Perfusable Biohybrid Designs for Bioprinted Skeletal Muscle Tissue

Abstract

Engineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival, and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately coprinted with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that i) coprinted synthetic structures display highly coherent interfaces with the living tissue, ii) perfusable designs preserve cells from hypoxia all over the scaffold volume, iii) constructs can undergo passive mechanical tension during matrix remodeling, and iv) the constructs can be used to study the distribution of drugs. Extrusion-based multimaterial bioprinting with the inks and design realizes in vitro matured biohybrid SMT for biomedical applications.

Centimeter-scale perfusable cultured meat with densely packed, highly aligned muscle fibers via hollow fiber bioreactor

“…The biofabrication of cultured whole-cut meats is a challenging process, as it requires the formation of densely packed, highly aligned muscle fibers across a length scale larger than centimeters. In comparison to the scaffold-based approaches and bioprinting methods which cannot achieve a high cell density uniformly throughout the whole tissue 5,15,[20][21][22] , modular assembly methods have been effective in increasing the cell density in the fabricated tissues 2,11,17,18,[23][24][25][26] . In detail, first, hydrogel precursors with a high cell concentration (typically > 5.0×10 7 cells/mL) with a submillimeter cross-sectional size were solidified and cultured to form the microtissue modules.…”

Lifelike Transformative Materials for Biohybrid Implants: Inspired by Nature, Driven by Technology

“…3D printing is also a powerful tool to advance the development of centimeter‐scale tissues, in which the development of a perfusable or vascularized network is critical for preserving cell viability within the cm‐scale tissue. [ 37 ] 3D printing offers the possibility to build structures containing micro‐channels or in which blocks of hydrogel can be evacuated by printing channels with sacrificial inks that can be removed. [ 38 ] An excellent example of complex cell‐laden constructs is presented by Kim and colleagues, in which they produced skeletal muscle constructs by bioprinting human muscle progenitor cells and human neural stem cells.…”

Multimaterial Hydrogel 3D Printing

“…In a good example, Filippi et al printed synthetic skeletal muscle tissue (based on GelMA and sodium alginate hydrogel ink) with microvascularization handled by the F-127 sacrificial ink component. [73] In another example from Ji et al, cellladen GelMA or methacrylated hyaluronic acid was extruded and partially cured by a UV light source. [74] Subsequently, into this partially-cured matrix was deposited a sacrificial hydrogel ink (F-127).…”