One of the major limitations of current tissue engineering technology is the lack of 3D vascularlized artificial tissue constructs. As tissue engineers attempt to form thicker cell- laden constructs, an internal microvascular network to provide nutrients (via media or blood) to cells deep within the construct will become necessary. While techniques derived from the semiconductor industry have been used to form 2D microfluidic structures inside biomaterials, the current strategies for fabrication of 3D microchannel networks (multi-layer stacking and 3D printing) are slow, difficult, and expensive. I propose to develop a technique based on sacrificial microfiber networks to form complex 3D fluidic microchannel networks inside of biomaterials. The microfiber networks are formed using a standard cotton candy machine and store-bought granulated sugar. Macrochannel interfaces may be formed using larger sticks of sugar stuck to the microfiber network. Once the full sacrificial sugar structure is formed, a matrix material is poured over the sugar and then crosslinked. The entire construct is then immersed in water to dissolve the sugar, leaving a complex 3D network of channels inside the matrix material. I plan to investigate two promising biomaterials in the beginning of the study, polyethylene glycol diacrylate (PEGDA), a photocurable hydrogel, and polygylcerol sebacate acrylate (PGSA), a photocurable biodegradable elastomer. Both of these materials have been shown to act as excellent scaffolds for cell growth. Once the microchannel network is formed in the biomaterial, I will grow human umbilical vein endothelial cells (HUVECs) on the channel walls to form a lining that will allow non- heparinized blood flow without clotting. Following this step, I will form constructs with cells seeded in the bulk of the matrix (which may need to be made porous). During all cell studies, cell viability will be measured using standard fluorescent dye techniques.
The progress of modern tissue engineering depends on the ability to form 3D microvascular networks that are able to provide nutrients inside of artificial tissue constructs. Using a new technique based on sacrificial sugar structures, we will be able to produce these networks rapidly and inexpensively, thereby rendering the resulting vascularized artificial tissue constructs accessible to the patient.
| Boire, Timothy C; Gupta, Mukesh K; Zachman, Angela L et al. (2015) Pendant allyl crosslinking as a tunable shape memory actuator for vascular applications. Acta Biomater 24:53-63 |
| Bellan, Leon M; Kniazeva, Tatiana; Kim, Ernest S et al. (2012) Fabrication of a hybrid microfluidic system incorporating both lithographically patterned microchannels and a 3D fiber-formed microfluidic network. Adv Healthc Mater 1:164-7 |
| Bellan, Leon M; Pearsall, Matthew; Cropek, Donald M et al. (2012) A 3D interconnected microchannel network formed in gelatin by sacrificial shellac microfibers. Adv Mater 24:5187-91 |
| Bellan, Leon M; Wu, Diana; Langer, Robert S (2011) Current trends in nanobiosensor technology. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3:229-46 |
