(5bf) Bioactive Materials for Controlled Release and Tissue Engineering Applications

Poly(ethylene glycol) (PEG) hydrogels possess many desirable properties making them an excellent material choice for numerous biomedical applications, including controlled delivery, tissue engineering, and regenerative medicine [1, 2]. The high water content of the PEG hydrogel environment preserves the bioactivity of protein therapeutics and facilitates rapid nutrient diffusion to support the survival of encapsulated cells. Further, the crosslinked, semi-permeable PEG network prevents direct contact of the encapsulated cells with immune cells and antibodies, and hence creates an immuno-isolation barrier. However, the use of PEG hydrogels also has disadvantages for protein and cell delivery. Firstly, due to the high water content of PEG hydrogels, it is a challenging task to effectively control molecular diffusion rates through the gel network without sacrificing the preferential hydrophilicity of the gels [3-5]. Further, the lack of biorecognition sites on the inert PEG polymer backbone hinders the survival and function of encapsulated anchorage-dependent cells.

Toward this end, we are developing bioactive peptide-functionalized PEG hydrogels for growth factors and cell delivery. Specifically, crosslinkable peptides exhibiting monovalent or multivalent affinity for basic fibroblast growth factor (bFGF) were incorporated in PEG hydrogels [5]. The architecture and presentation of the peptide motifs play an important role in regulating growth factor delivery. Utilizing the concept of affinity binding, we are also developing cytokine-antagonizing and chemokine-sequestering hydrogels to enhance the survival, function, and differentiation of encapsulated cells through controlling local inflammation [6]. Rat pheochromocytoma cells (PC12), human mesenchymal stem cells (hMSCs), and pancreatic beta-cells encapsulated in the cytokine-scavenging PEG hydrogels are less prone to pro-inflammatory cytokine TNF alpha-induced apoptosis. Finally, PEG hydrogels co-polymerized with bioactive peptides that signal pancreatic beta-cells directly are fabricated via facile thiol-acrylate photopolymerization to improve the survival and function of the encapsulated islets for the treatment of type 1 diabetes [7].

References:

1. C. -C. Lin and A. T. Metters, ?Hydrogels for controlled release formulations ? Network design and mathematical modeling.? Advanced Drug Delivery Reviews. 2006(58) 1379-1408.

2. C. -C. Lin and K. S. Anseth, ?PEG hydrogels for the controlled release of biomolecules in regenerative medicine.? Pharmaceutical Research. 2009(26) 631-43.

3. C. -C. Lin and A. T. Metters, ?Metal-chelating affinity hydrogels for sustained protein release.? Journal of Biomedical Materials Research: Part A. 2007(83) 954-964.

4. C. -C. Lin and A. T. Metters, ?Bifunctional monolithic affinity hydrogels for dual-protein delivery.? Biomacromolecules. 2008(9) 789-795.

5. C. -C. Lin and K. S. Anseth, ?Controlling affinity binding in peptide functionalized poly(ethylene glycol) hydrogels.? Advanced Functional Materials. 2009 (In press).

6. C. -C. Lin, A. T. Metters, and K. S. Anseth, ?Bio-interactive PEG-peptide hydrogels to modulate local inflammation induced by the pro-inflammatory cytokine TNFα.? (Submitted).

7. C. -C. Lin and K. S. Anseth, ?Glucagon-like peptide-1 functionalized PEG hydrogels promote survival and function of encapsulated pancreatic β-cells? (Submitted).