Compressing Time and Space for an In Situ Dermal Graft Printing Paradigm

Clinical adoption of stem cell-based products is currently hampered by low yields and considerable functional uncertainty in the progenitor cell population, resulting in poor efficacy and mixed therapeutic outcomes. In the context of pressure ulcers that are inherently heterogeneous in their spatial characteristics and clinical time constraints, this functional uncertainty in the stem cell population is amplified. To address the dual challenges of time and space, this proposal advances a rapid, super-resolution fabrication process for producing stem cell culture substrates with a spatially distributed patterned architecture. Compressing the fabrication time with well-defined mapping of produced substrate geometries to lineage commitment promises a quantum leap in the yield and quality of regenerative therapies in complex ulcer wound management for immobile or plegic military Service members and Veterans suffering a range of acute and chronic diseases, injuries, and disabilities. By exploring and optimizing unusual processing conditions to exceed conventional build speeds and spatial limits for a super-resolution 3D printing process, this proposal will enable the rapid in situ fabrication of a first-of-its-kind stem cell template for direct culture on a simulated bleeding wound bed. The proposed research outcomes will set the stage for future investigations to leverage the native wound microenvironment as the optimal bioreactor for a stem cell-based dermal graft. This fundamentally new functional class of dermal grafts will exhibit controlled stem cell expansion and functional outcomes that enable permanent wound closure.