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1. Characterization of Bioengineered Tissues by Digital Holographic Vibrometry and 3D Shape Deep Learning

   https://doi.org/10.1007/978-3-031-17471-1_10  

   Hiscox, C.; Li, J.; Gao, Z.; Korkin, D.; Furlong, C.; Billiar, K. (July 2023, 2022 Conference Proceedings of the Society for Experimental Mechanics Series)

   Lin, MT.; Furlong, C.; Hwang, CH.; Naraghi, M.; DelRio, F. (Ed.)

   Tissue engineering is an active field and one of its aims is to produce tissues to repair the human body. The Advanced Regenerative Medicine Initiative (ARMI) currently seeks to help increase the manufacturability of tissue engineering products (TEMPs). One of the critical components of large-scale manufacturing is the sensing of information for quality control and critical feedback of tissue growth patterns. Modern sensors that provide information about physical qualities of tissues, however, are invasive or destructive. The goal of this project is to develop noninvasive methodologies to measure the mechanical properties of TEMPs. Our approach is to utilize acoustic waves to induce nano-scale level vibrations in the enginineered tissues in which corresponding displacements are measured in full-field with quantitative optical techniques. In our work, a digital holographic system images the tissue’s vibration at significant modes and provides the displacement patterns of the tissue at various points along the sinusoidal excitation curve. These data are applied to a neural network to compare the experimental vibrational modes to the ones obtained by FEA simulation to estimate the physical properties of the tissue. This methodology has the promise of yielding critical control parameters that would allow technicians to noninvasively and consistently determine when samples are ready to be packaged or if their growth deviates from expected time frames or if there are defects in the tissue. It is expected that this approach will streamline several components of the quality control and production process. 

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2. Wireless Magnetic Robot for Precise Hierarchical Control of Tissue Deformation

   https://doi.org/10.1002/advs.202308619  

   Wang, Chao; Zhao, Zhi; Han, Joonsu; Sharma, Arvin_Ardebili; Wang, Hua; Zhang, Xiaojia_Shelly (July 2024, Advanced Science)

   Abstract Mechanotherapy has emerged as a promising treatment for tissue injury. However, existing robots for mechanotherapy are often designed on intuition, lack remote and wireless control, and have limited motion modes. Herein, through topology optimization and hybrid fabrication, wireless magneto‐active soft robots are created that can achieve various modes of programmatic deformations under remote magnetic actuation and apply mechanical forces to tissues in a precise and predictable manner. These soft robots can quickly and wirelessly deform under magnetic actuation and are able to deliver compressing, stretching, shearing, and multimodal forces to the surrounding tissues. The design framework considers the hierarchical tissue‐robot interaction and, therefore, can design customized soft robots for different types of tissues with varied mechanical properties. It is shown that these customized robots with different programmable motions can induce precise deformations of porcine muscle, liver, and heart tissues with excellent durability. The soft robots, the underlying design principles, and the fabrication approach provide a new avenue for developing next‐generation mechanotherapy. 

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3. Stem Cell Based Approaches to Modulate the Matrix Milieu in Vascular Disorders

   https://doi.org/10.3389/fcvm.2022.879977  

   S, Sajeesh; Dahal, Shataakshi; Bastola, Suraj; Dayal, Simran; Yau, Jimmy; Ramamurthi, Anand (June 2022, Frontiers in Cardiovascular Medicine)

   The extracellular matrix (ECM) represents a complex and dynamic framework for cells, characterized by tissue-specific biophysical, mechanical, and biochemical properties. ECM components in vascular tissues provide structural support to vascular cells and modulate their function through interaction with specific cell-surface receptors. ECM–cell interactions, together with neurotransmitters, cytokines, hormones and mechanical forces imposed by blood flow, modulate the structural organization of the vascular wall. Changes in the ECM microenvironment, as in post-injury degradation or remodeling, lead to both altered tissue function and exacerbation of vascular pathologies. Regeneration and repair of the ECM are thus critical toward reinstating vascular homeostasis. The self-renewal and transdifferentiating potential of stem cells (SCs) into other cell lineages represents a potentially useful approach in regenerative medicine, and SC-based approaches hold great promise in the development of novel therapeutics toward ECM repair. Certain adult SCs, including mesenchymal stem cells (MSCs), possess a broader plasticity and differentiation potential, and thus represent a viable option for SC-based therapeutics. However, there are significant challenges to SC therapies including, but not limited to cell processing and scaleup, quality control, phenotypic integrity in a disease milieu in vivo , and inefficient delivery to the site of tissue injury. SC-derived or -inspired strategies as a putative surrogate for conventional cell therapy are thus gaining momentum. In this article, we review current knowledge on the patho-mechanistic roles of ECM components in common vascular disorders and the prospects of developing adult SC based/inspired therapies to modulate the vascular tissue environment and reinstate vessel homeostasis in these disorders. 

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4. Generation, Transmission, and Regulation of Mechanical Forces in Embryonic Morphogenesis

   https://doi.org/10.1002/smll.202103466  

   Sutlive, Joseph; Xiu, Haning; Chen, Yunfeng; Gou, Kun; Xiong, Fengzhu; Guo, Ming; Chen, Zi (November 2021, Small)

   Abstract Embryonic morphogenesis is a biological process which depicts shape forming of tissues and organs during development. Unveiling the roles of mechanical forces generated, transmitted, and regulated in cells and tissues through these processes is key to understanding the biophysical mechanisms governing morphogenesis. To this end, it is imperative to measure, simulate, and predict the regulation and control of these mechanical forces during morphogenesis. This article aims to provide a comprehensive review of the recent advances on mechanical properties of cells and tissues, generation of mechanical forces in cells and tissues, the transmission processes of these generated forces during cells and tissues, the tools and methods used to measure and predict these mechanical forces in vivo, in vitro, or in silico, and to better understand the corresponding regulation and control of generated forces. Understanding the biomechanics and mechanobiology of morphogenesis will not only shed light on the fundamental physical mechanisms underlying these concerted biological processes during normal development, but also uncover new information that will benefit biomedical research in preventing and treating congenital defects or tissue engineering and regeneration. 

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5. MICROMECHANICAL MODEL OF MECHANOSENSITIVE COLLAGEN TISSUES

   Younger, Kalyn G; Cortes, William; Reich, Daniel H; Nguyen, Thao D (June 2022, Summer Biomechanics, Bioengineering and Biotransport Conference)

   The mechanical behavior of soft collagenous tissues is largely influenced by the reinforcing collagen fiber microstructure. The anisotropic collagen microstructure can remodel in response to changes in mechanical loading, which can dramatically alter the mechanical properties of the tissues and the mechanical environment of the resident cells. It is important to study the remodeling mechanisms of collagen tissues to understand the pathophysiology of various connective tissue diseases. We hypothesize that the collagen structure actively changes in response to mechanical stimuli through concurrent processes of collagen deposition and degradation and that the rates of these processes are altered by collagen mechanochemistry, mechanosensitive collagen production, and cellular contraction. In prior studies, we developed micromechanical models of collagen tissues to investigate the role of collagen mechanochemistry and mechanosensitive collagen production in remodeling the collagen fiber structure and tissue growth.[1,2] We found that stress inhibition of enzymatic degradation and stimulation of collagen production can explain many phenomena, including remodeling the anisotropic collagen structure along the directions of the maximum principal stress and the development of stress homeostasis. The goal of this study is to investigate the effect of mechanical loading on the active behavior of the cells. Our approach uses a model 3D microtissue systems, self-assembled on a magnetically actuated two-pillar system (µTUG), to investigate these cell-collagen interactions and effects of mechanical loading. The micropillar support allows for measurement of the active cellular contraction, while the magnetic tweezer allows for mechanical testing of the microtissue under a controlled stress rate. Digital image analysis is applied to measure the local two-dimensional (2D) strain field. To analyze the mechanical measurements for mechanical properties of the collagen structure and active behavior of the cells, we developed a micromechanical model for the mechanical behavior of the microtissue. The micromechanical model includes the elastic behavior of the anisotropic collagen structure and the anisotropic active behavior of the cells. To describe mechanosensitive cellular contraction, we assume concurrent polymerization/depolymerization of actin filaments, where the polymerization rate increases with the fiber stress. In this paper, we will briefly summarize the model and describe an initial model validation by comparing to µTUG experiments measuring the stress-strain behavior of the microtissue to load-unload tests. 

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