Neural Tissue Engineering

SCI is resistant to therapies due to the complex inflammatory reaction and inhibitory factors to regeneration (1). There are diverse approaches to SCI treatment, including drug/gene delivery, cell transplantation for both regeneration and neuroprotection. One field of research not widely used within SCI repair is materials science, yet it has many forms – from injectable hydrogels to nanoparticles, porous scaffolds to nerve guides (2-6). The past decade has seen an unprecedented expansion in the development of biomedical materials with new forms and functions that are extremely useful in advancing SCI repair and fundamental research.

A phase separated hydrogel scaffold is shown with SEM/histology (A) and implanted into the dorsal horn. After 24h the scaffold is filled with neutrophils (B). Similarly an implant in the dorsal funicular has predominantly activated macrophages/microglia after 6d (C).
A phase separated hydrogel scaffold is shown with SEM/histology (A) and implanted into the dorsal horn. After 24h the scaffold is filled with neutrophils (B). Similarly an implant in the dorsal funicular has predominantly activated macrophages/microglia after 6d (C). After 14d neuronal cell bodies survive within 150 microns of the scaffold (D).

Inflammatory Reactions to Biomaterials

Tissue engineering (TE) of the nervous system typically involves the in vivo implantation of some type of biocompatible construct (6). The capacity for a material to permit regeneration and neurite penetration has been the major focus of histological assessment for such porous scaffolds. Furthermore, most TE scaffolds in the spinal cord are histologically examined four to six weeks after injury where potential influences on the inflammatory reaction are missed (3). My research on SCI focuses on the innate immune reaction associated with implanting a foreign material into an injury site that is largely affected by inflammatory processes (8).

References

  1. Dalton PD & Mey J (2009) Neural interactions with materials. Front Biosci, 14, 769-795.
  2. Volpatto F, Führmann T, Migliaresi C, Hutmacher DW, Dalton PD. (2013) Using extracellular matrix for regenerative medicine in the spinal cord. Biomaterials, 34, 4945-55.
  3. Dalton PD, Harvey AR, Oudega M, Plant GW (2008) Tissue Engineering of the Nervous System, in Tissue Engineering. C Van Blitterswijk, P Thomsen, A Lindahl, J Hubbell, D Williams, R Cancedda, J de Bruijn and J Sohier (Ed.) Academic Press. p611-647.
  4. Tsai E, Dalton PD, Shoichet MS, Tator CH (2004) Synthetic guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection. J Neurotrauma, 21, 789-804.
  5. Dalton PD, Flynn L, Shoichet MS (2002) Manufacture of poly(2-hydroxyethyl-co-methyl methacrylate) hydrogel tubes for use as nerve guidance channels. Biomaterials, 22, 3843-3851.
  6. Chirila TV, Hong Y, Dalton PD, Artificial Vitreous Body in The Polymeric Materials Encyclopedia: Synthesis, Properties and Applications, J.C. Salamone (Ed.), CRC Press, Boca Raton, FL, 8619-26, 1996.
  7. Dalton PD, Woodfield T, Hutmacher DW (2009) Snapshot: Polymer scaffolds for tissue engineering. Biomaterials, 30, 701-702.
  8. Li HY, Führmann T, Zhou Y, Dalton PD. (2013) Host reaction to poly(2-hydroxyethyl methacrylate) scaffolds in a small spinal cord injury model. J Mat Sci Mater Med,  24, 2001-2011.