Duraplasty of PHBV/PLA/Col membranes promotes axonal regeneration by inhibiting NLRP3 complex and M1 macrophage polarization in rats with spinal cord injury

FASEB J. 2020 Sep;34(9):12147-12162. doi: 10.1096/fj.202000190RR. Epub 2020 Jul 20.

Abstract

Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1β, TNF-α, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.

Keywords: PHBV/PLA/Col membranes; duraplasty after decompression; inflammasome; macrophage; polarization; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / pathology
  • Collagen / chemistry
  • Collagen / pharmacology
  • Female
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Membranes, Artificial*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Polyesters / chemistry
  • Polyesters / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration*
  • Spinal Cord Injuries* / metabolism
  • Spinal Cord Injuries* / pathology
  • Spinal Cord Injuries* / therapy

Substances

  • Membranes, Artificial
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Polyesters
  • poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate)
  • poly(lactide)
  • Collagen