Secretome from In Vitro Mechanically Loaded Myoblasts Induces Tenocyte Migration, Transition to a Fibroblastic Phenotype and Suppression of Collagen Production

It is known that mechanical loading of muscles increases the strength of healing tendon tissue, but the mechanism involved remains elusive. We hypothesized that the secretome from myoblasts in co-culture with tenocytes affects tenocyte migration, cell phenotype, and collagen (Col) production and that the effect is dependent on different types of mechanical loading of myoblasts. To test this, we used an in vitro indirect transwell co-culture system. Myoblasts were mechanically loaded using the FlexCell® Tension system. Tenocyte cell migration, proliferation, apoptosis, collagen production, and several tenocyte markers were measured. The secretome from myoblasts decreased the Col I/III ratio and increased the expression of tenocyte specific markers as compared with tenocytes cultured alone. The secretome from statically loaded myoblasts significantly enhanced tenocyte migration and Col I/III ratio as compared with dynamic loading and controls. In addition, the secretome from statically loaded myoblasts induced tenocytes towards a myofibroblast-like phenotype. Taken together, these results demonstrate that the secretome from statically loaded myoblasts has a profound influence on tenocytes, affecting parameters that are related to the tendon healing process.

Smart Device for Biologically Enhanced Functional Regeneration of Osteo–Tendon Interface

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffold to mimic the fascicle direction of the tendon tissue. The scaffold obtained showed tendon-like mechanical performance, depending on HP content and tube size. The PL proteins were able to cross the scaffold wall, and in vitro studies have demonstrated that tenocytes and osteoblasts are able to adhere to and proliferate onto the scaffold in the presence of PL; moreover, they were also able to produce either collagen or sialoproteins, respectively—important components of ECM. These results suggest that HP and PL have a synergic effect, endorsing PL-loaded HP-doped aligned tubular scaffolds as an effective strategy to support new tissue formation in tendon-to-bone interface regeneration.

Microscopic characterization of local strain field in healing tissue in the central third defect of mouse patellar tendon at early-phase of healing

Tendons exhibit a hierarchical collagen structure, wherein higher-level components, such as collagen fibres and fascicles, are elongated, slid, and rotated during macroscopic stretching. These mechanical behaviours of collagen fibres play important roles in stimulating tenocytes, imposing stretching, compression, and shear deformation. It was hypothesised that a lack of local fibre behaviours in healing tendon tissue may result in a limited application of mechanical stimuli to cells within the tissue, leading to incomplete recovery of tissue structure and functions in regenerated tendons. Therefore, the present study aimed to measure the microscopic strain field in the healing tendon tissue. A central third defect was created in the patellar tendon of mice, and the regenerated tissue in the defect was examined by tensile testing, collagen fibre analysis, and local strain measurement using confocal microscopy at 3 and 6 weeks after surgery. Healing tissue at 3 weeks exhibited a significantly lower strength and disorganised collagen fibre structure compared with the normal tendon. These characteristics at 6 weeks remained significantly different from those of the normal tendon. Moreover, the magnitude of local shear strain in the healing tissue under 4% tissue strain was significantly smaller than that in the normal tendon. Differences in the local strain field may be reflected in the cell nuclear shape and possibly the amount of mechanical stimuli applied to the cells during tendon deformation. Accordingly, restoration of a normal local mechanical environment in the healing tissue may be key to a better healing outcome of tendon injury.

Advances in the Development of Anti-Adhesive Biomaterials for Tendon Repair Treatment

Background: Peritendinous adhesion that simultaneous with tendon healing link the healing tendon to the surrounding tissue. It results in functional disability, and has a significant adverse impact on health as well as social and economic development. Methods: Based on a search in the PubMed and Web of Science database, the research articles were screened by their time, main idea, impact factor index, while the ones with no credibility were excluded. Afterwards, we go through the analysis of the reliability and characteristics of the results were further screened from selected articles. Results: A total of 17 biomaterials used to evaluate the adhesion mechanism and the properties of the material were found. All of these biomaterials contained randomized controlled studies and detailed descriptions of surgical treatment that support the reliability of their results which indicates that biomaterials act as barriers to prevent the formation of adhesion, and most of them exhibit satisfactory biocompatibility, biodegradability or selective permeability. Moreover, a few had certain mechanical strength, anti-inflammatory, or carrier capacities. However, there still existed some defects, such as time, technology, clinical trials, material targeting and different measurement standards which also lowered the reliability of their results. Conclusion: In future, anti-adhesion biomaterials should focus on affordable raw materials with wide sources, and the production process should be simplified, in this way, the versatility and targeting of materials will be improved.

Platelet-rich plasma in the treatment of equine orthopaedic disease

Platelet-rich plasma is a blood-derived, autologous product, which contains a mixture of growth factors, cells and cytokines. These substances are integral in the regulation of the inflammatory process and repair of tissues, although their methods of action are highly complex and not fully elucidated. The content of a platelet-rich plasma product is variable and the optimal concentrations of prime constituents such as platelets, growth factors and leucocytes are not known. A lack of uniformity of products and treatment protocols, along with study design limitations, means that the efficacy of platelet-rich plasma in healing tendon and ligament injuries is yet to be proven or disproven. Nevertheless platelet-rich plasma has gained widespread use in clinical practice primarily for the treatment of these injuries, among other applications. There are no widespread published or anecdotal concerns over the safety of platelet-rich plasma; however, synovial fluid analysis reveals an acute inflammatory response following intra-articular injection of a leucocyte-rich product.

Instrumented immobilizing boot quantifies reduced Achilles tendon loading during gait

ABSTRACTAchilles tendon ruptures are common injuries that lead to functional deficits in two-thirds of patients. Progressively loading the healing tendon has been associated with superior outcomes, but the loading profiles that patients experience throughout rehabilitation have not yet been established. In this study, we developed and calibrated an instrumented immobilizing boot paradigm that is aimed at longitudinally quantifying patient loading biomechanics to develop personalized rehabilitation protocols. We used a 3-part instrumented insole to quantify the ankle loads generated by the Achilles tendon and secured a load cell in-line with the posterior strut of the immobilizing boot to quantify boot loading. We then collected gait data from five healthy young adults to demonstrate the validity of this instrumented immobilizing boot paradigm to assess Achilles tendon loading during ambulation. We developed a simple calibration procedure to improve the measurement fidelity of the instrumented insole needed to quantify Achilles tendon loading while ambulating with an immobilizing boot. By assessing Achilles tendon loading with the ankle constrained to 0 degrees and 30 degrees plantar flexion, we confirmed that walking with the foot supported in plantar flexion decreased Achilles tendon loading by 60% (P < 0.001). This instrumented immobilizing boot paradigm leverages commercially available sensors and logs data using a small microcontroller secured to the boot and a handheld device, making our paradigm capable of continuously monitoring biomechanical loading outside of the lab or clinic.

Autologous platelet rich plasma for regeneration of tendon injuries in horses

Digital flexor tendon injuries are the most common cause of early retirement and economic loss in the equine industry due to the poor healing tendency of the tendons. This study was conducted to improve the quality of tendon healing by using Autologous Platelet Rich Plasma incorporated collagen scaffold. Using ultrasound guidance, autologous Platelet Rich Plasma with and without collagen scaffold was engrafted intra-lesionally into 12 affected digital flexor tendons of 11 horses and healing was assessed periodically. Lameness score decreased in all the horses and the therapeutic outcome of intra-lesional engraftment of Autologous Platelet Rich Plasma with collagen scaffold was found to be superior in terms of clinical outcome, ultrasonographic and biochemical assessment. Ultrasonography served as an effective tool for diagnosis and for evaluation of healing tendon injuries.