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Development of Microvascularized Tissue-Engineered Products: Flow Characterization and Scaffold Fabrication

Vijayakumar Janakiraman1, Brian Kienitz1, and Harihara Baskaran2. (1) Chemical Engineering, Case Western Reserve University, A.W.Smith Building, 10900 Euclid Avenue, Cleveland, OH 44106, (2) Chemical Engineering and Biomedical Engineering, Case Western Reserve University, A.W. Smith Building, 111C, 10900 Euclid Avenue, Cleveland, OH 44106

Nutrient mass transfer limitations pose a serious problem for current tissue-engineered (TE) products. Several strategies including porous matrices, hydrogels, and angiogenic factor delivery, have been employed to address the nutrient limitations. However these strategies fail to overcome the problem as mass transfer primarily occurs by passive diffusion until the product is vascularized in vivo through angiogenesis. An ideal TE product will feature a built-in microvasculature, leading to convective delivery of nutrients, and will succeed in eliminating this mass transfer limitation. The primary goal of our research is to design and develop capillary flow networks with optimal transport characteristics to be integrated with natural biodegradable scaffolds for skin tissue engineering (Figure 1). The built-in endothelialized flow networks would efficiently deliver nutrients and remove waste products from the TE product with minimal frictional losses for better host integration. This will form a basis for generating a scalable design that can be used for tissue engineering of three dimensionally complex tissues.

Choosing skin as the tissue model and utilizing planar bifurcating networks as our basic design, we previously obtained optimal designs of micron scale flow networks. In this work, we will present results of network flow characterization studies, including flow distribution and pressure drop measurements across the network devices. We will also present preliminary results of network fabrication in collagen-glycosaminoglycans (collagen-GAG) scaffolds and network endothelialization.

By using standard photo/soft lithography techniques, the network designs were obtained in poly-dimethyl siloxane (PDMS) molds. Subsequently, microfluidics was established in the PDMS networks and the differential pressure drop across the network was measured using an amplified low pressure sensor. The pressure drop-flow rate relationship was obtained as a function of network generations and network porosity. Figure 2 shows preliminary results for 1-3 generation devices. All devices obey the Poiseuille flow behavior. In addition, flow velocities were measured at different segments of the network devices using particle image velocimetry and the flow distribution efficacy of the networks was quantified. We developed a new soft-lithography technique for fabricating the micron scale flow networks onto collagen-GAG scaffolds. Four process parameters were optimized to obtain well-resolved and stable features: acetic acid (AA) solution concentration, surface dissolution time, applied pressure and glutaraldehyde concentration. The collagen-GAG networks were subsequently endothelialized with BAEC's and cell growth and viability were assessed. Collectively, the results validate our approach for incorporating synthetic ‘vascular' networks with TE products.