R A Stile | PubMed Health

PubMed2001

Thermo-responsive peptide-modified hydrogels for tissue regeneration.

Loosely cross-linked hydrogels consisting of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were synthesized, characterized, and used as model scaffolds for studying cell-material interactions in three-dimensions (3D). The AAc groups were functionalized with peptides containing the -RGD- and -FHRRIKA- sequences found in bone sialoprotein. Chemical modification of the hydrogels was verified via solid-state (1)H nuclear magnetic resonance spectroscopy, lower critical solution temperature studies, and volume change studies. The peptide-modified hydrogels were pliable at 22 degrees C and could be injected through a small-diameter aperture. Rat calvarial osteoblasts (RCO) seeded into the peptide-modified hydrogels were viable for at least 21 days of in vitro culture. The RCO spread more and demonstrated significantly greater proliferation when cultured within the peptide-modified hydrogels, as compared to control hydrogels. These peptide-modified P(NIPAAm-co-AAc) hydrogels serve as useful tools for studying cell-material interactions within 3D structures and have the potential to be used as injectable scaffolds for tissue engineering applications.

Acrylamides↗

PubMed1999

Designing biomaterials to direct biological responses.

We have set forth a design strategy for creating biomimetic materials that direct the formation of tissue surrounding implants or regeneration within porous scaffolds. Our studies have established that heterogeneous mimetic peptide surfaces (MPS) containing both the -RGD- (cell-binding) and-FHRRIKA- (putative heparin-binding) peptides, unique to BSP, in the ratio of 75:25 (MPS II) or 50:50 (MPS III) proved to be more biologically relevant and specific for RCO cell function. The initial response of human osteoblast-like cells to these surfaces was mediated by the collagen (alpha 2 beta 1) and vitronectin receptors (alpha v beta 3), whereas the vitronectin receptor alone dominated longer-term events (> 30 min). MPS II and III surfaces enhanced cell spreading and long-term events such as mineralization of the extracellular matrix compared to homogenous peptide surfaces and controls. Furthermore, extensive mineralization of the ECM deposited by RCOs occurred when the peptide was coupled to an interfacial interpenetrating polymer network (IPN) that resisted protein deposition (i.e., non-specific adsorption) and fouling. Work on thermo-reversible P(NIPAAm-co-AAc) hydrogels demonstrated the ability to create materials that can be delivered to the body in a minimally invasive manner and support tissue regeneration. These hydrogels can be modified to incorporate biofunctional components such as the biomimetic peptides, theoretically enhancing their ability to foster tissue regeneration. These results suggest that biomaterials can be engineered to mimic ECM components of bone (e.g., various organs) by grafting peptides in the appropriate ratios of the cell and heparin-binding domains, and ultimately modulate the expression of the osteoblast cell phenotype. Approaches similar to the one presented in this work can be used to design materials for hybrid artificial organs and other tissues.

Amino Acid Sequence↗