Hierarchical anisotropy structure directing 3D cellular orientation plays a crucial role in designing tendon tissue engineering scaffolds. Despite recent development of fabrication technologies for controlling cellular organization and design of scaffolds that mimic the anisotropic structure of native tendon tissue, improvement of tenogenic differentiation remains challenging. Herein, we present 3D aligned poly (ε-caprolactone) nanofiber yarns (NFYs) of varying diameter, fabricated using a dry-wet electrospinning approach, that integrate with nano- and micro-scale structure to mimic the hierarchical structure of collagen fascicles and fibers in native tendon tissue. These aligned NFYs exhibited good in vitro biocompatibility, and their ability to induce 3D cellular alignment and elongation of tendon stem/progenitor cells was demonstrated. Significantly, the aligned NFYs with a diameter of 50 μm were able to promote the tenogenic differentiation of tendon stem/progenitor cells due to the integration of aligned nanofibrous structure and suitable yarn diameter. Rat tendon repair results further showed that bundled NFYs encouraged tendon repair in vivo by inducing neo-collagen organization and orientation. These data suggest that electrospun bundled NFYs formed by aligned nanofibers can mimic the aligned hierarchical structure of native tendon tissue, highlighting their potential as a biomimetic multi-scale scaffold for tendon tissue regeneration.

BackgroundOver the past decade, numerous advances have been made in the research on electrical stimulation of skeletal muscle. However, the developing status and future direction of this field remain unclear. This study aims to visualize the evolution and summarize global research hot topics and trends based on quantitative and qualitative evidence from bibliometrics.MethodsLiterature search was based on the Web of Science Core Collection (WoSCC) database from 2011 to 2021. CiteSpace and VOSviewer, typical bibliometric tools, were used to perform analysis and visualization.ResultsA total of 3,059 documents were identified. The number of literature is on the rise in general. Worldwide, researchers come primarily from North America and Europe, represented by the USA, France, Switzerland, and Canada. The Udice French Research Universities is the most published affiliation. Millet GY and Maffiuletti NA are the most prolific and the most co-cited authors, respectively. Plos One is the most popular journal, and the Journal of Applied Physiology is the top co-cited journal. The main keywords are muscle fatigue, neuromuscular electrical stimulation, spinal cord injury, tissue engineering, and atrophy. Moreover, this study systematically described the hotspots in this field.ConclusionAs the first bibliometric analysis of electrical stimulation of skeletal muscle research over the past decade, this study can help scholars recognize hot topics and trends and provide a reference for further exploration in this field.

Despite numerous studies on tissue-engineered injectable cartilage, it is still difficult to realize stable cartilage formation in preclinical large animal models because of suboptimal biocompatibility, which hinders further application in clinical settings. In this study, we proposed a novel concept of cartilage regeneration units (CRUs) based on hydrogel microcarriers for injectable cartilage regeneration in goats. To achieve this goal, hyaluronic acid (HA) was chosen as the microparticle to integrate gelatin (GT) chemical modification and a freeze-drying technology to create biocompatible and biodegradable HA-GT microcarriers with suitable mechanical strength, uniform particle size, a high swelling ratio, and cell adhesive ability. CRUs were then prepared by seeding goat autologous chondrocytes on the HA-GT microcarriers and culturing in vitro. Compared with traditional injectable cartilage methods, the proposed method forms relatively mature cartilage microtissue in vitro and improves the utilization rate of the culture space to facilitate nutrient exchange, which is necessary for mature and stable cartilage regeneration. Finally, these precultured CRUs were used to successfully regenerate mature cartilage in nude mice and in the nasal dorsum of autologous goats for cartilage filling. This study provides support for the future clinical application of injectable cartilage.