Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance ConduitsClick to copy article linkArticle link copied!
- Riley A. SuharRiley A. SuharDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United StatesMore by Riley A. Suhar
- Laura M. MarquardtLaura M. MarquardtDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United StatesDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305, United StatesMore by Laura M. Marquardt
- Shang SongShang SongDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, United StatesMore by Shang Song
- Hana BuabbasHana BuabbasDepartment of Biology, Stanford University, Stanford, California 94305, United StatesMore by Hana Buabbas
- Vanessa M. DoulamesVanessa M. DoulamesDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305, United StatesMore by Vanessa M. Doulames
- Patrik K. JohanssonPatrik K. JohanssonDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United StatesMore by Patrik K. Johansson
- Katarina C. KlettKatarina C. KlettProgram in Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, United StatesMore by Katarina C. Klett
- Ruby E. DewiRuby E. DewiDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United StatesMore by Ruby E. Dewi
- Annika M. K. EnejderAnnika M. K. EnejderDepartment of Materials Science and Engineering, Stanford University, Stanford, California 94305, United StatesMore by Annika M. K. Enejder
- Giles W. PlantGiles W. PlantDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305, United StatesMore by Giles W. Plant
- Paul M. GeorgePaul M. GeorgeDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, United StatesStanford Stroke Center, Stanford University School of Medicine, Stanford, California 94305, United StatesMore by Paul M. George
- Sarah C. Heilshorn*Sarah C. Heilshorn*Email: [email protected] (S.C.H.).Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United StatesMore by Sarah C. Heilshorn
Abstract

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 ELP-filled 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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