Enthesitis - Wikipedia
of the interface between bone and tendon/ligament, also known as the () Where tendons and ligaments meet bone: attachment sites ('entheses') in. Entheses (insertion sites, osteotendinous junctions, osteoligamentous junctions) are sites of stress concentration at the region where tendons. the spine, particularly the points where tendons and ligaments attach to bone. Best TM, Milz S. Where tendons and ligaments meet bone: attachment sites.
Demineralized bone matrix DBM is another material proposed to enhance healing at the bone-tendon interface by providing a robust, osteoinductive scaffold at the site of repair [ 89 ].
After 6, 9 and 12 weeks, DBM treated animals showed significantly more fibrocartilaginous tissue than the control group in an ovine patellar model [ 89 ]. While the insertion site of the DBM group contained more fibrocartilage and mineralized fibrocartilage than the control group, the amount of bone formed in both groups was similar, indicating that DBM may produce a more physiologically similar enthesis [ 89 ].
However, the mechanical strength of the interface has yet to be determined. Similar to the idea of implanting a scaffold at the insertion site, Wong et al [ 90 ] have reported that an autologous cartilage plug can be inserted between the soft and hard tissue at the repair site, and that this will increase fibrocartilaginous tissue formation.
The addition of cells to the insertion site at the healing bone-tendon interface has had limited success in regenerating a fibrocartilaginous transition.
Addition of bone marrow stromal cells BMSCs resulted in no difference in cartilage production, collagen orientation or failure strength in the treatment group of a rat rotator cuff repair model [ 36 ].
Tendon vs. ligament: MedlinePlus Medical Encyclopedia Image
Conversely, coating the ends of a tendon allograft with BMSCs in a fibrin gel leads to the formation of a zone of fibrocartilage and increased mechanical properties at the interface in a rabbit ACL replacement model [ 92 ] and BMSC addition in fibrin glue alone can also increase the mechanical properties of the interface and result in an organized enthesis at 45 days after surgery in a rat Achilles tendon model [ 93 ].
In addition, BMSCs that had been transduced with scleraxis were applied to the insertion site in a fibrin glue and resulted in a positive effect on bone-tendon healing, with increased failure load, stiffness, strength and fibrocartilage production after 4 weeks when compared with the control group [ 37 ]. Similarly, MSCs transduced with a matrix metalloproteinase MMP gene exhibited increased fibrocartilage, load, stress, and stiffness at the insertion site after 4 weeks [ 94 ].
Finally, a chondrocyte pellet facilitated the formation of a fibrocartilaginous zone in a rabbit model [ 95 ], however, while addition of chondrocytes within a fibrin glue matrix resulted in increased mechanical properties when compared to controls, there was a lack of organised tissue structure at the interface [ 93 ]. While promotion of certain factors may prove beneficial to interface formation, it is also clear that inhibition of other factors may also lead to a favorable healing response.
Enhanced bone healing [ 96 ] and increased collagen levels [ 97 ] have been reported, but no difference in the mechanics of the treatment and control group was noted [ 97 ].
Ligaments, tendons, and joints (video) | Khan Academy
However, another MMP inhibitor, doxycycline, has led to an increased load to failure in the treatment group when compared to the control [ 98 ].
Some treatments have also proved to be beneficial in accelerating healing at the osteotendinous junction.
Low intensity pulsed ultrasound LIPUS can promote healing at the interface in both rat and rabbit patellar tendon models , whereas extracorporeal shock wave therapy can also increase osteogenesis and fibrocartilaginous tissue formation in the treatment groups [ ]. Interestingly, another treatment, paralysis caused by botulinum toxin, has had mixed results when used to enhance healing at the osteotendinous junction.
Although paralysis seemed to increase collagen alignment in the treatment group, it also resulted in the reduction in muscle weight and volume over 8 weeks. This was recovered after 24 weeks, but it is thought that the longevity of muscle paralysis was detrimental to interface formation and that a shorter length of paralysis would be more beneficial to recapitulation of the normal enthesis structure [ ].
The effect of mechanical loading following surgery has also been under investigation recently. While one study has determined that delayed mechanical loading results in increased maximum loads at the bone-tendon interface when compared to immediate early loading or immobilization [ ], a follow-up study by the same research group has stated that low-levels of controlled loading in the immediate post-operative period are not detrimental to bone-tendon junction healing [ ].
It is clear that future work in this area is extremely important for improving the quality of bonetendon healing in a clinical setting. Understanding the effects of postoperative conditioning is pertinent to establishing the most successful rehabilitation regimes to provide the best possible outcome for the patient following surgery.
Although modifying the local environment with growth factors and osteoinductive materials has shown some promising results, the problems faced by surgeons to allow formation of multi-tissue gradients at the enthesis remain challenging.
As stated, the formation of a fibrocartilaginous zone is a vital process absent from enthesis healing. It has also been mentioned that cartilaginous tissue lacks a bloody supply and therefore exists in a physiologically hypoxic environment. Interestingly, a recent review has highlighted the importance that the hypoxic environment may have on regeneration of the enthesis by stimulating chondrogenesis [ ].
Tendon vs. ligament
Hypoxia has been shown to be vital for the processes of chondrogenesis, osteogenesis and angiogenesis  and the fact that the native bone-tendon interface region is lacking in vascularisation heavily suggests that the enthesis is in a physiologically hypoxic environment [ ]. To this end, Zhao et al. The first of these is a model involving the creation of a haematoma in the bone tunnel during bone to tendon fixation [ ]. These options seem particularly promising and could potentially give an exciting step forward in the understanding and repair of bone-tendon junction sites in vivo.
- Ligaments, tendons, and joints
- Current Progress in Enthesis Repair: Strategies for Interfacial Tissue Engineering
Interfacial tissue engineering ITE options for repair — in vitro studies While several methods have been described as augmenting the strength of the ligament-bone graft fixation site, the fact that the majority of failures still occur at the transition of graft to native tissue, highlights the need for an appropriate transition between tissues if implants are to be successful.
In the case of manufacturing artificial tissues for implantation, this would involve the engineering of the complex tissue interface in vitro. As described earlier, the relatively new field of ITE is aimed at attempting to recreate complex tissue interfaces in vitro.
Achievement of this goal would propel the prospect of implantation of musculoskeletal tissues after disease or trauma towards being a clinical reality. Several groups have realized this importance of engineering composite tissue constructs for the repair of musculoskeletal tissues and are producing innovative solutions to the gradient design and multi-tissue requirements for tissue-engineered musculoskeletal constructs. While some groups have chosen to focus on the production of a scaffold to be inserted as an adjunct to native tissue repair, in the form of a multi-phase multi-cellular scaffold or plug [ 40, ], others have attempted to engineer graded interfaces with one cell type [ ] or have engineered a whole multiphasic tissue from end to end with the goal of implantation to the injured site [ - ].
Each of these techniques will be discussed and evaluated as possible methods of musculoskeletal tissue repair. Developing multiphasic scaffolds for replication of the insertion site: Following fabrication of the scaffold, fibroblasts were seeded onto the PLGA sheets, osteoblasts were seeded onto the bioactive glass, and although cell migration into the central core was observed [ 40 ], there was no formation of a fibrocartilage-like region in the central core.
This novel approach permitted evaluation of the interaction of fibroblasts and osteoblasts as would be found in vivo at the bone-ligament insertion.
Interactions between the different cell types reduced the proliferation rate, altered the alkaline phosphate ALP activity of osteoblasts and had a positive effect on the expression of matrix proteins present at the enthesis, such as collagen type II, aggrecan and cartilage oligometric matrix protein COMP [ ]. However, despite fibrocartilage-like markers being present, a fibrocartilaginous interface region was not formed in culture.
In subsequent studies, chondrocytes were included both in 2D and 3D [1 0 7, ]. In both situations, a fibrocartilage-like region was formed during triculture [ ], thus developing a transition that replicates native tissue structure at the insertion. It is thought that by using these techniques, the triphasic scaffold will promote biological fixation of soft tissue grafts to bone and re-establish the gradual transition of soft tissue to bone in such a way as to transfer load smoothly.
However, the tensile properties of this triphasic scaffold have not been reported, nor has the attachment potential of the scaffold with either the hard or soft tissues. Establishing the tensile properties will help to determine whether introducing a triphasic scaffold provides a mechanically sound attachment between ligament or bone or whether the three phases of the scaffold are mechanically distinct, and therefore increasing the number of interface regions and the propensity for implant failure.
Another research group has successfully manufactured a continuous bone-soft tissue mimetic interface, using only one cell type fibroblasts seeded onto polymeric scaffolds containing a gradient of the transcription factor runt-related transcription factor 2 Runx2 [ ]. Runx2 is a bone specific transcription factor that plays a critical role in bone development and osteoblast differentiation.Deltoid Ligament Reconstruction
By controlling the spatial distribution of Runx2 within the scaffolds, osteoblastic differentiation and mineralized matrix deposition occurred in a graded fashion throughout the scaffold [ ]. The mechanical properties of the scaffolds were examined by uniaxial tensile testing and increased mineral deposition resulted in increased construct stiffness, demonstrating the ability to produce a construct with graded mechanical properties with only one cell type, as opposed to the multicellular, multilayer constructs described elsewhere [ 40, ].
Furthermore, the 3D gradient resulted in a zonal organisation of fibroblastic and osteoblastic cell phenotypes in vivo after 14 days of implantation into an ectopic site [ ], achieving an important recapitulation of the native transition. However, the fibrocartilaginous region was not present in these constructs therefore these constructs do not fully replicate the native bone-ligament insertion [ ]. Nevertheless, future development of this technique may allow for fibrocartilaginous tissue induction to duplicate the native tissue transition for enthesis repair.
Developing whole multi-tissue constructs: The authors group has previously reported the production of a full artificial ligament construct for potential repair of the anterior cruciate ligament [ - ]. By forming an attachment between the anchor and the soft tissue, the fibrin gel is held under tension, known to be important in the formation of fibripositors and production of aligned collagen fibers within this system [ ].
The molecular parameters indicative of adaptation to mechanical stress are evaluated, and the basis on which entheses are classified is explained. A distinction is made between different locations of fat at entheses, and possible functions include space-filling and proprioception.
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The ability of entheses for self-repair is emphasized and a range of enthesopathies common in sport are reviewed e. Attention is drawn to the degenerative, rather than inflammatory, nature of most enthesopathies in sport. The biomechanical factors contributing to the development of enthesopathies are reviewed and the importance of considering the muscle—tendon—bone unit as a whole is recognized. Bony spur formation is assessed in relation to other changes at entheses which parallel those in osteoarthritic synovial joints.
They distribute the loads applied to them dynamically in order to execute movement patterns.
Their complex response to loading allows for multi-axis bending, and this adds to the stress concentration in the region where they attach to bone. It is stress concentration at the hard—soft tissue interface which makes entheses vulnerable to acute or overuse injuries in sport. Conditions such as tennis and golfer's elbow, jumper's knee and various Achilles insertional tendinopathies are well known to primary-care physicians, orthopaedic surgeons, rheumatologists and sports medicine specialists alike.