A Novel Semi-autonomous Surgeon-in-the-loop in situ Robotic Bioprinting System for Functional and Cosmetic Restoration of Volumetric Muscle Loss Injuries

摘要/摘要： 我们的长期目标是开发一种史无前例的半自主外科医生在环手术机器人 系统和互补的计算机辅助算法，以实现直观的就地机器人 人体组织和器官的生物打印。更具体地说，使用这种基于挤压的生物打印系统， 外科医生可以(I)首先利用高分辨率三维(3D)点云相机来规划任意空间 在目标解剖表面上打印几何图形，(Ii)与机器人系统合作以操纵定制- 设计的生物打印仪器精确地遵循计划的打印几何图形，并且(Iii)执行直观的 以及精确沉积工程生物墨水，以在目标解剖表面上构建组织结构，同时 (4)直接控制和监督印刷过程，确保印刷过程的安全和成功。这个 这项建议的重点是同时进行大容量肌肉的功能和美容修复 利用我们在Terasaki的合作者开发的一种新型工程生物墨水，实现VML损伤 生物医学创新研究所，一个互补的机器人生物打印系统，以及直观的计算机- 辅助算法。 严重的肌肉骨骼损伤可导致VML，其中广泛的肌肉骨骼损伤和组织丢失 导致永久性功能丧失。在小范围的损伤或劳损中，肌肉能够内源性 再生和完全功能恢复。然而，这种能力在VML中减弱了，因为本机 不再存在促进组织再生的生物物理和生化信号线索。当前状态- 最先进的体外组织工程VML治疗程序受到各种问题的困扰，包括(I)延长 在体内植入之前需要增强功能的生物反应器的培养周期； 体外3D打印水凝胶支架与残馀肌肉的粘连失败，无论是注射，缝合，还是 放置在伤口中；以及(Iii)无法在大型VML的不规则曲面3D表面上精确打印 受伤。 我们的中心假设是，所提出的半自主生物打印系统可以共同 通过以下方式解决当前最先进解决方案的上述局限性：(I)降低复杂性、外科 时间和与当前VML治疗相关的并发症，(Ii)立即递送和原位打印 将适当的生物墨水应用于目标解剖结构，并利用人体作为自然生物反应器来诱导组织 成熟度和功能，以及(Iii)提供关于3D生物打印构造的实时反馈以及 外科医生和患者的动作，以确保生物打印程序的准确性，同时功能和 美容修复受伤的肌肉。拟议的项目是多学科的，弥补了目前的差距。 在机器人手术、组织工程和生物打印领域之间。贡献是巨大的，很高的 影响，创新，可以彻底改变目前的临床模式。

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.