Superporous hydrogels as novel scaffolds for tissue engineering.

摘要

Formulating scaffolds and the tissue matrix environment remains an unmet need for the field of tissue engineering that preludes successful tissue engineered human organs. Insufficient interconnected macroporosity in scaffolds is one of the limiting factors in cell colonization, new tissue formation and vascularization in 3D tissue engineered grafts. Given these problems, the focus of my research was to develop a poly(ethylene glycol) diacrylate (PEGDA) tissue engineering scaffold that will enable stem cell infiltration, survival and differentiation, and also permit vascularization within the scaffold.;We synthesized PEGDA based superporous hydrogels with highly interconnected macropores architecture that enabled rapid cell uptake within the scaffold with high incorporation efficiencies and uniform distribution, without the use of external force or device for cell seeding. When human mesenchymal stem cells (MSCs) were seeded within the superporous hydrogels scaffolds, the cells anchored within the SPHs in presence of serum proteins, and secreted extra-cellular matrix molecules, such as, fibronectin, laminin, collagen type I and collagen type IV even in the absence of cell adhesive peptides. The highly porous architecture enabled stem cell survival for over 7 weeks in vitro. Within the porous network, the MSCs retained their ability to differentiate to the three primary mesenchyme lineages upon appropriate chemical induction. Differentiation was specific to the induction medium used and no trans-differentiation between groups was observed. The biomimetic environment of the scaffolds thus, supported stem cell survival while retaining 'sternness'.;The highly interconnected, macroporous architecture of the scaffolds provided a 'bioinspired' material for bone tissue engineering by supporting stem cell induced osteogenesis within the scaffolds. The atomic composition of the mineralized matrix was further found to be similar to calcium-deficient hydroxyapatite, the amorphous biological precursor of bone. In addition to supporting stem cell survival and differentiation, the scaffolds also demonstrated potential for in vivo cellular infiltration and vascular ingrowths. The rapid neovasularization and limited fibrotic response observed suggested that, the architecture may be conducive to cell survival and rapid vessel development. Given the shortcomings of current auto and allograft tissue implants, this study provided an alternative polymer scaffold for tissue engineering.