Biodegradable scaffolds promote tissue remodeling and functional improvement in non-human primates with acute spinal cord injury

Jonathan R Slotkin; Christopher D Pritchard; Brian Luque; Janice Ye; Richard T Layer; Mathew S Lawrence; Timothy M O'Shea; Roland R Roy; Hui Zhong; Isabel Vollenweider; V Reggie Edgerton; Grégoire Courtine; Eric J Woodard; Robert Langer

doi:10.1016/j.biomaterials.2017.01.024

Biodegradable scaffolds promote tissue remodeling and functional improvement in non-human primates with acute spinal cord injury

Biomaterials. 2017 Apr:123:63-76. doi: 10.1016/j.biomaterials.2017.01.024. Epub 2017 Jan 25.

Authors

Affiliations

¹ Department of Neurosurgery, Geisinger Clinic, Danville, PA, USA.
² Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ InVivo Therapeutics Corporation, Cambridge, MA, USA.
⁴ InVivo Therapeutics Corporation, Cambridge, MA, USA. Electronic address: [email protected].
⁵ RxGen, Hamden, CT, USA.
⁶ Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Brain Research Institute, University of California, Los Angeles, CA, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
⁸ Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
⁹ Center for Neuroprosthetics and Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
¹⁰ Brain Research Institute, University of California, Los Angeles, CA, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA; Departments of Neurobiology and Neurology, University of California, Los Angeles, CA, USA.
¹¹ Department of Neurosurgery, New England Baptist Hospital, Boston, MA, USA.
¹² Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

PMID: 28167393
DOI: 10.1016/j.biomaterials.2017.01.024

Abstract

Tissue loss significantly reduces the potential for functional recovery after spinal cord injury. We previously showed that implantation of porous scaffolds composed of a biodegradable and biocompatible block copolymer of Poly-lactic-co-glycolic acid and Poly-l-lysine improves functional recovery and reduces spinal cord tissue injury after spinal cord hemisection injury in rats. Here, we evaluated the safety and efficacy of porous scaffolds in non-human Old-World primates (Chlorocebus sabaeus) after a partial and complete lateral hemisection of the thoracic spinal cord. Detailed analyses of kinematics and muscle activity revealed that by twelve weeks after injury fully hemisected monkeys implanted with scaffolds exhibited significantly improved recovery of locomotion compared to non-implanted control animals. Twelve weeks after injury, histological analysis demonstrated that the spinal cords of monkeys with a hemisection injury implanted with scaffolds underwent appositional healing characterized by a significant increase in remodeled tissue in the region of the hemisection compared to non-implanted controls. The number of glial fibrillary acidic protein immunopositive astrocytes was diminished within the inner regions of the remodeled tissue layer in treated animals. Activated macrophage and microglia were present diffusely throughout the remodeled tissue and concentrated at the interface between the preserved spinal cord tissue and the remodeled tissue layer. Numerous unphosphorylated neurofilament H and neuronal growth associated protein positive fibers and myelin basic protein positive cells may indicate neural sprouting inside the remodeled tissue layer of treated monkeys. These results support the safety and efficacy of polymer scaffolds in a primate model of acute spinal cord injury. A device substantially similar to the device described here is the subject of an ongoing human clinical trial.

Keywords: Functional improvement; Polymeric scaffolds; Primates; Spinal cord injury; Tissue engineering; Tissue remodeling.

MeSH terms

Absorbable Implants*
Animals
Chlorocebus aethiops
Equipment Design
Equipment Failure Analysis
Gait Disorders, Neurologic / pathology
Gait Disorders, Neurologic / physiopathology*
Gait Disorders, Neurologic / therapy*
Guided Tissue Regeneration / instrumentation
Humans
Male
Recovery of Function
Spinal Cord Injuries / pathology
Spinal Cord Injuries / physiopathology*
Spinal Cord Injuries / therapy*
Spinal Cord Regeneration / physiology*
Tissue Scaffolds*