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In this study, a cell-free tissue-engineered tracheal substitute was developed, which is based on a 3D-printed polycaprolactone scaffold coated with a gelatin-methacryloyl (GelMA) hydrogel, with transforming growth factor-β1 (TGF-β) and stromal cell-derived factor-1α (SDF-1) sequentially embedded, to facilitate cell recruitment and differentiation toward chondrocyte-phenotype. TGF-β was loaded onto polydopamine particles, and then encapsulated into the GelMA together with SDF-1, and called G/S/P@T, which was used to coat 3D-printed PCL scaffold to form the tracheal substitute. A rapid release of SDF-1 was observed during the first week, followed by a slow and sustained release of TGF-β for approximately four weeks. The tracheal substitute significantly promoted the recruitment of mesenchymal stromal cells (MSCs) or human bronchial epithelial cells in vitro, and enhanced the ability of MSCs to differentiate towards chondrocyte phenotype. Implantation of the tissue-engineered tracheal substitute with a rabbit tracheal anterior defect model improved regeneration of airway epithelium, recruitment of endogenous MSCs and expression of markers of chondrocytes at the tracheal defect site. Moreover, the tracheal substitute maintained airway opening for 4 weeks in a tracheal full circumferential defect model with airway epithelium coverage at the defect sites without granulation tissue accumulation in the tracheal lumen or underneath. The promising results suggest that this simple, cell-free tissue-engineered tracheal substitute can be used directly after tracheal defect removal and should be further developed towards clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aligned topographical cue has been demonstrated as a critical role in neuronal guidance, and it is highly beneficial to develop a scaffold with aligned structure for peripheral nerve tissue regeneration. Although considerable efforts have been devoted to guiding neurite alignment and extension, it remains a remarkable challenge for developing a biomimetic scaffold for enhancing 3D aligned neuronal outgrowth. Herein, we present a core-shell scaffold based on aligned conductive nanofiber yarns (NFYs) within the hydrogel to mimic the 3D hierarchically aligned structure of the native nerve tissue. The aligned NFYs assembled by a bundle of aligned nanofibers composed of polycaprolactone (PCL), silk fibroin (SF), and carbon nanotubes (CNTs) are prepared by a developed dry-wet electrospinning method, which has the ability to induce neurite alignment and elongation when PC12 cells and dorsal root ganglia (DRG) cells are cultured on their 3D peripheral surface. Particularly, such an aligned nanofibrous structure also induces aligned neurite extension and cell migration from DRG explants along the direction of nanofibers. 3D core-shell scaffolds are fabricated by encapsulating NFYs within the hydrogel shell after photocrosslinking, and these 3D aligned scaffolds are able to control cellular alignment and elongation of nerve cells in this 3D environment. Our results suggest that such 3D hierarchically aligned core-shell scaffold consists of NFYs that mimic the aligned nerve fiber structure to induce neurite alignment and extension and a hydrogel shell that mimics the epineurium layer to protect nerve cell organization within a 3D environment, which is largely promising for the design of biomimetic scaffolds in nerve tissue engineering. STATEMENT OF SIGNIFICANCE: Designing scaffolds with 3D aligned structure has been paid more attention for peripheral nerve tissue regeneration, because the aligned topographical cue is able to induce neurites alignment and extension. However, developing scaffolds mimicking the hierarchically aligned structure of native nerve tissue for directing 3D aligned neuronal outgrowth without external stimulation remains challenging. This work presented a simple and efficient strategy to prepare a 3D biomimetic core-shell scaffold based on electrospun aligned conductive nanofiber yarns within photocurable hydrogel shell to mimic the hierarchically aligned structure of native nerve tissue. These 3D aligned composite scaffolds performed the ability to direct 3D cellular alignment and elongation of nerve cells along with the nanofiber yarn direction, and the hydrogel shell mimicking the epineurium layer was able to protect nerve cells organization within the 3D environment, which indicated their great potential in peripheral nerve tissue engineering applications., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

Self-healing, adhesive conductive hydrogels are of great significance in wearable electronic devices, flexible printable electronics, and tissue engineering scaffolds. However, designing self-healing hydrogels with multifunctional properties such as high conductivity, excellent mechanical property, and high sensitivity remains a challenge. In this work, the conductive self-healing nanocomposite hydrogels based on nanoclay (laponite), multiwalled carbon nanotubes (CNTs), and N-isopropyl acrylamide are presented. The presented nanocomposite hydrogels displayed good electrical conductivity, rapid self-healing and adhesive properties, flexible and stretchable mechanical properties, and high sensitivity to near-infrared light and temperature. These excellent properties of the hydrogels are demonstrated by the three-dimensional (3D) bulky pressure-dependent device, human activity monitoring device, and 3D printed gridding scaffolds. Good cytocompatibility of the conductive hydrogels was also evaluated with L929 fibroblast cells. These nanocomposite hydrogels have great potential for applications in stimuli-responsive electrical devices, wearable electronics, and so on.

Controlling cellular alignment and elongation has been demonstrated as an important parameter for developing nerve tissue engineering scaffolds. Many approaches have been developed to guide cellular orientation for nerve regeneration such as micropatterning techniques. However, most of materials used for developing micropatterning scaffolds lack of bioactivity and biofunctionability. Here we present a functional conductive micropatterned scaffold based on bioactive conductive biodegradable polyurethane prepared using a micro-molding technique. These conductive micropatterned scaffolds are able to not only induce the Schwann cells (SCs) alignment and elongation by the micropatterned surface but also enhance the nerve growth factor (NGF) gene expression of SCs by the bioactivity of these materials. Additionally, the combined effect of the bioactivity of such conductive materials and the micropatterned structure also dramatically promotes the neurite extension and elongation of PC12 cells in a highly aligned direction. These data suggest that these conductive micropatterned scaffolds that easily control cellular orientation and organization, and dramatically enhance NGF gene expression and significantly induce the neurite extension of PC12 cells, have a great potential for nerve regeneration applications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The key factor in skeletal muscle tissue engineering is regeneration of the functional skeletal muscles. Materials that could promote the myoblast proliferation and myogenic differentiation are promising candidates in skeletal muscle tissue engineering. Herein, we developed an elastic conductive poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS) grafted aniline pentamer (AP) copolymer that could promote the formation of myotubes by differentiating the C2C12 myoblast cells. The results of hydration behavior and water contact angle suggested that by adjusting the poly(ethylene glycol) (PEG) and AP content, this film showed a proper surface hydrophilicity for cell attachment. Additionally, these films showed tunable conductivity and mechanical properties that can be altered by changing the AP content. The maximum conductivity of the films was 1.84 × 10 -4 S/cm and the Young's modulus of these films ranged from 14.58 ± 1.35 MPa to 24.62 ± 0.61 MPa. Our findings indicate that the PEGS-AP films promote the proliferation and myogenic differentiation of C2C12 cells, suggesting that they are promising biomaterials for skeletal muscle tissue engineering.

Silk fibroin (SF) with good biocompatibility and degradability has great potential for tissue engineering. However, the SF based scaffolds lack the electroactivity to regulate the myogenic differentiation for the regeneration of muscle tissue, which is sensitive to electrical signal. Herein, a series of electroactive biodegradable scaffolds based on SF and water-soluble conductive poly(aniline-co-N-(4-sulfophenyl) aniline) (PASA) via a green method for skeletal muscle tissue engineering are designed. SF/PASA scaffolds are prepared by vortex of aqueous solution of SF and PASA under physiological condition. Murine-derived L929 fibroblast and C2C12 myoblast cells are used to evaluate cytotoxicity of SF/PASA scaffolds. Moreover, myogenic differentiation of C2C12 cells is investigated by analyzing the morphology of myotubes and related gene expression. These results suggest that electroactive SF/PASA scaffolds with a suitable microenvironment, which can enhance the myogenic differentiation of C2C12 cells, have a great potential for skeletal muscle regeneration., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mimicking the anisotropic cardiac structure and guiding 3D cellular orientation play a critical role in designing scaffolds for cardiac tissue regeneration. Significant advances have been achieved to control cellular alignment and elongation, but it remains an ongoing challenge for engineering 3D cardiac anisotropy using these approaches. Here, we present a 3D hybrid scaffold based on aligned conductive nanofiber yarns network (NFYs-NET, composition: polycaprolactone, silk fibroin, and carbon nanotubes) within a hydrogel shell for mimicking the native cardiac tissue structure, and further demonstrate their great potential for engineering 3D cardiac anisotropy for cardiac tissue engineering. The NFYs-NET structures are shown to control cellular orientation and enhance cardiomyocytes (CMs) maturation. 3D hybrid scaffolds were then fabricated by encapsulating NFYs-NET layers within hydrogel shell, and these 3D scaffolds performed the ability to promote aligned and elongated CMs maturation on each layer and individually control cellular orientation on different layers in a 3D environment. Furthermore, endothelialized myocardium was constructed by using this hybrid strategy via the coculture of CMs on NFYs-NET layer and endothelial cells within hydrogel shell. Therefore, these 3D hybrid scaffolds, containing NFYs-NET layer inducing cellular orientation, maturation, and anisotropy and hydrogel shell providing a suitable 3D environment for endothelialization, has great potential in engineering 3D cardiac anisotropy.

Electrohydrodynamic 3D printing is a promising strategy to controllably fabricate hierarchical fibrous architectures that mimic the structural organizations of native extracellular matrix. However, most of the existing investigations are mainly based on viscous melted biopolymers which make it difficult to uniformly incorporate bioactive or functional nanobiomaterials into the printed microfibers for functionization. Here we investigated the feasibility of employing solution-based electrohydrodynamic 3D printing to fabricate microscale poly (ε-caprolactone) (PCL) scaffolds with multi-walled carbon nanotubes (MWCNTs). The effect of polyethylene oxide (PEO) content in the acetic acid solution of PCL on the 3D profile and dimension of the electrohydrodynamically printed walls was studied for an optimal PEO-PCL composition. When the contents of PEO and PCL are 8 w/v % and 5 w/v %, respectively, 3D fibrous lactic structures with different MWCNTs content could be stably printed with the fiber diameter about 10 μm, close to the size of living cells. Biological experiments showed that although the addition of MWCNTs negatively affected cellular attachment compared with PEO-PCL scaffolds, the electrohydrodynamically printed PEO-PCL-MWCNT scaffolds facilitated cell alignment. It is envisioned that the presented electrohydrodynamic 3D printing might provide a new strategy to flexibly incorporate various nanobiomaterials into microscale fibrous structures for specific functionality or mimicking of hierarchically organized nanocomposites in vivo.

Mimicking native functional dynamics for traditional biomaterials such as thermoset elastomers is limited due to their lack of responsiveness to biological stimuli and difficulties to incorporate biofunctionalities. Furthermore, the mechanical fracture of traditional thermoset elastomers caused by irreversible covalent bond rupture would lead to their permanent loss of properties. To overcome these challenges, degradable self-healed supramolecular bioelastomers are designed by an elastic poly(glycerol sebacate) (PGS) backbone and multiple hydrogen-bonding ureido-pyrimidinone (UPy) grafts. These supramolecular elastic polymers exhibit efficient self-healing, rapid shape-memory abilities and highly tunable mechanical properties due to the dynamic supramolecular interactions, and perform a good biocompatibility in vitro and a mild host response in vivo. By combining modular approaches, these supramolecular bioelastomers have been further assembled into a multifunctional platform to expand their applications in different biomedical fields. These include a complex 3D scaffold with shape-memory capacity and anisotropic mechanical properties, a controllable drug delivery model via a layer-by-layer technique, a surface antibacterial composite by physical modification, and a spatial oriented cell co-culture system via incorporating different cell-laden self-healing films, demonstrating their potential as building blocks in a wide range of biomedical applications where dynamic properties and biological functions are desired., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

It remains a challenge to develop electroactive and elastic biomaterials to mimic the elasticity of soft tissue and to regulate the cell behavior during tissue regeneration. We designed and synthesized a series of novel electroactive and biodegradable polyurethane-urea (PUU) copolymers with elastomeric property by combining the properties of polyurethanes and conducting polymers. The electroactive PUU copolymers were synthesized from amine capped aniline trimer (ACAT), dimethylol propionic acid (DMPA), polylactide, and hexamethylene diisocyanate. The electroactivity of the PUU copolymers were studied by UV-vis spectroscopy and cyclic voltammetry. Elasticity and Young's modulus were tailored by the polylactide segment length and ACAT content. Hydrophilicity of the copolymer films was tuned by changing DMPA content and doping of the copolymer. Cytotoxicity of the PUU copolymers was evaluated by mouse C2C12 myoblast cells. The myogenic differentiation of C2C12 myoblasts on copolymer films was also studied by analyzing the morphology of myotubes and relative gene expression during myogenic differentiation. The chemical structure, thermal properties, surface morphology, and processability of the PUU copolymers were characterized by NMR, FT-IR, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and solubility testing, respectively. Those biodegradable electroactive elastic PUU copolymers are promising materials for repair of soft tissues such as skeletal muscle, cardiac muscle, and nerve.

Designing scaffolds that can mimic native skeletal muscle tissue and induce 3D cellular alignment and elongated myotube formation remains an ongoing challenge for skeletal muscle tissue engineering. Herein, we present a simple technique to generate core-shell composite scaffolds for mimicking native skeletal muscle structure, which comprise the aligned nanofiber yarn (NFY) core and the photocurable hydrogel shell. The aligned NFYs are prepared by the hybrid composition including poly(caprolactone), silk fibroin, and polyaniline via a developed dry-wet electrospinning method. A series of core-shell column and sheet composite scaffolds are ultimately obtained by encapsulating a piece and layers of aligned NFY cores within the hydrogel shell after photo-cross-linking. C2C12 myoblasts are seeded within the core-shell scaffolds, and the good biocompatibility of these scaffolds and their ability to induce 3D cellular alignment and elongation are successfully demonstrated. Furthermore, the 3D elongated myotube formation within core-shell scaffolds is also performed after long-term cultivation. These data suggest that these core-shell scaffolds combine the aligned NFY core that guides the myoblast alignment and differentiation and the hydrogel shell that provides a suitable 3D environment for nutrition exchange and mechanical protection to perform a great practical application for skeletal muscle regeneration.

Preparation of functional shape memory polymer (SMP) for tissue engineering remains a challenge. Here the synthesis of strong electroactive shape memory polymer (ESMP) networks based on star-shaped polylactide (PLA) and aniline trimer (AT) is reported. Six-armed PLAs with various chain lengths were chemically cross-linked to synthesize SMP. After addition of an electroactive AT segment into the SMP, ESMP was obtained. The polymers were characterized by (1)H NMR, GPC, FT-IR, CV, DSC, DMA, tensile test, and degradation test. The SMP and ESMP exhibited strong mechanical properties (modulus higher than GPa) and excellent shape memory performance: short recovery time (several seconds), high recovery ratio (over 94%), and high fixity ratio (almost 100%). Moreover, cyclic voltammetry test confirmed the electroactivity of the ESMP. The ESMP significantly enhanced the proliferation of C2C12 cells compared to SMP and linear PLA (control). In addition, the ESMP greatly improved the osteogenic differentiation of C2C12 myoblast cells compared to PH10 and PLA in terms of ALP enzyme activity, immunofluorescence staining, and relative gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). These intelligent SMPs and electroactive SMP with strong mechanical properties, tunable degradability, good electroactivity, biocompatibility, and enhanced osteogenic differentiation of C2C12 cells show great potential for bone regeneration.

Electroactive degradable porous tubular scaffolds were fabricated from the blends of polycaprolactone and a hyperbranched degradable conducting copolymer at different feed ratios by a solution-casting/salt-leaching method. Scaning electron microscopy (SEM) and microcomputed tomography tests indicated that these scaffolds had homogeneously distributed interconnected pores on the cross-section and surface. The electrical conductivity of films with the same composition as the scaffolds was between 3.4×10(-6) and 3.1×10(-7) S cm(-1), depending on the ratio of hyperbranched degradable conducting copolymer to polycaprolactone. A hydrophilic surface with a contact angle of water about 30° was achieved by doping the films with (±)-10-camphorsulfonic acid. The mechanical properties of the films were investigated by tensile tests, and the morphology of the films was studied by SEM. The scaffolds were subjected to the WST test (a cell proliferation and cytotoxicity assay using water-soluble tetrazolium salts) with HaCaT keratinocyte cells, and the results show that these scaffolds are non-cytotoxic. These degradable electroactive tubular scaffolds are good candidates for neural tissue engineering application., (Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Biomaterial scaffolds are increasingly being used to drive tissue regeneration. The limited success so far in human tissues rebuilding and therapy application may be due to inadequacy of the functionality biomaterial scaffold. We developed a new decellularized method to obtain complete anatomical skin biomatrix scaffold in situ with extracellular matrix (ECM) architecture preserved, in this study. We described a skin scaffold map by integrated proteomics and systematically analyzed the interaction between ECM proteins and epidermal cells in skin microenvironment on this basis. They were used to quantify structure and function of the skin's Matrisome, comprised of core ECM components and ECM-associated soluble signals that are key regulators of epidermal development. We especially revealed that ECM played a role in determining the fate of epidermal stem cells through hemidesmosome components. These concepts not only bring us a new understanding of the role of the skin ECM niche, they also provide an attractive combinational strategy based on tissue engineering principles with skin biomatrix scaffold materials for the acceleration and enhancement of tissue regeneration. [ABSTRACT FROM AUTHOR]

Mimicking the nanofibrous structure similar to extracellular matrix and conductivity for electrical propagation of native myocardium would be highly beneficial for cardiac tissue engineering and cardiomyocytes-based bioactuators. Herein, we developed conductive nanofibrous sheets with electrical conductivity and nanofibrous structure composed of poly( l -lactic acid) (PLA) blending with polyaniline (PANI) for cardiac tissue engineering and cardiomyocytes-based 3D bioactuators. Incorporating of varying contents of PANI from 0 wt% to 3 wt% into the PLA polymer, the electrospun nanofibrous sheets showed enhanced conductivity while maintaining the same fiber diameter. These PLA/PANI conductive nanofibrous sheets exhibited good cell viability and promoting effect on differentiation of H9c2 cardiomyoblasts in terms of maturation index and fusion index. Moreover, PLA/PANI nanofibrous sheets enhanced the cell-cell interaction, maturation and spontaneous beating of primary cardiomyocytes. Furthermore, the cardiomyocytes-laden PLA/PANI conductive nanofibrous sheets can form 3D bioactuators with tubular and folding shapes, and spontaneously beat with much higher frequency and displacement than that on cardiomyocytes-laden PLA nanofibrous sheets. Therefore, these PLA/PANI conductive nanofibrous sheets with conductivity and extracellular matrix like nanostructure demonstrated promising potential in cardiac tissue engineering and cardiomyocytes-based 3D bioactuators. Statement of Significance Cardiomyocytes-based bioactuators have been paid more attention due to their spontaneous motion by integrating cardiomyocytes into polymer structures, but developing suitable scaffolds for bioactuators remains challenging. Electrospun nanofibrous scaffolds have been widely used in cardiac tissue engineering because they can mimic the extracellular matrix of myocardium. Developing conductive nanofibrous scaffolds by electrospinning would be beneficial for cardiomyocytes-based bioactuators, but such scaffolds have been rarely reported. This work presented a conductive nanofibrous sheet based on polylactide and polyaniline via electrospinning with tunable conductivity. These conductive nanofibrous sheets performed the ability to enhance cardiomyocytes maturation and spontaneous beating, and further formed cardiomyocytes-based 3D bioactuators with tubular and folding shapes, which indicated their great potential in cardiac tissue engineering and bioactuators applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of anisotropic conductive degradable hydrogels were synthesized. • These hydrogels can achieve in situ rapid crosslinking by photoinitiation. • External magnetic field induces nanohybrids to guide cell oriented arrangement. • Cell arrangement and myogenic differentiation promote skeletal muscle regeneration. For volumetric muscle loss regeneration, tissue engineering scaffolds with anisotropic characteristics could mimic the structure of natural skeletal muscle and guide the growth of myoblasts in a specific direction. In addition, scaffolds with conductivity and biodegradability that can provide a suitable microenvironment to facilitate cell growth and myogenic differentiation are also critical for skeletal muscle repair. In this study, a series of anisotropic conductive in situ hydrogels, based on hyaluronic acid methacrylate (HAMA (HM)) and methacrylamide-modified gelatin (GelMA (GM)), induced by magnetic fields are prepared for promoting skeletal muscle regeneration. Polydopamine (PDA)-chelated carbon nanotube (CNT)-Fe 3 O 4 (PFeCNT (PFeC)) nanohybrids are used as magnetic nanohybrids for magnetic field induction and conductive components. These hydrogels (HM/GM/PFeC) show clear anisotropic structure, electrical conductivity and interconnected porous morphology. These cytocompatible anisotropic hydrogels could effectively promote cell oriented alignment. After tryptophan (Trp) loaded, hydrogel (HM/GM/PFeC/Trp) further enhanced myogenic differentiation of mouse myoblasts (C2C12) cells. Regeneration results in SD rat tibialis anterior muscle defect model indicated that HM/GM/PFeC/Trp hydrogels promoted skeletal muscle regeneration, reduced inflammatory response and enhanced the myogenic differentiation factors expression. Therefore, this hydrogel could serve as a promising scaffold for promoting skeletal muscle regeneration by inducing cell alignment and promoting myogenic differentiation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Conducive self-healing hydrogels based on hyaluronic acid-grafted-polyaniline was successfully synthesized. • The hydrogels as cell recruitment niches for autologous cells recruitment to trauma sites promoted skeletal muscle regeneration. • The hydrogels as a leucine loading carrier can be used as a bioactive hydrogel to promote myogenic differentiation of myoblasts. Scaffold is one of the most important roles in skeletal muscle tissue engineering. Being capable of mimicking extracellular matrix components, having electrical conductivity, and recruiting cells proactively to meet the cell-free requests are the proper characteristics of tissue engineering scaffolds. In this work, a series of leucine (Leu) loaded self-healing conductive hydrogels based on aminated hyaluronic acid-graft-polyaniline (AHA-PANI) and oxidized hyaluronic (OHA) were prepared for skeletal muscle tissue engineering. Leu can promote skeletal myogenesis and hydrogel can provide a suitable growth environment for cells. They have self-healing properties, antioxidant activity, suitable modulus, good electrical conductivity, high porosity, and proper swelling ratio. Additionally, these hydrogels have good cytocompatibility and can provide a 3D culture environment for C2C12 and hADSC cells. The Leu-loaded hydrogel has recruiting ability of cells and can promote myogenic differentiation of C2C12 cells. Besides, these hydrogels enable sustained cell delivery, and have good in vivo degradability and exhibited promoting effect on skeletal muscle regeneration in the rat tibialis anterior muscle defect model with reduced post-repair inflammatory factor expression and enhanced myogenic differentiation-related gene expression. All the results indicated that these conductive hydrogels as self-healing cell recruitment niches are excellent biomaterial for the treatment of volumetric muscle loss injury. [ABSTRACT FROM AUTHOR]

• 3D aligned conductive tubular cryogel scaffolds was designed and obtained. • These cryogel scaffolds exhibited mechanical anisotropy like natural muscle. • The scaffolds induced 3D myoblast cell alignment, and enhanced differentiation. • The scaffolds significantly enhanced in vivo skeletal muscle regeneration. Developing 3D conductive aligned cryogels has great potential for skeletal muscle trauma treatment because they can mimic anisotropic structure, conductivity, and recoverable cyclic compression of the microenvironment of native skeletal muscle. In this work, a series of cryogels possessing 3D aligned morphology, conductivity, and excellent anisotropic mechanical compression property based on gelatin (GT) and polydopamine coated carbon nanotubes (PCNTs) were fabricated as skeletal muscle tissue scaffolds by using unidirectional freeze casting technology. The aligned microstructure of cryogels depended on gelatin concentration, and GT7.5 (with the gelatin content of 7.5% w/v) showed excellent aligned structure. Interestingly, the mechanical property of the aligned cryogels was similar to that of native skeletal muscle in terms of the dynamic contraction behavior and the anisotropic compression property due to the internal anisotropy structure. The aligned cryogel GT7.5 with good biocompatibility significantly promoted the alignment and elongation of C2C12 myoblasts. Moreover, the introduction of PCNTs enhanced the mechanical properties of cryogel GT7.5 and had a positive effect on myogenic differentiation of C2C12 cells. The aligned conductive GT7.5C2 cryogel significantly promoted new born muscle tissue generation compared to non-aligned group (GT7.5C2N) and non-conductive group (GT7.5) in a rat tibialis anterior muscle defect model. These data suggested that the 3D aligned conductive cryogel with conductivity and anisotropic compression property is a promising scaffold candidate for skeletal muscle tissue engineering. [ABSTRACT FROM AUTHOR]