Editors' ChoiceSpinal Cord Injury

Porous polymeric platform repairs primates after spinal cord injury

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Science Translational Medicine  22 Feb 2017:
Vol. 9, Issue 378, eaam6068
DOI: 10.1126/scitranslmed.aam6068

Abstract

Amine-containing polymers immobilized on mesh and placed at trauma sites scavenge biomolecules that initiate a damaging immune response.

Trauma-induced spinal cord injuries (SCIs) can cause substantial damage to the cord parenchyma and stroma, greatly decreasing patients’ quality of life and causing sensory deficiency, motor impairment, and other functional limitations. The initial damage can be quite limiting, but secondary damage resulting from neural tissue destruction and immune-mediated processes can be at least as responsible for long-term dysfunction. Currently available approaches to SCI repair involve cell and tissue transplantation, which are promising but have severe limitations, such as cost, efficacy, and contamination risk. To address this, Slotkin et al. designed degradable polymeric implants that can guide endogenous spinal cord regeneration, avoiding the need for exogenous cells.

The authors chose a porous scaffold fabricated from a block copolymer consisting of the U.S. Food and Drug Administration–cleared poly-lactic-co-glycolic acid (PLGA) and cell adhesive poly-ʟ-lysine (PLL) because previously published results from the laboratory demonstrated its positive performance in rats and safety in nonhuman primates. To test the performance of the construct in a higher-order mammal, they induced a lateral hemisection thoracic SCI in African green monkeys and compared locomotion return and neural regeneration between animals with and without the PLGA-PLL scaffolds. A limitation of the study was that surgical variability induced two different lesion types: partial (incomplete) and full (complete). Fortunately, enough animals were included in both the control and experimental groups to allow for assessment of the scaffold in each of these SCI types. Over the 12 weeks of the study, primates with incomplete lesions exhibited only limited differences in locomotive function between the groups, whereas the animals with complete lesions appeared to show better return of locomotive function with the scaffold, but the results were not statistically different. SCIs treated with scaffolds did show an appreciable improvement in remodeled tissue regardless of injury type.

These data indicate that the scaffolds enhanced biological outcomes, even if physical outcomes were not dramatically improved. Next generations of this technology could expand upon these initial results by focusing on controlling the physical properties of the scaffold, as well as inductive biomolecule delivery. Nevertheless, this work has shown enough potential to be leveraged for human clinical trials, which have already begun.

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