Microrobots: Pioneering a new era in musculoskeletal system treatments

The musculoskeletal system comprises bones, muscles, cartilage, tendons, ligaments, and other connective tissues that link organs together, providing structural support, stability, and enabling movement. Diseases affecting this system include sarcopenia, fractures, osteoporosis, osteoarthritis, tendon/ligament injuries, and various acute or chronic anatomical conditions, all of which are characterized by a decline in muscle mass and strength, increased bone fragility, decreased cartilage elasticity, and reduced flexibility in tendons and ligaments. With advances in tissue engineering and regenerative medicine, a growing number of treatment options have emerged, such as stem cells, biomaterials, exosomes, and gene therapy. Currently, stem cell transplantation holds the most promise. However, limitations such as low targeting efficiency, reduced cell viability and functionality, and the inability to generate the correct cell line post-transplantation have led to suboptimal therapeutic outcomes despite large doses of stem cells. This significantly hampers its clinical application. Achieving targeted delivery and precise control of stem cells or drugs in a minimally invasive manner is crucial for treating early-stage, refractory musculoskeletal diseases. Targeted delivery systems based on microrobots may offer a solution to the key challenges associated with stem cell or drug delivery in the musculoskeletal system.

Teng Gaojun and his team from Southeast University have outlined the characteristics of the musculoskeletal system and regenerative medicine, common musculoskeletal disorders, treatment strategies, and current challenges. They also comprehensively reviewed the latest advancements in microrobotics for the musculoskeletal system, focusing on the associated driving and imaging systems that enable precise control, real-time monitoring, and post-operative tracking.

Microrobots in the musculoskeletal system serve two primary roles: (1) as a delivery system for stem cells or drugs, enabling precise targeting to transport exogenous cells or regulate endogenous cells to facilitate tissue regeneration, and (2) as "scavengers" for tissue damage, converting harmful substances into beneficial ones to improve the pathological microenvironment of damaged tissues. To achieve minimally invasive, targeted, intelligent, and adaptive delivery of stem cells and other therapeutics for precise treatment of musculoskeletal system disorders (MSDs), several fundamental components of microrobots must be considered, including core materials, driving/navigation systems, and imaging/tracking systems.

First, core materials used in vivo must demonstrate excellent biocompatibility. Additionally, they should respond to physical or chemical stimuli, allowing the microrobots to move autonomously. For microrobots delivering cells, it is crucial to establish a suitable three-dimensional microenvironment that supports the adhesion, survival, proliferation, and function of stem cells. Second, the targeted delivery of microrobots must align with the driving system. Lastly, directional tracking of microrobots is essential. Current in vivo imaging modalities include X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and fluorescence imaging.

Different tissues within the musculoskeletal system (bones, cartilage, muscles, tendons) are interconnected yet distinct. These tissues possess varying repair mechanisms and self-healing capabilities, so microrobot applications in each tissue need to be discussed separately. Cartilage damage and osteoarthritis are major clinical causes of chronic disability in the elderly. Due to the lack of blood vessels and nerves, articular cartilage exhibits very limited regenerative capacity, and there are currently no effective drugs or treatments available to significantly delay or reverse cartilage damage and the progression of osteoarthritis. In recent years, microrobots—owing to their minimally invasive, autonomous movement, multifunctionality, safety, and adaptability—have been widely employed in cartilage repair, offering new perspectives for treating cartilage-related conditions.

The driving technology is key to the movement of microrobots. Depending on the power source, microrobot motion can be categorized as either self-propelled or externally driven. Self-propelled motion typically involves chemical propulsion, including bubble generation, self-diffusiophoresis, self-electrophoresis, and Marangoni effect propulsion, while external driving methods include magnetic, acoustic, and optoelectronic driving. Microrobots can be designed to move according to the specific requirements of treating different diseases.

Imaging and driving systems are closely linked and work in tandem. Most microrobot research in the musculoskeletal system is still in the in vitro experimental stage. As a result, much of the current research focuses on improving the manufacturing and operational systems of microrobots, without adequate attention to in vivo imaging. Given the minimally invasive and targeted nature of microrobots, well-designed imaging systems are essential for real-time navigation of their movement.

Microrobots are steadily transitioning from cutting-edge technology to clinical application. In the future, researchers from clinical medicine, mechanical engineering, materials science, and life sciences will work together, focusing on addressing current core issues to advance the clinical translation of microrobotic systems for the musculoskeletal system and regenerative medicine.