Delivering Microrobots in the Musculoskeletal System

Abstract

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions. Microrobots have been gradually used in organisms due to their advantages of intelligent, precise and minimally invasive targeted delivery. Through the combination of control and imaging systems, microrobots with good biosafety can be delivered to the desired area for treatment. In the musculoskeletal system, microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body. Compared to traditional biomaterial and tissue engineering strategies, active motion improves the efficiency and penetration of local targeting of cells/drugs. This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system. We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

Keywords: Magnetic actuation; Microrobot; Microrobotic systems; Musculoskeletal system; Targeted delivery.

Fig. 1

The characteristics of microrobots applied in the musculoskeletal system. The microrobots used to treat bone, cartilage, muscle, and tendon diseases are illustrated

Fig. 2

Outline of the four refractory diseases of the musculoskeletal system and their current treatments. Notes: NSAIDs, nonsteroidal anti-inflammatory drugs

Fig. 3

Typical applications of microrobots in the musculoskeletal system. a Spiral MCT improved the viability and osteogenic differentiation of stem cells [161]. Copyright (2019) John Wiley and Sons. b Targeted delivery of porous spherical microrobots to repair cartilage defects in vivo under arthroscopy [106]. Copyright (2020) American Association for the Advancement of Science. c Microswimmers for precise muscle stimulation in the presence of magnetic fields and NIR [181]. Copyright (2022) American Chemical Society. d Nanomotors loaded in microneedles improved the therapeutic efficiency of EXOs in Achilles tendinopathy [108]. Copyright (2021) American Chemical Society

Fig. 4

The development and future prospects of microrobot systems applied in cartilage repair. a Janus microspheres encapsulated half with stem cells and half with magnetic particles [104]. Copyright (2018) Elsevier. b Magnetic PLGA microrobots [109]. Copyright (2017) John Wiley and Sons. c EMA system applied to cartilage targeting in rabbits [106]. Copyright (2020) American Association for the Advancement of Science. d Schematic and confocal images of a porous microrobot with stem cells [106]. Copyright (2020) American Association for the Advancement of Science. e Wearable magnetic device fixed on the rabbit's knee and a phantom [106, 120]. Copyright (2020) American Association for the Advancement of Science, MDPI. f Targeted delivery of microrobots to cartilage defects under arthroscopic guidance [106]. Copyright (2020) American Association for the Advancement of Science. g Microrobots with programmable morphology for different application scenarios [105]. Copyright (2020) American Chemical Society. h PDA-coated microcarriers [122]. Copyright (2021) John Wiley and Sons. i The wearable magnet array device consisting of magnet modules [122]. Copyright (2021) John Wiley and Sons. j Arthroscopic-guided microrobot delivery [105]. Copyright (2020) American Chemical Society. k X-ray-guided microrobot delivery [105]. Copyright (2020) American Chemical Society. l 2D nonchiral waffle-shaped microswimmers [134]. Copyright (2023) American Chemical Society. m Microrobots with different sizes and magnetizations for cartilage and subchondral bone repair [125]. Copyright (2023) MDPI. n Microswimmers assemble to form cell-supported 3D structures [134]. Copyright (2023) American Chemical Society. o Microrobots moved sequentially to the subchondral bone and cartilage defects [125]. Copyright (2023) MDPI

Fig. 5

Different motion modes of microrobots. a Concentration-dependent autonomous diffusion [41]. Copyright (2022) John Wiley and Sons. b Linear and helical motions driven by chemical reactions [107]. Copyright (2021) American Chemical Society. c Linear motion in a gradient magnetic field [109]. Copyright (2017) John Wiley and Sons. d Trajectory of a microswimmer following a predesigned track of “N” [181]. Copyright (2022) American Chemical Society. e Spiral propulsion of helical microrobots under rotating magnetic fields [161]. Copyright (2019) John Wiley and Sons. f Spinning, rolling, and translation of hairbots [155]. Copyright (2019) Elsevier. g Move through complex channels by a combination of rolling and swimming motions [134]. Copyright (2023) American Chemical Society. h Targeted delivery through narrow channels [105]. Copyright (2020) American Chemical Society. i–k Targeted delivery in 3D knee models [105, 109, 125]. Copyright (2017) John Wiley and Sons, (2020) American Chemical Society, (2023) MDPI

Fig. 6

Imaging-guided delivery of microrobots from in vitro to in vivo. a Microsphere motions recorded by the camera [104]. Copyright (2018) Elsevier. b Microrobot motions recorded by fluorescence microscopy [109]. Copyright (2017) John Wiley and Sons. c Schematic of X-ray guided microrobot delivery [105]. Copyright (2020) American Chemical Society. d Imaging of microrobots motion using X-ray imaging in the thoracic cavity of rats [105]. Copyright (2020) American Chemical Society. e Targeted delivery under arthroscopy [106]. Copyright (2020) American Association for the Advancement of Science. f Magnetic implant targeting system under arthroscopy [122]. Copyright (2021) John Wiley and Sons. g Hairbots imaging under ultrasound [155]. Copyright (2019) Elsevier. h Ultrasound imaging of the diffusion of self-driven nanomotors [41]. Copyright (2022) John Wiley and Sons

Fig. 7

Prospects for clinical translation of microrobotic systems in the musculoskeletal system in the future