PEGs use in Tissue Engineering

Tissue engineering applications routinely use biomaterial carriers which function as synthetic mimics of the extracellular matrix.  They provide a substrate for transplanted cell attachment, localize the cells in vivo once implanted, and serve as a template for new tissue formation derived from both the transplanted cells and the surrounding host cells. These functions are crucial since they may help prevent anoikis (i.e. programmed cell death of anchorage-dependent cells in absence of cellular attachment sites) in the transplanted cells, as well as provide a quorum effect where cells do better when in crowds. In addition, the material’s ability to allow vascularization to the transplanted cells can be vital to the cells’ survival and engraftment in the host environment.  

In the past decade, a great deal of progress has been made in engineering microenvironments for implanted cells by incorporating specific biochemical cues to improve viability and direct cellular phenotype, including the differentiation of encapsulated stem cells¹.  Polyethylene glycol diacrylate (PEGDA) and polyethylene glycol tetraacrylate (PEGTA) are linear or 4-armed PEGs, respectively, which form a hydrogel in the presence of a photoinitiator (such as Irgacure 2959).  These acrylated PEGs benefit not only from PEGs inherent hydrophilicity and biocompatibility but also from their flexibility in functionalization and use.  Since PEG-based hydrogels are non degradable in vivo and resist cell attachment, researchers have inserted degradation sequences into the PEG molecule as well as covalently added specific cellular attachment sites².  In addition, PEGDA hydrogels have been engineered through different polymer chain lengths and photolithographic patterning techniques to provide a substrate that has different substrate rigidity characteristics in two and three dimensions³. 

Recently, two forms of PEGDA hydrogels have been examined that have relevance to tissue engineering since they can be readily seeded with cells and implanted.  For example, human mesenchymal stem cells (hMSCs) can be differentiated into chondrogenic cells and osteogenic cells, encapsulated in PEGDA hydrogel, and subsequently implanted in vivo into rodent models⁴.  In addition, superporous forms of PEGDA hydrogels have been developed which allow host cells to infiltrate the scaffold as well as permit host vascularization compared to nonporous hydrogel controls when implanted into murine models⁵.

References

1. Khetan S and Burdick J, Cellular encapsulation in 3D hydrogels for tissue engineering. J. Vis. Exp. (2009).
2. Gobin AS and West JL, Cell migration through defined, synthetic extracellular matrix analogues. FASEB J. (2002).
3. Nemir S et al, PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidity. Biotech. Bioeng (2009) 105: 636-644.
4. Troken A et al, Tissue engineering of the synovial joint: the role of cell density. Proc. Inst. Mech. Eng. Part H. (2007) 429-440.
5. Keskar V et al, Initial evaluation of vascular ingrowth into superporous hydrogels. J Tissue Eng Regen Med. (2009) 3:486-90.