Article pubs.acs.org/journal/abseba
In Vivo Peripheral Nerve Repair Using Tendon-Derived Nerve Guidance Conduits Kyle A. Alberti, Caleb I. Neufeld, Jun Wang, and Qiaobing Xu* Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, Massachusetts 02155, United States S Supporting Information *
ABSTRACT: There is an urgent need for a peripheral nerve repair product that can match or exceed the abilities of the current “goldstandard”, nerve autografts. Using a sectioning-based fabrication technique, decellularized tendon sections formed into tubular conduits that maintain the native structure of the collagen. Our previous studies have demonstrated that these collagen structures provide nanotopographical growth guidance cues for regenerating neurons and support glia. Here, the regenerative abilities of the tendon-derived nerve guidance conduits to repair a critically sized defect (15 mm) are evaluated in a rat sciatic nerve model. Using the conduits, functional recovery occurs at a similar rate to isografts, when evaluated with a sciatic function index test. However, muscular recovery, as measured by gastrocnemius weight, was not as great in the conduit-treated group. Both conduit and isograft repairs are histologically evaluated using Masson’s trichrome stain and immunofluorescent staining for neurofilament-160 and S100 (markers for neurons and Schwann cells, respectively). This evaluation shows that by week 14, conduits promote regrowth of both neuronal tissue and some physiological support structures, such as blood vessels and epi/perineurium-like structures. Lastly, positive staining for these two markers at week 14 is calculated as a quantitative means of assessment, and shows greater total content of neurofilament-160 and S100 in conduits than in isografts, but a smaller percent area, which may be a result of the greater cross-sectional area of the conduit. KEYWORDS: tendon, tissue slice, biomaterials, nerve repair, sciatic nerve both synthetic polymers such as PLGA,8 PGA,9 and PCL,10 and natural polymers like silk11−13 and collagen.14−16 Several of these conduits are currently available clinically, including the Neurolac (Polyganics), Neurotube (Synovis), and Salubridge (SaluMedica), comprised of PLCL, PGA, and PVA, respectively. FDA-approved collagen NGCs are also available: NeuraGen (Integra Life Science), Neuroflex, and NeuroMatrix (Collagen Matrix Inc.). These conduits primarily comprise type-I collagen that has been solubilized and then recast into the desired shape through various techniques. These conduits have shown positive results preclinically;17 however, clinical success when repairing defects greater than 3 cm has been limited,4,7,18 leaving room for improvement. The solubilization treatments that are often used to process collagen, denature, and disrupt the collagen’s native triplehelical structure,19 as well as the highly aligned hierarchical fiber organization found in tissue such as tendon. Maintenance of these structures would be beneficial: several studies have shown that aligned structures provide topographical cues to extending neurites that improve regeneration, while also promoting a
1. INTRODUCTION Every year there are roughly 100 000 cases of peripheral nerve damage that require surgical intervention in the United States and Europe.1 These can result from vehicular accidents, bone fractures, explosions, surgical complications, or other traumatic injuries. Following injury, nerves will normally only regenerate over very small distances on their own. If the damaged portion of the nerve is very short (
