Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries.

Millions of people worldwide are affected by peripheral nerve injuries (PNI), involving billions of dollars in healthcare costs. Common outcomes for patients include paralysis and loss of sensation, often leading to lifelong pain and disability. Engineered Neural Tissue (EngNT) is being developed as an alternative to the current treatments for large-gap PNIs that show underwhelming functional recovery in many cases. EngNT repair constructs are composed of a stabilised hydrogel cylinder, surrounded by a sheath of material, to mimic the properties of nerve tissue. The technology also enables the spatial seeding of therapeutic cells in the hydrogel to promote nerve regeneration. The identification of mechanisms leading to maximal nerve regeneration and to functional recovery is a central challenge in the design of EngNT repair constructs. Using in vivo experiments in isolation is costly and time-consuming, offering a limited insight on the mechanisms underlying the performance of a given repair construct. To bridge this gap, we derive a cell-solute model and apply it to the case of EngNT repair constructs seeded with therapeutic cells which produce vascular endothelial growth factor (VEGF) under low oxygen conditions to promote vascularisation in the construct. The model comprises a set of coupled non-linear diffusion-reaction equations describing the evolving cell population along with its interactions with oxygen and VEGF fields during the first 24h after transplant into the nerve injury site. This model allows us to evaluate a wide range of repair construct designs (e.g. cell-seeding strategy, sheath material, culture conditions), the idea being that designs performing well over a short timescale could be shortlisted for in vivo trials. In particular, our results suggest that seeding cells beyond a certain density threshold is detrimental regardless of the situation considered, opening new avenues for future nerve tissue engineering.

Artificial intelligence and obesity management: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2023.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides clinicians an overview of Artificial Intelligence, focused on the management of patients with obesity. Methods: The perspectives of the authors were augmented by scientific support from published citations and integrated with information derived from search engines (i.e., Chrome by Google, Inc) and chatbots (i.e., Chat Generative Pretrained Transformer or Chat GPT). Results: Artificial Intelligence (AI) is the technologic acquisition of knowledge and skill by a nonhuman device, that after being initially programmed, has varying degrees of operations autonomous from direct human control, and that performs adaptive output tasks based upon data input learnings. AI has applications regarding medical research, medical practice, and applications relevant to the management of patients with obesity. Chatbots may be useful to obesity medicine clinicians as a source of clinical/scientific information, helpful in writings and publications, as well as beneficial in drafting office or institutional Policies and Procedures and Standard Operating Procedures. AI may facilitate interactive programming related to analyses of body composition imaging, behavior coaching, personal nutritional intervention & physical activity recommendations, predictive modeling to identify patients at risk for obesity-related complications, and aid clinicians in precision medicine. AI can enhance educational programming, such as personalized learning, virtual reality, and intelligent tutoring systems. AI may help augment in-person office operations and telemedicine (e.g., scheduling and remote monitoring of patients). Finally, AI may help identify patterns in datasets related to a medical practice or institution that may be used to assess population health and value-based care delivery (i.e., analytics related to electronic health records). Conclusions: AI is contributing to both an evolution and revolution in medical care, including the management of patients with obesity. Challenges of Artificial Intelligence include ethical and legal concerns (e.g., privacy and security), accuracy and reliability, and the potential perpetuation of pervasive systemic biases.

An integrated theoretical-experimental approach to accelerate translational tissue engineering.

Implantable devices utilizing bioengineered tissue are increasingly showing promise as viable clinical solutions. The design of bioengineered constructs is currently directed according to the results of experiments that are used to test a wide range of different combinations and spatial arrangements of biomaterials, cells and chemical factors. There is an outstanding need to accelerate the design process and reduce financial costs, whilst minimizing the required number of animal-based experiments. These aims could be achieved through the incorporation of mathematical modelling as a preliminary design tool. Here we focus on tissue-engineered constructs for peripheral nerve repair, which are designed to aid nerve and blood vessel growth and repair after peripheral nerve injury. We offer insight into the role that mathematical modelling can play within tissue engineering, and motivate the use of modelling as a tool capable of improving and accelerating the design of nerve repair constructs in particular. Specific case studies are presented in order to illustrate the potential of mathematical modelling to direct construct design. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Validation of Patient-Specific Cerebral Blood Flow Simulation Using Transcranial Doppler Measurements.

We present a validation study comparing results from a patient-specific lattice-Boltzmann simulation to transcranial Doppler (TCD) velocity measurements in four different planes of the middle cerebral artery (MCA). As part of the study, we compared simulations using a Newtonian and a Carreau-Yasuda rheology model. We also investigated the viability of using downscaled velocities to reduce the required resolution. Simulations with unscaled velocities predict the maximum flow velocity with an error of less than 9%, independent of the rheology model chosen. The accuracy of the simulation predictions worsens considerably when simulations are run at reduced velocity, as is for example the case when inflow velocities from healthy individuals are used on a vascular model of a stroke patient. Our results demonstrate the importance of using directly measured and patient-specific inflow velocities when simulating blood flow in MCAs. We conclude that localized TCD measurements together with predictive simulations can be used to obtain flow estimates with high fidelity over a larger region, and reduce the need for more invasive flow measurement procedures.

The counterbend dynamics of cross-linked filament bundles and flagella.

Cross-linked filament bundles, such as in cilia and flagella, are ubiquitous in biology. They are considered in textbooks as simple filaments with larger stiffness. Recent observations of flagellar counterbend, however, show that induction of curvature in one section of a passive flagellum instigates a compensatory counter-curvature elsewhere, exposing the intricate role of the diminutive cross-linking proteins at large scales. We show that this effect, a material property of the cross-linking mechanics, modifies the bundle dynamics and induces a bimodal L2 - L3 length-dependent material response that departs from the Euler-Bernoulli theory. Hence, the use of simpler theories to analyse experiments can result in paradoxical interpretations. Remarkably, the counterbend dynamics instigates counter-waves in opposition to driven oscillations in distant parts of the bundle, with potential impact on the regulation of flagellar bending waves. These results have a range of physical and biological applications, including the empirical disentanglement of material quantities via counterbend dynamics.