Paul Wrede

Last Name

Wrede

First Name

Paul

ORCID

0000-0002-0702-6428

Organisational unit

09648 - Razansky, Daniel / Razansky, Daniel

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Publications 1 - 7 of 7

Upconversion Nanoparticle-Covalent Organic Framework Core-shell Particles as Therapeutic Microrobots Trackable With Optoacoustic Imaging
Kim, Dong Wook; Wrede, Paul; Rodríguez-Camargo, Andrés; et al. (2025)
Advanced Materials
Despite the development of various medical imaging contrast agents, integrating contrast signal generation with therapeutic and microrobotic functions remains challenging without complicated fabrication processes. In this study, upconversion nanoparticle-covalent organic framework (UCNP-COF) core-shell sub-micron particles are developed that function as therapeutic microrobots trackable with multi-spectral optoacoustic tomography (MSOT) imaging and can be loaded with desired therapeutic molecular agents in a customizable manner. The mechanism of optoacoustic signal generation in UCNP-COF particles is attributed to the quenching of upconversion luminescence emitted by the UCNPs, which is absorbed by the encapsulating COF and subsequently converted into acoustic waves. Unlike other microparticulate agents previously imaged with MSOT, UCNP-COF particles do not pose concerns about their stability and biocompatibility. Simultaneously, the mesoporous texture of the COF provides a large surface area, allowing for the efficient loading of various drug molecules, which can be released at target sites. Furthermore, the magnetic UCNP-COF Janus particles can be magnetically navigated through in vivo vasculature while being visualized in real-time with volumetric MSOT. This study proposes an approach to design photonic materials with multifunctionality, enabling high-performance medical imaging, drug delivery, and microrobotic manipulation toward their future potential clinical use.
Synergistic integration of materials in medical microrobots for advanced imaging and actuation
Wrede, Paul; Remlova, Eva; Chen, Yi; et al. (2025)
Nature Reviews Materials
Medical microrobotics capitalizes on smart materials to target specific body sites effectively, precisely and locally, thus holding promise to revolutionize precision medicine in the future. Advances in material science and microfabrication or nanofabrication techniques have facilitated the implementation of a myriad of functionalities into microrobots. Efficient navigation and monitoring of microrobots within the highly dynamic and often inaccessible environment of living mammalian tissues is paramount for their effective in vivo applications and eventual clinical translation. This need calls for the deployment of biomedical imaging modalities with adequate sensitivity, penetration depth and spatiotemporal resolution, as well as for efficient integration of biocompatible contrast materials into microrobots. In this Review, we discuss emerging approaches for multiplexed imaging and actuation of microrobots within complex biological environments, focusing on the synergistic combination of responsive and contrasting materials to achieve desired morphological and functional properties, in vivo visibility and biosafety. The convergence between microrobotics and biomedical imaging paves the way for a new generation of medical microrobots enabling the use of energy for both mechanical actuation and efficient monitoring of their activity in vivo.
Immune Cell-Based Microrobots for Remote Magnetic Actuation, Antitumor Activity, and Medical Imaging
Dogan, Nihal Olcay; Suadiye, Eylül; Wrede, Paul; et al. (2024)
Advanced Healthcare Materials
Translating medical microrobots into clinics requires tracking, localization, and performing assigned medical tasks at target locations, which can only happen when appropriate design, actuation mechanisms, and medical imaging systems are integrated into a single microrobot. Despite this, these parameters are not fully considered when designing macrophage-based microrobots. This study presents living macrophage-based microrobots that combine macrophages with magnetic Janus particles coated with FePt nanofilm for magnetic steering and medical imaging and bacterial lipopolysaccharides for stimulating macrophages in a tumor-killing state. The macrophage-based microrobots combine wireless magnetic actuation, tracking with medical imaging techniques, and antitumor abilities. These microrobots are imaged under magnetic resonance imaging and optoacoustic imaging in soft-tissue-mimicking phantoms and ex vivo conditions. Magnetic actuation and real-time imaging of microrobots are demonstrated under static and physiologically relevant flow conditions using optoacoustic imaging. Further, macrophage-based microrobots are magnetically steered toward urinary bladder tumor spheroids and imaged with a handheld optoacoustic device, where the microrobots significantly reduce the viability of tumor spheroids. The proposed approach demonstrates the proof-of-concept feasibility of integrating macrophage-based microrobots into clinic imaging modalities for cancer targeting and intervention, and can also be implemented for various other medical applications.
Roadmap for Clinical Translation of Mobile Microrobotics
Bozuyuk, Ugur; Wrede, Paul; Yildiz, Erdost; et al. (2024)
Advanced Materials
Medical microrobotics is an emerging field to revolutionize clinical applications in diagnostics and therapeutics of various diseases. On the other hand, the mobile microrobotics field has important obstacles to pass before clinical translation. This article focuses on these challenges and provides a roadmap of medical microrobots to enable their clinical use. From the concept of a "magic bullet" to the physicochemical interactions of microrobots in complex biological environments in medical applications, there are several translational steps to consider. Clinical translation of mobile microrobots is only possible with a close collaboration between clinical experts and microrobotics researchers to address the technical challenges in microfabrication, safety, and imaging. The clinical application potential can be materialized by designing microrobots that can solve the current main challenges, such as actuation limitations, material stability, and imaging constraints. The strengths and weaknesses of the current progress in the microrobotics field are discussed and a roadmap for their clinical applications in the near future is outlined.
MRI-powered Magnetic Miniature Capsule Robot with HIFU-controlled On-demand Drug Delivery
Tiryaki, Mehmet Efe; Dogangun, Fatih; Dayan, Cem Balda; et al. (2023)
ArXiv
Magnetic resonance imaging (MRI)-guided robotic systems offer great potential for new minimally invasive medical tools, including MRI-powered miniature robots. By re-purposing the imaging hardware of an MRI scanner, the magnetic miniature robot could be navigated into the remote part of the patient's body without needing tethered endoscopic tools. However, the state-of-art MRI-powered magnetic miniature robots have limited functionality besides navigation. Here, we propose an MRI-powered magnetic miniature capsule robot benefiting from acoustic streaming forces generated by MRI-guided high-intensity focus ultrasound (HIFU) for controlled drug release. Our design comprises a polymer capsule shell with a submillimeter-diameter drug-release hole that captures an air bubble functioning as a stopper. We use the HIFU pulse to initiate drug release by removing the air bubble once the capsule robot reaches the target location. By controlling acoustic pressure, we also regulate the drug release rate for multiple location targeting during navigation. We demonstrated that the proposed magnetic capsule robot could travel at high speed up to 1.13 cm/s in ex vivo porcine small intestine and release drug to multiple target sites in a single operation, using a combination of MRI-powered actuation and HIFU-controlled release. The proposed MRI-guided microrobotic drug release system will greatly impact minimally invasive medical procedures by allowing on-demand targeted drug delivery.
MRI-powered Magnetic Miniature Capsule Robot with HIFU-controlled On-demand Drug Delivery
Tiryaki, Mehmet Fie; Doganguen, Fatih; Dayan, Cem Balda; et al. (2023)
2023 IEEE International Conference on Robotics and Automation (ICRA)
Magnetic resonance imaging (MRI)-guided robotic systems offer great potential for new minimally invasive medical tools, including MRI-powered miniature robots. By re-purposing the imaging hardware of an MRI scanner, the magnetic miniature robot could be navigated into the remote part of the patient's body without needing tethered endoscopic tools. However, state-of-art MRI-powered magnetic miniature robots have limited functionality besides navigation. Here, we propose an MRI-powered magnetic miniature capsule robot benefiting from acoustic streaming forces generated by MRI-guided high-intensity focus ultrasound (HIFU) for controlled drug release. Our design comprises a polymer capsule shell with a submillimeter-diameter drug-release hole that captures an air bubble functioning as a stopper. We use the HIFU pulse to initiate drug release by removing the air bubble once the capsule robot reaches the target location. By controlling acoustic pressure, we also regulate the drug release rate for multiple locations targeting during navigation. We demonstrated that the proposed magnetic capsule robot could travel at high speed, up to 1.13 cm/s in ex vivo porcine small intestine, and release drug to multiple target sites in a single operation, using a combination of MRI-powered actuation and HIFU-controlled release. The proposed MRI-guided microrobotic drug release system will greatly impact minimally invasive medical procedures by allowing on-demand targeted drug delivery.
Hierarchical Nanostructures as Acoustically Manipulatable Multifunctional Agents in Dynamic Fluid Flow
Kim, Dong Wook; Wrede, Paul; Estrada Beltran, Héctor Andrés; et al. (2024)
Advanced Materials
Acoustic waves provide a biocompatible and deep-tissue-penetrating tool suitable for contactless manipulation in in vivo environments. Despite the prevalence of dynamic fluids within the body, previous studies have primarily focused on static fluids, and manipulatable agents in dynamic fluids are limited to gaseous core-shell particles. However, these gas-filled particles face challenges in fast-flow manipulation, complex setups, design versatility, and practical medical imaging, underscoring the need for effective alternatives. In this study, flower-like hierarchical nanostructures (HNS) into microparticles (MPs) are incorporated, and demonstrated that various materials fabricated as HNS-MPs exhibit effective and reproducible acoustic trapping within high-velocity fluid flows. Through simulations, it is validated that the HNS-MPs are drawn to the focal point by acoustic streaming and form a trap through secondary acoustic streaming at the tips of the nanosheets comprising the HNS-MPs. Furthermore, the wide range of materials and modification options for HNS, combined with their high surface area and biocompatibility, enable them to serve as acoustically manipulatable multimodal imaging contrast agents and microrobots. They can perform intravascular multi-trap maneuvering with real-time imaging, purification of wastewater flow, and highly-loaded drug delivery. Given the diverse HNS materials developed to date, this study extends their applications to acoustofluidic and biomedical fields.

Publications 1 - 7 of 7

Paul Wrede

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