Mark W. Tibbitt

Last Name

Tibbitt

First Name

Mark W.

ORCID

0000-0002-4917-7187

Organisational unit

09472 - Tibbitt, Mark / Tibbitt, Mark

Show all metadata

Search Results

Publications 1 - 10 of 117

Reinforced Polymer-Nanoparticle Hydrogels for Subcutaneous and Sustained Delivery of Trastuzumab
Bovone, Giovanni; Bernhard, Stéphane; Jacquot, Guillaume; et al. (2025)
Advanced Healthcare Materials
In oncology, the advent of monoclonal antibody (mAb) therapeutics represents a breakthrough in various cancer diseases. However, these therapies often necessitate iterative hospital visits for intravenous infusion that alter patient quality of life and contribute to the chronic saturation of hospitals. Subcutaneous formulations of mAbs offer a promising alternative facilitating faster administration compared with traditional intravenous methods, while still maintaining the same dosing schedule and providing time-saving advantages. Here, an injectable mAb delivery platform using alpha-cyclodextrin (alpha CD)-reinforced polymer-nanoparticle hydrogels to perform subcutaneous mAb depots and delay their release is developed. By leveraging mAb-polymer electrostatic complexation, hyaluronic acid- and alginate-based injectable drug depots are formulated by simply mixing components that are generally regarded as safe. Trastuzumab is included as a clinically relevant therapeutic antibody. These formulations delayed mAb release both in vitro and in vivo mice models, with a similar pharmacokinetic performance to the clinically approved Herceptin SC (Roche) formulation composed of trastuzumab with recombinant human hyaluronidase (rHuPH20).
Dynamic Biomaterials from Reversible Covalent Interactions
Cousin, Lucien; Tibbitt, Mark W. (2025)
World Scientific Series on Emerging Technologies ~ Advanced Polymer Life Science
Biomaterials are a transformative technology in biomedicine, providing strategies for improved tissue repair, the design of microphysiological systems, and advanced drug delivery systems. Traditional polymeric biomaterials are engineered using biocompatible polymers that often contain or interact through permanent covalent bonds. Incorporating reversible covalent interactions into biomaterials design is increasingly used to introduce dynamic properties to engineered biomaterials. Reversible covalent biomaterials can enable minimally invasive application through injection, are viscoelastic, and exhibit stimuli responsive behavior. In this chapter, we survey recent advances in the fundamental understanding of reversible covalent networks from chemical design to physical understanding. We then link this to several prominent biomedical applications of reversible covalent biomaterials.
Matryoshka-Inspired Micro-Origami Capsules to Enhance Loading, Encapsulation, and Transport of Drugs
Huang, Hen-Wei; Tibbitt, Mark W.; Huang, Tian-Yun; et al. (2019)
Soft Robotics
Injectable Senolytic Hydrogel Depot for the Clearance of Senescent Cells
Garau Paganella, Lorenza; Bovone, Giovanni; Cuni, Filippo; et al. (2025)
Biomacromolecules
Small molecules are frontline therapeutics for many diseases; however, they are often limited by their poor solubility. Therefore, hydrophobic small molecules are often encapsulated or prepared as pure drug nanoparticles. Navitoclax, used to eliminate senescent cells, is one such small molecule that faces challenges in translation due to its hydrophobicity and toxic side effects. Further, as senescent cells exhibit context-dependent pathologic or beneficial properties, it is preferable to eliminate senescent cells locally. To formulate navitoclax and enable local treatment, we designed an injectable hydrogel loaded with navitoclax nanoparticles as a senolytic delivery vehicle. Navitoclax nanoparticles (& Oslash; similar to 110 nm) were prepared via solvent-antisolvent nanoprecipitation and formulated in an injectable polymer-nanoparticle (PNP) hydrogel to create a local senolytic depot. Navitoclax-loaded PNP hydrogels selectively cleared senescent cells in vitro in senescent endothelial monolayers. This work demonstrates the value of formulating lipophilic small molecules and the potential of localized drug delivery strategies to improve senolytic therapies.
Variations in fluid chemical potential induce fibroblast mechano-response in 3D hydrogels
Garau Paganella, Lorenza; Badolato, Asia; Labouesse, Celine; et al. (2024)
Biomaterials Advances
Mechanical deformation of skin creates variations in fluid chemical potential, leading to local changes in hydrostatic and osmotic pressure, whose effects on mechanobiology remain poorly understood. To study these effects, we investigate the specific influences of hydrostatic and osmotic pressure on primary human dermal fibroblasts in three-dimensional hydrogel culture models. Cyclic hydrostatic pressure and hyperosmotic stress enhanced the percentage of cells expressing the proliferation marker Ki67 in both collagen and PEG-based hydrogels. Osmotic pressure also activated the p38 MAPK stress response pathway and increased the expression of the osmoresponsive genes PRSS35 and NFAT5. When cells were cultured in two-dimension (2D), no change in proliferation was observed with either hydrostatic or osmotic pressure. Furthermore, basal, and osmotic pressure-induced expression of osmoresponsive genes differed in 2D culture versus 3D hydrogels, highlighting the role of dimensionality in skin cell mechanotransduction and stressing the importance of 3D tissue-like models that better replicate in vivo conditions. Overall, these results indicate that fluid chemical potential changes affect dermal fibroblast mechanobiology, which has implications for skin function and for tissue regeneration strategies.
Design principles for adaptive and evolving engineered living materials
Cui , Yifan; Tibbitt, Mark W.; Lu , Timothy K.; et al. (2026)
Current Opinion in Biotechnology
Engineered living materials (ELMs) combine living cells, typically microorganisms, such as bacteria, yeasts, or filamentous fungi, with structural carrier matrices to form systems capable of sensing, growth, and self-repair. Most current designs emphasize programming the microbes to render otherwise static materials functional. A less explored dimension is leveraging reciprocal microbial–material interactions themselves to engineer adaptive and evolving living materials as integrated systems. Achieving such dynamic behavior requires understanding how support matrices influence microbial behavior and how cells, in turn, reshape material properties over time. This review outlines key modes of cell–material interactions as a framework for expanding the functional toolbox of ELMs and for creating sustainable and programmable materials that respond to their environments and evolve.
Mechanical memory and dosing influence stem cell fate
Yang, Chun; Tibbitt, Mark W.; Basta, Lena; et al. (2014)
Nature Materials
Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics
van der Valk, Dewy C.; Van der Ven, Casper F.T.; Blaser, Mark; et al. (2018)
Nanomaterials
In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD.
Additive manufacturing in drug delivery: Innovative drug product design and opportunities for industrial application
Ragelle, Héloïse; Rahimian, Sima; Guzzi, Elia A.; et al. (2021)
Advanced Drug Delivery Reviews
Additive manufacturing (AM) or 3D printing is enabling new directions in product design. The adoption of AM in various industrial sectors has led to major transformations. Similarly, AM presents new opportunities in the field of drug delivery, opening new avenues for improved patient care. In this review, we discuss AM as an innovative tool for drug product design. We provide a brief overview of the different AM processes and their respective impact on the design of drug delivery systems. We highlight several enabling features of AM, including unconventional release, customization, and miniaturization, and discuss several applications of AM for the fabrication of drug products. This includes products that have been approved or are in development. As the field matures, there are also several new challenges to broad implementation in the pharmaceutical landscape. We discuss several of these from the regulatory and industrial perspectives and provide an outlook for how these issues may be addressed. The introduction of AM into the field of drug delivery is an enabling technology and many new drug products can be created through productive collaboration of engineers, materials scientists, pharmaceutical scientists, and industrial partners.
Immunofunctional photodegradable poly(ethylene glycol) hydrogel surfaces for the capture and release of rare cells
LeValley, Paige J.; Tibbitt, Mark W.; Noren, Ben; et al. (2019)
Colloids and Surfaces B: Biointerfaces

Publications 1 - 10 of 117

Mark W. Tibbitt

Last Name

First Name

ORCID

Organisational unit

Filters

Search Results