Rapid model-guided design of organ-scale synthetic vasculature for biomanufacturing

Our ability to produce human-scale bio-manufactured organs is critically limited by the need for vascularization and perfusion. For tissues of variable size and shape, including arbitrarily complex geometries, designing and printing vasculature capable of adequate perfusion has posed a major hurdle. Here, we introduce a model-driven design pipeline combining accelerated optimization methods for fast synthetic vascular tree generation and computational hemodynamics models. We demonstrate rapid generation, simulation, and 3D printing of synthetic vasculature in complex geometries, from small tissue constructs to organ scale networks. We introduce key algorithmic advances that all together accelerate synthetic vascular generation by more than 230-fold compared to standard methods and enable their use in arbitrarily complex shapes through localized implicit functions. Furthermore, we provide techniques for joining vascular trees into watertight networks suitable for hemodynamic CFD and 3D fabrication. We demonstrate that organ-scale vascular network models can be generated in silico within minutes and can be used to perfuse engineered and anatomic models including a bioreactor, annulus, bi-ventricular heart, and gyrus. We further show that this flexible pipeline can be applied to two common modes of bioprinting with free-form reversible embedding of suspended hydrogels and writing into soft matter. Our synthetic vascular tree generation pipeline enables rapid, scalable vascular model generation and fluid analysis for bio-manufactured tissues necessary for future scale up and production.Comment: 58 pages (19 main and 39 supplement pages), 4 main figures, 9 supplement figure

Review of the mathematical foundations of data fusion techniques in surface metrology

The recent proliferation of engineered surfaces, including freeform and structured surfaces, is challenging current metrology techniques. Measurement using multiple sensors has been proposed to achieve enhanced benefits, mainly in terms of spatial frequency bandwidth, which a single sensor cannot provide. When using data from different sensors, a process of data fusion is required and there is much active research in this area. In this paper, current data fusion methods and applications are reviewed, with a focus on the mathematical foundations of the subject. Common research questions in the fusion of surface metrology data are raised and potential fusion algorithms are discussed

3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries

Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the Finite Element Method. In this paper, we describe the use of our recently rewritten mesh processing software, GAMer 2, to bridge the gap between poorly conditioned meshes generated from segmented micrographs and boundary marked tetrahedral meshes which are compatible with simulation. We demonstrate the application of a workflow using GAMer 2 to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and show that the resulting meshes are suitable for finite element simulations. This work is an important step towards making physical simulations of biological processes in realistic geometries routine. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery at the interface of geometry and cellular processes. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open.Comment: 39 pages, 14 figures. High resolution figures and supplemental movies available upon reques

Topological and geometric inference of data

The overarching problem under consideration is to determine the structure of the subspace on which a distribution is supported, given only a finite noisy sample thereof. The special case in which the subspace is an embedded manifold is given particular attention owing to its conceptual elegance, and asymptotic bounds are obtained on the admissible level of noise such that the manifold can be recovered up to homotopy equivalence. Attention is turned on how to accomplish this in practice. Following ideas from topological data analysis, simplicial complexes are used as discrete analogues of spaces suitable for computation. By utilising the prior assumption that the data lie on a manifold, topologically inspired techniques are proposed for refining the simplicial complex to better approximate this manifold. This is applied to the problem of nonlinear dimensionality reduction and found to improve accuracy of reconstructing several synthetic and real-world datasets. The second chapter focuses on extending this work to the case where the ambient space is non-Euclidean. The interfaces between topological data analysis, functional data analysis, and shape analysis are thoroughly explored. Lipschitz bounds are proved which relate several metrics on the space of positive semidefinite matrices; they are then interpreted in the context of topological data analysis. This is applied to diffusion tensor imaging and phonology. The final chapter explores the case where the points are non-uniformly distributed over the embedded subspace. In particular, a method is proposed to overcome the shortcomings of witness complex construction when there are large deviations in the density. The theory of multidimensional persistence is leveraged to provide a succinct setting in which the structure of the data can be interpreted as a generalised stratified space.EPSR