ADVANCED MANUFACTURING OF REGENERATIVE EXTRACELLULAR MATRIX SCAFFOLDS

The convergence of regenerative and personalized medicine has the potential to revolutionize treatment of awide range of diseases and traumatic injuries by harnessing a patient’s own immune system together withextracellular matrix (ECM) scaffolds to achieve tissue repair. However, the advances being made in academicresearch have been slow to translate to the clinic, due in large part to the inability to manufacture thesetherapies in a standardized, reproducible and patient-specific manner. The advanced manufacturing ofcomplex biologic products can solve this problem, serving as the enabling technology for these emergingapplications. Yet while advanced manufacturing of synthetic polymer and titanium implants has alreadyreceived FDA-approval, the 3D printing of ECM and cells has proved far more challenging. Here we propose todevelop new technologies critically needed to translate regenerative ECM scaffolds in to the clinic byaddressing key manufacturing needs for ECM scaffold 3D printing. Specifically, we have identified in processmonitoring, multiscale ECM scaffold fabrication and decellularized ECM bioinks as critical capabilities. To dothis we will leverage our expertise in near-IR imaging, decellularized ECM, and 3D biofabrication. The work tobe conducted is summarized in three specific aims. One, to engineer an integrated 3D bioprinting and OCTimaging system to enable in process monitoring and real-time feedback during biofabrication. The goal of thisaim is to enable nondestructive 3D imaging of ECM scaffolds during the 3D bioprinting process in order torapidly assess success/failure. Two, to develop a multi-scale biofabrication process that can combine multiple3D printing methods in a single construct to recapitulate native tissue composition and architecture. The goal ofthis aim is to address the challenge of building large volumetric ECM scaffolds that also require nano- to micro-scale resolution to form intricate anatomical structures. Three, to establish the ability to 3D bioprintregenerative ECM scaffolds for volumetric muscle repair, matched to patient-specific anatomical defects. Thegoal of this aim is to transition our existing regenerative ECM scaffolds for volumetric muscle repair from amanual fabrication process to an automated, advanced manufacturing process and use CT and MRI imagingdata to match patient-specific tissue defects. This would have profound consequences by leading towardsclinically-relevant therapeutic strategies to regenerate tissues and develop the advanced manufacturingcapabilities necessary to achieve industrial scale-up and translation.