Biological Assemblies Provide Novel Templates for the Synthesis of Biocomposites and Facilitate Cell Adhesion

Mechanical mismatch and the lack of interactions between implants and the natural tissue environment are major drawbacks in bone tissue engineering. Biomaterials mimicking the self‐assembly process and the composition of the bone matrix should provide new routes for fabricating biomaterials possessing novel osteoconductive and osteoinductive properties for bone repair. In the present study, bioinspired strategies are employed to design de novo self‐assembled chimeric protein hydrogels comprising leucine zipper motifs flanking a dentin matrix protein 1 domain, which is characterized as a mineralization nucleator. Results show that this chimeric protein could function as a hydroxyapatite nucleator in pseudo‐physiological buffer with the formation of highly oriented apatites similar to biogenic bone mineral. It could also function as an inductive substrate for osteoblast adhesion, promote cell surface integrin presentation and clustering, and modulate the formation of focal contacts. Such biomimetic “bottom‐up” construction with dual osteoconductive and osteoinductive properties should open new avenues for bone tissue engineering.

[1]  S. Aota,et al.  Fibronectin regulates calvarial osteoblast differentiation. , 1996, Journal of cell science.

[2]  D. Wirtz,et al.  Reversible hydrogels from self-assembling artificial proteins. , 1998, Science.

[3]  Berl,et al.  Template-induced and molecular recognition directed hierarchical generation of supramolecular assemblies from molecular strands , 2000, Chemistry.

[4]  R. Müller,et al.  A synthetic leucine zipper-based dimerization system for combining multiple promoter specificities , 2001, Gene Therapy.

[5]  B. Gutte,et al.  Fusion proteins from artificial and natural structural modules. , 2001, Current protein & peptide science.

[6]  M. Folin,et al.  Novel osteoblast-adhesive peptides for dental/orthopedic biomaterials. , 2002, Journal of biomedical materials research.

[7]  Arthur Veis,et al.  Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1 , 2003, Nature materials.

[8]  K. Schulten,et al.  Molecular biomimetics: nanotechnology through biology , 2003, Nature materials.

[9]  A. George,et al.  Dentin Matrix Protein 1 Immobilized on Type I Collagen Fibrils Facilitates Apatite Deposition in Vitro* , 2004, Journal of Biological Chemistry.

[10]  J. F. Stoddart,et al.  Template-directed synthesis of multiply mechanically interlocked molecules under thermodynamic control. , 2005, Chemistry.

[11]  Chan Beum Park,et al.  Template-directed self-assembly and growth of insulin amyloid fibrils. , 2005, Biotechnology and bioengineering.

[12]  S. Mann,et al.  Template-directed synthesis of silica-coated J-aggregate nanotapes. , 2005, Chemical communications.

[13]  Toshihiro Akaike,et al.  Bio-functional inorganic materials: an attractive branch of gene-based nano-medicine delivery for 21st century. , 2005, Current gene therapy.

[14]  Manoj Kumar,et al.  Designer protein-based performance materials. , 2006, Biomacromolecules.

[15]  J. Harden,et al.  Self-assembling protein hydrogels with modular integrin binding domains. , 2006, Biomacromolecules.

[16]  Jeffrey R Capadona,et al.  Integrin specificity and enhanced cellular activities associated with surfaces presenting a recombinant fibronectin fragment compared to RGD supports. , 2006, Biomaterials.

[17]  M. Stevens,et al.  Novel materials for bone and cartilage regeneration. , 2006, Current opinion in chemical biology.

[18]  A. George,et al.  Matrix Macromolecules in Hard Tissues Control the Nucleation and Hierarchical Assembly of Hydroxyapatite* , 2007, Journal of Biological Chemistry.

[19]  A. Jen,et al.  Assembly of nanomaterials through highly ordered self-assembled monolayers and peptide-organic hybrid conjugates as templates. , 2007, Journal of Nanoscience and Nanotechnology.

[20]  Maxim G. Ryadnov,et al.  Peptide α-helices for synthetic nanostructures , 2007 .

[21]  E. Gazit,et al.  Biological and chemical decoration of peptide nanostructures via biotin-avidin interactions. , 2007, Journal of nanoscience and nanotechnology.