title: Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells.
abstract: Ideal material characteristics for tissue engineering or regenerative medicine approaches to volumetric muscle loss (VML) include the ability to deliver cells, growth factors, and molecules that support tissue formation from a system with a tunable degradation profile. Two different types of human hair-derived keratins were tested as options to fulfill these VML design requirements: (1) oxidatively extracted keratin (keratose) characterized by a lack of covalent crosslinking between cysteine residues, and (2) reductively extracted keratin (kerateine) characterized by disulfide crosslinks. Human skeletal muscle myoblasts cultured on coatings of both types of keratin had increased numbers of multinucleated cells compared to collagen or Matrigel(TM) and adhesion levels greater than collagen. Rheology showed elastic moduli from 10(2) to 10(5) Pa and viscous moduli from 10(1) to 10(4) Pa depending on gel concentration and keratin type. Kerateine and keratose showed differing rates of degradation due to the presence or absence of disulfide crosslinks, which likely contributed to observed differences in release profiles of several growth factors. In vivo testing in a subcutaneous mouse model showed that keratose hydrogels can be used to deliver mouse muscle progenitor cells and growth factors. Histological assessment showed minimal inflammatory responses and an increase in markers of muscle formation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 864-879, 2016.
authors.affiliation: KeraNetics, LLC, Winston-Salem, North Carolina, 27101.
authors.forename: Seth
authors.initials: S
authors.lastname: Tomblyn
authors.affiliation: KeraNetics, LLC, Winston-Salem, North Carolina, 27101.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Pettit Kneller
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, 27157.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Walker
authors.affiliation: KeraNetics, LLC, Winston-Salem, North Carolina, 27101.
authors.forename: Mary D
authors.initials: MD
authors.lastname: Ellenburg
authors.affiliation: Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, Virginia, 24061.|Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio, 45056.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Kowalczewski
authors.affiliation: Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Blacksburg, Virginia, 24061.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Dyke
authors.affiliation: KeraNetics, LLC, Winston-Salem, North Carolina, 27101.
authors.forename: Luke
authors.initials: L
authors.lastname: Burnett
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, Ohio, 45056.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Saul
mesh_terms: D016503:Drug Delivery Systems; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000494:pharmacology; D007633:Keratins / Q000737:chemistry / Q000494:pharmacology; D032446:Myoblasts / Q000145:classification / Q000378:metabolism*
chemical_list: D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; D007633:Keratins
keywords: controlled release; growth factor; hydrogel; regenerative medicine; tissue engineering