ABSTRACT
I. Introduction .................................................................................................................... 218
A. Animal Derived ECM and Synthetic Scaffolds .................................................... 218
B. PuraMatrix Peptide Nanofiber Scaffolds ............................................................... 219
1. Nanofiber Scale Synthetic ECM ..................................................................... 219
2. Defined Three-Dimensional Microenvironments for
Cell Biology .................................................................................................... 219
C. Three-Dimensional Cell Culture vs. Two-Dimensional ....................................... 219
D. Nanoscale Fibers vs. Microscale ........................................................................... 220
E. Ideal Synthetic Biological Scaffolds ..................................................................... 220
II. Self-Assembling Peptides .............................................................................................. 221
A. Discovery and Development of Self-Assembling Peptides .................................. 221
1. Simple Repeating Units of Amino Acids Assemble into
Nanofiber Scaffolds ......................................................................................... 221
2. Amenable to Design Incorporating Functional Motifs .................................. 221
B. Structural Properties of Self-Assembling Peptides ............................................... 221
III. Peptide Nanofiber Scaffolds .......................................................................................... 222
A. EAK16-II ............................................................................................................... 222
B. RADA16 ................................................................................................................ 222
C. KFE8 and KLD12 .................................................................................................. 223
IV. PuraMatrix In Vitro Cell Culture Examples ................................................................. 225
A. Hepatocytes ............................................................................................................ 225
B. Adult Liver Progenitor Cells ................................................................................. 226
C. Chondrocytes Form Molded Cartilage in Cell Culture ........................................ 226
D. Extensive Neurite Outgrowth and Active Synapse Formation
on PuraMatrix ........................................................................................................ 228
E. Organotypic Hippocampal Tissue Culture in PuraMatrix .................................... 229
F. Osteoblasts ............................................................................................................. 229
V. Standard In Vitro Toxicology and Biocompatibility Studies ....................................... 229
A. Cytotoxicity ........................................................................................................... 229
B. Hemolysis .............................................................................................................. 231
C. Coagulation Prothrombin Time ............................................................................. 231
VI. In Vivo Biocompatibility and Toxicology Studies ........................................................ 231
A. ADME and Biodegradability ................................................................................. 232
B. Rabbit Muscle Implant (2 Weeks) ........................................................................ 232
C. Intracutaneous Reactivity ...................................................................................... 232
D. Rabbit Pyrogen ...................................................................................................... 233
VII. Future Perspectives .......................................................................................................... 233
A. Compatible with Bioproduction and Clinical
Applications ........................................................................................................... 233
B. Synthetic Origin, Clinical-Grade Quality, Clinical Delivery ............................... 236
C. Tailor-Made PuraMatrix ........................................................................................ 236
Acknowledgments ...................................................................................................................... 236
References .................................................................................................................................. 237
The fields of tissue engineering and regenerative medicine require two key complementary
components: (1) a suitable biological scaffold that creates a microenvironment niche for a given cell
type, and (2) that the given cell type can rapidly integrate and coalesce into the needed tissue.
