Biofabrication techniques to analyze and steer mechanobiology of epithelia

Project Area D
The motivation for Project Area D is to develop novel biofabrication techniques, tailored biomaterials, and methods to analyze how (stem)cells and epithelia respond to structural, physical, and mechanical properties and forces in 3D constructs and to study how their functions and behavior can be steered. The biomaterial constructs can be designed and produced to control these properties on the nm, µm, and mm scale, while they can be programmed to be dynamically altered via response to cell-induced or external triggers, such as magnetic, acoustic, or electric fields and light. Development of engineering tools that operate at the required time and length scale and allow for multimodal stimulation and measurements require know-how in mechanical, chemical, and electrical engineering. Project area D bundles this type of engineering expertise and is tightly linked to the research in project areas A-C in order to understand the experimental necessities and answer mechanobiological questions. Depending on the needs for each project, the building blocks can be adjusted - especially with regard to stiffness, degradation kinetics, orientation - can be bioprinted into the desired architectures, and can finally be analyzed in situ in the cross-talk with the embedded cells

Teams

DWI - Leibniz Institute for Interactive Materials

Pre-programming anisometric microgels to orthogonally study the effect of mechanical signals on epithelia in 3D tissue models

Laura De Laporte
Principal Investigator
Ramin Nasehi
Associated Postdoctoral Researcher
Iris Doolaar
Associated Doctoral Researcher
Light-responsive hydrogels to understand mechanotransduction in skeletal muscle and epithelia
Laura Klasen
Associated Doctoral Researcher
Thesis Title
Carolina Itzin
Doctoral Researcher
Thesis Title
Key aspects of experimental approaches in D1. (A) shows a comparison of spheroid outgrowth in PEG hydrogels (6.5% [w/w]) with different ratios of degradable crosslinkers. (B) PEG hydrogel stiffening and softening can be induced on demand with UV light. (C) Nerve growth and alignment depends on microgel stiffness in Anisogel. (D) The angle of orientation of the microgels inside an Anisogel can be preprogrammed by pre-aligning ellipsoidal maghemite nanoparticles, resulting in orthogonal alignment of microgels and cells. (E) presents RGD-functionalized ester-linked PEG microgels (8-arm, 20 kDa, 5% [w/v]) covered with immortalized CD10 kidney epithelial cells after 4 days of cultivation. (F) Degradation of ester-linked PEG microgels is observed after adding 20 mg/ml cellulase (8-arm, 20 kDa, 5% [w/v]; degradation time: 10 h).
Department of Dental Materials and Biomaterials Research (ZWBF), Uniklinik RWTH Aachen

Mechanobiological challenges related to hydrogel-based bioprinting technology for manufacturing novel 3D cell culture models

Horst Fischer
Principal Investigator
Alejandro Gómez Montoya
Associated Doctoral Researcher
Thesis Title
Mert Karpat
Doctoral Researcher
Thesis Title
Key aspects of project D2. (A) Collagen fibers align in response to defined dynamic stress application. (B) shows a biorector to investigate the effect of fluid shear stress on epithelial cells. (C) The acoustic bioprinting principle is used for realization of advanced 3D in vitro epithelial models. Single cells and cell clusters can be precisely printed in 3D and are subjected to much less shear stress during printing due to the nozzle-less technology developed in our lab [84].