Natural Algae-Inspired Microrobots for Emerging Biomedical Applications and Beyond

Algae-inspired microrobots (AIMs) have attracted intense research over the past decade owing to the abundant desired properties of natural microalgae, such as biocompatibility, autofluorescence, and pharmaceutical activity, which make them ideal candidates for biomedical and related applications. With the deepening and widening of applied research, the functions of AIMs have been greatly enriched and enhanced to meet the needs of demanding application scenarios including targeted drug delivery, anticancer/antibacterial therapy, cell stimulation, wound healing, and biomolecule sensing. Notwithstanding, multiple challenges remain to be tackled for transformative advances and clinical translation. In this review, we aim to provide a comprehensive survey of representative advances in AIMs accompanied by the underlying biological/technological backgrounds. We also highlight existing issues that need to be overcome in AIM developments and suggest future research directions in this field.</p

Micro/nanoscale magnetic robots for biomedical applications

Magnetic small-scale robots are devices of great potential for the biomedical field because of the several benefits of this method of actuation. Recent work on the development of these devices has seen tremendous innovation and refinement toward ​improved performance for potential clinical applications. This review briefly details recent advancements in small-scale robots used for biomedical applications, covering their design, fabrication, applications, and demonstration of ability, and identifies the gap in studies and the difficulties that have persisted in the optimization of the use of these devices. In addition, alternative biomedical applications are also suggested for some of the technologies that show potential for other functions. This study concludes that although the field of small-scale robot research is highly innovative ​there is need for more concerted efforts to improve functionality and reliability of these devices particularly in clinical applications. Finally, further suggestions are made toward ​the achievement of commercialization for these devices

Medical Imaging of Microrobots: Toward In Vivo Applications

Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications

Magnetically Driven Micro and Nanorobots

Manipulation and navigation of micro and nanoswimmers in different fluid environments can be achieved by chemicals, external fields, or even motile cells. Many researchers have selected magnetic fields as the active external actuation source based on the advantageous features of this actuation strategy such as remote and spatiotemporal control, fuel-free, high degree of reconfigurability, programmability, recyclability, and versatility. This review introduces fundamental concepts and advantages of magnetic micro/nanorobots (termed here as "MagRobots") as well as basic knowledge of magnetic fields and magnetic materials, setups for magnetic manipulation, magnetic field configurations, and symmetry-breaking strategies for effective movement. These concepts are discussed to describe the interactions between micro/nanorobots and magnetic fields. Actuation mechanisms of flagella-inspired MagRobots (i.e., corkscrew-like motion and traveling-wave locomotion/ciliary stroke motion) and surface walkers (i.e., surface-assisted motion), applications of magnetic fields in other propulsion approaches, and magnetic stimulation of micro/nanorobots beyond motion are provided followed by fabrication techniques for (quasi)spherical, helical, flexible, wire-like, and biohybrid MagRobots. Applications of MagRobots in targeted drug/gene delivery, cell manipulation, minimally invasive surgery, biopsy, biofilm disruption/eradication, imaging-guided delivery/therapy/surgery, pollution removal for environmental remediation, and (bio)sensing are also reviewed. Finally, current challenges and future perspectives for the development of magnetically powered miniaturized motors are discussed

Additive Manufacturing of Bio and Synthetic Polymers

Additive manufacturing technology offers the ability to produce personalized products with lower development costs, shorter lead times, less energy consumed during manufacturing and less material waste. It can be used to manufacture complex parts and enables manufacturers to reduce their inventory, make products on-demand, create smaller and localized manufacturing environments, and even reduce supply chains. Additive manufacturing (AM), also known as fabricating three-dimensional (3D) and four-dimensional (4D) components, refers to processes that allow for the direct fabrication of physical products from computer-aided design (CAD) models through the repetitious deposition of material layers. Compared with traditional manufacturing processes, AM allows the production of customized parts from bio- and synthetic polymers without the need for molds or machining typical for conventional formative and subtractive fabrication.In this Special Issue, we aimed to capture the cutting-edge state-of-the-art research pertaining to advancing the additive manufacturing of polymeric materials. The topic themes include advanced polymeric material development, processing parameter optimization, characterization techniques, structure–property relationships, process modelling, etc., specifically for AM

Magnetic systems for cancer immunotherapy

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies. Immune cell modulation through the administration of drugs, proteins, and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors. Magnetic systems offer several advantages for improving the performance of immunotherapies, including increased spatiotemporal control over transport, release, and dosing of immunomodulatory drugs within the body, resulting in reduced off-target effects and improved efficacy. Compared to alternative methods for stimulating drug release such as light and pH, magnetic systems enable several distinct methods for programming immune responses. First, we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release. Second, we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites. Third, we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs. Fourth, we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity. Finally, we discuss translational considerations of these systems, such as toxicity, clinical compatibility, and future opportunities for improving cancer treatment. &nbsp;</p

Formulation and characterization of siRNA embedded nanoparticles for pulmonary delivery

Advancing existing or developing novel nanoparticle carrier systems is a crucial part of successful nucleic acid delivery for therapeutic purposes. The overall aim of nanoparticle formulations is to deliver their cargo to the site of action. During this procedure, nanoparticles need to show qualities to be internalized into the cell and release their cargo. Dependent on the application route and prior to cell uptake, nanoparticles can be transferred into a form of administration that improves conformation and leads to long-term storage stability. The aim of this thesis is to identify various small interfering RNA (siRNA)-nanoparticle formulations as drug delivery systems with potential to target the lungs (Chapter I + II). Nanoparticles carrier systems comprised of polymers, lipids or a hybrid combination encapsulating nucleic acids and were formed using the concept of microfluidic mixing. The thesis can be separated into two main parts. The first part addresses the common dilemma of the endosomal escape problem by improving existing polymers through chemical modification (Chapter III), synthesizing a novel amphiphilic polymer (Chapter IV) and forming hybrid lipid polyplex nanoparticles (Chapter V). The second section focuses on the development of a spray-drying approach (Chapter VI) and the long-term storage under various conditions (Chapter VI) for siRNA-lipid nanoparticles (LNPs) based on an adapted Onpattro® formulation. The endosomal release problem of polymeric nanoparticles was tackled looking at physicochemical nanoparticle characterization and in vitro performance assessment. Throughout Chapters III - V, sizes of 100 – 200 nm were reached, the zeta potential was kept neutral to positive, and the encapsulation efficiency of siRNA showed values > 90% resulting in an improved in vitro knockdown performance (> 50%) in comparison to polyethylene imine (PEI) polyplexes or triblock copolymer polyplexes cores. The establishment of a spray drying platform for LNPs (Chapter VI) and subsequent drying for storage stability (Chapter VII) resulted in spray dried powders that maintained LNP integrity and stability by loosing up to 15% of siRNA and lipid content. The aerodynamic properties showed ideal characteristics for pulmonary delivery with sizes of 3 μm. The in vitro performance reached knockdown levels of > 95% and a house keeping gene silencing of > 50% was established ex vivo in human precision cut lung slices. In conclusion, this thesis should give an overview of several non-viral siRNA nanoparticles as nucleic acid delivery systems that on the one hand improve the endosomal escape problem of polymeric nanoparticles, and on the other hand are established for pulmonary delivery through a spray drying method