Providing the right cues in nerve guidance conduits: Biofunctionalization versus fiber profile to facilitate oriented neuronal outgrowth.

Following peripheral nerve injury, rapid and spatially oriented axonal outgrowth from the proximal nerve stump is required for successful tissue regeneration. Regenerative strategies such as introducing fiber bundles into the nerve guidance conduits improve the directional growth of neurons and Schwann cells. Recently, it has been proposed that fiber profiling increases cell alignment and could accelerate neuronal growth. Here, we evaluate the impact of fiber profiling on the extent of neurite outgrowth in vitro as compared to non-profiled round fibers. We developed novel profiled trilobal poly(lactic acid) (PLA) fibers and systematically tested their potency to support nerve regeneration in vitro. The profiled fibers did not improve neurite outgrowth as compared to the round fibers. Instead, we show that growing neurites are merely guided by the type and quantity of proteins adsorbed on the polymer surface. Together this data has significant implications for in vivo experiments focusing on directional regrowth of severed axons across lesion sites during peripheral nerve regeneration.

Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration.

Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB) induced ectopic bone formation after implantation into the back muscle of rats. The objective of our in vivo study was to evaluate the osteogenic potential of pure PHB patches in surgically created cranial defects. For this, PHB patches were analyzed after implantation in surgically created defects on the cranium of adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue specimens containing PHB patches were processed and analyzed histologically as well as molecular-biologically. After 4 weeks, the PHB patches were completely embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration proceeding from bearing bone was found in 50% of all treated animals, whereas all PHB treated cavities showed both bone formation and embedding of the patches in bone 12 weeks after surgery. Furthermore, all slices showed pronounced development of blood vessels. Histomorphometric analysis presented a regenerated bone mean value between 46.4 ± 16.1% and 54.2 ± 19.3% after 4-12 weeks of healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold increased expression in PHB treated defects compared to controls. Real-time RT-PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in cranium defects after treatment with PHB patches compared to untreated bony defects of the same cranium. Within the limits of the presented animal investigation, it could conclude that the tested PHB patches featured a good biocompatibility and an osteoconductive character.