Tendon reattachment to bone in an ovine tendon defect model of retraction using allogenic and xenogenic demineralised bone matrix incorporated with mesenchymal stem cells

BACKGROUND: Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. MATERIALS AND METHODS: In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. RESULTS: Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. CONCLUSION: Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft

Generic, Geometric Finite Element Analysis of the Transtibial Residual Limb and Prosthetic Socket

Finite element analysis was used to investigate the stress distribution between the residual limb and prosthetic socket of persons with transtibial amputation (TTA). The purpose of this study was to develop a tool to provide a quantitative estimate of prosthetic interface pressures to improve our understanding of residual limb/prosthetic socket biomechanics and prosthetic fit. FE models of the residual limb and prosthetic socket were created. In contrast to previous FE models of the prosthetic socket/residual limb system, these models were not based on the geometry of a particular individual, but instead were based on a generic, geometric approximation of the residual limb. These models could then be scaled for the limbs of specific individuals. The material properties of the bulk soft tissues of the residual limb were based upon local in vivo indentor studies. Significant effort was devoted toward the validation of these generic, geometric FE models; prosthetic interface pressures estimated via the FE model were compared to experimentally determined interface pressures for several persons with TTA in a variety of socket designs and static load/alignment states. The FE normal stresses were of the same order of magnitude as the measured stresses (0-200 kPa); however, significant differences in the stress distribution were observed. Although the generic, geometric FE models do not appear to accurately predict the stress distribution for specific subjects, the models have practical applications in comparative stress distribution studies

Finite-element modelling of mechanobiological factors influencing sesamoid tissue morphology in the patellar tendon of an ostrich

The appearance and shape of sesamoid bones within a tendon or ligament wrapping around a joint are understood to be influenced by both genetic and epigenetic factors. Ostriches (Struthio camelus) possess two sesamoid patellae (kneecaps), one of which (the distal patella) is unique to their lineage, making them a good model for investigating sesamoid tissue development and evolution. Here we used finite-element modelling to test the hypothesis that specific mechanical cues in the ostrich patellar tendon favour the formation of multiple patellae. Using three-dimensional models that allow application of loading conditions in which all muscles, or only distal or only proximal muscles to be activated, we found that there were multiple regions within the tendon where transformation from soft tissue to fibrocartilage was favourable and therefore a potential for multiple patellae based solely upon mechanical stimuli. While more studies are needed to better understand universal mechanobiological principles as well as full developmental processes, our findings suggest that a tissue differentiation algorithm using shear strain and compressive strain as inputs may be a roughly effective predictor of the tissue differentiation required for sesamoid development

Modified margin convergence: over-under lacing suture technique

The principle of margin convergence can be applied to rotator cuff repair to enhance the security of fixation by decreasing the mechanical strain at the margins of the tear. We describe a suture technique, over-under lacing, that reproduces the same margin convergence, with equal tissue tension across the entire surface area of the cuff. A consecutive series of patients affected by massive U-shaped rotator cuff tears were treated by this repair technique. Preoperative diagnosis, tear assessment, and grading of fatty infiltration of the cuff muscles were based on arthro-computed tomography evaluation. The technique passes 2 sutures from the medial to lateral margin of the tear, with a knotless suture anchor for tendon-to-bone fixation. The proposed technique seems to reduce tensile strain on the repaired tendon, can reconstruct the rotator cuff cable, and can attain the balanced pull of the tendon in a medial-to-lateral fashion. The over-under lacing suture technique is both simple and reproducible. This technique may achieve the goals of margin convergence with satisfactory preliminary clinical results for patients with massive rotator cuff tears

Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model.

In vitro experiments are essential to understand biological mechanisms; however, the gap between monolayer tissue culture and human physiology is large, and translation of findings is often poor. Thus, there is ample opportunity for alternative experimental approaches. Here we present an approach in which human cells are isolated from human anterior cruciate ligament tissue remnants, expanded in culture, and used to form engineered ligaments. Exercise alters the biochemical milieu in the blood such that the function of many tissues, organs and bodily processes are improved. In this experiment, ligament construct culture media was supplemented with experimental human serum that has been 'conditioned' by exercise. Thus the intervention is more biologically relevant since an experimental tissue is exposed to the full endogenous biochemical milieu, including binding proteins and adjunct compounds that may be altered in tandem with the activity of an unknown agent of interest. After treatment, engineered ligaments can be analyzed for mechanical function, collagen content, morphology, and cellular biochemistry. Overall, there are four major advantages versus traditional monolayer culture and animal models, of the physiological model of ligament tissue that is presented here. First, ligament constructs are three-dimensional, allowing for mechanical properties (i.e., function) such as ultimate tensile stress, maximal tensile load, and modulus, to be quantified. Second, the enthesis, the interface between boney and sinew elements, can be examined in detail and within functional context. Third, preparing media with post-exercise serum allows for the effects of the exercise-induced biochemical milieu, which is responsible for the wide range of health benefits of exercise, to be investigated in an unbiased manner. Finally, this experimental model advances scientific research in a humane and ethical manner by replacing the use of animals, a core mandate of the National Institutes of Health, the Center for Disease Control, and the Food and Drug Administration

Current Issues and Regulations in Tendon Regeneration and Musculoskeletal Repair with Mesenchymal Stem Cells

Mesenchymal stem cells are multipotent stromal cells residing within the connective tissue of most organs. Their surface phenotype has been well described. Most commonly, mesenchymal stem cells demonstrate the ability to differentiate into mesenchymal tissues (bone, catailge, fat, etc...), however, under the proper conditions these cells can differentiate into epithelial cells and neuroectoderm derived lineages. Their developmental plasticity also depends on the ability of mesenchymal stem cells to alter the tissue microenvironment by secreting soluble factors, as well as their capacity for differentiation in tissue repair. It is the cell-matrix interaction which defines the tissue characteristics. The molecular and functional heterogeneity of this cell population may confound interpretation of their differentiation potential, but it is this heterogeneity that is believed to provide for their therapeutic efficacy. Stem cell therapies are an attractive therapeutic approach for soft tissues as they offer a vehicle for repair and regeneration at the end of a needle. The early introduction of stem cell treatments into the therapeutic armamentarium involves both commercial and non-commercial multidisciplinary partnerships and has occurred in a climate of regulatory reform, so not all the relevant information resides in the public domain, but early clinical studies have shown promising results. Against this backdrop, novel techniques and early results of a small series of tendon and musculotendinous junction interventions are being published and other ongoing studies are yet to report their results. The issue of ensuring governance of these novel technologies falls upon both the scientific community and the established licensing authorities

Contact area, pressure distribution and mechanical stability in external arthrodesis of the ankle joint

The ankle joint is often affected by arthritis, giving a joint that is painful, stiff, and restricts movement. This can result in a huge loss of mobility for the sufferer. Unlike replacement of the hip, the replacement of a diseased ankle joint is not as straightforward and the outcomes do not reach the same success levels. The preferred surgical choice is arthrodesis, a procedure whereby the two bones forming the joint are fused together to eliminate the joint and hence pain. The success of the procedure is dependent upon several factors, two of the most significant being the levels of contact area and pressure achieved during the compression period, during which bone growth occurs across the two bones being compressed together. These factors influence joint stability and micromotion at the bone to bone interface during this growth phase. This study investigates the levels of contact areas and pressures that can be achieved for different arthodesis variables. These variables include the joint shape, which can be curved or flat, and the position of the compression pin within the talus, namely anteriorly or centrally positioned with reference to the talar dome. Influence of the Achilles tendon in joint stability is also investigated. A test rig was developed allowing load/deflection curves to be determined for various configurations of these variables. Models representing the bones under consideration, together with pressure sensitive film, allowed measurement of contact areas and pressures within the joint under compression, achieved using pins and instrumented compression rods. Results indicate there is little significant variation in contact area and pressure for the different shaped joint cuts, however, if the talar pin is placed in a more anterior position then the contact area can be improved over a centrally positioned pin. Anterior pin placement also gives increased resistance to motion and mechanical stability. It has been established that the athrodesis construct is especially weak in terms of rotation about the tibial axis, and the results from this study indicate that through the use of a curved joint shape the resistance to this motion can be improved greatly

Dose-dependent new bone formation by extracorporeal shock wave application on the intact femur of rabbits

Background: Whereas various molecular working mechanisms of shock waves have been demonstrated, no study has assessed in detail the influence of varying energy flux densities (EFD) on new bone formation in vivo. Methods: Thirty Chinchilla bastard rabbits were randomly assigned to 5 groups (EFD 0.0, 0.35, 0.5, 0.9 and 1.2 mJ/mm(2)) and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses; 1 Hz frequency). To investigate new bone formation, animals were injected with oxytetracycline at days 5-9 after shock wave application and sacrificed on day 10. Histological sections of all animals were examined using broad-band epifluorescent illumination, contact microradiography and Giemsa-Eosin staining. Results: Application of shock waves induced new bone formation beginning with 0.5 mJ/mm(2) EFD and increasing with 0.9 mJ/mm(2) and 1.2 mJ/mm(2). The latter EFD resulted in new bone formation also on the dorsal cortical bone; cortical fractures and periosteal detachment also occurred. Conclusion: Here, for the first time, a threshold level is presented for new bone formation after applying shock waves to intact bone in vivo. The findings of this study are of considerable significance for preventing unwanted side effects in new approaches in the clinical application of shock waves. Copyright (c) 2008 S. Karger AG, Basel