Vascular conduits are often needed for repair of congenital heart defects in children. However, current vascular grafts are not ideal for pediatric population. In particular, the graft's inability to adjust to children's growth will lead to multiple surgeries, and the risk of thrombosis will lead to life-long anti-coagulation therapy which is also undesired in pediatric age group. These limitations support the clear notion that a living, biologic tissue which can remodel and grow with the child is the key to solve all of these problems. The gold standard in pediatric vascular conduit repair remains autologous vessels, which have demonstrated good clinical outcomes, but with limited availability. Tissue engineered vascular grafts hold great promise to solve these challenges. However, the current tissue engineered vascular grafts are mostly tubular constructs, which cannot meet the demanding requirement of wide array of anatomies present in children with cardiovascular defects in a patient-specific manner. To create vascular conduit that matches the exact size and geometry of individual patient, 3-D bioprinting is a promising enabling technology, but doing so requires new printable biomaterials that can mimic the elastic properties of native soft tissues. Current available hydrogels in 3-D bioprinting are very fragile and are not able to withstand the surgical manipulation and pulse pressure when implanted in vivo. To overcome these challenges, we have developed a new class of printable elastic biomaterials that can be easily cross- linked with visible light without causing cell damage during the printing process. It is biocompatible, biodegradable and has tunable mechanical properties. The benefit of the new material is that it is synthesized from FDA approved materials and is compatible with many other newly developed biomaterial approaches thus will facilitate easy clinical translation and incorporation of the most recent biomaterial techniques for future optimization. The elastic material will allow us to engineer a vascular construct to match the native tissue biomechanics and geometries therefore avoid the compliance mismatch with better hemodynamic profile. In this work, we will further develop this elastic biomaterial for soft tissue bioprinting, and apply it toward 3-D bioprinting of vascular conduits for pediatric congenital heart repairs.
The proposed research is relevant to public health because developing elastic printable biomaterials and the bioprinting techniques to construct soft tissues are ultimately expected to improve our current strategies in vascular conduit reconstruction in the pediatric congenital heart defect repairs. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge and new tools that will help to reduce the burdens of human disability.
|Dorsey, Taylor B; Kim, Diana; Grath, Alexander et al. (2018) Multivalent biomaterial platform to control the distinct arterial venous differentiation of pluripotent stem cells. Biomaterials 185:1-12|
|Xu, Cancan; Lee, Wenhan; Dai, Guohao et al. (2018) Highly Elastic Biodegradable Single-Network Hydrogel for Cell Printing. ACS Appl Mater Interfaces 10:9969-9979|
|Dorsey, Taylor B; Grath, Alexander; Wang, Annling et al. (2018) Evaluation of Photochemistry Reaction Kinetics to Pattern Bioactive Proteins on Hydrogels for Biological Applications. Bioact Mater 3:64-73|