Three-dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D-printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval. The customizability and unique build processes of 3D-printed medical devices pose unique challenges in meeting regulatory standards related to the manufacturing quality assurance. Consistent material powder properties and optimal printing parameters such as build orientation and laser power must be addressed and communicated to the FDA to ensure a quality build. Post-printing considerations unique to 3D-printed devices, such as cleaning, finishing and sterilization are also discussed. In this manuscript we illustrate how such regulatory hurdles can be navigated by discussing our experience with our group’s 3D-printed bioresorbable implantable device.

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Objectives/Hypothesis Reconstruction of craniofacial cartilagenous defects are among the most challenging surgical procedures in facial plastic surgery. Bioengineered craniofacial cartilage holds immense potential to surpass current reconstructive options but limitations to clinical translation exist. We endeavored to determine the viability of utilizing adipose-derived stem cell-chondrocyte co-culture and three-dimensional (3D) printing to produce 3D bioscaffolds for cartilage tissue engineering. We describe a feasibility study revealing a novel approach for cartilage tissue engineering with in vitro and in vivo animal data. Methods Porcine adipose-derived stem cells and chondrocytes were isolated and co-seeded at 1:1, 2:1, 5:1, 10:1, and 0:1 experimental ratios in a hyaluronic acid/collagen hydrogel in the pores of 3D-printed polycaprolactone scaffolds to form 3D bioscaffolds for cartilage tissue engineering. Bioscaffolds were cultured in vitro without growth factors for 4 weeks then implanted into the subcutaneous tissue of athymic rats for an additional 4 weeks before sacrifice. Bioscaffolds were subjected to histologic, immunohistochemical, and biochemical analysis. Results Successful production of cartilage was achieved using a co-culture model of adipose-derived stem cells and chondrocytes, without the use of exogenous growth factors. Histology demonstrated cartilage growth for all experimental ratios at the post-in vivo time point confirmed with type II collagen immunohistochemistry. There was no difference in sulfated-glycosaminoglycan production between experimental groups. Conclusion Tissue engineered cartilage was successfully produced on 3D-printed bioresorbable scaffolds using an adipose-derived stem cell and chondrocyte co-culture technique. This potentiates co-culture as a solution for several key barriers to a clinically-translatable cartilage tissue engineering process.