title: Implantable biomaterial based on click chemistry for targeting small molecules.
abstract: Specific and targeted delivery of medical therapies continues to be a challenge for the optimal treatment of multiple medical conditions. Technological advances permit physicians to target most sites of the body. However, after the intervention, physicians rely on systemic medications that need frequent dosing and may have noxious side effects. A novel system combining the temporal flexibility of systemic drug delivery and the spatial control of injectable biomaterials would improve the spatiotemporal control of medical therapies. Here we present an implantable biomaterial that harnesses in vivo click chemistry to enhance the delivery of suitable small molecules by an order of magnitude. The results demonstrate a simple and modular method to modify a biomaterial with small molecules in vitro and present an example of a polysaccharide modified hours after in vivo implantation. This approach provides the ability to precisely control the moment when biochemical and/or physical signals may appear in an implanted biomaterial. This is the first step towards the construction of a biomaterial that enhances the spatial location of systemic small molecules via in vivo chemical delivery.
authors.affiliation: Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA. Electronic address: jose.mejiaoneto@gmail.com.
authors.forename: José M
authors.initials: JM
authors.lastname: Mejía Oneto
authors.affiliation: Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA.
authors.forename: Munish
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA; Department of Biomedical Engineering, University of California, Davis, 451 Health Sciences Drive, Davis, CA 95616, USA.
authors.forename: J Kent
authors.initials: JK
authors.lastname: Leach
authors.affiliation: Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, 451 Health Sciences Drive, Davis, CA 95616, USA; Department of Internal Medicine, Division of Hematology/Oncology, University of California, Davis, Sacramento, CA 95817, USA; Center for Molecular and Genomic Imaging, University of California, Davis, 451 Health Sciences Drive, Davis, CA 95616, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Sutcliffe
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D057930:Click Chemistry / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants / Q000138:chemical synthesis*; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods*
chemical_list: D000464:Alginates; D004343:Drug Implants; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: Alginate; Click chemistry; Drug delivery; Hydrogel; In vivo imaging