title: An extracorporeal blood-cleansing device for sepsis therapy.
abstract: Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin--mannose-binding lectin (MBL)--that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. [2] Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, USA. [4].
authors.forename: Joo H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. [2].
authors.forename: Michael
authors.initials: M
authors.lastname: Super
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. [2] Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Chong Wing
authors.initials: CW
authors.lastname: Yung
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. [2] Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Harvard-MIT Health Sciences and Technology Graduate Program, Cambridge, Massachusetts, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Cooper
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Karel
authors.initials: K
authors.lastname: Domansky
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Graveline
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mammoto
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Berthet
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Tobin
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cartwright
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Watters
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. [2].
authors.forename: Martin
authors.initials: M
authors.lastname: Rottman
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Waterhouse
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mammoto
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Nazita
authors.initials: N
authors.lastname: Gamini
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Rodas
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Anxhela
authors.initials: A
authors.lastname: Kole
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Valentin
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: 1] Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. [2] Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D000818:Animals; D001187:Artificial Organs; D001698:Biomedical Engineering; D040761:Biomimetic Materials; D004731:Endotoxins / Q000097:blood / Q000302:isolation & purification; D004867:Equipment Design; D004926:Escherichia coli / Q000302:isolation & purification; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D006801:Humans; D008280:Magnetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D046210:Microfluidic Analytical Techniques; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000097:blood* / Q000382:microbiology / Q000628:therapy*; D013154:Spleen; D013211:Staphylococcus aureus / Q000302:isolation & purification
chemical_list: D004731:Endotoxins; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D009895:Opsonin Proteins