Developing scaffolds to enhance muscle regeneration and mimic natural muscle biomechanics is vital for treating volumetric muscle loss (VML). Current scaffolds struggle to achieve both low elastic modulus and high toughness. These limitations result in inadequate load-bearing capacity, delaying early functional recovery, extending treatment duration, and adversely affecting patients’ life. Additionally, the single functionality of current scaffolds restricts their capacity to meet the diverse and complex needs of clinical applications. To address these challenges, Professor Cheng-Hui Li’s group, in collaboration with Professor Pengfei Zheng’s group at the Children’s Hospital of Nanjing Medical University, drew inspiration from natural muscle structures. They designed a soft, ultra-tough and multifunctional artificial muscle (Figure 1).
Figure 1. Development of a multifunctional artificial muscle with tissue-like modulus inspired by biomimetic design.
Perfluoropolyether (PFPE), with a glass transition temperature below -100 °C and flexible chain segments, serves as a soft segment to enhance the polymer’s flexibility. Polycaprolactone (PCL), a crystallizable hard segment, provides mechanical strength. Interactions between PFPE and PCL, both within and between chains (e.g., dipole-dipole interactions), facilitate self-assembly and the formation of microphase-separated structures while inhibiting the crystallization behavior of PCL. Thus, the polymer stays amorphous at room temperature, maintaining flexibility (Figure 2). Under tensile stress, the amorphous polymer chains initially aggregated within the material unfold, align, and reorient along the direction of the applied load. This transformation boosts tensile strength and enhances energy dissipation during deformation. These properties endow the polymer with high tensile strength, excellent toughness, as well as superior tear and puncture resistance. During cyclic loading, PCL chains form interchain microcrystalline structures aligned with the load. This process endows the polymer with training reinforcement properties, akin to the adaptive strengthening observed in natural muscles (Figure 3).
Figure 2. Characterization and comparative analysis of the mechanical properties of PFPEx-PCLy.
Figure 3. Investigation of the training reinforcement properties and underlying mechanisms of the artificial muscles.
Additionally, the material exhibits outstanding shape memory behavior and actuation capabilities, rapidly recovering to its original configuration upon heating. It achieves an actuation strain of up to 600% and an energy density of 1450 J/kg. Under thermal stimulation, the material is capable of lifting loads exceeding 5000 times its own weight. Furthermore, this artificial muscle reliably performs cyclic contraction and extension through repeated heating and cooling, successfully mimicking the actuation functionality of natural muscles. These properties demonstrate its significant potential for applications in prosthetic actuators (Figure 4).
Figure 4. Characterization of the actuation performance, tear resistance, and puncture resistance of the artificial muscles.
The artificial muscle demonstrates excellent biocompatibility, as evidenced by live/dead staining and CCK-8 cell viability assays. These tests confirmed that the material is non-toxic to muscle cells, with cell viability comparable to the control group, indicating no adverse effects on muscle cells. When co-cultured with C2C12 muscle cells for 7 days, MHC staining revealed that the muscle cells formed myotubes aligned along the material’s stretching direction. This alignment suggests that the material supports muscle cell growth and differentiation, thereby promoting muscle tissue regeneration (Figure 5). In a rat VML model, implantation of the artificial muscle demonstrated remarkable elasticity and softness, enabling the polymer to move seamlessly with residual muscles. This avoided complications such as muscle atrophy and joint dysfunction, which are common with traditional surgical suturing and plaster fixation. Additionally, the material’s high mechanical strength allowed the rats to maintain regular activities following scaffold implantation. Post-implantation histological analysis showed that the material effectively guided muscle tissue regeneration along the scaffold, with regenerated muscle displaying well-organized structure and morphology by the fourth week. Furthermore, vascular regeneration, assessed through CD31 and α-SMA staining, exhibited significant improvements. These findings highlight the artificial muscle’s potential to enhance vascularization, a critical factor for successful muscle regeneration (Figure 6).
Figure 5. Assessment of cytotoxicity, in vitro proliferation and differentiation potential, and evaluation of muscle’s contractile force.
Figure 6. Promotion of angiogenesis and muscle repair 4 weeks after PFPE1-PCL3 implantation in vivo.
This study proposes an innovative method to regulate inter/intra-chain interactions between PFPE and PCL segments, facilitating the formation of self-assembled and microphase-separated structures and developing an artificial muscle with low modulus and high toughness. The artificial muscle shows promising potential for volumetric muscle loss (VML) treatment and prosthetic actuation, providing a novel pathway for scaffolds development and expanding the clinical applications of artificial muscles. This work entitled A soft, ultra-tough and multifunctional artificial muscle for volumetric muscle loss treatment was published in National Science Review (DOI: 10.1093/nsr/nwae422). PhD student Peng-Fei Qiu and postdoctoral researcher Lei Qiang from the Children’s Hospital of Nanjing Medical University are co-first authors of the paper, while Professor Cheng-Hui Li and Professor Pengfei Zheng from the Children’s Hospital of Nanjing Medical University are co-corresponding authors. This work was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities.