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BRP Key Accomplishments
- Peptide amphiphiles (PA) designed to promote neuronal survival and neurite extension have been successfully synthesized and strategies to macroscopically align PA nanofibers to enhance cellular alignment have been developed.
- A multi-epitope PA gel was successfully made consisting of PAs displaying the IKVAV epitope mixed with smaller amounts of PAs with binding epitopes for the neurotrophins NT-3, GDNF, and NgR. Dorsal root ganglia cultured in these PA gels remained viable for over 3 weeks in culture were observed to extend neurites into the three dimensional PA gel. These results show the potential of these new PA systems for spinal cord injury.
- The biological mechanisms behind the bioactivity of peptide amphiphiles (PA) scaffolds within a spinal cord injury were revealed indicating that injection of IKVAV-PA into the injured spinal cord inhibits the generation of astrocytes while increasing the generation of oligodendoglial cells from progenitor cells by massively stimulating b1-integrin signaling.
- Poly(lactide-co-glycolide) bridges with controlled pore size and channel diameter were shown to promote preferential growth of neural fibers within the bridge channels and prevented astrocyte infiltration in vivo.
- A new gene delivery strategy from poly(lactide-co-glycolide) bridge scaffolds has been developed that incorporates DNA complexed to lipids to form lipoplexes, which are then immobilized to the substrate. Incorporation of these lipoplexes resulted in higher transfection levels in a spinal cord model compared to using plasmid DNA alone. Addition of bioactive peptides to the lipoplexes was also shown to further enhance transfection efficiencies.
- The epididymal fat pad has been established to be an appropriate extrahepatic transplant site, providing for a less invasive method for islet transplantation.
- Gene-loaded layered scaffolds incorporating genes encoding for FGF-2 and HIF-1a were implanted in an vivo rodent model. Results demonstrated that the transgene expression levels from gene-loaded layered scaffolds over a 4-week period were sufficient to induce an angiogenic response. Islets transplanted on exendin-4-releasing layered scaffolds exhibit enhanced function relative to those transplanted on control scaffolds.
- Diabetic mice implanted with polymer scaffolds modified with extracellular matrix components were found to achieve euglycemia fastest and responded to glucose challenge similar to normal mice.
- Hydrogels designed to present survival- and function-enhancing peptides were shown to increase islet cell survival and enhance insulin secretion.
- Adhesive hydrogels for islet immobilization in vivo were found to be biocompatible and efficacious in tranplantating islets to alternative implantation sites (i.e. at the epididymal fat pad or surface of the pancreas).
- Protein polymer MRI contrast agents that were designed for tracking tissue engineering scaffolds in vivo were found to support good cell viability, biodegradability, ability to be cross-linked into hydrogels, and contrast enhancement.
- Treatment of islets with peptide amphiphile microscaffolds was found to enhance islet viability and increase sprouting activity.
- Peptide amphiphile systems incorporating cell adhesion moieties and designed to promote mineralization have been shown to significantly enhance the formation of bone in an in vivo rat critical sized femoral defect model.
- Peptide amphiphile systems incorporating binding epitopes to transforming growth factor b1 was shown to significantly enhance cartilage regeneration in an in vivo rabbit articular cartilage defect model.
- New self-assembling peptide amphiphile-polymer membrane and sac structures with hierarchical order across the scales have been discovered and developed. These new constructs have significant potential as delivery vehicles for cells, growth factors, and drugs for a variety of regenerative medicine targets.
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