James Zhang

Introduction. Osteoarthritis is the most common joint disease in the world and a leading cause of disability in the United States yet remains largely irreversible. 3D printing is a rapidly growing technology that shows great promise in cartilage repair and may offer a less invasive alternative to joint replacement or cartilage transplantation. In order to make in situ robotic 3D bioprinting a viable treatment option for chondral defects, several key challenges must be overcome, including designing accurate printed geometry, identifying a printable bio ink with high biocompatibility and viability of chondrocytes, and limiting invasiveness. Methods. Several novel 3D printing technologies were examined for their application in in situ 3D printing for cartilage repair. First, 3D scans constructed from still images were used to design 3D print geometry to fill in chondral lesions and evaluated for accuracy post-printing¹. Then, a photocrosslinkable bioink, norbornene-modified hyaluronic acid (NorHA), was deposited and evaluated for biocompatibility after 7 and 56 days⁶. Finally, two different methods, a flexible magnetically controlled print nozzle laden with Neodymium iron boron (NdFeB)⁷ and ex vivo irradiation with near-infrared (NIR)⁸, were used to limit invasiveness. Results. Fast 3D scanning using only still images from three different angles and simple boolean subtraction could provide the necessary print geometry with high accuracy, yielding under 0.3mm of average error for a 9mm by 6mm lesion¹. NorHA demonstrated high biocompatibility with 85% chondrocyte viability and 7-fold increase in collagen type II 7 and 56 days after printing, respectively⁶. Additionally, reinforcement of NorHA with a melt-electrowriting (MEW) mesh resulted in increases of compressive modulus to ∼350 kPa10. Flexible tubing laden with NdFeB could be magnetically controlled to print in vivo on organ surfaces through 3mm incisions⁷. Finally, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) nanoinitiators allowed for conversion of external NIR light to 365nm light for curing of injected bioink without need for an incision⁸. Conclusion. Promising technologies have arisen to tackle the challenges of designing accurate printed geometry, identifying a printable bioink with high biocompatibility and viability of chondrocytes, and limiting invasiveness and incision sizes of procedures. For 3D printing to truly be a clinical treatment option, we must further evaluate the stability of prints in articular load-bearing cartilage, the long-term viability of chondrocytes, and the speed of printing within the confines of a joint space. Current results, however, show that the new technologies that have arisen in the past few years may make in situ robotic 3D bioprinting a viable solution for chondral defects in the near future.

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