Morey S. Moreland

Growth factors improve muscle healing in vivo

Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.

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.

Anatomic anterior cruciate ligament reconstruction: a changing paradigm

Injury to the anterior cruciate ligament (ACL) of the knee is potentially devastating for the patient and can result in both acute and long-term clinical problems. Consequently, the ACL has always been and continues to be of great interest to orthopaedic scientists and clinicians worldwide. Major advancements in ACL surgery have been made in the past few years. ACL reconstruction has shifted from an open to arthroscopic procedure, in which a two- and later one-incision technique was applied. Studies have found that traditional, transtibial arthroscopic single-bundle reconstruction does not fully restore rotational stability of the knee joint, and as such, a more anatomic approach to ACL reconstruction has emerged. The goal of anatomic ACL reconstruction is to replicate the knee’s normal anatomy and restore its normal kinematics, all while protecting long-term knee health. This manuscript describes the research that has changed the paradigm of ACL reconstruction from traditional techniques to present day anatomic and individualized concepts.

Complications following iliac crest bone grafting.

Avulsion of the anterior superior iliac spine occurred after procurement of bicortical bone grafts from the anterior superior iliac crest area in two patients. The defect in the anterior ilium with a weak spike of bone created a significant stress riser and led to avulsion of the anterior superior iliac spine by the action of the sartorius and tensor fascia lata. Bicortical grafts should be taken from areas as much as 5 cm posterior to the anterior superior iliac spine to avoid this complication.

Femur fractures resulting from stair falls among children: an injury plausibility model.

Background. Stair falls are common among young children and are also common false histories in cases of child abuse. When a child presents with a femur fracture and a stair-fall history, a judgment of plausibility must be made. A lack of objective injury and biomechanical data makes plausibility determination more difficult. Our objective was to characterize key features associated with femur fractures from reported stair falls, to develop a model for assessing injury plausibility (IP). Methods. Children 2 to 36 months of age who presented with a femur fracture from a reported stair fall were studied prospectively. Detailed history recording, examinations, fracture characterization, and injury scene analyses were conducted, and biomechanical measures associated with injury prediction were calculated. With our proposed IP model, all cases were then scored for the detail of history, biomechanical compatibility of fracture morphologic features, time to seeking care, and presence of other injuries. Results. Twenty-nine children were diagnosed with a femur fracture resulting from a reported stair fall. The IP model made a clear distinction between 2 groups, designated plausible and suspicious. Significant differences were observed for the detail of history, biomechanical compatibility of fracture, time to seeking care, presence of other injuries, and total IP scores. In the plausible group, the minimal linear momentum associated with a transverse fracture was almost 10-fold greater than that for spiral or buckle fracture types. Conclusions. This study adds new information to the current body of knowledge regarding injury biomechanics and fractures among children. The IP model provides an objective means of assessing plausibility of reported stair-fall–related femur fractures and identifies key characteristics to facilitate decision-making.

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.

Muscle-based gene therapy and tissue engineering for treatment of growth plate injuries.

Growth plate injuries may lead to a progressive angular deformity or longitudinal growth disturbance. The authors investigated the feasibility of gene therapy and tissue engineering based on autologous muscle-and adenoviral-mediated gene transfer of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) to treat tibial physeal defects in rabbits. The medial half of the left proximal tibial growth plate was completely excised in 44 6-week-old New Zealand white rabbits. Four experimental groups were created: no treatment (I), autologous muscle interposition (II), autologous muscle interposition injected with adIGF-1 (III), and autologous muscle interposition injected with adBMP-2 (IV). Radiographic and histologic assessments were obtained postoperatively. Significant tibial shortening and a compact osseous bridge were observed in groups I and IV. Growth plates remained open in groups II and III. This experiment demonstrates that IGF-1 had a supportive effect on physeal chondrocytes, while BMP-2 caused increased osteogenic activity in the injured growth plates.

Early versus late femoral fracture stabilization in multiply injured pediatric patients with closed head injury.

The purpose of this study was to analyze retrospectively pediatric femur fracture patients with concomitant head injury to determine whether time to fracture fixation affects central nervous system, orthopaedic, or additional complications. Twenty-five patients with a Head Abbreviated Injury Scale score of ≥3 and a femoral shaft fracture were reviewed. Patients were divided by time to treatment for their femur fracture. Average stay was 10.5 days for the early group and 18.5 days for the late group, the only statistically significant finding. Orthopaedic and central nervous system complications were similar between the two groups. Sixteen additional complications were found in the late group versus three for the early group. Femur fractures in the head-injured pediatric patient can be adequately addressed with early or late fixation with similar long-term outcomes. Early femur fracture fixation may decrease the length of hospital stay and the number of nonorthopaedic, nonneurologic complications.

Proposed curriculum model for resident education in pediatric orthopaedic surgery.

A curriculum developed for pediatric orthopaedic residency training is described. The curriculum is practice based, emphasizing those components thought to be necessary for orthopaedic practice. Highly technical or esoteric topics are deemphasized, because they are not relevant to practice capabilities at the end of residency training. The curriculum is designed to serve as a guide for educational direction in pediatric orthopaedic residency training, and not as a description of competency. Resource materials are being developed to provide the educator with relevant clinical material, objectives, and bibliography. The advantages of a practice based curriculum warrant further development of this model for other orthopaedic subspecialties.