title: Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy.
abstract: BACKGROUND
  In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages.
  
  
  METHODS
  A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed ex vivo and on beating porcine hearts.
  
  
  RESULTS
  Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an ex vivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model.
  
  
  CONCLUSIONS
  A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Robotics Institute, Carnegie Mellon University, Pittsburgh, Pennsylvania.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Wood
authors.affiliation: The Robotics Institute, Carnegie Mellon University, Pittsburgh, Pennsylvania.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fok
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Tomo
authors.initials: T
authors.lastname: Yoshizumi
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Dae Woo
authors.initials: DW
authors.lastname: Park
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: David S
authors.initials: DS
authors.lastname: Schwartzman
authors.affiliation: Department of Surgery, Harvard University, Boston, Massachusetts.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Zenati
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Uchibori
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: wagnerwr@upmc.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
authors.affiliation: The Robotics Institute, Carnegie Mellon University, Pittsburgh, Pennsylvania.
authors.forename: Cameron N
authors.initials: CN
authors.lastname: Riviere
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D007267:Injections; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D011760:Pyrrolidinones; D012371:Robotics; D013552:Swine; D020257:Ventricular Remodeling
chemical_list: D001672:Biocompatible Materials; D011760:Pyrrolidinones; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C042670:N-vinyl-2-pyrrolidinone