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      Poly(ethylene glycol)–Norbornene as a Photoclick Bioink for Digital Light Processing 3D Bioprinting

      1 , 2 , 1
      ACS Applied Materials & Interfaces
      American Chemical Society (ACS)

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          Abstract

          Digital light processing (DLP) bioprinting is an emerging technology for three-dimensional bioprinting (3DBP) owing to its high printing fidelity, fast fabrication speed, and higher printing resolution. Low-viscosity bioinks such as poly(ethylene glycol) diacrylate (PEGDA) are commonly used for DLP-based bioprinting. However, the cross-linking of PEGDA proceeds via chain-growth photopolymerization that displays significant heterogeneity in cross-linking density. In contrast, step-growth thiol-norbornene photopolymerization is not oxygen inhibited and produces hydrogels with an ideal network structure. The high cytocompatibility and rapid gelation of thiol-norbornene photopolymerization have lent itself to the cross-linking of cell-laden hydrogels but have not been extensively used for DLP bioprinting. In this study, we explored eight-arm PEG-norbornene (PEG8NB) as a bioink/resin for visible light-initiated DLP-based 3DBP. The PEG8NB-based DLP resin showed high printing fidelity and cytocompatibility even without the use of any bioactive motifs and high initial stiffness. In addition, we demonstrated the versatility of the PEGNB resin by printing solid structures as cell culture devices, hollow channels for endothelialization, and microwells for generating cell spheroids. This work not only expands the selection of bioinks for DLP-based 3DBP but also provides a platform for dynamic modification of the bioprinted constructs.

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          Multivascular networks and functional intravascular topologies within biocompatible hydrogels

          Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.
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            Progress in 3D bioprinting technology for tissue/organ regenerative engineering

            Escalating cases of organ shortage and donor scarcity worldwide are alarming reminders of the need for alternatives to allograft tissues. Within the last three decades, research efforts in the field of regenerative medicine and tissue engineering continue to address the unmet need for artificial tissues and organs for transplant. Work in the field has evolved to create what we consider a new field, Regenerative Engineering, defined as the Convergence of advanced materials science, stem cell science, physics, developmental biology and clinical translation towards the regeneration of complex tissues and organ systems. Included in the regenerative engineering paradigm is advanced manufacturing. Three-dimensional (3D) bioprinting is a promising and innovative biofabrication strategy to precisely position biologics, including living cells and extracellular matrix (ECM) components, in the prescribed 3D hierarchal organization to create artificial multi-cellular tissues/organs. In this review, we outline recent progress in several bioprinting technologies used to engineer scaffolds with requisite mechanical, structural, and biological complexity. We examine the process parameters affecting bioprinting and bioink-biomaterials and review notable studies on bioprinted skin, cardiac, bone, cartilage, liver, lung, neural, and pancreatic tissue. We also focus on other 3D bioprinting application areas including cancer research, drug testing, high-throughput screening (HTS), and organ-on-a-chip models. We also highlight the current challenges associated with the clinical translation of 3D bioprinting and conclude with the future perspective of bioprinting technology.
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              In vitro microvessels for the study of angiogenesis and thrombosis.

              Microvascular networks support metabolic activity and define microenvironmental conditions within tissues in health and pathology. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of complex vascular phenomena, including angiogenesis and thrombosis. We have engineered living microvascular networks in three-dimensional tissue scaffolds and demonstrated their biofunctionality in vitro. We describe the lithographic technique used to form endothelialized microfluidic vessels within a native collagen matrix; we characterize the morphology, mass transfer processes, and long-term stability of the endothelium; we elucidate the angiogenic activities of the endothelia and differential interactions with perivascular cells seeded in the collagen bulk; and we demonstrate the nonthrombotic nature of the vascular endothelium and its transition to a prothrombotic state during an inflammatory response. The success of these microvascular networks in recapitulating these phenomena points to the broad potential of this platform for the study of cardiovascular biology and pathophysiology.
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                Author and article information

                Contributors
                Journal
                ACS Applied Materials & Interfaces
                ACS Appl. Mater. Interfaces
                American Chemical Society (ACS)
                1944-8244
                1944-8252
                January 18 2023
                January 06 2023
                January 18 2023
                : 15
                : 2
                : 2737-2746
                Affiliations
                [1 ]Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202, United States
                [2 ]Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, United States
                Article
                10.1021/acsami.2c20098
                10279506
                36608274
                e7fdfa88-2f8e-446b-8a12-c152228f2cb8
                © 2023

                https://doi.org/10.15223/policy-029

                https://doi.org/10.15223/policy-037

                https://doi.org/10.15223/policy-045

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