Öncay Yasa

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Yasa

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Öncay

ORCID

0000-0002-0282-6127

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Publications 1 - 10 of 13

Magnetic Soft Robots for Targeted Bacterial Delivery and Enhanced Tumor Spheroid Disaggregation
Krauss, Tamara; Yasa, Öncay; Pustovalov, Vitaly; et al. (2025)
Advanced Intelligent Systems
Bacterial cancer therapy has great potential due to the mobility of bacteria within tissues and their active function in tumor localization. However, rapid uncontrolled division and off-target distribution of bacteria hinder their therapeutic use. To enhance the bacteria's targeting ability, bacteria are modified with magnetic materials that respond to external control signals. Nonetheless, this approach still tackles the rapid division of bacteria, their slow locomotion speed, and the control of their localization. Therefore, it is proposed to confine bacteria within a more extensive hydrogel-based platform that can be controlled with external stimuli. Specifically, a millimeter-scale magnetic soft robot incorporating probiotic bacteria is reported, which allows for the rapid, concentrated, and targeted delivery of living therapeutics with external alternating magnetic fields. In addition to remaining viable and multiplying within the hydrogel network, the bacteria escape from the robot after one hour and successfully disrupt colorectal tumor spheroids in vitro. Moreover, this robot demonstrates mobility across rough terrain made up of multiple materials and can target a polyp inside a phantom of the colon. Overall, this magnetic soft robotic platform provides a new strategy for a potential targeted cancer treatment based on the concentrated delivery of tens of millions of bacteria.
Perfusable Biohybrid Designs for Bioprinted Skeletal Muscle Tissue
Filippi, Miriam; Yasa, Öncay; Giachino, Jan; et al. (2023)
Advanced Healthcare Materials
Engineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival, and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately coprinted with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that i) coprinted synthetic structures display highly coherent interfaces with the living tissue, ii) perfusable designs preserve cells from hypoxia all over the scaffold volume, iii) constructs can undergo passive mechanical tension during matrix remodeling, and iv) the constructs can be used to study the distribution of drugs. Extrusion-based multimaterial bioprinting with the inks and design realizes in vitro matured biohybrid SMT for biomedical applications.
Multidirectional Filamented Light Biofabrication Creates Aligned and Contractile Cardiac Tissues
Jones, Lewis; Filippi, Miriam; Michelis, Mike Yan; et al. (2024)
Advanced Science
Biofabricating 3D cardiac tissues that mimic the native myocardial tissue is a pivotal challenge in tissue engineering. In this study, we fabricate 3D cardiac tissues with controlled, multidirectional cellular alignment and directed or twisting contractility. We show that multidirectional filamented light can be used to biofabricate high-density (up to 60 × 106 cells mL−1) tissues, with directed uniaxial contractility (3.8x) and improved cell-to-cell connectivity (1.6x gap junction expression). Furthermore, by using multidirectional light projection, we can partially overcome cell-induced light attenuation, and fabricate larger tissues with multidirectional cellular alignment. For example, we fabricate a tri-layered myocardium-like tissue and a bi-layered tissue with torsional contractility. The approach provides a new strategy to rapidly fabricate aligned cardiac tissues relevant to regenerative medicine and biohybrid robotics.
3D-Printed Biodegradable Microswimmer for Theranostic Cargo Delivery and Release
Ceylan, Hakan; Yasa, Immihan Ceren; Yasa, Öncay; et al. (2019)
ACS Nano
Untethered mobile microrobots have the potential to leverage minimally invasive theranostic functions precisely and efficiently in hard-to-reach, confined, and delicate inner body sites. However, such a complex task requires an integrated design and engineering, where powering, control, environmental sensing, medical functionality, and biodegradability need to be considered altogether. The present study reports a hydrogel-based, magnetically powered and controlled, enzymatically degradable microswimmer, which is responsive to the pathological markers in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical architecture enabling volumetric cargo loading and swimming capabilities under rotational magnetic fields and a 3D-printed optimized 3D microswimmer (length = 20 μm and diameter = 6 μm) using two-photon polymerization from a magnetic precursor suspension composed from gelatin methacryloyl and biofunctionalized superparamagnetic iron oxide nanoparticles. At normal physiological concentrations, we show that matrix metalloproteinase-2 (MMP-2) enzyme could entirely degrade the microswimmer in 118 h to solubilized nontoxic products. The microswimmer rapidly responds to the pathological concentrations of MMP-2 by swelling and thereby boosting the release of the embedded cargo molecules. In addition to delivery of the drug type of therapeutic cargo molecules completely to the given microenvironment after full degradation, microswimmers can also release other functional cargos. As an example demonstration, anti-ErbB 2 antibody-tagged magnetic nanoparticles are released from the fully degraded microswimmers for targeted labeling of SKBR3 breast cancer cells in vitro toward a potential future scenario of medical imaging of remaining cancer tissue sites after a microswimmer-based therapeutic delivery operation.
Hydroelastomers: soft, tough, highly swelling composites
Moser, Simon; Feng, Yanxia; Yasa, Öncay; et al. (2022)
Soft Matter
Inspired by the cellular design of plant tissue, we present an approach to make versatile, tough, highly water-swelling composites. We embed highly swelling hydrogel particles inside tough, water-permeable, elastomeric matrices. The resulting composites, which we call hydroelastomers, combine the properties of their parent phases. From their hydrogel component, the composites inherit the ability to highly swell in water. From the elastomeric component, the composites inherit excellent stretchability and fracture toughness, while showing little softening as they swell. Indeed, the fracture properties of the composite match those of the best-performing, tough hydrogels, exhibiting fracture energies of up to 10 kJ m(-2). Our composites are straightforward to fabricate, based on widely-available materials, and can easily be molded or extruded to form shapes with complex swelling geometries. Furthermore, there is a large design space available for making hydroelastomers, since one can use any hydrogel as the dispersed phase in the composite, including hydrogels with stimuli-responsiveness. These features make hydroelastomers excellent candidates for use in soft robotics and swelling-based actuation, or as shape-morphing materials, while also being useful as hydrogel replacements in other fields.
Biohybrid and Synthetic Microswimmers for Targeted Cargo Delivery
Yasa, Öncay (2019)
Bilayered Biofabrication Unlocks the Potential of Skeletal Muscle for Biohybrid Soft Robots
Balciunaite, Aiste; Yasa, Öncay; Filippi, Miriam; et al. (2024)
2024 IEEE 7th International Conference on Soft Robotics (RoboSoft)
The emerging field of biohybrid robotics aims to create the next generation of soft and sustainable robots by using engineered biological muscle tissues integrated with soft materials as artificial muscles, called bio-actuators. Both cardiac and skeletal muscle cells can be utilized for biohybrid actuation. Generally, cardiac bio-actuators take the shape of thin cellular films, while locomotive skeletal muscle bio-actuators form bulk tissues. The geometry of a bio-actuator should be optimized for the type of desired motion, e.g., thin film layers are optimal for swimming actuators mimicking fish. Until now, the geometry of skeletal muscle bio-actuators has been constrained to ring- or block-like tissues generally differentiated around a pair of pillars due to the need to oppose the contraction force exerted during the skeletal muscle differentiation process. In this work, we extend the possible geometry of skeletal muscle bio-actuators by demonstrating a bilayered design that mimics the motion of jellyfish. We take advantage of a volumetric printing method, i.e., xolography, which allows us to micropattern poly(ethylene glycol) diacrylate and gelatin methacrylate hydrogels to serve as scaffolds for seeding a layer of the skeletal muscle cell matrix. We demonstrate that the locomotion speed of our bio-actuators is 2.5 × faster than that of previously reported counterparts. In addition, our skeletal bio-actuators outperform most cardiac ones. Further optimization of our bilayer biofabrication for improved reproducibility of the maturation process of the skeletal muscle tissue will pave the way for the next generation of performant skeletal muscle-based actuators for biohybrid robots.
Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery
Akolpoglu, Mukrime Birgul; Alapan, Yunus; Dogan, Nihal Olcay; et al. (2022)
Science Advances
Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuliresponsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coli with ~90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli–based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.
Will microfluidics enable functionally integrated biohybrid robots?
Filippi, Miriam; Yasa, Öncay; Kamm, Roger D.; et al. (2022)
Proceedings of the National Academy of Sciences of the United States of America
The next robotics frontier will be led by biohybrids. Capable biohybrid robots require microfluidics to sustain, improve, and scale the architectural complexity of their core ingredient: biological tissues. Advances in microfluidics have already revolutionized disease modeling and drug development, and are positioned to impact regenerative medicine but have yet to apply to biohybrids. Fusing microfluidics with living materials will improve tissue perfusion and maturation, and enable precise patterning of sensing, processing, and control elements. This perspective suggests future developments in advanced biohybrids.
Engineered Magnetic Nanocomposites to Modulate Cellular Function
Filippi, Miriam; Garello, Francesca; Yasa, Öncay; et al. (2022)
Small
Magnetic nanoparticles (MNPs) have various applications in biomedicine, including imaging, drug delivery and release, genetic modification, cell guidance, and patterning. By combining MNPs with polymers, magnetic nanocomposites (MNCs) with diverse morphologies (core-shell particles, matrix-dispersed particles, microspheres, etc.) can be generated. These MNCs retain the ability of MNPs to be controlled remotely using external magnetic fields. While the effects of these biomaterials on the cell biology are still poorly understood, such information can help the biophysical modulation of various cellular functions, including proliferation, adhesion, and differentiation. After recalling the basic properties of MNPs and polymers, and describing their coassembly into nanocomposites, this review focuses on how polymeric MNCs can be used in several ways to affect cell behavior. A special emphasis is given to 3D cell culture models and transplantable grafts, which are used for regenerative medicine, underlining the impact of MNCs in regulating stem cell differentiation and engineering living tissues. Recent advances in the use of MNCs for tissue regeneration are critically discussed, particularly with regard to their prospective involvement in human therapy and in the construction of advanced functional materials such as magnetically operated biomedical robots.

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