Summary/Abstract: Our long-goal is to develop an unprecedented semi-autonomous surgeon-in-the-loop surgical robotic system and complementary computer-assisted algorithms to enable an intuitive in situ robotic bioprinting of human tissues and organs. More specifically, using this extrusion-based bioprinting system, a surgeon can (i) first utilize a high-resolution three-dimensional (3D) point cloud camera to plan an arbitrary spatial printing geometry on the target anatomical surface, (ii) co-operate with a robotic system to manipulate a custom- designed bioprinting instrument to precisely follow the planned printing geometry, and (iii) perform an intuitive and precise deposition of engineered bioinks to make tissue constructs on the target anatomical surface, while (iv) directly control and monitor the printing process to ensure the safety and success of the procedure. The focus of this proposal is simultaneous functional and cosmetic restoration of large volumetric muscle loss (VML) injuries by utilizing a novel engineered bioink- developed by our collaborators at the Terasaki Institute of Biomedical Innovation, a complementary robotic bioprinting system, and intuitive computer- assisted algorithms. Severe musculoskeletal injuries can lead to VML, where extensive musculoskeletal damage and tissue loss result in permanent loss of function. In small-scale injuries or strains, muscle is capable of endogenous regeneration and complete functional restoration. However, this ability is abated in VML, where the native biophysical and biochemical signaling cues are no longer present to facilitate tissue regeneration. Current state- of-the-art in vitro tissue engineering VML treatment procedures suffer from various issues including (i) prolonged culturing period in bioreactors demanding functionality enhancement prior to implantation in the body; (ii) adhesion failure of in vitro 3D printed hydrogel scaffolds to the remnant muscle, whether injected, sutured, or placed into the wound; and (iii) inability to be printed precisely in irregular curved 3D surfaces of large VML injuries. It is our central hypothesis that the proposed semi-autonomous robotic bioprinting system can collectively address the mentioned limitations of the current state-of-the-art solutions by (i) reducing complexity, surgical time, and complications associated with current VML treatments, (ii) immediately delivering and in situ printing of appropriate bioinks to the target anatomy and utilizing the human body as a natural bioreactor to induce tissue maturation and function, and (iii) providing real-time feedback on the 3D bioprinted constructs as well as the surgeon’s and patient’s motions to ensure precision of the bioprinting procedure for simultaneous functional and cosmetic restoration of the injured muscle. The proposed project is multidisciplinary and bridges the current gap between the robotic surgery, tissue engineering, and bioprinting fields. The contribution is significant, high impact, and innovative and can revolutionize the current clinical paradigm.

PROJECT NARRATIVE This project aims to reduce surgical complications and improve current volumetric muscle loss treatment procedures by developing a novel semi-autonomous surgeon-in-the-loop in situ robotic bioprinting system. The proposed transformative approach (1) significantly reduces the pain, complexity, and surgical time of the current surgical procedures; (2) immediately delivers and prints engineered muscle tissues on the injured surfaces, and (3) provides a safe and intuitive robotic bioprinting procedure for surgeons.