ABSTRACT
BACKGROUND: Previous studies have shown that neurotrophin 3 (NT3)-chitosan can induce endogenous neurogenesis and axon regeneration in rats with spinal cord injury, and promote recovery of motor and sensory functions in rats. OBJECTIVE: To observe the effect of rehabilitation training combined with NT3-chitosan biomaterial scaffold on skeletal muscle morphological changes and functional recovery in rats with complete spinal cord injury. METHODS: Fifty adult female Wistar rats were randomly divided into five groups, 10 in each group. The sham group was not modeled; the remaining four groups were prepared with T7-T8 complete 5-mm spinal cord injury model, and the lesion control was not performed any intervention after modeling. The other three groups were given rehabilitation training, NT3-chitosan active biomaterial scaffold, NT3-chitosan active biomaterial scaffold combined with rehabilitation training intervention. Rehabilitation training started 2 weeks after modeling. Before operation, 2, 4, 6, 8, 10, and 12 weeks after operation, all of rats were subjected to double-blind open-field BBB scores. After 12 weeks, the skeletal muscles of the hind limbs (tibialis anterior muscle, gastrocnemius muscle, and soleus muscle) were taken for hematoxylin-eosin staining and acetylcholinesterase staining. The changes in muscle atrophy and motor endplates were assessed in each group. The experimental plan was approved by the Animal Experiment Committee of Capital Medical University (approval No. AEEI-2018-105). RESULTS AND CONCLUSION: (1) The BBB score at each time point in the sham group was higher than that in the other four groups (P < 0.05); and the scores at 8, 10, and 12 weeks after the NT3-chitosan combined rehabilitation training group were higher than the lesion control group, the lesion control combined rehabilitation training group, and NT3-chitosan group (P < 0.05). (2) At 12 weeks after operation, hematoxylin-eosin staining showed that the cross-sectional area and diameter of muscle fibers of each skeletal muscle were smaller in the other four groups than that in the sham group (P < 0.05). The cross-sectional area and diameter of muscle fibers of each skeletal muscle in the NT3-chitosan combined rehabilitation training group were higher than the lesion control group, the lesion control combined rehabilitation training group, and NT3-chitosan group (P < 0.05). (3) At 12 weeks after operation, the acetylcholinesterase staining showed that the average optical density of the acetylcholinesterase on motor endplate of the muscle was lower in the other four groups than that in the sham group (P < 0.05); the average optical density of the acetylcholinesterase of the motor endplate in the NT3-chitosan combined rehabilitation training was significantly higher than that in the lesion control, lesion control combined rehabilitation training, and NT3-chitosan groups (P < 0.05). (4) The results show that NT3-chitosan combined with rehabilitation training can effectively prevent muscular atrophy of hind limb skeletal muscles in rats with complete spinal cord injury, improve the average optical density of the acetylcholinesterase of the motor endplate, reduce neuromuscular joint degeneration, and improve rat hindlimb motor function.
ABSTRACT
BACKGROUND: Since non-coding RNAs maintain bone homeostasis through various pathways, applications of non-coding RNAs as bioactive molecules in bone tissue engineering for bone defect repair has become an increasing area of interest. OBJECTIVE: To introduce non-coding RNAs as bioactive molecules in bone tissue engineering. METHODS: A computer-based online search of Web of Science, PubMed, SpringerLink databases was performed by the first author between December 2018 and March 2019 using the search terms “bone tissue engineering, ncRNA (miRNA, siRNA or lncRNA), scaffold, drug delivery system” to retrieve papers published during 2004-2019. A total of 1754 papers were preliminarily retrieved, and 95 of them were eligible for final analysis. RESULTS AND CONCLUSION: Because non-coding RNAs play a key role in osteogenic differentiation, they can be used as important bioactive factors for bone tissue engineering. At present, bone tissue engineering repair methods based on non-coding RNA bioactive factors have become a research hotspot in bone defect repair. There are two major application strategies: (1) The non-coding RNA transcription within the seed cells is purposefully altered and combines with the bone tissue-engineered scaffold to promote bone defect repair. (2) a specifically designed bone engineered scaffold can controllably and purposefully alter the expression of non-coding RNA in the seed cells, which promotes bone defect repair. In addition, the function of more and more non-coding RNAs has been identified in the process of bone regeneration. This shows good application prospects of non-coding RNAs.