BRP Project Aims

The specific aims of the 2004 BRP research started with improvements in the basic technologies, developed through hybridization of basic technologies into new forms, and progressed with an assessment of each technology’s performance in CNS and diabetes cell therapies through in vitro and subsequently in vivo models:

Aim 1. Develop the technology of bioactive self-assembling "peptide amphiphile" nanofibers that mimic collagen fibrils in architecture, cause liquid-to-solid transformations in seconds or minutes under physiological conditions, and also have capacity for programmable delivery of growth factors or programmable biodegradation.

Aim 2. Develop epitope-polyvalent peptide networks formed by enzyme-mediated crosslinking of soluble components, and their molecular composites with the self-assembling nanofibers of aim 1. This integrated technology of two phase materials offers cells two different modes for biological signal presentation or therapeutic delivery in a single material. These systems also offer great flexibility in design of scaffold mechanical properties.

Aim 3. Synthesis of high molar mass recombinant proteins that can be post-translationally modified into comb-like macromolecular architectures bearing bioactive side chains, and enzymatically crosslinkable sequences with the strategy of aim 2. for in vitro or in vivo liquid-to-solid transformations using only biomolecular chemistry.

Aim 4. Develop foamed microporous scaffolds for sustained release of relevant proteins or DNA for our biological targets, and their use as substrates for hierarchical scaffolds on which the nanoscale bioactive scaffolds of aim 1. are assembled. This hybrid regenerative scaffold technology will integrate features 10 times larger and 1000 times smaller than cells to customize bioactivity and programmable delivery.

Aim 5. Test in vitro the cell survival, proliferation, and lineage commitment of neural progenitor cells when encapsulated in all self-assembling and enzymatic liquid-to-solid scaffolds developed by the technology group in the BRP team.

Aim 6. Based on results from aim 5., test in vivo selected systems in aco-transplantation mode that combines scaffolds plus pre-differentiated or genetically engineered stem cells as therapeutic strategies for repair of spinal cord injury or for recovery from middle cerebral artery occlusion. These studies will include behavioral analyses, tract-tracing, and anatomic studies of the spinal cord to evaluate efficacy of the interventions.

Aim 7. Test in vivo in diabetic mice the use of pre-fabricated foamed microporous and micro-nano hierarchical scaffolds with protein delivery capacity to enhance the efficacy of islet transplants. This aim targets the development of a subcutaneous pancreas transplant.