title: Silk-hyaluronan-based composite hydrogels: a novel, securable vehicle for drug delivery.
abstract: A new, biocompatible hyaluronic acid (HA)-silk hydrogel composite was fabricated and tested for use as a securable drug delivery vehicle. The composite consisted of a hydrogel formed by cross-linking thiol-modified HA with poly(ethylene glycol)-diacrylate, within which was embedded a reinforcing mat composed of electrospun silk fibroin protein. Both HA and silk are biocompatible, selectively degradable biomaterials with independently controllable material properties. Mechanical characterization showed the composite tensile strength as fabricated to be 4.43 ± 2.87 kPa, two orders of magnitude above estimated tensions found around potential target organs. In the presence of hyaluronidase (HAse) in vitro, the rate of gel degradation increased with enzyme concentration although the reinforcing silk mesh was not digested. Composite gels demonstrated the ability to store and sustainably deliver therapeutic agents. Time constants for in vitro release of selected representative antibacterial and anti-inflammatory drugs varied from 46.7 min for cortisone to 418 min for hydrocortisone. This biocomposite showed promising mechanical characteristics for direct fastening to tissue and organs, as well as controllable degradation properties suitable for storage and release of therapeutically relevant drugs.
authors.affiliation: Department of Biomedical Engineering, Tufts University, Science and Technology Center, Medford, MA 02155, USA. roberto.elia@tufts.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Elia
authors.forename: Danny R
authors.initials: DR
authors.lastname: Newhide
authors.forename: Paul D
authors.initials: PD
authors.lastname: Pedevillano
authors.forename: G Russell
authors.initials: GR
authors.lastname: Reiss
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Firpo
authors.forename: Edward W
authors.initials: EW
authors.lastname: Hsu
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
authors.forename: Robert A
authors.initials: RA
authors.lastname: Peattie
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001696:Biomechanical Phenomena; D001698:Biomedical Engineering; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005349:Fibroins / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D047011:Silk / Q000737:chemistry; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D016207:Cytokines; D020100:Hydrogels; D047011:Silk; D042461:Vascular Endothelial Growth Factor A; D006820:Hyaluronic Acid; D005349:Fibroins; D006821:Hyaluronoglucosaminidase