A hyaluronan-based nerve guide: in vitro cytotoxicity, subcutaneous tissue reactions, and degradation in the rat

Biomaterials. 2004 Feb;25(3):483-9. doi: 10.1016/s0142-9612(03)00544-1.


We investigated possible cytotoxic effects, biocompatibility, and degradation of a hyaluronan-based conduit for peripheral nerve repair. We subjected the conduits to an in vitro fibroblast cytotoxicity test and concluded that the conduits were not cytotoxic. Subsequently, we implanted the conduits subcutaneously in rats, in order to investigate tissue reactions and biodegradation. Initially, a fibrin matrix was formed around the material, while the surroundings were relatively quiet. Macrophages (MØ) migrated to the conduits and formed giant cells next to the material after 5 days. The maximum presence of MØ was found after 3-6 weeks. The appearance of MHC class II cells showed a similar pattern. Highest numbers of giants reached a maximum after 6-12 weeks. Angiogenesis was started in the surroundings of the hyaluronan-based conduit within a few days. Massive ingrowth of blood vessels into the biomaterial was found after 6 weeks as well as cellular ingrowth into the lumen of the tube. At that time the tubular structure of the conduit was lost and loose biomaterial fibers were observed. The results show that a hyaluronan-based conduit is not cytotoxic and shows good biocompatibility. Such a conduit may be suitable as a guide in peripheral nerve repair.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Biocompatible Materials / pharmacology
  • Cell Division
  • Cell Line
  • Fibrin / chemistry
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Hyaluronan Receptors / biosynthesis
  • Hyaluronic Acid / chemistry*
  • Hyaluronic Acid / pharmacology*
  • Immunohistochemistry
  • In Vitro Techniques
  • Macrophages / metabolism
  • Male
  • Mice
  • Microscopy, Electron, Scanning
  • Neovascularization, Pathologic
  • Nerve Regeneration
  • Nerve Tissue
  • Neurons / metabolism*
  • Peripheral Nerves / pathology
  • Peripheral Nervous System / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors


  • Adjuvants, Immunologic
  • Biocompatible Materials
  • Hyaluronan Receptors
  • Fibrin
  • Hyaluronic Acid