Nerve-specific, xenogeneic extracellular matrix hydrogel promotes recovery following peripheral nerve injury

J Biomed Mater Res A. 2018 Feb;106(2):450-459. doi: 10.1002/jbm.a.36235. Epub 2017 Oct 23.

Abstract

Peripheral nerve possesses the inherent ability to regrow and recover following injury. However, nerve regeneration is often slow and incomplete due to limitations associated with the local microenvironment during the repair process. Manipulation of the local microenvironment at the site of nerve repair, therefore, represents a significant opportunity for improvement in downstream outcomes. Macrophages and Schwann cells play a key role in the orchestration of early events after peripheral nerve injury. We describe the production, characterization, and use of an injectable, peripheral nerve-specific extracellular matrix-based hydrogel (PNSECM) for promoting modulation of the local macrophage and Schwann cell responses at the site of nerve repair in a rodent model of sciatic nerve injury. We show that PNSECM hydrogels largely maintain the matrix structure associated with normal native peripheral nerve tissue. PNSECM hydrogels were also found to promote increased macrophage invasion, higher percentages of M2 macrophages and enhanced Schwann cell migration when used as a lumen filler in a rodent model of nerve gap repair using an inert nerve guidance conduit. These results suggest that an injectable PNSECM hydrogel can provide a supportive, bioactive scaffold which promotes repair of peripheral nerve in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 450-459, 2018.

Keywords: extracellular matrix; hydrogel; macrophage; nerve; regenerative medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Dogs
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / ultrastructure
  • Female
  • Hindlimb / physiopathology
  • Hydrogels / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Nerve Regeneration / drug effects*
  • Organ Specificity
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / physiopathology*
  • Rats, Sprague-Dawley
  • Recovery of Function* / drug effects
  • Schwann Cells / drug effects
  • Schwann Cells / pathology
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism*

Substances

  • Hydrogels