(398bn) Oligodendrocyte Precursor Cell Maturation in a 3D Hydrogel System through the Incorporation of Drug Delivery Nanoparticles or Topographical Cues (Grad Student Award)

In the central nervous system, oligodendrocyte precursor cells are capable of differentiating into oligodendrocytes responsible for generating the myelin sheath. This electrically insulating layer enables neuronal axons to send electrical signals rapidly and efficiently to surrounding neurons. Following diseases or injuries this myelin sheath is broken down as oligodendrocytes are damaged and oligodendrocyte precursor cells (OPCs) are often unable to differentiate into mature myelinating oligodendrocytes in the damaged tissue, leaving patients with long-term disabilities and pain. While many biomaterial systems enable neuronal maturation and axon extension, few systems have been investigated in terms of oligodendrocyte precursor cells and the biomaterial properties that are necessary for regenerating functional, myelinating oligodendrocytes.

Here, we investigate the influence of controlled drug delivery and topographical cues on oligodendrocyte precursor cell maturation in a 3D polyethylene glycol based hydrogel. OPCs were encapsulated in poly(ethylene glycol)-dimethacrylate gels made through photoinitiation with lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate. In some gels, nanoparticles releasing platelet derived growth factor-alpha (PDGFR-α) were encapsulated along with cells. Poly(lactic acid-co glycolic acid) nanoparticles were made using the double emulsion, W/O/W method with varying lactic acid to glycolic acid (L:G) ratios and resulting release profiles. Nanoparticles had diameters ranging from 0.959 to 3.46 micrometers, measured via scanning electron microscopy. The fastest release system was the 50:50 (L:G) 0.59IV nanoparticle which released 90% of the load in the first 24 hours. Interestingly, cells responded to faster release rates by upregulating RNA for the mature oligodendrocyte marker, myelin basic protein. This was found with a four fold increase in myelin basic protein RNA, calculated through RT-PCR, in gels containing the fastest release rate nanoparticles compared to those without nanoparticles. In addition to nanoparticles, topographical cues were incorporated into some gels through the addition of electrospun fibers. On going work is investigating how the incorporation of polystyrene electrospun fibers affect the differentiation of oligodendrocyte precursor cells as well, however it is believed that topographical cues play an important role in oligodendrocyte differentiation and maturation. In 2D cells plated on fibers are observed extending processes towards the polystyrene fibers, much like oligodendrocytes would to axons in the central nervous system. These results taken together indicate the importance of biochemical and topographical cues on the differentiation of oligodendrocyte precursor cells in 3D biomaterial systems and their potential application towards nervous system regeneration.