Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis.

Peptide amphiphile (PA) nanofibers formed by self-assembly can be customized for specific applications in regenerative medicine through the use of molecules that display bioactive signals on their surfaces. Here, the use of PA nanofibers with binding affinity for the bone promoting growth factor BMP-2 to create a gel scaffold for osteogenesis is reported. With the objective of reducing the amount of BMP-2 used clinically for successful arthrodesis in the spine, amounts of growth factor incorporated in the scaffolds that are 10 to 100 times lower than that those used clinically in collagen scaffolds are used. The efficacy of the bioactive PA system to promote BMP-2-induced osteogenesis in vivo is investigated in a rat posterolateral lumbar intertransverse spinal fusion model. PA nanofiber gels displaying BMP-2-binding segments exhibit superior spinal fusion rates relative to controls, effectively decreasing the required therapeutic dose of BMP-2 by 10-fold. Interestingly, a 42% fusion rate is observed for gels containing the bioactive nanofibers without the use of exogenous BMP-2, suggesting the ability of the nanofiber to recruit endogenous growth factor. Results obtained here demonstrate that bioactive biomaterials with capacity to bind specific growth factors by design are great targets for regenerative medicine.

Acetaminophen-induced forestomach lesion in normal rats following intravenous exposure.

Four groups of ten male and ten female rats each were treated intravenously with saline, 400 mg/kg/day of a commercially available injectable acetaminophen formulation, or 400 mg/kg/day of a new injectable acetaminophen formulation with (aged) or without (fresh) impurities daily for fourteen days. Gross observations of the mucosal surface of the stomachs from treated rats included multifocal to diffuse pale, elevated foci confined to the nonglandular region of the stomach. Treatment-related histologic observations consisted of epithelial hyperplasia and hyperkeratosis of the nonglandular mucosa of the stomach. The epithelial hyperplasia was characterized by a thickened epithelium, frequently accompanied by the development of undulations at the basement membrane zone, resulting in the formation of rete ridgelike structures protruding into the underlying tissue. The submucosa was usually expanded by edema and occasionally contained an infiltrate of neutrophils, eosinophils, and macrophages. The hyperplasia was usually accompanied by hyperkeratosis resulting in thickening of the stratum corneum. The incidence and severity of the gastric changes were similar across all treatment regimens. Although considered clinically irrelevant since humans do not have a forestomach equivalent, these results are significant in that this appears to be the first report of forestomach hyperplasia and hyperkeratosis following intravenous exposure to acetaminophen.