Advanced Manufacturing of Regenerative Extracellular Matrix Scaffolds

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The convergence of regenerative and personalized medicine has the potential to revolutionize treatment of a wide range of diseases and traumatic injuries by harnessing a patient’s own immune system together with extracellular matrix (ECM) scaffolds to achieve tissue repair. However, the advances being made in academic research have been slow to translate to the clinic, due in large part to the inability to manufacture these therapies in a standardized, reproducible and patient-specific manner. The advanced manufacturing of complex biologic products can solve this problem, serving as the enabling technology for these emerging applications. Yet while advanced manufacturing of synthetic polymer and titanium implants has already received FDA-approval, the 3D printing of ECM and cells has proved far more challenging. Here we propose to develop new technologies critically needed to translate regenerative ECM scaffolds in to the clinic by addressing key manufacturing needs for ECM scaffold 3D printing. Specifically, we have identified in process monitoring, multiscale ECM scaffold fabrication and decellularized ECM bioinks as critical capabilities. To do this we will leverage our expertise in near-IR imaging, decellularized ECM, and 3D biofabrication. The work to be conducted is summarized in three specific aims. One, to engineer an integrated 3D bioprinting and OCT imaging system to enable in process monitoring and real-time feedback during biofabrication. The goal of this aim is to enable nondestructive 3D imaging of ECM scaffolds during the 3D bioprinting process in order to rapidly assess success/failure. Two, to develop a multi-scale biofabrication process that can combine multiple 3D printing methods in a single construct to recapitulate native tissue composition and architecture. The goal of this 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 bioprint regenerative ECM scaffolds for volumetric muscle repair, matched to patient-specific anatomical defects. The goal of this aim is to transition our existing regenerative ECM scaffolds for volumetric muscle repair from a manual fabrication process to an automated, advanced manufacturing process and use CT and MRI imaging data to match patient-specific tissue defects. This would have profound consequences by leading towards clinically-relevant therapeutic strategies to regenerate tissues and develop the advanced manufacturing capabilities necessary to achieve industrial scale-up and translation.