title: Biocompatibility of a coacervate-based controlled release system for protein delivery to the injured spinal cord.
abstract: The efficacy of protein-based therapies for treating injured nervous tissue is limited by the short half-life of free proteins in the body. Affinity-based biomaterial delivery systems provide sustained release of proteins, thereby extending the efficacy of such therapies. Here, we investigated the biocompatibility of a novel coacervate delivery system based on poly(ethylene argininylaspartate diglyceride) (PEAD) and heparin in the damaged spinal cord. We found that the presence of the [PEAD:heparin] coacervate did not affect the macrophage response, glial scarring or nervous tissue loss, which are hallmarks of spinal cord injury. Moreover, the density of axons, including serotonergic axons, at the injury site and the recovery of motor and sensorimotor function were comparable in rats with and without the coacervate. These results revealed the biocompatibility of our delivery system and supported its potential to deliver therapeutic proteins to the injured nervous system.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Britta M
authors.initials: BM
authors.lastname: Rauck
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Tabitha L
authors.initials: TL
authors.lastname: Novosat
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: moudega@pitt.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Oudega
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: yaw20@pitt.edu.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations; D005260:Female; D053823:Hedgehog Proteins / Q000737:chemistry / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013124:Spinal Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D003692:Delayed-Action Preparations; D053823:Hedgehog Proteins; D010455:Peptides; D011091:Polyesters; C546888:Shh protein, rat; C572412:poly(ethylene argininylaspartate diglyceride); D006493:Heparin
keywords: Biocompatibility; Growth factor delivery; Nervous tissue loss; Sonic hedgehog; Spinal cord injury