The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

BACKGROUND: Tendon and ligament injuries accounted for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year and thus imposed a significant burden to the society and the economy. Damaged tendon and ligament can severely affect the normal body movement and might lead to many complications if not treated promptly and adequately. Current conventional treatment through surgical repair and tissue graft are ineffective with a high rate of recurrence.METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament.RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro.CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.
Bioreactors ; Exosomes ; In Vitro Techniques ; Incidence ; Ligaments ; Physiology ; Recurrence ; Referral and Consultation ; Stem Cells ; Tendons ; Tissue Engineering ; Transplants

OBJECTIVETo investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells.

METHODSParallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation.

RESULTSParallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder.

CONCLUSIONParallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing.

Collagen ; chemistry ; Extracellular Matrix ; physiology ; Freeze Drying ; Freezing ; Humans ; Stem Cells ; cytology ; Tendons ; cytology ; growth & development ; Tissue Engineering ; Tissue Scaffolds ; chemistry

BACKGROUNDRecent studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 (GDF-6) on the tenogenic differentiation of BMSCs in vitro, and then combined with small intestine submucous (SIS) to promote tendon regeneration in vivo.

METHODSThe BMSCs were isolated from the green fluorescent protein (GFP) rats, and were characterized by multi-differentiation assays following our previous study protocol. BMSCs cultured with different concentrations of GDF-6, without growth factors served as control. After 2 weeks, mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6. Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P ≤ 0.05 was regarded as statistically significant. The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model, the BMSCs combined with SIS served as control. After 12 and 4 weeks in nude mice and tendon injury model, the samples were collected for histology.

RESULTSAfter the BMSCs were treated with different concentration of GDF-6 for 2 weeks, the fold changes of the specific markers (Tenomodulin and Scleraxis) mRNA expression were significantly higher in GDF-6 (20 ng/ml) group (P ≤ 0.05), which was also confirmed by Western blotting result. The BMSCs became parallel in orientation after GDF-6 (20 ng/ml) treatment, but the BMSCs in control group were randomly oriented. The GDF-6 (20 ng/ml) treated BMSCs were combined with SIS, and were implanted in nude mice for 12 weeks, the histology showed neo-tendon formation. In the SD rat patellar tendon window injury model, the histology also indicated the GDF-6 (20 ng/ml) treated BMSCs combined with SIS could promote tendon regeneration.

CONCLUSIONSGDF-6 has tenogenic effect on the tenogenic differentiation of BMSCs, and GDF-6 (20 ng/ml) has better tenogenic effect compared to other concentrations. The GDF-6 (20 ng/ml) treated BMSCs combined with SIS can form neo-tendons and promote tendon regeneration.

Animals ; Cell Differentiation ; drug effects ; Growth Differentiation Factor 6 ; pharmacology ; Male ; Membrane Proteins ; genetics ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Mice ; Mice, Nude ; Rats ; Rats, Sprague-Dawley ; Regeneration ; drug effects ; Tendons ; drug effects ; physiology

BACKGROUND: Current examination methods to assess the anatomical variations of flexor digitorum superficialis (FDS) tendon in the little finger necessitate a strong external force applied by the examiner and cause false negatives. A new examination method was designed to detect the variations more accurately. METHODS: We examined the little fingers of 220 adult hands (110 subjects) by 2 methods: the expanded examination method advocated by Tan et al., and a new examination method. Variations of the FDS in the little finger were examined by both methods and categorized separately as having independent FDS function, FDS connection to the tendons of the ring finger or of the multiple adjacent fingers, and functional substitution of the flexor digitorum profundus (FDP) with or without tendinous connection to the ring or multiple adjacent fingers. By our new method, we could further divide the FDS connection or FDP substitution with connection to the ring finger into 2 subtypes: loose and close connections. Data were reported as case numbers and percent. Date on symmetry were statistically analyzed by matched case-control studies. RESULTS: Among 220 hands, 113 hands (51.4%) had independent FDS function by the new examination method, which was lower than the incidence (55.5%) detected with the existing expanded examination method. In the hands with connections between FDS tendons of the little and the ring fingers, 32 hands (14.5%) demonstrated loose and 37 (16.8%) close connections. Three hands (1.4%) had loose and 19 (8.6%) had close FDP substitution with tendinous connection to the ring finger. Among 110 hands without independent FDS function, variants of 42 hands (38.2%) were asymmetric. There was no statistical significance in symmetry of variations. CONCLUSIONS: This new examination method offers other assessment variations of FDS tendon in the little finger. We recommend using this test to assess the variations and function of the FDS of the little finger.
Adult ; *Anatomic Variation ; Female ; Fingers/*anatomy & histology/physiology ; Humans ; Male ; Middle Aged ; Physical Examination/*methods ; Tendons/*anatomy & histology/physiology ; Young Adult

Calcifying tendinopathy is a tendon disorder with calcium deposits in the mid-substance presented with chronic activity-related pain, tenderness, local edema and various degrees of incapacitation. Most of current treatments are neither effective nor evidence-based because its underlying pathogenesis is poorly understood and treatment is usually symptomatic. Understanding the pathogenesis of calcifying tendinopathy is essential for its effective evidence-based management. One of the key histopathological features of calcifying tendinopathy is the presence of chondrocyte phenotype which surrounds the calcific deposits, suggesting that the formation of calcific deposits was cell-mediated. Although the origin of cells participating in the formation of chondrocyte phenotype and ossification is still unknown, many evidences have suggested that erroneous tendon cell differentiation is involved in the process. Recent studies have shown the presence of stem cells with self-renewal and multi-differentiation potential in human, horse, mouse and rat tendon tissues. We hypothesized that the erroneous differentiation of tendon-derived stem cells (TDSCs) to chondrocytes or osteoblasts leads to chondrometaplasia and ossification and hence weaker tendon, failed healing and pain, in calcifying tendinopathy. We present a hypothetical model on the pathogenesis and evidences to support this hypothesis. Understanding the key role of TDSCs in the pathogenesis of calcifying tendinopathy and the mechanisms contributing to their erroneous differentiation would provide new opportunities for the management of calcifying tendinopathy. The re-direction of the differentiation of resident TDSCs to tenogenic or supplementation of MSCs programmed for tenogenic differentiation may be enticing targets for the management of calcifying tendinopathy in the future.
Animals ; Cell Differentiation ; physiology ; Humans ; Mice ; Rats ; Stem Cells ; pathology ; Tendinopathy ; etiology ; pathology ; Tendons ; pathology

OBJECTIVETo study the effect of continuous passive motion (CPM) on basic fibroblast growth factor (b-FGF) expression during tendon-bone repair in rabbits and explore the role of stress in the postoperative repair after acute rotator cuff injury.

METHODSSixteen rabbits randomized into CPM group (n=8) and non-CPM group (n=8) were subjected to surgically induced acute rupture of the supraspinatus tendon and subsequent surgical repair, with another two rabbits serving as the control. Two weeks after the operation, the rabbits in CPM group underwent CPM training, and those in non-CPM group were normally fed only. At 2, 4, 6, and 8 weeks after the operation, 2 rabbits from each group were sacrificed and the tissue samples were obtained for detecting the changes in b-FGF expression.

RESULTSTwo weeks after the operation, b-FGF expression was detected in both groups, and the CPM group showed slightly higher and more diffusive expression. At 4 weeks, b-FGF expression was significantly higher and distributed over a greater area in CPM group and in the non-CPM group. A large number of fibroblasts positive for b-FGF expression were identified in CPM group, aligning in parallel with the tendon membrane. At 6 weeks, b-FGF in the CPM group showed no obvious changes but that in the non-CPM group became lightened. At 8 weeks, b-FGF expression was reduced in both groups, which was more obvious in the non-CPM group.

CONCLUSIONCPM can promote b-FGF expression to enhance type III collagen synthesis at the tendon-bone interface in early stage of tendon-bone repair following acute rupture of supraspinatus tendon in rabbits, thereby contributing to tendon-bone recovery after rotator cuff injury.

Animals ; Bone Remodeling ; drug effects ; physiology ; Fibroblast Growth Factor 2 ; metabolism ; Male ; Postoperative Period ; Rabbits ; Random Allocation ; Range of Motion, Articular ; Rupture ; surgery ; Tendon Injuries ; rehabilitation ; surgery ; Tendons ; metabolism ; Wound Healing ; physiology

In order to provide data for clinical approach to Hand-functional rehabilitation, we conducted this study on the relationships among flexor tendon load, tendon excursion and finger joint angle. Using the dynamic biomechanical test, three-dimension motion image analysis and computer analysis, we investigated eight intact normal male cadavers, hand mechanics of flexor tendon load, tendon excursion and joint angle. The results showed that, at the time when the top of finger touched the palm, the mean tendon load of flexor digitorum profundus(FDP) tendon was 7.9 N, the mean tendon excursion 43.4 mm, the mean total range of motion 237.0 degree. When the top of finger touched the palm, the mean tendon load of flexor digitorum superficial(FDS) tendon was 8.9 N, the mean tendon excursion 38.5 mm, and the mean total range of motion 206.3 degree. These findings demonstrated that there are some curvilinear relationships between flexor tendon load, tendon excursion and finger joint motion. When we flex our fists, the proximal interphalangeal(PIP) joint plays an important role in both FDP and FDS tendon.
Biomechanical Phenomena ; Cadaver ; Finger Joint ; physiology ; Fingers ; physiology ; Humans ; Male ; Muscle Contraction ; Muscle, Skeletal ; physiology ; Range of Motion, Articular ; Tendons ; physiology

OBJECTIVETo observe the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the tendon-bone healing in rabbits after anterior cruciate ligament reconstruction.

METHODSThirty normal adult New Zealand rabbits were divided into 3 groups for anterior cruciate ligament reconstruction using autologous semitendinosus tendons as the graft material. In the rhBMP-2 group, fibrin glue (FG) containing rhBMP-2 was applied to the interface between the tendon graft and the bone tunnel, while in the FG control group, only FG was applied. The blank control group received no treatment after the surgery. The grafts were collected at 2, 4, 8 weeks after the surgery for gross observation and histological examination of the graft incorporation.

RESULTSIn the FG control group, the tendon-bone interface was filled with granulation tissue 2 weeks after the surgery, and the newly generated tissue growing into the bone tunnel and fibroblasts were observed at 4 weeks. Till week 8, Sharpey's fibers were found in the interface with the formation of indirect insertion. In the rhBMP-2 group, the tendon-bone interface was filled with cartilage tissue at 2 weeks, and the four-layer direct insertion was formed at 4 weeks; till week 8, the interface was mainly composed of the direct insertion.

CONCLUSIONrhBMP-2 can induce direct insertion formation in the tendon-bone interface after early anterior cruciate ligament reconstruction. The direct insertion possesses better biomechanical properties than indirect insertion.

Animals ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Injuries ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; therapeutic use ; Bone Regeneration ; drug effects ; Bone and Bones ; physiology ; Humans ; Rabbits ; Recombinant Proteins ; therapeutic use ; Reconstructive Surgical Procedures ; methods ; Tendons ; physiology ; Transforming Growth Factor beta ; therapeutic use ; Wound Healing ; drug effects

A dynamics model of human lower extremity, which combines musculotendon dynamics and muscle excitation-contraction dynamics, is presented. With this model, a motion process of normal gait during swing phase is numerically analyzed by use of the optimal control theory. The model was verified using experimental kinematics, muscles activation, and electromyographic data. The result showed that the tri-phasic activation pattern and synergistic muscles displayed during a normal gait in swing phase. The pattern consists of three distinct phases, i. e., acceleration during moving initiation, braking the moving segment, and posture control at the final specified position.
Biomechanical Phenomena ; Computer Simulation ; Electromyography ; Gait ; physiology ; Humans ; Kinetics ; Lower Extremity ; physiology ; Models, Biological ; Muscle, Skeletal ; physiology ; Tendons ; physiology