The inability of current synthetic scaffold materials to direct osteogenic cells to proliferate, differentiate into osteoblasts, and produce sufficient quantities of bone tissue limits the development of synthetic scaffolds for bone grafting applications in crucial areas such as orthopedic, dental, and craniofacial procedures. Our long-term goal is to create rationally designed, bio-inspired tissue-engineered constructs that promote bone formation and enhanced bone repair. As a first step toward this goal, the objective of this application is to engineer novel scaffolds with controlled architectures and improved mechanical properties that present biomimetic ligands by exploiting phase separation and self-assembly properties of rod-coil block copolymers. The central hypothesis is that precise control of polymer block design and structure through integration of """"""""living"""""""" polymerization and self-assembly at the supramolecular levels will lead to scaffolds with enhanced mechanical and structural properties and functionality.
In Aim 1, self-assembly properties at the meso-scale of rod-coil block copolymers in combination with covalent cross-linking strategies will be exploited in order to engineer scaffolds with controlled structural and mechanical properties.
In Aim 2, functionalized copolymers based on poly(lactic acid) will be prepared which allow for grafting of protein-resistant poly(ethylene glycol) coatings and the immobilization of fibronectin-mimetic ligands through pendant anchoring units. Osteoblast adhesion, proliferation, and differentiation will be evaluated on functionalized and non-functionalized polymers and scaffolds as well as films of current biomedical polymers. This research is expected to yield the following outcomes: a) establishment of basic design principles for the synthesis, characterization, self-assembly, and foaming of poly(norbornene)/poly(lactic acid) block copolymers as biomimetic scaffolds, b) verification of the proposed strategy of using photoinitiated covalent cross-linking to reinforce three-dimensional foamed structures and c) establishment of a modular approach towards the functionalization of poly(lactic acid)s with biological active moieties. Collectively, these studies will validate the proposed novel concepts towards high strength biomimetic scaffolds.
| Noga, David E; Petrie, Timothy A; Kumar, Anjli et al. (2008) Synthesis and modification of functional poly(lactide) copolymers: toward biofunctional materials. Biomacromolecules 9:2056-62 |
| Yoon, Kunsang; Goyal, Poorva; Weck, Marcus (2007) Monofunctionalization of dendrimers with use of microwave-assisted 1,3-dipolar cycloadditions. Org Lett 9:2051-4 |
| Gerhardt, Warren W; Noga, David E; Hardcastle, Kenneth I et al. (2006) Functional lactide monomers: methodology and polymerization. Biomacromolecules 7:1735-42 |
