The molecular and physical information coded within the extracellular milieu is informing the development of a new generation of biomaterials for tissue engineering. Several powerful extracellular influences have already found their way into cell-instructive scaffolds, while others remain largely unexplored. Yet for commercial success tissue engineering products must be not only efficacious but also cost-effective, introducing a potential dichotomy between the need for sophistication and ease of production. This is spurring interest in recreating extracellular influences in simplified forms, from the reduction of biopolymers into short functional domains, to the use of basic chemistries to manipulate cell fate. In the future these exciting developments are likely to help reconcile the clinical and commercial pressures on tissue engineering.

Complexity in biomaterials for tissue engineering

Entheses (insertion sites, osteotendinous junctions, osteoligamentous junctions) are sites of stress concentration at the region where tendons and ligaments attach to bone. Consequently, they are commonly subject to overuse injuries (enthesopathies) that are well documented in a number of sports. In this review, we focus on the structure-function correlations of entheses on both the hard and the soft tissue sides of the junction. Particular attention is paid to mechanical factors that influence form and function and thus to exploring the relationship between entheses and exercise. The molecular parameters indicative of adaptation to mechanical stress are evaluated, and the basis on which entheses are classified is explained. The application of the 'enthesis organ' concept (a collection of tissues adjacent to the enthesis itself, which jointly serve the common function of stress dissipation) to understanding enthesopathies is considered and novel roles of adipose tissue at entheses are reviewed. A distinction is made between different locations of fat at entheses, and possible functions include space-filling and proprioception. The basic anchorage role of entheses is considered in detail and comparisons are explored between entheses and other biological 'anchorage' sites. The ability of entheses for self-repair is emphasized and a range of enthesopathies common in sport are reviewed (e.g. tennis elbow, golfer's elbow, jumper's knee, plantar fasciitis and Achilles insertional tendinopathies). 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.

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Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load

Background: A child who has an acutely irritable hip can pose a diagnostic challenge. The purposes of this study were to determine the diagnostic value of presenting variables for differentiating between septic arthritis and transient synovitis of the hip in children and to develop an evidence-based clinical prediction algorithm for this differentiation. Methods: We retrospectively reviewed the cases of children who were evaluated at a major tertiary-care children's hospital between 1979 and 1996 because of an acutely irritable hip. Diagnoses of true septic arthritis, presumed septic arthritis, and transient synovitis were explicitly defined on the basis of the white blood-cell count in the joint fluid, the results of cultures of joint fluid and blood, and the clinical course. Univariate analysis and multiple logistic regression analysis were used to compare groups. A probability algorithm for differentiation between septic arthritis and transient synovitis on the basis of independent multivariate predictors was constructed and tested. Results: Patients who had septic arthritis differed significantly (p < 0.05) from those who had transient synovitis with regard to the erythrocyte sedimentation rate, serum white blood-cell count and differential, weight-bearing status, history of fever, temperature, evidence of effusion on radiographs, history of chills, history of recent antibiotic use, hematocrit, and gender. Patients who had true septic arthritis differed significantly (p < 0.05) from those who had presumed septic arthritis with regard to history of recent antibiotic use, history of chills, temperature, erythrocyte sedimentation rate, history of fever, gender, and serum white blood-cell differential. Four independent multivariate clinical predictors were identified to differentiate between septic arthritis and transient synovitis: history of fever, non-weight-bearing, erythrocyte sedimentation rate of at least forty millimeters per hour, and serum white blood-cell count of more than 12,000 cells per cubic millimeter (12.0 x 109 cells per liter). The predicted probability of septic arthritis was determined for all sixteen combinations of these four predictors and is summarized as less than 0.2 percent for zero predictors, 3.0 percent for one predictor, 40.0 percent for two predictors, 93.1 percent for three predictors, and 99.6 percent for four predictors. The chi-square test for trend and the area under the receiver operating characteristic curve indicated excellent diagnostic performance of this group of multivariate predictors in identifying septic arthritis. Conclusions: Although several variables differed significantly between the group that had septic arthritis and the group that had transient synovitis, substantial overlap in the intermediate ranges made differentiation difficult on the basis of individual variables alone. However, by combining variables, we were able to construct a set of independent multivariate predictors that, together, had excellent diagnostic performance in differentiating between septic arthritis and transient synovitis of the hip in children.

Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm.

Biologics for tendon repair.

Acromioclavicular joint injuries and, more specifically, separations are commonplace both in general practice and during athletic participation. This article reviews the traditional classification as well as the clinical evaluation of patients with acute and chronic acromioclavicular joint separations. It also highlights many recent advances, principally in the anatomy and biomechanics of the acromioclavicular joint ligamentous complex. The concept of increases in superior translation as well as disturbances in horizontal translation with injuries to this joint and ligaments are discussed. This information, coupled with the unpredictable long-term results with the Weaver-Dunn procedure and its modifications, have prompted many recent biomechanical studies evaluating potential improvements in the surgical management of acute and chronic injuries. The authors present these recent works investigating cyclic loading and ultimate failure of traditional reconstructions, augmentations, use of free graft, and the more recent anatomic reconstruction of the conoid and trapezoid ligaments. The clinical results (largely retrospective), including acromioclavicular joint repair, reconstruction and augmentation with the coracoclavicular ligament, supplemental sutures, and the use of free autogenous grafts, are summarized. Finally, complications and the concept of the failed distal clavicle resection and reconstruction are addressed. The intent is to provide a current, in-depth treatise on all aspects of acromioclavicular joint complex injuries to include anatomy, biomechanics, benchmark studies on instability and reconstruction, clinical and radiographic evaluation, and to present the most recent clinical research on surgical outcomes.

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Evaluation and Treatment of Acromioclavicular Joint Injuries

Bone biomarkers included formation, resorption and regulator are released during the bone remodeling processes. These bone biomarkers have attracted much attention in the clinical assessment of osteoporosis treatment in the past decade. Combination with the measurement of bone mineral density, the clinical applications of bone biomarkers have provided comprehensive information for diagnosis of osteoporosis. However, the analytical approaches of the bone biomarkers are still the challenge for further clinical trials. In this mini-review, we have introduced the functions of bone biomarkers and then recently developed techniques for bone biomarker measurements have been systematically integrated to discuss the possibility for osteoporosis assessment in the early stage.

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Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives

We examined the anatomy and measured the in situ force in ligaments at the acromioclavicular joint using a universal force-moment sensor. The in situ force in the coracoacromial, conoid, trapezoid, superior acromioclavicular capsular, and inferior acromioclavicular capsular ligaments of 10 fresh-frozen cadaveric shoulders was determined for a load of 70 N applied to the clavicle in anteroposterior and superoinferior directions. The lengths of the conoid and trapezoid ligaments were found to be 15.1 +/- 4.1 and 11.5 +/- 2.2 mm, respectively; the widths of the conoid and trapezoid ligaments were 10.7 +/- 1.5 and 11.0 +/- 2.8 mm, respectively. The in situ force of the trapezoid (42.9 +/- 15.4 N) was significantly greater than that for the other ligaments during posterior displacement. Otherwise, no statistically significant differences could be found between any of the in situ forces in each ligament during all other motions examined. During anterior displacement, the inferior acromioclavicular capsular ligament appeared to be the major restraint. The trapezoid ligament was the primary restraint during posterior displacement and provided 55.8% +/- 20.0% of the resisting force. Our results suggest that the coracoclavicular and other acromioclavicular joint capsular ligaments should be considered for reconstruction to restore normal joint function, especially in the anterior, posterior, and superior directions.

Functional Evaluation of the Ligaments at the Acromioclavicular Joint during Anteroposterior and Superoinferior Translation

Background:Biceps long-head tendon lesion is commonly associated with rotator cuff tendon pathology. This study is to determine the pathologic spectrum of biceps long-head tendon in surgical cases with complete full-thickness rotator cuff tear.Methods:Between 1993 and 2002, 122 complete rotator cuff

Incidence and severity of biceps long head tendon lesion in patients with complete rotator cuff tears.

Successful anterior cruciate ligament reconstruction with a tendon graft necessitates solid healing of the tendon graft in the bone tunnel. Improvement of graft healing to bone is crucial for facilitating an early and aggressive rehabilitation and ensuring rapid return to pre-injury levels activity. Tendon graft healing in a bone tunnel requires bone ingrowth into the tendon. Indirect Sharpey fiber formation and direct fibrocartilage fixation confer different anchorage strength and interface properties at the tendon-bone interface. For enhancing tendon graft-to-bone healing, we introduce a strategy that includes the use of periosteum, hydrogel supplemented with periosteal progenitor cells and bone morphogenetic protein-2, and a periosteal progenitor cell sheet. Future studies include the use of cytokines, gene therapy, stem cells, platelet-rich plasma, and mechanical stress for tendon-to-bone healing. These strategies are currently under investigation, and will be applied in the clinical setting in the near future.

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Graft healing in anterior cruciate ligament reconstruction

Background: Nonunion frequently follows distal clavicle fracture. Traditional pinning methods using the through acromioclavicular articulation may result in osteoarthritic changes or ankylosis. This study introduces a direct pinning technique in which the acromioclavicular joint is spared. Methods: Twelve patients with displaced distal clavicle fractures received open reduction and fixation with Kirschner wires (K-wires) and tension-band wires, from May 1996 to March 1997. The indication for surgery was type IIa fracture or fracture with displacement. Unrestricted passive and active range of motion was performed as soon as possible after the operation. Stretching and exertional exercises were permitted after radiographs showed an osseous union and after the implants were removed. Results: Eleven patients achieved osseous union with painless full motion. Union time ranged from 3 to 6 months. One patient suffered from more comminuted fracture because of a fall 2 months after operation. This patient received a revision surgery with distal clavicle resection and coracoclavicle reconstruction. Symptomless ossification around the coracoclavicle ligament was noted on radiographs in one patient. The ossification did not progress after the 9-month follow-up. Conclusion: Edwards reported a rate of 45% delayed union and 30% nonunion in type II fractures. Several techniques had been described in the relevant literature. In our practice, fixation with Kirschner wires and tension-band wires has been successful in the treatment for displaced distal clavicle fracture.

Chih Hwa Chen

Papers

Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives

Functional Evaluation of the Ligaments at the Acromioclavicular Joint during Anteroposterior and Superoinferior Translation

Incidence and severity of biceps long head tendon lesion in patients with complete rotator cuff tears.

Graft healing in anterior cruciate ligament reconstruction

Treatment of distal clavicle fracture using Kirschner wires and tension-band wires.