has low utility value due to its focus on “education about” entrepreneurship rather than “education for” entrepreneurship. It is not aligned with the EE policy goals, nor with students’ levels of study. The curriculum content lacks validity because it is not aligned with students’ current and future career needs and competencies as it does not reflect differences in students’ disciplines as well as its outmoded and devoid-of-technology emphasis nature; the feasibility of the content delivery is impacted by a low quality of delivery and inhibited accessibility to the EE training; the combination of the content issues and the delivery shortcomings impacts negatively the achievement of students and graduates entrepreneurial skills, entrepreneurial self-efficacy, and internal locus of control. Beneficiaries of the compulsory EE programme in Nigerian HEIs, therefore, cannot produce graduates who can drive the economy through job creation, thereby enhancing the country’s human capital status.
A major contribution of this study to EE theory is the confirmation that the quality of EE curriculum content and its delivery is a pertinent factor that impacts graduates' and undergraduates’ propensity to develop entrepreneurial skills and other attributes such as self-efficacy and internal locus of control. Moreover, pertinent contextual factors identified in this study point to specific areas where action is required in Nigeria’s EE policy and its implementation, and this further contributes to enriching EE policy formulation and practice in the country. However, it is important to note that few instances exist where students' and graduates' experience in the programme are positively different, either because they attend private universities, they have wealthy parents who fill the gap where the authorities have failed, or they resort to self-help to participate in the EE training effectively. The implementation of the policy is therefore not uniform across the HEIs. Finally, the study opens windows of research opportunities, such as comparative studies of EE implementation in public versus private universities in Nigeria
Artificial intelligence in the construction sector: how can it improve talent management
No full textThis is an accepted manuscript of a conference paper presented at On the Border: Management Challenges, Business Opportunities and Disrupted Institutional Contexts. 39th British Academy of Management Conference, the 1-5th September 2026, Kent Business School, University of Kent, United Kingdom.
The accepted version of the publication may differ from the final published version.The construction industry is continually challenged due to the skills deficit throughout the sector. This is currently impacting numerous projects throughout the UK including the housing programme, HS2 and significant infrastructure upgrades. There is a reluctance to change to new and improved methods within the sector, however, Industry 4.0 technologies are essential to the built environment and offers improvements in many areas of the workplace. This paper discusses the benefits of artificial intelligence in the sector and the requirements for investment by the UK Government and businesses throughout the construction industry
Decarbonising the healthcare sector: a critical review
No full textStrategy-as-practice virtual paper session delivered at the 39th British Academy of Management Conference, 1st - 5th September 2025 at Kent Business School, University of Kent.It is an undeniable fact that the healthcare sector is vulnerable to climate change, but at the same time it is also a significant contributor. As a result of decarbonisation of the healthcare sector, the terms ‘climate change, net-zero carbon emission,’ and ‘renewable energy’ are used more frequently and often interchangeably. The research has noted that there is limited review available on the challenges the healthcare sector face in its effort to decarbonise. This implies that there have not been successful decarbonisation undertakings by many healthcare organisations. Therefore, in order to identify the challenges, the healthcare sector face in its effort to decarbonise, the healthcare sector must take aggressive step towards decarbonisation.
The novelty of this paper is stem from its synergistic combination of large-scale literature review analysis and systematic expert elicitation to meticulously examine the decarbonisation of the healthcare sector through a macro lens. The healthcare sector is known to have high energy consumption, due to complex building functions, continuous hours of operation, and high density of electrical equipment for diagnosis and treatment. After an attempt has been made to decarbonise the healthcare sector, the study has identified some challenges the healthcare could face in its attempt to decarbonise