Mark Skylar-Scott, Postdoctoral Faculty Sponsor
- Biofabrication of Heterogeneous, Multi-Layered, and Human-Scale Tissue Transplants Using Eluting Mold Casting ADVANCED FUNCTIONAL MATERIALS 2023
Synergizing Algorithmic Design, Photoclick Chemistry and Multi-Material Volumetric Printing for Accelerating Complex Shape Engineering.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
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 2023
Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co-Engineering of Blood and Lymphatic Vasculature
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
2022; 34 (45): e2204301
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