Spiny-decorated Millirobot Towards Biomedical Applications

面向生物醫學應用的尖刺狀毫米級機器人

Student thesis: Doctoral Thesis

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Award date23 Aug 2022

Abstract

Many contributions and potential applications of magnetic millirobots to biomedicine have been invented, developed, and improved in recent years to fulfill effective therapy. Magnetic actuation has been proposed to diversify electromagnetic coil configurations with control techniques and types of magnetic fields to power those tiny robots wirelessly. Small-scale (ranging in size from millimeters to micrometers) soft robots show promise for a new paradigm shift in biomedical applications, such as target therapy, minimally invasive surgery, and disease diagnosis, benefiting from their tiny size, soft nature, and untethered control. To date, diversified structures of small-scale soft robots have been evaluated in delicate body sites, such as nervous and circulatory systems, the fetus, and the eyes. Yet, to expand their applications to real-world scenarios of in-body operation, biocompatibility and biodegradability are the most premier peculiarities to avoid any negative immune reaction. Although different materials have been shown to be biodegradable in specific conditions, there are still limitations for in-vivo biomedical application reinforcement, such as effective locomotion capacity in harsh environments, multiple drug loading, and self-adaptive drug release capabilities. Considering the future avenue of small-scale soft robots in translation to the clinical practice of target drug delivery, controllable delivery and release of multiple drugs with programmable kinetics corresponding to external stimulus, e.g., mechanical force, chemical reaction, temperature response, and physical field (ultrasonic, electric, and magnet), could be an effective solution to perform effective treatment in biomedical applications. This study investigates and proposes two types of entirely biodegradable millirobots.

In the first part, a selective pH-responsive biodegradable soft nanofiber-constructed millirobot (Fibot) is presented. The developed Fibot is able to deliver and release embedded drugs stepwisely and exhibit superior locomotion adaptivity, pH-sensitive degradability, desirable cytotoxicity as well, which provides a general and powerful construction concept for the small-scale biomedical robot’s development and will find a wide spectrum of applications for robotic-aided stepwise combination therapeutic drug delivery and programmable release. Distinct from the conventional methods, Fibot is developed by a bottom-up magnetic field assisted electrospun platform. Here, both the soft body and the tapered legs will be fabricated from non-cytotoxic biodegradable materials (Eudragit L100 and Eudragit S100 for the nanofiber-based membrane; Eudragit L100-55 and iron microparticles for the legs) and different drugs can be embedded in the body and legs during the fabrication process simultaneously.

In the second part, an oral pH-responsive biodegradable spiny milli-ball robot (SMB-bot) is proposed to replace subcutaneous macromolecule injections. The developed SMB-bot would be able to deliver and release biological macromolecular in the GI tract with superior locomotion adaptivity, pH-sensitive degradability and desirable cytotoxicity. The robot will provide a general and powerful construction concept for the small-scale biomedical robot's development and find a broad spectrum of applications in biomedical treatment, which may shed light on the realization of macromolecular drug-disease medication, selected high-dose chemotherapy and local inflammation treatment by oral administration.

In the third part, there are two spiny-decorated millirobots showing great biomedical applications in vivo. In the rabbit model, in order to achieve intestinal anchoring, Fibot traveled in the harsh gastrointestinal environment, anchored at the desired location, and gradually released the embedded drug by overcoming the peristalsis of the gastrointestinal tract. In addition, SMB-bot successfully achieved intestinal anchoring and the delivery of macromolecular drugs to the rabbit intestine. HI slices validated the robot's ability to insert into the gastrointestinal tract, and continuous blood glucose measurements verified the robot's effectiveness at delivering macromolecular medications. These robots illustrate a simple and low-cost approach for the future oral delivery of macromolecular drug disease medications, selective high-dose chemotherapy, and localized inflammatory therapy.

Overall, these indicate that such a kind of spiny-decorated medical robot is promising to be used in the human body. This research opens up new possibilities for developing and using medical millirobots, which are expected to have a long-term effect on biomedical fields like medical treatment, in vitro/vivo targeted therapy, and macromolecular medicine.

    Research areas

  • magnetic millirobot, spiny-decorated medical robot, pH regulated degradation, intestine anchoring, drug delivery, drug release