title: Three-dimensionally presented anti-fouling zwitterionic motifs sequester and enable high-efficiency delivery of therapeutic proteins.
abstract: Zwitterions are well known for their anti-biofouling properties. Past investigations of zwitterionic materials for biomedical uses have been centered on exploiting their ability to inhibit non-specific adsorption of proteins. Here, we report that zwitterionic motifs, when presented in three dimensions (e.g. in crosslinked hydrogels), could effectively sequester osteogenic bone morphogenetic protein-2 (rhBMP-2). The ionic interactions between rhBMP-2 and the 3-D zwitterionic network enabled dynamic sequestering and sustained release of the protein with preserved bioactivity. We further demonstrated that the zwitterionic hydrogel confers high-efficiency in vivo local delivery of rhBMP-2. It can template the functional healing of critical-size femoral segmental defects in rats with rhBMP-2 at a loading dose substantially lower than those required for current natural or synthetic polymeric carriers. These findings reveal a novel function of zwitterionic materials beyond their commonly perceived anti-biofouling property, and may establish 3-D zwitterionic matrices as novel high-efficiency vehicles for protein/ionic drug therapeutic delivery.
authors: Department of Orthopedics & Physical Rehabilitation, Department of Cell & Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Pingsheng
authors: P
authors: Liu
authors: Department of Orthopedics & Physical Rehabilitation, Department of Cell & Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Jordan D
authors: JD
authors: Skelly
authors: Department of Orthopedics & Physical Rehabilitation, Department of Cell & Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: Jie.song@umassmed.edu.
authors: Jie
authors: J
authors: Song
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005269:Femur / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D055767:Immobilized Proteins
keywords: 3-D zwitterionic materials; Anti-fouling; Bone tissue engineering; rhBMP-2 delivery