Dominic Ruetsche

All Publications

• Human Dermal Microvascular Arterial and Venous Blood Endothelial Cells and Their Use in Bioengineered Dermo-Epidermal Skin Substitutes SMALL METHODS Ruetsche, D., Nanni, M., Cheng, P., Caflisch, N., Tastanova, A., Jenni, C., Levesque, M. P., Moehrlen, U., Klar, A. S., Biedermann, T. 2025: e2401588

  Abstract

  The bioengineering of vascular networks is pivotal to create complex tissues and organs for regenerative medicine applications. However, bioengineered tissues comprising an arterial and venous plexus alongside a lymphatic capillary network have not been explored yet. Here, scRNA-seq is first employed to investigate the arterio-venous endothelial cell marker patterning in human fetal and juvenile skin. Transcriptomic analysis reveals that arterial and venous endothelial cell markers NRP1 (neuropilin 1) and NR2F2 (nuclear receptor subfamily 2 group F member 2) are broadly expressed in fetal and juvenile skin. In contrast, expression of NRP1 and NR2F2 on the protein level is cell-type specific and is retained in 2D (2-dimensional) cultures in vitro. Finally, distinct arterial and venous capillaries are bioengineered in 3D (3-dimensional) hydrogels and rapid anastomosis is demonstrated with the host vasculature in vivo. In summary, the bioengineering of human arterial, venous, and lymphatic capillaries is established, hence paving the way for these cells to be used in regenerative medicine and future clinical applications.

  View details for DOI 10.1002/smtd.202401588

  View details for Web of Science ID 001406844400001

  View details for PubMedID 39871784

• A Low-Cost, Open-Source 3D Printer for Multimaterial and High-Throughput Direct Ink Writing of Soft and Living Materials. Advanced materials (Deerfield Beach, Fla.) Weiss, J. D., Mermin-Bunnell, A., Solberg, F. S., Tam, T., Rosalia, L., Sharir, A., Rütsche, D., Sinha, S., Choi, P. S., Shibata, M., Palagani, Y., Nilkant, R., Paulvannan, K., Ma, M., Skylar-Scott, M. A. 2025: e2414971

  Abstract

  Direct ink writing is a 3D printing method that is compatible with a wide range of structural, elastomeric, electronic, and living materials, and it continues to expand its uses into physics, engineering, and biology laboratories. However, the large footprint, closed hardware and software ecosystems, and expense of commercial systems often hamper widespread adoption. This work introduces a compact, low-cost, multimaterial, and high-throughput direct ink writing 3D printer platform with detailed assembly files and instructions provided freely online. In contrast to existing low-cost 3D printers and bioprinters, which typically modify off-the-shelf plastic 3D printers, this system is built from scratch, offering a lower cost and full customizability. Active mixing of cell-laden bioinks, high-throughput production of auxetic lattices using multimaterial multinozzle 3D (MM3D) printing methods, and a high-toughness, photocurable hydrogel for fabrication of heart valves are introduced. Finally, hardware for embedded multinozzle and 3D gradient nozzle printing is developed for producing high-throughput and graded 3D parts. This powerful, simple-to-build, and customizable printing platform can help stimulate a vibrant biomaker community of engineers, biologists, and educators.

  View details for DOI 10.1002/adma.202414971

  View details for PubMedID 39748617

• Hydrostatic pressure drives sprouting angiogenesis via adherens junction remodelling and YAP signalling COMMUNICATIONS BIOLOGY Al-Nuaimi, D., Rutsche, D., Abukar, A., Hiebert, P., Zanetti, D., Cesarovic, N., Falk, V., Werner, S., Mazza, E., Giampietro, C. 2024; 7 (1): 940

  Abstract

  Endothelial cell physiology is governed by its unique microenvironment at the interface between blood and tissue. A major contributor to the endothelial biophysical environment is blood hydrostatic pressure, which in mechanical terms applies isotropic compressive stress on the cells. While other mechanical factors, such as shear stress and circumferential stretch, have been extensively studied, little is known about the role of hydrostatic pressure in the regulation of endothelial cell behavior. Here we show that hydrostatic pressure triggers partial and transient endothelial-to-mesenchymal transition in endothelial monolayers of different vascular beds. Values mimicking microvascular pressure environments promote proliferative and migratory behavior and impair barrier properties that are characteristic of a mesenchymal transition, resulting in increased sprouting angiogenesis in 3D organotypic model systems ex vivo and in vitro. Mechanistically, this response is linked to differential cadherin expression at the adherens junctions, and to an increased YAP expression, nuclear localization, and transcriptional activity. Inhibition of YAP transcriptional activity prevents pressure-induced sprouting angiogenesis. Together, this work establishes hydrostatic pressure as a key modulator of endothelial homeostasis and as a crucial component of the endothelial mechanical niche.

  View details for DOI 10.1038/s42003-024-06604-9

  View details for Web of Science ID 001283503200005

  View details for PubMedID 39097636

  View details for PubMedCentralID PMC11297954

• Light from Afield: Fast, High-Resolution, and Layer-Free Deep Vat 3D Printing. Chemical reviews Chansoria, P., Rizzo, R., Rütsche, D., Liu, H., Delrot, P., Zenobi-Wong, M. 2024

  Abstract

  Harnessing light for cross-linking of photoresponsive materials has revolutionized the field of 3D printing. A wide variety of techniques leveraging broad-spectrum light shaping have been introduced as a way to achieve fast and high-resolution printing, with applications ranging from simple prototypes to biomimetic engineered tissues for regenerative medicine. Conventional light-based printing techniques use cross-linking of material in a layer-by-layer fashion to produce complex parts. Only recently, new techniques have emerged which deploy multidirection, tomographic, light-sheet or filamented light-based image projections deep into the volume of resin-filled vat for photoinitiation and cross-linking. These Deep Vat printing (DVP) approaches alleviate the need for layer-wise printing and enable unprecedented fabrication speeds (within a few seconds) with high resolution (>10 μm). Here, we elucidate the physics and chemistry of these processes, their commonalities and differences, as well as their emerging applications in biomedical and non-biomedical fields. Importantly, we highlight their limitations, and future scope of research that will improve the scalability and applicability of these DVP techniques in a wide variety of engineering and regenerative medicine applications.

  View details for DOI 10.1021/acs.chemrev.4c00134

  View details for PubMedID 38967405

• Biofabrication of Heterogeneous, Multi-Layered, and Human-Scale Tissue Transplants Using Eluting Mold Casting ADVANCED FUNCTIONAL MATERIALS Tosoratti, E., Rutsche, D., Asadikorayem, M., Ponta, S., Fisch, P., Flegeau, K., Linder, T., Guillon, P., Zenobi-Wong, M. 2023

  View details for DOI 10.1002/adfm.202305651

  View details for Web of Science ID 001088646100001

• Synergizing Algorithmic Design, Photoclick Chemistry and Multi-Material Volumetric Printing for Accelerating Complex Shape Engineering. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Chansoria, P., Rutsche, D., Wang, A., Liu, H., D'Angella, D., Rizzo, R., Hasenauer, A., Weber, P., Qiu, W., Ibrahim, N. B., Korshunova, N., Qin, X., Zenobi-Wong, M. 2023: e2300912

  Abstract

  The field of biomedical design and manufacturing has been rapidly evolving, with implants and grafts featuring complex 3D design constraints and materials distributions. By combining a new coding-based design and modeling approach with high-throughput volumetric printing, a new approach is demonstrated to transform the way complex shapes are designed and fabricated for biomedical applications. Here, an algorithmic voxel-based approach is used that can rapidly generate a large design library of porous structures, auxetic meshes and cylinders, or perfusable constructs. By deploying finite cell modeling within the algorithmic design framework, large arrays of selected auxetic designs can be computationally modeled. Finally, the design schemes are used in conjunction with new approaches for multi-material volumetric printing based on thiol-ene photoclick chemistry to rapidly fabricate complex heterogeneous shapes. Collectively, the new design, modeling and fabrication techniques can be used toward a wide spectrum of products such as actuators, biomedical implants and grafts, or tissue and disease models.

  View details for DOI 10.1002/advs.202300912

  View details for PubMedID 37400372

• Multiscale Hybrid Fabrication: Volumetric Printing Meets Two-Photon Ablation ADVANCED MATERIALS TECHNOLOGIES Rizzo, R., Ruetsche, D., Liu, H., Chansoria, P., Wang, A., Hasenauer, A., Zenobi-Wong, M. 2023

  View details for DOI 10.1002/admt.202201871

  View details for Web of Science ID 000952989100001

• Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co-Engineering of Blood and Lymphatic Vasculature ADVANCED MATERIALS Rutsche, D., Nanni, M., Rudisser, S., Biedermann, T., Zenobi-Wong, M. 2023: e2209476

  Abstract

  Adequate vascularization is required for the successful translation of many in vitro engineered tissues. This study presents a novel collagen derivative that harbors multiple recognition peptides for orthogonal enzymatic crosslinking based on sortase A (SrtA) and Factor XIII (FXIII). SrtA-mediated crosslinking enables the rapid co-engineering of human blood and lymphatic microcapillaries and mesoscale capillaries in bulk hydrogels. Whereas tuning of gel stiffness determines the extent of neovascularization, the relative number of blood and lymphatic capillaries recapitulates the ratio of blood and lymphatic endothelial cells originally seeded into the hydrogel. Bioengineered capillaries readily form luminal structures and exhibit typical maturation markers both in vitro and in vivo. The secondary crosslinking enzyme Factor XIII is used for in situ tethering of the VEGF mimetic QK peptide to collagen. This approach supports the formation of blood and lymphatic capillaries in the absence of exogenous VEGF. Orthogonal enzymatic crosslinking is further used to bioengineer hydrogels with spatially defined polymer compositions with pro- and anti-angiogenic properties. Finally, macroporous scaffolds based on secondary crosslinking of microgels enable vascularization independent from supporting fibroblasts. Overall, this work demonstrates for the first time the co-engineering of mature micro- and meso-sized blood and lymphatic capillaries using a highly versatile collagen derivative.

  View details for DOI 10.1002/adma.202209476

  View details for Web of Science ID 000946989200001

  View details for PubMedID 36724374

• Filamented Light (FLight) Biofabrication of Highly Aligned Tissue-Engineered Constructs ADVANCED MATERIALS Liu, H., Chansoria, P., Delrot, P., Angelidakis, E., Rizzo, R., Rutsche, D., Applegate, L., Loterie, D., Zenobi-Wong, M. 2022; 34 (45): e2204301

  Abstract

  Cell-laden hydrogels used in tissue engineering generally lack sufficient 3D topographical guidance for cells to mature into aligned tissues. A new strategy called filamented light (FLight) biofabrication rapidly creates hydrogels composed of unidirectional microfilament networks, with diameters on the length scale of single cells. Due to optical modulation instability, a light beam is divided optically into FLight beams. Local polymerization of a photoactive resin is triggered, leading to local increase in refractive index, which itself creates self-focusing waveguides and further polymerization of photoresin into long hydrogel microfilaments. Diameter and spacing of the microfilaments can be tuned from 2 to 30 µm by changing the coherence length of the light beam. Microfilaments show outstanding cell instructive properties with fibroblasts, tenocytes, endothelial cells, and myoblasts, influencing cell alignment, nuclear deformation, and extracellular matrix deposition. FLight is compatible with multiple types of photoresins and allows for biofabrication of centimeter-scale hydrogel constructs with excellent cell viability within seconds (<10 s per construct). Multidirectional microfilaments are achievable within a single hydrogel construct by changing the direction of FLight projection, and complex multimaterial/multicellular tissue-engineered constructs are possible by sequentially exchanging the cell-laden photoresin. FLight offers a transformational approach to developing anisotropic tissues using photo-crosslinkable biomaterials.

  View details for DOI 10.1002/adma.202204301

  View details for Web of Science ID 000865232400001

  View details for PubMedID 36095325