Biobased Elastomer Nanofibers Guide Light-Controlled Human-iPSC-Derived Skeletal Myofibers.

Generating skeletal muscle tissue that mimics the cellular alignment, maturation, and function of native skeletal muscle is an ongoing challenge in disease modeling and regenerative therapies. Skeletal muscle cultures require extracellular guidance and mechanical support to stabilize contractile myofibers. Existing microfabrication-based solutions are limited by complex fabrication steps, low throughput, and challenges in measuring dynamic contractile function. Here, the synthesis and characterization of a new biobased nanohybrid elastomer, which is electrospun into aligned nanofiber sheets to mimic the skeletal muscle extracellular matrix, is presented. The polymer exhibits remarkable hyperelasticity well-matched to that of native skeletal muscle (≈11-50 kPa), with ultimate strain ≈1000%, and elastic modulus ≈25 kPa. Uniaxially aligned nanofibers guide myoblast alignment, enhance sarcomere formation, and promote a ≈32% increase in myotube fusion and ≈50% increase in myofiber maturation. The elastomer nanofibers stabilize optogenetically controlled human induced pluripotent stem cell derived skeletal myofibers. When activated by blue light, the myofiber-nanofiber hybrid constructs maintain a significantly higher (>200%) contraction velocity and specific force (>280%) compared to conventional culture methods. The engineered myofibers exhibit a power density of ≈35 W m-3 . This system is a promising new skeletal muscle tissue model for applications in muscular disease modeling, drug discovery, and muscle regeneration.

Three-dimensional characterization of collagen remodeling in cell-seeded collagen scaffolds via polarization second harmonic generation.

In this study, we use non-linear imaging microscopy to characterize the structural properties of porous collagen-GAG scaffolds (CGS) seeded with human umbilical vein endothelial cells (HUVECs), as well as human mesenchymal stem cells (hMSCs), a co-culture previously reported to form vessel-like structures inside CGS. The evolution of the resulting tissue construct was monitored over 10 days via simultaneous two- and three-photon excited fluorescence microscopy. Time-lapsed 2- and 3-photon excited fluorescence imaging was utilized to monitor the temporal evolution of the vascular-like structures up to 100 µm inside the scaffold up to 10 days post-seeding. 3D polarization-dependent second harmonic generation (PSHG) was utilized to monitor collagen-based scaffold remodeling and determine collagen fibril orientation up to 200 µm inside the scaffold. We demonstrate that polarization-dependent second harmonic generation can provide a novel way to quantify the reorganization of the collagen architecture in CGS simultaneously with key biomechanical interactions between seeded cells and CGS that regulate the formation of vessel-like structures inside 3D tissue constructs. A comparison between samples at different days in vitro revealed that gradually, the scaffolds developed an orthogonal net-like architecture, previously found in real skin.

Inflammatory response and survival of pedicled abdominal flaps in a rat model after perivascular application of botulinum toxin type A.

BACKGROUND: In addition to the numerous applications of botulinum toxin type A, the authors have documented improvements in surgical flap survival through vasoactive effects. This study aimed to investigate its effect on the expression of inflammatory mediators. METHODS: In 54 male Sprague-Dawley rats, cutaneous flaps based on the superficial epigastric vessels were elevated. Botulinum toxin type A, lidocaine, or saline was administered to the vascular pedicle. After 1, 2, and 7 days, mRNA expression for tumor necrosis factor-α, interleukin-1, and vascular endothelial growth factor-165 was compared along with flap survival. RESULTS: Vascular endothelial growth factor-165 mRNA expression was lower in the botulinum toxin type A group compared with (1) the saline group at days 1 and 2 (p < 0.01) and (2) the lidocaine group at day 2 (p < 0.05). The expression of interleukin-1 was significantly less at each time point in the botulinum toxin type A group compared with the lidocaine group (p < 0.02), and at day 2 compared with the saline group (p < 0.01). Tumor necrosis factor-α mRNA expression in the botulinum toxin type A group was lower at 2 days and 7 days compared with both other groups (p < 0.04). Finally, both the botulinum toxin type A and lidocaine groups had a greater survival area (p < 0.05) compared with the saline group. CONCLUSION: The presence of botulinum toxin type A in the postsurgical flap microenvironment augments tissue perfusion and its inflammatory response and, ultimately, survival.

Use of artificial dermal substitute as a bridge in complex finger reconstruction.

Few reports exist regarding the use of an artificial dermal substitute ([ADS] Integra™) in the treatment of finger injuries. This retrospective case series evaluated the use of ADS as a bridge for finger reconstruction following complex injuries. The authors' facility treated 26 complex finger injury patients using ADS. Graft take was 92.3% (22/26), with most patients experiencing satisfactory range of motion (88.5% or 23/26). The authors conclude that ADS, as a bridge for reconstruction of complex finger injuries, offers advantages, such as improved contour, functionality, and decreased need for native flaps.