Bioinks and Bioprinting Strategies for Skeletal Muscle Tissue Engineering

Abstract

Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold-standard approach, is limited due to donor shortage, donor-site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.

Colloidal multiscale porous adhesive (bio)inks facilitate scaffold integration

“…36,60 However, its low viscosity and relatively slow cross-linking have been a challenge for its applications in extrusion-based 3D bioprinting. 52 Several strategies have been used to improve the printability of GelMA, such as increasing the precursor concentration, partial pre-cross-linking to increase its viscosity, and integration of other hydrogels, such as alginate and gelatin, to improve the rheological properties and facilitate the rapid cross-linking of the hybrid hydrogel. 61,62 However, increasing the precursor concentration may result in reduced cellular activity inside the GelMA scaffold.…”

“…72 As a result, a cell-favorable biomaterial with large porosities is required to form a large scaffold at injury site and facilitate the migration of cells from the remnant tissue for regeneration of the tissue to a functional muscle. 52 In vivo printing of the foam resulted in significantly improved soft tissue contour following the injury, with restoration of blood vessels, skeletal muscle fibers abutting the area of muscle injury, and neuromuscular junctions. In comparison, although placement of scaffolds without mesoporosities may improve the hypertrophy of remnant muscle fibers and limit fibrosis, they are limited in promoting skeletal muscle regeneration, angiogenesis, or neurogenesis within the scaffold itself.…”

“…Taken together, treatment of an acute VML injury with a foam scaffold promoted composite restoration of the muscle defect, which is improved as compared to soft tissue regeneration offered by less porous scaffolds. 51,52 To further quantify the functional recovery of the injured muscles, the in situ generated forces were measured using a force transducer machine. To evaluate the functional muscle recovery, at 8 weeks post injury, the gastrocnemius muscle was isolated in each mouse and subjected to in situ strength testing using a force transducer instrument.…”

(Bio)manufactured Solutions for Treatment of Bone Defects with an Emphasis on US‐FDA Regulatory Science Perspective

“…3D bioprinting is the use of 3D printing techniques to directly print bioinks including cells and bioactive molecules and growth factors to form a 3D tissue structure. [209,210] Similar to 3D printing, the method steps include imaging, (computer-aided design) CAD model, material selection (natural and synthetic polymers, cell type, bioactive molecules, and growth factors), and printing. The last step is the cells maturation step which happens in prefusion bioreactors to mimic the body environment for the cells as precisely as possible.…”

“…[218] However, piezoelectric printers are limited to low viscosity inks, as the acoustic waves are unable to move high viscosities. [219,220] The benefits of inkjet 3D bioprinting are high speed (up to 10 000 droplets s À1 ), [221,222] high resolution (%20-100 μm), [209] high cell viability, [221] and low cost. [223] Typical materials used as bioink in this method are alginate, fibrinogen, HA, PCL, PEG, and PVP.…”