Jacques Menetrey

Current Trends in Anterior Cruciate Ligament Reconstruction Part II. Operative Procedures and Clinical Correlations

Surgical management of the anterior cruciate ligament-deficient knee has evolved from primary repair to extracapsular augmentation to anterior cruciate ligament reconstruction using biologic tissue grafts. The technique of anterior cruciate ligament reconstruction has improved over the last few decades with the aid of knowledge gained from basic science and clinical research. The biology and biomechanics of anterior cruciate ligament reconstruction were analyzed in the previously published first part of this article. In this second part, current operative concepts of anterior cruciate ligament reconstruction as well as clinical correlations are discussed. The latest information regarding anterior cruciate ligament reconstruction is presented with a goal of demonstrating the correlation between the application of basic science knowledge and the improvement of clinical outcomes.

Suturing Versus Immobilization of a Muscle Laceration A Morphological and Functional Study in a Mouse Model

Muscle laceration remains a difficult problem for orthopaedic surgeons. Despite many studies related to the muscles ability to regenerate after muscle degeneration, very few reports are available regarding structural and functional recovery after skeletal muscle laceration. We developed an animal model of muscle laceration in mice, where the gastrocnemius muscles were reproducibly transected. We compared the effect of a surgical repair versus a short period of immobilization (5 days) on the muscle healing. The natural course of muscle recovery was monitored at several points after injury using histologic, immunohistochemical, and functional testing. In the injured muscle, we observed a high number of regenerating myofibers and development of fibrotic scar tissue. Suturing the lacerated muscle immediately after injury promoted better healing of the injured muscle and prevented the development of deep scar tissue in the lacerated muscle; conversely, immobilization resulted in slower muscle regeneration and the development of a large area of scar tissue. Tetanus strength 1 month after injury was 81% of control muscles for the sutured muscles, 35% for the lacerated muscles with no treatment, and 18% for the immobilized muscles. Based on this study, suturing a muscle laceration with a modified Kessler stitch results in the best morphologic and functional healing.

Development of approaches to improve the healing following muscle contusion

Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscles ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.

Biologic intervention in muscle healing and regeneration

Muscle injuries are a challenging problem in traumatology and the most frequently occurring injuries in sports medicine. Even though muscles retain their ability to regenerate after injury, the healing process of muscles after such injuries has been found to be slow and often leads to an incomplete muscle recovery. In an attempt to develop approaches to improve muscle healing after injury, the authors have developed reproducible injury models for muscle contusion, strain, and laceration. The authors show that muscle regeneration occurs after those injuries, but the development of scar tissue greatly limits the natural healing process. It is likely that an enhancement of muscle growth and regeneration can be used to improve muscle healing after injuries. The authors have then identified growth factors that enhance myoblast proliferation and differentiation in vitro and muscle regeneration in the injured muscles, which improves muscle healing after injuries. Furthermore, different gene transfer systems, including cell and gene therapy, have been found successful in delivering genes into injured muscles and may open new opportunities to deliver growth factors and improve muscle healing after lacerations, contusions, and strains.

The use of growth factors, gene therapy and tissue engineering to improve meniscal healing

Abstract The meniscus plays important roles in the knee joint, including load transmission at the tibiofemoral articulation, shock absorption, lubrication, and stabilization of the knee joint, though its healing capacity remains limited. Meniscal healing requires the proliferation of meniscal fibrochondrocytes from either an intrinsic source at the site of injury or an extrinsic source from the blood supply or synovium. We have characterized the effects of various doses of nine growth factors on the meniscal fibrochondrocyte proliferation and collagen and non-collagen synthesis, and identified epidermal growth factor (EGF), transforming growth factor alpha (TGFα), basic fibroblast growth factor (bFGF) and platelet derived growth factor AB (PDGF-AB) as candidate molecules to improve meniscal healing. The direct administration of the human recombinant growth factor protein is likely to be limited by the short biological half-life of these proteins and the rapid clearance of the injected proteins. We have therefore evaluated the feasibility of gene therapy and tissue engineering to deliver marker genes into the meniscus and found that direct and myoblast mediated ex vivo gene transfer can be used to deliver high levels and persistent expression of these growth factors into the injured meniscus. This study will help in the development of strategies to improve meniscal healing using new innovative technologies such as gene therapy approaches.

Muscle-Based Tissue Engineering for Orthopaedic Applications

The advent of gene therapy and tissue engineering has facilitated novel approaches to the treatment of orthopaedic disorders. The delivery of growth factors, cells, and therapeutic genes promises therapeutic possibilities not contemplated by previous generations of orthopaedic surgeons. Significant scientific contributions have been made in the last 3 decades toward the understanding of skeletal muscle biology and its potential therapeutic applications. However, despite tremendous progress, many questions remain unanswered. This chapter reviews the current status of muscle-based tissue engineering for musculoskeletal disorders and discusses the focus of ongoing research.

The Development of Approaches Based on Gene Therapy to Improve Muscle Healing Following Injury

Muscle injuries are common, with an incidence varying from 10% to 55% of all injuries sustained in sports (Lehto and Jarvinen 1991). Muscle injuries are divided into 2 types: a shearing injury, in which both the myofibers and the connective tissue framework are torn, or an in situ injury, in which only the myofibers are damaged and the basal lamina and connective tissue sheaths do not undergo significant harm. Shearing injuries, the most frequent muscle injuries related to sports, may be lacerations, contusions, or strains, depending on the mechanism of injury (Lehto and Jarvinen 1991). Contusion is sustained through a significant compressive force to the muscle, such as a direct blow, a common occurrence in contact sports. A strain occurs when a forceful eccentric contraction is applied to an overstretched muscle, especially in jumping or sprinting (Garrett, Jr. 1990; Lehto and Jarvinen 1991). Injury is common near the musculotendinous junction (MTJ) of a superficial muscle that crosses 2 joints, such as the rectus femoris, semitendinosus, and gastrocnemius muscles. Though rather rare in sports, muscle laceration is a dramatic injury that consistently incapacitates athletes for long periods of time and often jeopardizes their professional careers.