Electroactive hydrogels (EAH) that exhibit large deformation in response to an electric field have received great attention as a potential actuating material for soft robots and artificial muscle. However, their application has been limited due to the use of traditional two-dimensional (2D) fabrication methods. Here we present soft robotic manipulation and locomotion with 3D printed EAH microstructures. Through 3D design and precise dimensional control enabled by a digital light processing (DLP) based micro 3D printing technique, complex 3D actuations of EAH are achieved. We demonstrate soft robotic actuations including gripping and transporting an object and a bidirectional locomotion.

Large volume deficiencies in skeletal muscle tissue fail to heal with conservative treatments, and improved treatment methods are needed. Tissue engineered scaffolds for skeletal muscle need to mimic the optimal environment for muscle development by providing the proper electric, mechanical, and chemical cues. Electroactive polymers, polymers that change in size or shape in response to an electric field, may be able to provide the optimal environment for muscle growth. In this study, an electroactive polymer made from poly(ethylene glycol) diacrylate (PEGDA) and acrylic acid (AA) is characterized and optimized for movement and biocompatibility. Hydrogel sample thickness, overall polymer concentration, and the ratio of PEGDA to AA were found to significantly impact the actuation response. C2C12 mouse myoblast cells attached and proliferated on hydrogel samples with various ratios of PEGDA to AA. Future experiments will produce hydrogel samples combined with aligned guidance cues in the form of electrospun fibers to provide a favorable environment for muscle development.

Skeletal muscle is made up of hundreds of multinucleated, aligned fibers that work together during contraction. While smaller injuries are typically able to be repaired by the body, large volumetric muscle loss (VML) typically results in loss of function. Tissue engineering (TE) applications that use cells seeded onto hydrogels are one potential option for regenerating the lost tissue. Hydrogels are described as soft crosslinked polymeric networks with high water content that simulates the body's natural aqueous environment. They can be formulated from many different starting materials into biocompatible, biodegradable systems. Fabrication methods such as electrospinning, freeze-drying, molding, and 3D printing can be used with the hydrogel solution to form 3D structures. In this review, natural, semi-synthetic, synthetic, and composite hydrogels for skeletal muscle regeneration are discussed. It was ascertained that the majority of the current research focused on natural polymeric hydrogels including collagen, gelatin, agarose, alginate, fibrin, chitosan, keratin, and combinations of the aforementioned. This category was followed by a discussion of composite hydrogels, defined in this review as at least one synthetic and one natural polymer combined to form a hydrogel, and these are the next most favored materials. Synthetic polymer hydrogels came in third with semi-synthetic polymers, chemically modified natural polymers, being the least common. While many of the hydrogels show promise for skeletal muscle regeneration, continued investigation is needed in order to regenerate a functional muscle tissue replacement. Lay SummarySkeletal muscle tissue engineering focuses on regenerating large amounts of skeletal muscle tissue lost due to tumor removal, traumatic injuries, and/or disease. Neither natural repair processes by the body nor current medical interventions are able to completely restore function after volumetric muscle loss. Thus, scientists are investigating alternative approaches to regenerate the lost muscle, restore function, and increase patient quality of life. This review paper summarizes the research from 2013 to early 2018 using hydrogels, a soft material with a high water content, as a tool to regenerate muscle. The review is categorized into hydrogels made from natural materials, semi-synthetic materials, synthetic materials, and composite materials (at least one natural and one synthetic material combined).

Injuries to peripheral nerves and/or skeletal muscle can cause scar tissue formation and loss of function. The focus of this article is the creation of a conductive, biocompatible scaffold with appropriate mechanical properties to regenerate skeletal muscle. Poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles (Np) were electrospun with poly(ɛ-caprolactone) (PCL) to form conductive scaffolds. During electrospinning, ribboning, larger fiber diameters, and unaligned scaffolds were observed with increasing PEDOT amounts. To address this, PEDOT Np were sonicated prior to electrospinning, which resulted in decreased conductivity and increased mechanical properties. Multi-walled carbon nanotubes (MWCNT) were added to the 1:2 solution in an effort to increase conductivity. However, the addition of MWCNT had little effect on scaffold conductivity, and the elastic modulus and yield stress of the scaffold increased as a result. Rat muscle cells attached and were active on the 1-10, 1-2, 3-4, and 1-1 PCL-PEDOT scaffolds; however, the 3-4 scaffolds had the lowest level of metabolic activity. Although the scaffolds were cytocompatible, further development of the fabrication method is necessary to produce more highly aligned scaffolds capable of promoting skeletal muscle cell alignment and eventual regeneration.

Advancements in tissue engineering and biomaterial development have the potential to provide a scalable solution to the problem of large-volume skeletal muscle defects. Previous research on the development of scaffolds for skeletal muscle regeneration has focused on strategies for increasing conductivity, which has improved satellite cell attachment and differentiation. However, these strategies usually increase scaffold stiffness, which some studies suggest may be detrimental to myoblast development. In this study, the polymers polypyrrole (PPy) and polycaprolactone (PCL) were synthesized together into a copolymer (PPy-PCL) designed to increase scaffold conductivity without significantly influencing stiffness. Different scaffold groups were fabricated via electrospinning, characterized, and assessed for their suitability for myoblast proliferation and differentiation. The groups included an aligned and random iteration of pure PCL, 10% PPy-PCL, 20% PPy-PCL, and 40% PPy-PCL. Only the 40% PPy-PCL group had a measureable conductivity, and the addition of PPy-PCL had no significant effect on the stiffness of the scaffolds. The PPy-PCL copolymer significantly increased the attachment of C2C12 myoblasts as compared to pure PCL scaffolds, but the concentration of PPy-PCL did not significantly alter cell attachment. In addition, scaffolds with PPy-PCL promoted myoblast differentiation to a greater extent than scaffolds made of PCL as measured by fusion index and number of nuclei per myotube. Aligned scaffolds were superior to random scaffolds in almost all measures. These results suggest that conductivity may not be the key factor in improving skeletal muscle scaffolds. Instead, cell attachment and aligned guidance cues may have a greater impact on myoblast differentiation.