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      Inspired by Nature: Hydrogels as Versatile Tools for Vascular Engineering

      1 , 2 , 1
      Advances in Wound Care
      Mary Ann Liebert Inc

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          Abstract

          <p class="first" id="d10827931e176"> <b>Significance:</b> Diseases related to vascular malfunction, hyper-vascularization, or lack of vascularization are among the leading causes of morbidity and mortality. Engineered, vascularized tissues as well as angiogenic growth factor-releasing hydrogels could replace defective tissues. Further, treatments and testing of novel vascular therapeutics will benefit significantly from models that allow for the study of vascularized tissues under physiological relevant <i>in vitro</i> conditions. </p><p id="d10827931e184"> <b>Recent Advances:</b> Inspired by fibrin, the provisional matrix during wound healing, naturally derived and synthetic hydrogel scaffolds have been developed for vascular engineering. Today, engineers and biologists use commercially available hydrogels to pre-vascularize tissues, to control the delivery of angiogenic growth factors, and to establish vascular diseases models. </p><p id="d10827931e189"> <b>Critical Issue:</b> For clinical translation, pre-vascularized tissue constructs must be sufficiently large and stable to substitute function-relevant tissue defects and integrate with host vascular perfusion. Moreover, the continuous integration of knowhow from basic vascular biology with innovative, tailorable materials and advanced manufacturing technologies is key to achieving near-physiological tissue models and new treatments to control vascularization. </p><p id="d10827931e194"> <b>Future Directions:</b> For transplantation, engineered tissues must comprise hierarchically organized vascular trees of different caliber and function. The development of novel vascularization-promoting or -inhibiting therapeutics will benefit from physiologically relevant vessel models. In addition, tissue models representing treatment-relevant vascular tissue functions will increase the capacity to screen for therapeutic compounds and will significantly reduce the need for animals for their validation. </p>

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          Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology

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            Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.

            The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.
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              Three-dimensional bioprinting of thick vascularized tissues.

              The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.
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                Author and article information

                Journal
                Advances in Wound Care
                Advances in Wound Care
                Mary Ann Liebert Inc
                2162-1918
                2162-1934
                July 2018
                July 2018
                : 7
                : 7
                : 232-246
                Affiliations
                [1 ]Department of Obstetrics, University and University Hospital Zurich, Zurich, Switzerland.
                [2 ]Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
                Article
                10.1089/wound.2017.0760
                6032659
                29984113
                973a6958-0d7b-4cde-bd4b-c9afe4a01f03
                © 2018

                http://www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/

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