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.

Design and characterization of a scaffold for anterior cruciate ligament engineering.

Advances in biomedical engineering have led to an understanding of the human body's capacity for anterior cruciate ligament (ACL) healing if provided the correct impetus--a long-term bioresorbable scaffold that anticipates the defect site's requirements. Tissue engineering an ACL requires a scaffold that can meet multiple and often conflicting mechanical and biological design requirements. The design and characterization of a hydrophilic silk scaffold is presented as an example of the preclinical testing required to fully characterize a scaffold for ACL reconstruction. We hypothesize that by providing a structural scaffold which anticipates ACL repair mechanisms, an "engineered" autologous ligament with excellent functional integrity can be developed by the body itself. Mechanical, biological, and patient-clinician testing demonstrate that the hydrophilic silk scaffold is a mechanically robust, biocompatible, long-term bioresorbable ACL scaffold with demonstrated safety that can be implanted in accordance with standard surgical procedures.

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.

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.

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.

Surgical treatment of redisplaced fractures of the distal radius in patients older than 60 years.

Twenty patients aged 60 years or older (average age, 68 y) presented to our institution with a distal radius fracture made complex by virtue of displacement after a closed reduction and cast or external fixation immobilization. Ten of the fractures were volarly angulated and 10 were dorsally angulated. Fifteen patients' hands had associated soft-tissue swelling. Surgical exposure and stable internal fixation were undertaken to both realign the fracture as well as enable functional rehabilitation. The final functional result and radiographic results were physician rated and patient rated by using the Patient Rated Wrist Evaluation (PRWE). The patients' overall activity level was quantified and compared with population norms by using the Physical Activity Scale for the Elderly (PASE). At an average follow-up visit of 38 months, all the fractures healed and none of the implants loosened or broke. The functional results were excellent in 7, good in 11, and fair in 2. The average PRWE score was 14, which compares favorably with prior studies of adult patients of all ages treated for a distal radius fracture. The PASE score averaged 177, representing a return to preoperative activity levels in 17 of 20 patients. Complications included loss of alignment, tendon rupture, transient radial sensory neuritis, and nonfatal pulmonary embolism in 1 patient each. Six plates were removed because of soft-tissue irritation.

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.