Augmentation of Rotator Cuff Tendon-Bone Healing using Demineralised Bone Matrix and Mesenchymal Stem Cells

BACKGROUND: The results of surgery for tears of the rotator cuff are variable, with failure occurring in up to 94% of cases. Demineralised bone matrix (DBM) consists of a collagen scaffold containing multiple growth factors and has been used successfully to improve tendon-bone healing. By combining DBM with stem cells its effects may be enhanced given that many of the growth factors it contains are able to direct stem cell differentiation down tenogenic, chondrogenic, and osteogenic lineages. These cell lines produce elements essential to the formation of a naturally graded enthesis. AIM: To investigate the effect of DBM on regeneration of the tendon-bone interface, and whether its function can be enhanced by mesenchymal stem cells (MSCs). HYPOTHESIS: DBM will improve tendon-bone healing in an enthesis defect model, and its effect may be further enhanced by the incorporation of MSCs. METHODS: The following experiments were undertaken in order to investigate the hypothesis: 1. Tensile testing of allogenic and xenogenic cortical/cancellous DBM. 2. Evaluating the effect of allogenic and xenogenic DBM, incorporated with MSCs, on regeneration of the enthesis in a large animal model of severe tendon retraction. 3. Development of a chronic rotator cuff tear model. 4. Investigation of tendon-bone healing using DBM in a chronic rotator cuff tear model. 5. Investigation of tendon-bone healing using DBM and MSCs in a chronic rotator cuff tear model. RESULTS: Allogenic cortical DBM possessed the greatest tensile strength and was used in vivo to examine tendon-bone healing complicated by retraction. In this, DBM regenerated a direct enthesis characterised by fibrocartilage. A similar effect was noted in a chronic rotator cuff tear model with no additional effect conferred by the stem cells. CONCLUSION: This thesis has shown that DBM can regenerate a fibrocartilaginous enthesis in models of tendon retraction and chronic rotator cuff degeneration

Early detection of design faults relative to requirement specifications in agent-based models

Agent systems are used for a wide range of applications, and techniques to detect and avoid defects in such systems are valuable. In particular, it is desirable to detect issues as early as possible in the software development lifecycle. We describe a technique for checking the plan structures of a BDI agent design against the requirements models, specified in terms of scenarios and goals. This approach is applicable at design time, not requiring source code. A lightweight evaluation demonstrates that a range of defects can be found using this technique

Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon

Supraspinatus detachment causes musculotendinous degeneration and a reduction in bone mineral density at the enthesis in a rat model of chronic rotator cuff degeneration

BACKGROUND: To evaluate biological strategies that enhance tendon-bone healing in humans, it is imperative that suitable animal models accurately reproduce the pathological changes observed in the clinical setting following a tear. The purpose of the present study was to investigate rotator cuff degeneration in a rat, as well as assess the development of osteopenia at the enthesis following tendon detachment. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Specimens were retrieved at 4 weeks (n = 6), 6 weeks (n = 6) and 9 weeks (n = 6) postoperatively for histological analysis and peripheral quantitative computer tomography. RESULTS: Three weeks following tendon detachment, there was a significant increase in the modified Movin score, characterized by a loss of muscle mass, fatty infiltration, an increase in musculotendinous cellularity, loss of normal collagen fibre structure/arrangement, rounded tenocyte nuclei and an increase in the number of vascular bundles. This was accompanied by a reduction in bone mineral density at the tendon insertion site. After 3 weeks however, these changes were less prominent. CONCLUSIONS: The rotator cuff tendon-muscle-bone unit in a rat model 3 weeks after detachment of supraspinatus represents a valid model for investigating rotator cuff degeneration

Agent oriented modelling of tactical decision making

A key requirement in military simulation is to have executable models of tactical decision-making. Such models are used to simulate the behaviour of human entities such as submarine commanders, fighter pilots and infantry, with a view to producing realistic predictions about tactical outcomes. Tactics specify the means of achieving mission objectives, and should capture both reactive and deliberative behaviour. The lack of a methodology and supporting tools for designing computer-based models of tactics makes them difficult to create, maintain and reuse, and this is now a significant problem in military simulation domains. To address this, we have developed TDF (Tactics Development Framework), a tactics modelling methodology and tool based on the BDI (Beliefs, Desires, Intentions) paradigm, that supports agent-oriented structural modelling of tactics and related artefacts including missions, storylines, goals and plans. The methodology was initially assessed by analysts in the undersea warfare domain, and was subsequently evaluated using a simple scenario in the autonomous unmanned aerial vehicles domain. The latter evaluation involved a comparison with UML designs, indicating that our methodology provides significant benefits to those building and maintaining models of tactical decision-making

Checking consistency of agent designs against interaction protocols for early-phase defect location

Multi-agent systems are increasingly being used in complex applications due to features such as autonomy, proactivity, exibility, robustness and social ability. However, these very features also make verifying multi-agent systems a challeng- ing task. In this paper, we propose a mechanism, including automated tool support, for early phase defect detection by comparing agent interaction speci cations with the detailed design of the agents participating in the interactions. The basic intuition of our approach is to extract sets of possi- ble traces from the agent design and to verify whether these traces conform to the protocol speci cations. Our approach is based on the Prometheus agent design methodology but is applicable to other similar methodologies. Our initial eval- uation shows that even simple protocols developed by rela- tively experienced developers are prone to defects, and our approach is successful in uncovering some of these defects

Application of a Demineralized Cortical Bone Matrix and Bone Marrow-Derived Mesenchymal Stem Cells in a Model of Chronic Rotator Cuff Degeneration

BACKGROUND: The success of rotator cuff repair is primarily dependent on tendon-bone healing. Failure is common because weak scar tissue replaces the native enthesis, rendering it prone to reruptures. A demineralized bone matrix (DBM) consists of a network of collagen fibers that provide a sustained release of growth factors such as bone morphogenetic proteins. Previous studies have demonstrated that it can regenerate a fibrocartilaginous enthesis. HYPOTHESIS: The use of a DBM and mesenchymal stem cells (MSCs) at the healing enthesis will result in a higher bone mineral density at the tendon insertion and will enhance the regeneration of a morphologically superior enthesis when compared with an acellular human dermal matrix. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 received augmentation of the repair with a cortical allogenic DBM (n = 6); group 2 received augmentation with a nonmeshed, ultrathick, acellular human dermal matrix (n = 6); and group 3 underwent tendon-bone repair without a scaffold (n = 6). All animals received 1 × 10(6) MSCs delivered in fibrin glue to the repair site. Specimens were retrieved at 6 weeks postoperatively for histological analysis and the evaluation of bone mineral density. RESULTS: All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous enthesis. Although there were no significant differences in the enthesis maturation and modified Movin scores, repair augmented with a dermal matrix + MSCs exhibited a disorganized enthesis, abnormal collagen fiber arrangement, and greater cellularity compared with other MSC groups. Only repairs augmented with a DBM + MSCs reached a bone mineral density not significantly lower than nonoperated controls. CONCLUSION: A DBM enhanced with MSCs can augment rotator cuff healing at 6 weeks and restore bone mineral density at the enthesis to its preinjury levels. CLINICAL RELEVANCE: Biological augmentation of rotator cuff repair with a DBM and MSCs may reduce the incidence of retears, although further studies are required to determine its effectiveness

The effectiveness of demineralized cortical bone matrix in a chronic rotator cuff tear model.

BACKGROUND: The purpose of this study was to assess the effect of demineralized bone matrix (DBM) on rotator cuff tendon-bone healing. The hypothesis was that compared with a commercially available dermal matrix scaffold, DBM would result in a higher bone mineral density and regenerate a morphologically superior enthesis in a rat model of chronic rotator cuff degeneration. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 animals were repaired with DBM (n = 6); group 2 received augmentation with the dermal scaffold (n = 6); and group 3 (controls) underwent nonaugmented tendon-bone repair (n = 6). Specimens were retrieved at 6 weeks postoperatively for histologic analysis and evaluation of bone mineral density. RESULTS: No failures of tendon-bone healing were noted throughout the study. All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous interface. Dermal collagen specimens exhibited a disorganized structure with significantly more abnormal collagen fiber arrangement and cellularity than in the DBM-based repairs. Nonaugmented repairs exhibited a significantly higher bone mineral density than in DBM and the dermal collagen specimens and were not significantly different from control limbs that were not operated on. CONCLUSION: The application of DBM to a rat model of chronic rotator cuff degeneration did not improve the composition of the healing enthesis compared with nonaugmented controls and a commercially available scaffold. However, perhaps the most important finding of this study was that the control group demonstrated a similar outcome to augmented repairs

Revision shoulder arthroplasty for failed humeral head resurfacing hemiarthroplasty

Background The purpose of the present study was to analyze and report the clinical outcomes following revision shoulder arthroplasty for failed humeral head resurfacing hemiarthroplasty (HHRH). Methods All patients who underwent revision shoulder arthroplasty for failed HHRH at our institution were retrospectively reviewed. Twenty-two shoulders in 20 patients were available for analysis. Mean age at the time of HHRH was 60 years (range 42 years to 75 years). The cohort consisted of 17 females and three males. Results The mean time from HHRH to revision was 5 years (range 1 year to 8 years). Mean age at the time of revision surgery was 62 years (range 44 years to 80 years). Patients were followed-up for a mean of 3.3 years (range 2 years to 4 years) after revision. Following revision surgery, there was an increase in forward elevation from 67° (range 0° to 130°) to 97° (range 40° to 160°) (p = 0.04). This was accompanied by an improvement in both the Oxford Shoulder Score and the subjective shoulder value, which increased from 13 (range 2 to 28) to 39 (range 24 to 48) (p = 0.000) and from 23 (range 0 to 65) to 79 (range 25 to 100) (p = 0.000) respectively. Conclusions Revision shoulder arthroplasty for failed HHRH improves functional outcome