Ideally, implants should be designed with the ability to induce specific biological responses by promoting recognition of the biomaterial by particular proteins and/or cells, thereby promoting desired cell and tissue behavior. In the case of bone-contacting materials, this would mean that immediately following implantation the devices would be recognized by cells of the osteoblastic lineage, and the cells subsequently would be induced to form bone on or in close proximity to the surface. This could avoid fibrous encapsulation that often walls off implants and could lead to better integration into the surrounding bone. The overall goal of this project is to develop surface modification strategies to create biomaterials that are selective for particular cell surface molecules. It is hypothesized that these biospecific surfaces can induce desirable biomolecular and cellular events at the tissue-implant interface. The approach to be investigated involves imprinting surfaces with selective recognition sites having a specific shape and with a defined arrangement of functional groups.
In Specific Aim 1, versatile formulations will be developed for creating adherent molecularly imprinted coatings on orthopedic and dental biomaterials. Alkoxysilanes with ionic, polar, and hydrophobic terminal functional groups will be used to enhance noncovalent assembly of monomers and result in greater complementarity between imprinted surface and template biomolecule. Peptides mimicking the ligand-binding region of bone morphogenetic receptor IA (BMPR-IA) will be imprinted. The coatings will be chemically and morphologically characterized, and the selectivity of template binding to the surfaces will be quantified.
In Specific Aim 2, the methodology developed in Aim 1 will be used to test the hypothesis that coatings imprinted with cell surface molecules can control cell behavior. Two functional assessments, receptor activation and subsequent cell responses, will be used. In the case of surfaces imprinted with BMPR-IA, osteoblastic differentiation will be stimulated, ultimately leading to formation of a mineralized extracellular matrix. By promoting desired cell activities, biospecific biomaterials can control initial events at the cell-biomaterial interface.
| Brown, M E; Puleo, D A (2008) Protein Binding to Peptide-Imprinted Porous Silica Scaffolds. Chem Eng J 137:97-101 |
| Lee, K; Itharaju, R R; Puleo, D A (2007) Protein-imprinted polysiloxane scaffolds. Acta Biomater 3:515-22 |
| Arosarena, Oneida A; Puleo, David (2007) In vitro effects of combined and sequential bone morphogenetic protein administration. Arch Facial Plast Surg 9:242-7 |
| Lewis, K N; Thomas, M V; Puleo, D A (2006) Mechanical and degradation behavior of polymer-calcium sulfate composites. J Mater Sci Mater Med 17:531-7 |
| Puleo, David A; Thomas, Mark V (2006) Implant surfaces. Dent Clin North Am 50:323-38, v |
