Paul P. Weitzel

Matrix metalloproteinases and their clinical applications in orthopaedics.

Imbalance in the expression of matrix metalloproteinases and their inhibitors contribute considerably to abnormal connective tissue degradation prevalent in various orthopaedic joint diseases such as rheumatoid arthritis and osteoarthritis. Matrix metalloproteinase expression has been detected in ligament, tendon, and cartilage tissues in the joint. They are known to contribute to the development, remodeling, and maintenance of healthy tissue through their ability to cleave a wide range of extracellular matrix substrates. Their role has been extended to cell growth, migration, differentiation, and apoptosis. In orthopaedics, their clinical applications constantly are being explored. The multiple steps in matrix metalloproteinase regulation offer potential targets for inhibition, useful in drug therapy. The correlation between matrix metalloproteinases and progression in joint erosion presents potential prognostic and diagnostic tools in rheumatoid arthritis. Matrix metalloproteinases also can be incorporated into scaffold design to control the degradation rate of engineered tissue constructs. This current review aims to summarize and emphasize the importance of matrix metalloproteinases and their natural inhibitors in the maturation of musculoskeletal tissue through matrix remodeling and, therefore, in the generation of a new clinical potential in orthopaedics.

Future direction of the treatment of ACL ruptures

The future of treatment of the ACL rupture is changing as our understanding of the biology surrounding the ACL continues to increase. It is our expectation that clinically applicable treatments, including the repair of the ACL and the development of a biologically engineered ACL, will occur in the next decade.

The Use of Long-term Bioresorbable Scaffolds for Anterior Cruciate Ligament Repair

The absence of adequate options to restore full knee joint function through anterior cruciate ligament reconstruction prompts the need to develop new ligament replacement strategies. Recent focus within the ligament engineering field has been on the establishment of appropriate anterior cruciate ligament graft design requirements and evaluation methods. A range of biomaterials and graft constructions has been explored in an attempt to identify the optimal ligament replacement. Thorough and standardized evaluation methods are required throughout all phases of development, from initial in vitro bench screening through a large animal in vivo model. The initial positive clinical, gross pathologic, histologic, and mechanical results from a 12-month in vivo goat study demonstrate the potential of bioengineered ligament devices.

Characterization of transcript levels for matrix molecules and proteases in ruptured human anterior cruciate ligaments.

An improved understanding of cellular responses during normal anterior cruciate ligament (ACL) function or repair is essential for clinical assessments, understanding ligament biology, and the implementation of tissue engineering strategies. The present study utilized quantitative real-time RT-PCR combined with univariate and multivariate statistical analyses to establish a quantitative database of marker transcript expression that can provide a “blueprint” of ACL wound healing. Selected markers (collagen types I and III, biglycan, decorin, MMP-1, MMP-2, MMP-9, and TIMP-1) were assessed from 33 torn ACLs harvested during reconstructive surgery. Trends were observed between postinjury period and marker expressions. Significant correlations between marker expression existed and were most prominent between collagen types I and III. Canonical correlation analysis established a relationship between patient demographics and a combination of all marker expressions. The currently observed trends and correlations may assist in identifying appropriate tissue samples and provide a baseline information of marker expression level that can support in vitro optimization of environmental cues for ligament tissue engineering application.

Valgus slipped capital femoral epiphysis. Fact or fiction

The cases of 2 patients with valgus slipped capital femoral epiphysis are presented. Additional imaging studies provide support for true posterolateral epiphyseal displacement. Increased femoral anteversion and coxa valga contribute to the pathogenesis of valgus slipped capital femoral epiphysis. In situ pin fixation is recommended for stable valgus slipped capital femoral epiphysis. The importance of valgus slipped capital femoral epiphysis lies in its recognition and appropriate screw placement when internal fixation is used. The percutaneous technique should be used with caution. A limited open technique is recommended when the anterior skin portal is near the femoral neurovascular bundle.

Critical Evaluation of Different Scoring Systems of the Knee

Assessment of the natural history of various knee injuries and the effects of operative and nonoperative treatments requires validated outcome measures. We present and review various outcome measures for the knee, including subjective patient reporting systems, comprehensive patient and clinician instruments, and activity scales. The validated subjective scales we review here include the Lysholm score, the Knee Injury and Osteoarthritis Score, the Knee Outcome Survey, the American Academy of Orthopaedic Surgeons Sports Knee Instrument, and the Quality of Life Measure. We also review the widely used comprehensive instruments, including the Cincinnati Knee Rating System, the International Knee Documentation Committee Knee Evaluation Form, and the Hospital for Special Surgery Knee Score. We present analysis of several patellofemoral instruments and activity scales, and present and discuss studies that have compared various knee outcome measures.

Bioresorbable scaffolds for anterior cruciate ligament reconstruction: do we need an off-the-shelf ACL substitute?

Currently available anterior cruciate ligament (ACL) graft sources, autograft and allograft, present potential problems that a natural biomaterial ACL graft might be able to solve. Earlier efforts in the development of synthetic ACL grafts were less than optimal, and those devices have largely been abandoned. We can learn from these past failures, and potentially develop a bioresorbable scaffold for ACL reconstruction, which will provide immediate stability, promote and direct tissue in growth, and degrade at an appropriate rate, without harmful wear debris. We have developed a modified silk scaffold, which is currently being evaluated in humans in a pilot study.

Bone graft substitutes in sports medicine.

Bone graft substitutes are used commonly in orthopedic surgery as an alternative to autograft bone. Autograft bone has the advantages of being osteoconductive, osteoinductive, and osteogenic. However, the quantity of autograft bone available is limited in a given patient and the harvest of autograft bone has been associated with significant morbidity. Bone graft substitutes have become available in an attempt to address these issues and have found widespread use in many areas of orthopedic surgery including sports medicine. The various categories of bone graft substitutes are reviewed here, with an examination of their biologic mechanism of action. Clinical evidence to support their use is also reviewed, with a focus on sports medicine applications.

Complications of Articular Cartilage Surgery

The treatment of articular cartilage lesions of the knee has evolved tremendously in the past 2 decades. Traditional treatment including osteotomy, debridement, and bone marrow stimulation techniques (microfracture, drilling, and abrasion arthroplasty) have been used with predictable results with a relatively well defined set of complications. Newer techniques including autologous chondrocyte implantation (ACI), osteochondral autograft and allograft transplantation have gained increased enthusiasm. These present a new set of potential complications to potentially be avoided, identified, or treated. This article reviews the various options available, their indications and complications, and offers treatment recommendations after complications occur.

Primary Ligament Surgery in the Middle Age/Older Athlete Without Malalignment

Treatment of older athletes with ligament injuries is controversial, in large part because of limited information in the literature. We review the literature for treatment of primary ligament reconstruction in older individuals and describe our preferred surgical techniques and rehabilitation.