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Introduction
Living organisms have evolved to seamlessly integrate motor and sensory functions, particularly evident in the coordinated interplay between skeletal muscles and sensory skin in vertebrates. The skin, rich in diverse receptors (mechanoreceptors, thermoreceptors, nociceptors, etc.), gathers and encodes tactile data that guides muscle movement and environmental interpretation. This biological motor-sensor integration inspires the development of intelligent robotic systems, mimicking skin's softness for safe interaction with dynamic, unstructured, and uncertain environments, particularly when interfacing with biological tissues and organs for precision therapeutics. However, existing robots often lack the seamless integration of actuators, sensors, and controllers while maintaining physical softness and biocompatibility. The creation of bio-inspired somatosensory soft robots as implants promises to revolutionize medical technology in areas such as surgery, diagnosis, drug delivery, prostheses, artificial organs, and tissue-mimicking active simulators for rehabilitation. While various soft robotic implants demonstrate shape-morphing and functionalization capabilities, matching tissue compliance, retrieving functional signatures, and offering therapeutic treatments, significant challenges remain in designing materials and manufacturing technologies. These challenges encompass achieving compliant mechanics matching tissue softness, ensuring biocompatibility of constituent materials for implantation safety, providing structural adaptability for prolonged device longevity, and utilizing biomimicry to enhance device functionality. This research addresses these challenges by presenting concepts and designs for untethered soft robots that mimic the integrated nature of actuators, sensors, and stimulators found in biological systems. The aim is to minimize tissue damage, release stress at the biotic-abiotic interface, enhance biocompatibility, and improve multi-modal performance with spatiotemporal precision.
Literature Review
The existing literature highlights the need for soft, biocompatible robots for various medical applications. Studies have explored soft grippers for bladder volume detection and electrical stimulation [20], shape-memory polymers with integrated sensors for blood pressure measurement [21], and drug-eluting patches for targeted drug delivery [22]. These works underscore the potential of combining sensing and actuation to enhance diagnostic and therapeutic precision. However, a significant gap exists in creating fully integrated systems that mimic the complexity and adaptability of biological systems. The challenges associated with biocompatibility, long-term stability, and seamless integration of multiple functionalities remain significant hurdles. This paper directly addresses these gaps by presenting a new design strategy that integrates various sensing modalities and actuation mechanisms into a single, biocompatible platform. The in-situ fabrication method addresses the limitations of traditional methods like 3D printing, which often struggle to achieve the required level of integration and material diversity.
Methodology
The study employed an in-situ solution-based fabrication approach to create bio-inspired soft robots. These robots consist of two main layers: an electronic skin (e-skin) and an artificial muscle. The e-skin, a flexible nanocomposite layer, was fabricated using a solution-based method, allowing the integration of various sensing materials (reduced graphene oxide (RGO), silver nanowires (AgNWs), MXene, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)) into a polymer matrix (polyimide (PI) and polydimethylsiloxane (PDMS)). This approach enables the creation of multifunctional sensors capable of detecting temperature, pressure, strain, and chemical changes. The artificial muscle layer, a thermally responsive hydrogel (poly(N-isopropylacrylamide) (PNIPAM)), provides the actuation force. A thin bio-adhesive layer acts as a cushioning medium between the e-skin and artificial muscle. The PNIPAM hydrogel's lower critical solution temperature (LCST) can be adjusted by incorporating acrylamide (AAm) to tailor its responsiveness to different temperature ranges. The researchers demonstrated various designs inspired by natural structures, such as starfish and chiral seedpods, to achieve bending, expanding, and twisting motions. Wireless operation was achieved using a battery-free system with passive LC resonance circuits for sensing and electromagnetic power transmission for actuation. The performance of the soft robots was evaluated through in vitro experiments using artificial organ models (bladder, blood vessel, and stomach) and in vivo studies using a mouse model (for cardiac applications). Specific fabrication methods for each component (e.g., AgNWs, RGO, PNIPAM hydrogel, PAAm hydrogel, e-skin layers, etc.) are detailed in the methods section of the paper, along with the characterization techniques used (SEM, XPS, XRD, FTIR, thermal imaging, UV-vis spectroscopy). In-vitro biocompatibility assessments were conducted using 3T3-J-2 cells, and in-vivo studies involved histological analysis of tissue samples from mice. Finite element analysis (FEA) simulations were employed to model and predict the shape transformations of the soft robots under various stimuli.
Key Findings
The research successfully demonstrated the feasibility of creating multifunctional, bio-inspired soft robots using an in-situ solution-based fabrication method. The key findings include: 1. **Multifunctional e-skin:** The researchers successfully integrated various sensing materials into a flexible e-skin layer, enabling the detection of temperature, pressure, strain, and pH changes with high spatiotemporal resolution. The in-situ approach yielded superior mechanical and electrical performance compared to conventional methods like 3D printing. 2. **Biomimetic designs and actuation:** Inspired by natural structures, the soft robots demonstrated diverse actuation capabilities, including bending, twisting, and expansion. The PNIPAM hydrogel-based artificial muscle provided reliable and controllable actuation, with the ability to tailor the LCST for different application needs. The researchers demonstrated precise, on-demand actuation through electrothermal stimulation. 3. **Wireless operation:** The integrated battery-free wireless module enabled untethered operation and communication, crucial for implantable devices. The system effectively used passive LC resonance circuits for sensing and electromagnetic power transmission for actuation. 4. **In vitro and in vivo validation:** The versatility of the soft robots was demonstrated through in vitro experiments using artificial models of the bladder, blood vessels, and stomach. These experiments validated the ability of the robots to accurately measure pressure, volume, and pH changes. In vivo studies on a mouse model showcased the capability of a soft robotic thera-gripper to gently grasp the beating heart, measure cardiac contractility, and deliver electrical stimulation for therapeutic purposes. The in-vivo tests also confirmed the biocompatibility of the devices. 5. **Closed-loop control:** The soft robotic gripper for bladder control demonstrated a closed-loop system, where bladder volume measurements triggered electrical stimulation for treating bladder dysfunction. The in-vivo tests demonstrated the ability of the soft robotic thera-gripper to monitor and modulate cardiac activity. 6. **Biocompatibility:** The in vitro and in vivo tests confirmed the biocompatibility of the soft robots, with no observable adverse effects on cells or tissues after implantation in mice. The quantitative data presented includes specific measurements of pressure sensitivity, gauge factor, resonant frequency shifts, temperature sensitivity, bending angles, actuation force, pH response of sensors, drug release rates, ECG traces during stimulation, and measurements of cardiac contractility.
Discussion
This study successfully addressed the significant challenges in developing bio-inspired, soft robots for medical implants. The in-situ solution-based fabrication method offers a significant advantage over traditional techniques by enabling seamless integration of diverse functionalities within a single, biocompatible platform. The biomimetic designs, coupled with precise, on-demand actuation and wireless operation, open up exciting possibilities for minimally invasive medical procedures. The successful in vitro and in vivo validations demonstrate the potential of these soft robots for a range of applications, from bladder control to cardiac monitoring and therapy. The study's findings have implications for advancing the field of medical robotics and developing next-generation implantable devices. The ability to integrate multiple sensing modalities and actuation mechanisms into a single, compact device significantly enhances the capabilities and efficacy of implantable technologies. Future research directions could focus on further improving the long-term biocompatibility and stability of these devices, exploring more sophisticated control algorithms, and expanding the range of applications to other physiological systems.
Conclusion
This work presents a novel approach to designing and fabricating bio-inspired soft robots for electronic implants. The in-situ fabrication of a multifunctional e-skin and the integration of a thermally responsive artificial muscle enable diverse actuation capabilities and precise sensing of various parameters. The battery-free wireless system allows for untethered operation, ideal for minimally invasive applications. In vitro and in vivo studies demonstrated the devices' efficacy in bladder control, blood pressure monitoring, pH sensing, drug delivery, and cardiac function monitoring and modulation. This platform showcases significant potential for next-generation biomedical implants. Future research should focus on long-term biocompatibility studies and the exploration of even more complex applications.
Limitations
While the study demonstrates significant advancements in soft robotic implants, certain limitations exist. The long-term biocompatibility and stability of the devices in vivo require further investigation. The current designs primarily rely on thermal actuation, limiting the range of applications and potentially introducing challenges in precisely controlled actuation within the body's complex thermal environment. The in vivo experiments were conducted on a limited number of mice, and larger-scale studies may be needed to confirm the generalizability of the findings. The closed-loop control systems could be further refined to enhance responsiveness and adaptability in complex physiological settings. Further work is also needed to fully understand the clinical efficacy of the electrical stimulation provided by the devices for treating bladder dysfunction and cardiac conditions.
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