American Society for Peripheral Nerve
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Viral Vector Functionalized Bioengineered Core-Shell Scaffolds for Peripheral Nerve Repair
Jenny Yau, BS1; Steven Minderler, BS1; Nanke Cui, MD1; Iván Coto Hernández, PhD1; Ulrike G.K. Wegst, PhD2,3; Nate Jowett, MD, PhD4; Kaiyang Yin, PhD2,3,5
1Massachusetts Eye and Ear Infirmary, Boston, MA; 2Dartmouth College, Hanover, NH; 3Northeastern University, Boston, NH; 4Facial Nerve Center - Dept. of Otolaryngology, Harvard Medical School / Massachusetts Eye and Ear, Boston, MA; 5University of Freiburg, Baden-Württemberg, Germany

Introduction Peripheral nerve injuries yield devastating consequences. Gold standard treatment of nerve gaps comprises nerve autografting, that may yield functional loss and chronic pain at the donor site. There is need for high-performing off-the-shelf alternatives. Gene therapy functionalization of nerve guidance scaffolds represents a promising yet unexplored avenue for realizing the potential of bioengineered constructs in surgery. This study assessed the performance of bioengineered biocompatible core-shell design nerve guidance scaffolds and potential for biologic functionalization using adeno-associated viral (AAV) vectors.
Materials & Methods Nerve guidance scaffolds comprising 12 mm long chitosan-based cylindrical shells and 10 mm long plain collagen or collagen cellulose nanofiber based porous cores were manufactured using a freeze-casting technique and sterilized using ethylene oxide. Sciatic nerves of Sox10-Venus x Thy1-CFP transgenic mice were transected and repaired using biocompatible nerve guidance scaffolds of various configurations and substrates, with or without immersion in AAV8 vector solution encoding fluorescent reporter tdTomato. After four weeks, repair sites were harvested, processed, and imaged by multiphoton microscopy to assess conduit performance.
Results Collagen cellulose nanofiber (CNF) conduits showed robust Schwann cell and axonal ingrowth into the cores, while more limited Schwann cell and axonal ingrowth was noted for bovine and rat collagen cores (Figure 1). Transduction of cells within scaffolds immersed in AAV solution was observed, in contrast to controls (Figure 2).
Conclusions Proof-of-concept of core-shell scaffold design and adeno-associated viral vector functionalization of bioengineered nerve guidance scaffolds for peripheral nerve repair are demonstrated. Future work will explore scaffold performance over longer distances functionalized with AAV vectors encoding neurotrophic factors, and comparisons made against autograft performance.


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