Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 7, Issue 9, Pages 4209-4220Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c01053
Keywords
Nerve guidance conduit; peripheral nerve; protein engineering; elastin-like protein
Categories
Funding
- National Institutes of Health (NIH) Training Grant in Biotechnology [T32-GM008412]
- Training Grant in Stem Cell Biology and Regenerative Medicine [T32-GM119995, R21-NS114549, R01-EB027171, R01-EB027666, F32-HD098808, K08-NS089976]
- NIH [P2C-HD086843]
- Stanford Lieberman Fellowship
- National Science Foundation [ECCS-1542152, 1808415]
- Wu Tsai Neurosciences Institute Interdisciplinary Postdoctoral Fellowship
- Department of Defense (SCRIP) [SC170085]
- Wings for Life [WFL-US020/14]
- Wu Tsai Neurosciences Institute NeuroTranslate Award
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1808415] Funding Source: National Science Foundation
- CDMRP [1101312, SC170085] Funding Source: Federal RePORTER
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Synthetic nerve guidance conduits (NGCs) provide an alternative for treating peripheral nerve injury, utilizing both naturally derived and synthesized materials. Protein engineered recombinant ELP hydrogels as intraluminal fillers enhance tissue bridge formation and functional control, supporting peripheral nerve regeneration. Further study of these materials as off-the-shelf alternatives for nerve regeneration is warranted.
Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELPfilled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.
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