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Joshua Tashman PhD Thesis Defense titled Moving FRESH Towards the Clinic: In-Process Quality Control of Patient-Specific ECM Scaffolds

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Tissue engineering utilizes our understanding of biomechanics, biomaterials, and biology to build tissues and organs from scratch for diagnostics and therapeutics. This approach has been leveled at clinical and research problems in all organ systems. The recent development of 3D bioprinting has given researchers a new tool to mimic native tissues and organs by depositing cells, growth factors, and extracellular matrix (ECM) layer-by-layer in 3D patterns. However, the geometric complexity of 3D bioprinted constructs has been limited by the deformation of soft biomaterials printed in air, due to gravity. The freeform reversible embedding of suspended hydrogels (FRESH) bioprinting technique was developed to mitigate the effects of gravity by embedding biomaterials into a supportive bath, which locks them in place until printing is complete. FRESH can recapitulate the geometric complexity of tissues, but before FRESH constructs can be translated to the clinic, the hardware, technique, and printed objects must be quantified, validated, and demonstrated to provide benefit to pass review by regulatory agencies.

In this thesis, high-performance bioprinting hardware is developed, validated, and leveraged in a range of low-cost, open-source bioprinting systems to drive adoption and innovation of the FRESH technique. In chapter 3 a syringe pump optimized for bioprinting, the Replistruder 4, is designed and its performance is quantified. In chapter 4 the Replistruder 4 is used to convert a low-cost plastic printer into a customizable, open-source bioprinting platform. These developments are combined and improved in chapter 5 to build a high-precision 3D bioprinter with an integrated optical coherence tomography (OCT) imaging system. In-process imaging, quality control, and error detection is then demonstrated using OCT, an essential step towards providing regulatory agencies the consistency and accuracy information they need for clinical approval. Finally, in chapter 6, these technologies are utilized in a canine model of volumetric muscle loss for 24-hour turnaround of a quality-controlled, patient-specific, wound-filling decellularized ECM patch. Implantation and quantification of the benefits of this patch are the first step towards proving that the added complexity of FRESH provides sufficient benefit for clinical translation. Together the work presented in this thesis demonstrates the accuracy and adaptability of the FRESH bioprinting platform and its potential for producing patient-specific ECM scaffolds with the real potential for clinical translation.

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