Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review.
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ABSTRACT:
SUBMITTER: Aspenberg P
PROVIDER: S-EPMC2266668 | biostudies-other | 2007 Dec
REPOSITORIES: biostudies-other
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Project description:Tendon injuries often result from excessive or insufficient mechanical loading, impairing the ability of the local tendon cell population to maintain normal tendon function. The resident cell population composing tendon tissue is mechanosensitive, given that the cells are able to alter the extracellular matrix in response to modifications of the local loading environment. Natural tendon healing is insufficient, characterized by improper collagen fibril diameter formation, collagen fibril distribution, and overall fibril misalignment. Current tendon repair rehabilitation protocols focus on implementing early, well-controlled eccentric loading exercises to improve repair outcome. Tissue engineers look toward incorporating mechanical loading regimens to precondition cell populations for the creation of improved biological augmentations for tendon repair.
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Project description:Distal biceps tendon ruptures are uncommon injuries that can cause impairment in range of motion and function. While distal bicep tendon repair to the radial tuberosity has been demonstrated to restore function and strength, there is a lack of consensus on the optimal technique. The purpose of this Technical Note and video is to provide our preferred method of repair using an open, onlay-tissue fixation with all-suture anchors (FiberTak; Arthrex) and anatomic positioning of the biceps tendon on the radial tuberosity.
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Project description:BackgroundTo reduce incision complications, minimally invasive operative approaches for treatment with acute Achilles tendon rupture have been developed, such as Mini-open repair and percutaneous repair. Which technique is the better surgical option? In the present study, we compared the two surgical procedures- modified Mini-open repair versus percutaneous repair-in the treatment of acute Achilles tendon rupture.MethodsFrom January 2016 to November 2018, 68 matched patients with acute Achilles tendon rupture were divided into treatment group (Mini-open with modified Ma-Griffith technique) and control group (the Ma-Griffith technique). The patients were then treated with different surgical techniques and followed up for no less than 24 months, and the functional outcome scores and complications were retrospectively evaluated.ResultsThe mean follow-up time in Mini-open repair group was 29.0±2.9 months, and that in control group was 27.9±2.9 months (P=0.147). The Mini-open repair group showed reliably higher American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score and Achilles tendon Total Rupture Score (ATRS) than the control group in functional assessment (95.0±3.8 vs. 92.3±5.3, P=0.000; 93.8±3.8 vs. 90.9±4.5,P=0.000). There was no cases of sural nerve injury in Mini-open repair group, whereas the percutaneous repair group had 5 cases of the same (P=0.027). No significant differences were found in the calf circumference (32.3±3.9 vs. 31.8±3.6) (P=0.564), range of motion of the ankle (51.3±4.8 vs. 50.5±4.2, P=0.362), or wound complications (34/0 vs. 34/0) (P=1.000) between the two groups at the end of the follow-up time. However, the percutaneous repair group had a shorter average operating time (23.1±5.2 min) than that of the Mini-open repair group (27.7±4.3 min) (P=0.000).ConclusionsAcute Achilles tendon ruptures may be treated successfully with a new Mini-open repair system or percutaneous repair technique. However, the Mini-open repair system may represent a superior surgical option, since it offers advantages in terms of direct visual control of the repair, AOFAS Ankle-Hindfoot Score, Achilles tendon Total Rupture Score and risk of sural nerve palsy.Study designCase-control studies, Level of evidence, 3.
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Project description:Mechanical loading affects tendon healing and recovery. However, our understanding about how physical loading affects recovery of viscoelastic functions, collagen production and tissue organisation is limited. The objective of this study was to investigate how different magnitudes of loading affects biomechanical and collagen properties of healing Achilles tendons over time. Achilles tendon from female Sprague Dawley rats were cut transversely and divided into two groups; normal loading (control) and reduced loading by Botox (unloading). The rats were sacrificed at 1, 2- and 4-weeks post-injury and mechanical testing (creep test and load to failure), small angle x-ray scattering (SAXS) and histological analysis were performed. The effect of unloading was primarily seen at the early time points, with inferior mechanical and collagen properties (SAXS), and reduced histological maturation of the tissue in unloaded compared to loaded tendons. However, by 4 weeks no differences remained. SAXS and histology revealed heterogeneous tissue maturation with more mature tissue at the peripheral region compared to the center of the callus. Thus, mechanical loading advances Achilles tendon biomechanical and collagen properties earlier compared to unloaded tendons, and the spatial variation in tissue maturation and collagen organization across the callus suggests important regional (mechano-) biological activities that require more investigation.
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Project description:Tendon experiences a variety of multiscale changes to its extracellular matrix during mechanical loading at the fascicle, fibre and fibril levels. For example, tensile loading of tendon increases its stiffness, with organization of collagen fibres, and increases cell strain in the direction of loading. Although applied macroscale strains correlate to cell and nuclear strains in uninjured tendon, the multiscale response during tendon healing remains unknown and may affect cell mechanosensing and response. Therefore, this study evaluated multiscale structure-function mechanisms in response to quasi-static tensile loading in uninjured and healing tendons. We found that tendon healing affected the macroscale mechanical and structural response to mechanical loading, evidenced by decreases in strain stiffening and collagen fibre realignment. At the micro- and nanoscales, healing resulted in increased collagen fibre disorganization, nuclear disorganization, decreased change in nuclear aspect ratio with loading, and decreased indentation modulus compared to uninjured tendons. Taken together, this work supports a new concept of nuclear strain transfer attenuation during tendon healing and identifies several multiscale properties that may contribute. Our work also provides benchmarks for the biomechanical microenvironments that tendon cells may experience following cell delivery therapies.
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Project description:Percutaneous acute Achilles tendon rupture suturing has become a leading treatment option in recent years. A common complication after this mini-invasive procedure is sural nerve injury, which can reduce the patients' satisfaction and final outcomes. High-resolution ultrasound is a reliable method for localizing the sural nerve, and it can be performed intra-operatively; however, the long-term results are yet unknown. The aim of the study was to retrospectively evaluate the long-term results of percutaneous Achilles tendon repair supported with real-time ultrasound imaging. We conducted 57 percutaneous sutures of acute Achilles tendon rupture between 2005 and 2015; 30 were sutured under sonographic guidance, while 27 were performed without sonographic assistance. The inclusion criteria were acute (less than 7 days) full tendon rupture, treatment with the percutaneous technique, age between 18 and 65 years, and a body mass index (BMI) below 35. The operative procedure was carried out by two surgeons, according to the surgical technique reported by Maffulli et al. In total, 35 patients were available for this retrospective assessment; 20 (16 men and 4 women) were treated with sonographic guidance, while 15 (12 men and 3 women) underwent the procedure without it. The mean follow-up was 8 years (range, 3-13 years). The sural nerve was localized 10 mm to 20 mm (mean, 15.8; SD, 3.02) laterally from the scar of the Achilles tendon tear. There was no significant difference between groups with respect to the FAOQ score (P < 0.05). High-resolution ultrasounds performed intra-operatively can minimize the risk of sural nerve injury during percutaneous Achilles tendon repair.
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Project description:A growing number of studies have reported that mini-implants do not remain in exactly the same position during treatment, although they remain stable. The aim of this review was to collect data regarding primary displacement immediately straight after loading and secondary displacement over time. A systematic review was performed to investigate primary and secondary displacement. The amount and type of displacement were recorded. A total of 27 studies were included. Sixteen in vitro studies or studies using finite element analysis addressed primary displacement, and nine clinical studies and two animal studies addressed secondary displacement. Significant primary displacement was detected (6.4-24.4 µm) for relevant orthodontic forces (0.5-2.5 N). The mean secondary displacement ranged from 0 to 2.7 mm for entire mini-implants. The maximum values for each clinical study ranged from 1.0 to 4.1 mm for the head, 1.0 to 1.5 for the body and 1.0 to 1.92 mm for the tail part. The most frequent type of movement was controlled tipping or bodily movement. Primary displacement did not reach a clinically significant level. However, clinicians can expect relevant secondary displacement in the direction of force. Consequently, decentralized insertion within the inter-radicular space, away from force direction, might be favourable. More evidence is needed to provide quantitative recommendations.
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Project description:Tendons link skeletal muscles to bones and are important components of the musculoskeletal system. There has been much interest in the role of microRNA (miRNA) in the regulation of musculoskeletal tissues to mechanical loading, inactivity, and disease, but it was unknown whether miRNA is involved in the adaptation of tendons to mechanical loading. We hypothesized that mechanical loading and transforming growth factor-? (TGF-?) treatment would regulate the expression of several miRNA molecules with known roles in cell proliferation and extracellular matrix synthesis. To test our hypothesis, we subjected untrained adult rats to a single session of mechanical loading and measured the expression of several miRNA transcripts in Achilles tendons. Additionally, as TGF-? is known to be an important regulator of tendon growth and adaptation, we treated primary tendon fibroblasts with TGF-? and measured miRNA expression. Both mechanical loading and TGF-? treatment modulated the expression of several miRNAs that regulate cell proliferation and extracellular matrix synthesis. We also identified mechanosensitive miRNAs that may bind to the 3'-untranslated region of the basic helix-loop-helix transcription factor scleraxis, which is a master regulator of limb tendon development. The results from this study provide novel insight into the mechanobiology of tendons and indicate that miRNA could play an important role in the adaptation of tendons to growth stimuli.
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Project description:We have previously shown that changes in the microbiome influence how the healing tendon responds to different treatments. The aim of this study was to investigate if changes in the microbiome influence the response to mechanical loading during tendon healing. 90 Sprague-Dawley rats were used. Specific Opportunist and Pathogen Free (SOPF) rats were co-housed with Specific Pathogen Free (SPF) rats, carrying Staphylococcus aureus and other opportunistic microbes. After 6 weeks of co-housing, the SOPF rats were contaminated which was confirmed by Staphylococcus aureus growth. Clean SOPF rats were used as controls. The rats were randomized to full loading or partial unloading by Botox injections in their calf muscles followed by complete Achilles tendon transection. Eight days later, the healing tendons were tested mechanically. The results were analysed by a 2-way ANOVA with interaction between loading and contamination on peak force as the primary outcome and there was an interaction for both peak force (p = 0.049) and stiffness (p = 0.033). Furthermore, partial unloading had a profound effect on most outcome variables. In conclusion, the response to mechanical loading during tendon healing is influenced by changes in the microbiome. Studies aiming for clinical relevance should therefore consider the microbiome of laboratory animals.
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Project description:To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to short term (3 weeks) treadmill running, specifically moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed abnormal changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPARγ. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into TNCs, ITR causes the onset of tendinopathy development by inducing non-tenocyte differentiation of TSCs, which may eventually lead to the formation of non-tendinous tissues in tendon tissue after long term mechanical overloading conditions on the tendon.
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