Search

IntroductionThe healing of tendon-bone injuries is very difficult, often resulting in poor biomechanical performance and unsatisfactory functional recovery. The tendon-bone insertion has a complex four distinct layers structure, and previous studies have often focused on promoting the regeneration of the fibrocartilage layer, neglecting the role of its bone end repair in tendon-bone healing. This study focuses on the role of treadmill training in promoting bone regeneration at the tendon-bone insertion and its related mechanisms.MethodsAfter establishing the tendon-bone insertion injury model, the effect of treadmill training on tendon-bone healing was verified by Micro CT and HE staining; then the effect of CX3CL1 on osteoclast differentiation was verified by TRAP staining and cell culture; and finally the functional recovery of the mice was verified by biomechanical testing and behavioral test.ResultsTreadmill training suppresses the secretion of CX3CL1 and inhibits the differentiation of local osteoclasts after tendon-bone injury, ultimately reducing osteolysis and promoting tendon bone healing.DiscussionOur research has found the interaction between treadmill training and the CX3CL1-C3CR1 axis, providing a certain theoretical basis for rehabilitation training.

Aims: Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods: A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results: Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion: Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351.

Abstract Introduction Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing. Method A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes. Results The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation. Conclusions Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.

Abstract Background Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair and regeneration. Previously we found more adipocytes accumulated in the patellar tendon injury sites in aging rats compared with the young ones, of which the mechanism is still unknown. Here, we want to identify whether erroneous differentiation of TSPCs by aging accounts for the adipocyte accumulation. Methods TSPCs from young and aging rats were isolated and propagated. Both young and aging TSPCs were induced to differentiate into adipocytes, and Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunofluorescent staining were used to evaluate the capability of TSPCs. RNA sequencing was utilized to screen out different genes and signaling pathways related to adipogenesis between young and aging TSPCs. Results The Oil red O staining showed there were more adipocytes formed in young TSPCs. Besides, adipogenic markers perilipin, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins alpha (C/EBPα) and Fatty acid-binding protein 4 (FABP4) were elevated both at gene and protein level. PPARγ signaling pathway was selected as our target via RNA sequencing. After adding the signaling activators, Rosiglitazone maleate (RM), inhibited adipogenesis of aging TSCs was reversed. Conclusions In conclusion, aging inhibited adipogenesis of TSPCs by down‐regulating PPARγ signaling. It is not likely that the adipocyte accumulation in aging tendon during repair was due to the aging of TSPCs. This may provide new targets for curing aging tendon injuries or tendinopathies.

Purpose. The reconstruction of a tendon insertion on metal prostheses is a challenge in orthopedics. Of the available metal prostheses, porous metal prostheses have been shown to have better biocompatibility for tissue integration. Therefore, this study is aimed at identifying an appropriate porous structure for the reconstruction of a tendon insertion on metal prostheses. Methods. Ti6Al4V specimens with a diamond-like porous structure with triply periodic minimal surface pore sizes of 300, 500, and 700 μm and a porosity of 58% (designated Ti300, Ti500, and Ti700, respectively) were manufactured by selective laser melting and were characterized with micro-CT and scanning electron microscopy for their porosity, pore size, and surface topography. The porous specimens were implanted into the patellar tendon of rabbits. Tendon integration was evaluated after implantation into the tendon at 4, 8, and 12 weeks by histology, and the fixation strength was evaluated with a pull-out test at week 12. Results. The average pore sizes of the Ti300, Ti500, and Ti700 implants were 261, 480, and 668 μm, respectively. The Ti500 and Ti700 implants demonstrated better tissue growth than the Ti300 implant at weeks 4, 8, and 12. At week 12, the histological score of the Ti500 implant was 13.67±0.58, and it had an area percentage of type I collagen of 63.90%±3.41%; both of these results were significantly higher than those for the Ti300 and Ti700 implants. The pull-out load at week 12 was also the highest in the Ti500 group. Conclusion. Ti6Al4V implants with a diamond-like porous structure with triply periodic minimal surface pore size of 500 μm are suitable for tendon integration.

Purpose. Tendon injuries are common musculoskeletal system disorders, but the ability for tendon regeneration is limited. Silk fibroin (SF) film may be suitable for tendon regeneration due to its excellent biocompatibility and physical properties. This study is aimed at evaluating the application value of bionic SF film in tendon regeneration. Methods. Tendon stem/progenitor cells (TSPCs) were isolated from rat Achilles tendon and characterized based on their surface marker expression and multilineage differentiation potential. SF films with smooth or bionic microstructure surfaces (5, 10, 15, 20 μm) were prepared. The morphology and mechanical properties of natural tendons and SF films were characterized. TSPCs were used as the seed cells, and the cell viability and cell adhesion morphology were analyzed. The tendongenesis-related gene expression of TSPCs was also evaluated using quantitative polymerase chain reaction. Results. Compared to the native tendon, only the 10, 15, and 20 μm SF film groups had comparable maximum loading and ultimate stress, with the exception of the breaking elongation rate. The 10 μm SF film group had the highest percentage of oriented cells and the most significant changes in cell morphology. The most significant upregulations in the expression of COL1A1, TNC, TNMD, and SCX were also observed in the 10 μm SF film group. Conclusion. SF film with a bionic microstructure can serve as a tissue engineering scaffold and provide biophysical cues for the use of TSPCs to achieve proper cellular adherence arrangement and morphology as well as promote the tenogenic differentiation of TSPCs, making it a valuable customizable biomaterial for future applications in tendon repair.

Fibroblasts can be reprogrammed into induced neural stem cells (iNSCs) using transcription factors expressed in neural progenitors. Here the authors show that Ptf1a, which is normally expressed in postmitotic neurons, can reprogram fibroblasts to iNSCs through Notch independent interaction with Rbpj.