Miriam Filippi

Last Name

Filippi

First Name

Miriam

ORCID

0000-0002-9651-406X

Organisational unit

09689 - Katzschmann, Robert / Katzschmann, Robert

Show all metadata

Search Results

Publications1 - 10 of 45

Strategies to promote vascularization, survival, and functionality of engineered tissues
Filippi, Miriam; Später, Thomas; Herrmann, Marietta; et al. (2023)
Tissue Engineering (Third Edition)
The success of engineered tissues after their implantation strongly depends on the rapid establishment of an efficient vascular network throughout the implant, ensuring its long-term viability and functionality. Tremendous effort has been dedicated to exploring ways to promote the neo-vascularization of three-dimensional (3D) engineered tissue implants. Here, we present an overview of different relevant approaches. This chapter includes the description of in vitro strategies used to promote vascular ingrowth from the host tissue as well as methods to increase cellular viability within 3D constructs or ways to produce a vascular network before implantation. We further present ex vivo and in vivo techniques for the assessment of vascular growth and engraftment of the implants. Finally, we discuss the limitations of the current approaches and potential future directions.
Sensor-Embedded Muscle for Closed-Loop Controllable Actuation in Proprioceptive Biohybrid Robots
Filippi, Miriam; Balciunaite, Aiste; Georgopoulou, Antonia; et al. (2025)
Advanced Intelligent Systems
Biohybrid robots are soft robots that exploit unique characteristics of biological cells and tissues for motion generation. Skeletal muscle tissue-based bioactuators respond to externally applied stimuli, such as electrical fields. However, current bioactuation systems rely on open-loop control strategies that lack knowledge of the actuator's state. The regulation of output force and position of biohybrid robots requires self-sensing control systems that combine bioactuators with sensors and control paradigms. Herein, a soft, fiber-shaped mechanical sensor based on a piezoresistive composite is proposed that efficiently integrates with engineered skeletal muscle tissue and senses its contracting states in a cell culture environment in the presence of applied electrical fields. After testing the sensor's insulation and biocompatibility, its sensitivity for typical strains (<1%) is characterized, and its ability is proven to detect motions from contractile skeletal muscle tissue constructs. Finally, it is shown that the sensor response can feed an autonomous control system, thus demonstrating the first proprioceptive biohybrid robot that senses and responds to its contraction state. In addition to inspiring implantable systems, biomedical models, and other bioelectronic devices, the proposed technology will confer biohybrids with decisional autonomy, thus driving the paradigm shift between bioactuators and intelligent biohybrid robots.
Manufacturing of Human Tissues as off-the-Shelf Grafts Programmed to Induce Regeneration
Pigeot, Sébastien; Klein, Thibaut; Gullotta, Fabiana; et al. (2021)
Advanced Materials
Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported. The strategy relies on a customized human mesenchymal line expressing bone morphogenetic protein-2 (BMP-2), critically required for robust chondrogenesis and concomitant extracellular matrix (ECM) enrichment. Following apoptosis-driven devitalization, lyophilization, and storage, the resulting off-the-shelf cartilage tissue exhibits unprecedented osteoinductive properties, unmatched by synthetic delivery of BMP-2 or by living engineered grafts. Scalability and pre-clinical efficacy are demonstrated by bioreactor-based production and subsequent orthotopic assessment. The findings exemplify the broader paradigm of programming human cell lines as biological factory units to engineer customized ECMs, designed to activate specific regenerative processes.
Imaging of Inflammation in Spinal Cord Injury: Novel Insights on the Usage of PFC-Based Contrast Agents
Garello, Francesca; Boido, Marina; Miglietti, Martina; et al. (2021)
Biomedicines
Labeling of macrophages with perfluorocarbon (PFC)-based compounds allows the visualization of inflammatory processes by 19F-magnetic resonance imaging (19F-MRI), due to the absence of endogenous background. Even if PFC-labeling of monocytes/macrophages has been largely investigated and used, information is lacking about the impact of these agents over the polarization towards one of their cell subsets and on the best way to image them. In the present work, a PFC-based nanoemulsion was developed to monitor the course of inflammation in a model of spinal cord injury (SCI), a pathology in which the understanding of immunological events is of utmost importance to select the optimal therapeutic strategies. The effects of PFC over macrophage polarization were studied in vitro, on cultured macrophages, and in vivo, in a mouse SCI model, by testing and comparing various cell tracking protocols, including single and multiple administrations, the use of MRI or Point Resolved Spectroscopy (PRESS), and application of pre-saturation of Kupffer cells. The blood half-life of nanoemulsion was also investigated by ¹⁹F Magnetic Resonance Spectroscopy (MRS). In vitro and in vivo results indicate the occurrence of a switch towards the M2 (anti-inflammatory) phenotype, suggesting a possible theranostic function of these nanoparticles. The comparative work presented here allows the reader to select the most appropriate protocol according to the research objectives (quantitative data acquisition, visual monitoring of macrophage recruitment, theranostic purpose, rapid MRI acquisition, etc.). Finally, the method developed here to determine the blood half-life of the PFC nanoemulsion can be extended to other fluorinated compounds.
Use of nanoparticles in skeletal tissue regeneration and engineering
Filippi, Miriam; Born, Gordian; Felder-Flesch, Delphine; et al. (2020)
Histology and Histopathology
Bone and osteochondral defects represent one of the major causes of disabilities in the world. Derived from traumas and degenerative pathologies, these lesions cause severe pain, joint deformity, and loss of joint motion. The standard treatments in clinical practice present several limitations. By producing functional substitutes for damaged tissues, tissue engineering has emerged as an alternative in the treatment of defects in the skeletal system. Despite promising preliminary clinical outcomes, several limitations remain. Nanotechnologies could offer new solutions to overcome those limitations, generating materials more closely mimicking the structures present in naturally occurring systems. Nanostructures comparable in size to those appearing in natural bone and cartilage have thus become relevant in skeletal tissue engineering. In particular, nanoparticles allow for a unique combination of approaches (e.g. cell labelling, scaffold modification or drug and gene delivery) inside single integrated systems for optimized tissue regeneration. In the present review, the main types of nanoparticles and the current strategies for their application to skeletal tissue engineering are described. The collection of studies herein considered confirms that advanced nanomaterials will be determinant in the design of regenerative therapeutic protocols for skeletal lesions in the future.
Magnetic nanocomposite hydrogels and static magnetic field stimulate the osteoblastic and vasculogenic profile of adipose-derived cells
Filippi, Miriam; Dasen, Boris; Guerrero, Julien; et al. (2019)
Biomaterials
Exposure of cells to externally applied magnetic fields or to scaffolding materials with intrinsic magnetic properties (magnetic actuation) can regulate several biological responses. Here, we generated novel magnetized nanocomposite hydrogels by incorporation of magnetic nanoparticles (MNPs) into polyethylene glycol (PEG)-based hydrogels containing cells from the stromal vascular fraction (SVF) of human adipose tissue. We then investigated the effects of an external Static Magnetic Field (SMF) on the stimulation of osteoblastic and vasculogenic properties of the constructs, with MNPs or SMF alone used as controls. MNPs migrated freely through and out of the material following the magnetic gradient. Magnetically actuated cells displayed increased metabolic activity. After 1 week, the enzymatic activity of Alkaline Phosphatase (ALP), the expression of osteogenic markers (Runx2, Collagen I, Osterix), and the mineralized matrix deposition were all augmented as compared to controls. With magnetic actuation, strong activation of endothelial, pericytic and perivascular genes paralleled increased levels of VEGF and an enrichment in the CD31+ cells population. The stimulation of signaling pathways involved in the mechanotransduction, like MAPK8 or Erk, at gene and protein levels suggested an effect mediated through the mechanical stimulation. Upon subcutaneous implantation in mice, magnetically actuated constructs exhibited denser, more mineralized and faster vascularized tissues, as revealed by histological and micro-computed tomographic analyses. The present study suggests that magnetic actuation can stimulate both the osteoblastic and vasculogenic potentials of engineered bone tissue grafts, likely at least partially by mechanically stimulating the function of progenitor cells.
Biocompatible Ink Optimization Enables Functional Volumetric Bioprinting With Xolography
Brauer, Erik; Balciunaite, Aiste; Kollert, Matthias R.; et al. (2025)
Advanced Materials
Xolography is a novel linear volumetric manufacturing technique that offers unparalleled precision and speed. Yet, its application to bioprinting remains limited due to insufficient understanding of biocompatibility constraints. Here, this work establishes fundamental design principles for cell-compatible Xolography bioinks by dissecting the effects of extracellular pH, osmolality, and lysosomotropic stress on cell viability and function. By systematically studying the tolerances for these parameters, this work defines a framework for bioink formulations that enables fast, support-free fabrication of complex designs with maintained cell viability and function as validated in different murine and human cell lines, primary human cells and induced pluripotent stem cell (iPSC)-derived cells. These results show that, unlike triethanolamine, BisTris indeed can function as a fully biocompatible co-initiator enabling cell viability beyond 90% as well as uncompromised metabolic activity and differentiation performance when used in a tightly controlled formulation, contrasting previous reports. This work showcases the biomedical potential of the formulation by achieving fibroblast-driven extracellular matrix (ECM) formation, endothelial sprouting from pre-vascularized spheroids, and maintenance of an iPSC-derived hepatocyte differentiation phenotype within Xolography-printed constructs. These advancements transform Xolography into a powerful and foremost reliable bioprinting platform for fabrication of complex, cell-laden structures for versatile applications in tissue engineering, organ-on-a-chip models, and regenerative medicine.
Novel stable dendrimersome formulation for safe bioimaging applications
Filippi, Miriam; Patrucco, Deyssy; Martinelli, Jonathan; et al. (2015)
Nanoscale
Dendrimersomes are nanosized vesicles constituted by amphiphilic Janus dendrimers (JDs), which have been recently proposed as innovative nanocarriers for biomedical applications. Recently, we have demonstrated that dendrimersomes self-assembled from (3,5)12G1-PE-BMPA-G2-(OH)8 dendrimers can be successfully loaded with hydrophilic and amphiphilic imaging contrast agents. Here, we present two newly synthesized low generation isomeric JDs: JDG0G1(3,5) and JDG0G1(3,4). Though less branched than the above-cited dendrimers, they retain the ability to form self-assembled, almost monodisperse vesicular nanoparticles. This contribution reports on the characterization of such nanovesicles loaded with the clinically approved MRI probe Gadoteridol and the comparison with the related nanoparticles assembled from more branched dendrimers. Special emphasis was given to the in vitro stability test of the systems in biologically relevant media, complemented by preliminary in vivo data about blood circulation lifetime collected from healthy mice. The results point to very promising safety and stability profiles of the nanovesicles, in particular for those made of JDG0G1(3,5), whose spontaneous self-organization in water gives rise to a homogeneous suspension. Importantly, the blood lifetimes of these systems are comparable to those of standard liposomes. By virtue of the reported results, the herein presented nanovesicles augur well for future use in a variety of biomedical applications.
Dendrimersomes: A new vesicular nano-platform for MR-molecular imaging applications
Filippi, Miriam; Martinelli, Jonathan; Mulas, Gilberto; et al. (2014)
Chemical Communications
A new class of nanovesicles formed by the self-assembly of amphiphilic Janus dendrimers, dendrimersomes, loaded with hydrophilic or amphiphilic magnetic resonance imaging chelates shows promising properties as a novel, efficient and versatile nanoplatform for biomedical imaging.
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.

Publications1 - 10 of 45

Miriam Filippi

Last Name

First Name

ORCID

Organisational unit

Filters

Search Results