Christian Lattermann

Current trends in anterior cruciate ligament reconstruction. Part 1 : Biology and biomechanics of reconstruction

With todays increasing emphasis on sporting activities, the incidence of anterior cruciate ligament injuries has also increased. Epidemiologic studies estimate that the prevalence of anterior cruciate ligament injuries is about 1 per 3000 Americans. Management of these injuries has evolved from nonoperative treatment to extracapsular augmentation and primary ligament repair to anterior cruciate ligament reconstruction. Treatment of these injuries has significantly improved over the last few decades with the application of knowledge gained from both basic science and clinical research. This article is composed of two parts. The first part reviews the biology and biomechanics of the injured anterior cruciate ligament and the basic science of reconstruction. In the second part, to be published later, current operative concepts of reconstruction, as well as clinical correlations, are reviewed. Summarizing the latest information on basic scientific as well as clinical studies regarding the anterior cruciate ligament, this article intends to demonstrate the correlation between the application of basic science knowledge and improvement of clinical outcomes.

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.

Genetic enhancement of fracture repair: Healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene

This study evaluated the ability of gene transfer to enhance bone healing. Segmental defects were created surgically in the femora of New Zealand white rabbits. First generation adenoviruses were used as vectors to introduce into the defects genes encoding either human bone morphogenetic protein-2 (BMP-2) or, as a negative control, firefly luciferase. Representative specimens were evaluated histologically after 8 weeks. Healing of the defects was monitored radiographically for 12 weeks, after which time the repair tissue was evaluated biomechanically. By radiological criteria, animals receiving the BMP-2 gene had healed their osseous lesions after 7 weeks, whereas those receiving the luciferase gene had not. Histologic examination of representative rabbits at 8 weeks confirmed ossification across the entire defect in response to the BMP-2 gene, whereas the control defect was predominantly fibrotic and sparsely ossified. At the end of the 12-week experiment, the control femora still showed no radiological signs of stable healing. The difference in radiologically defined healing between the experimental and control groups was statistically significant (P < 0.002). biomechanical testing of the femora at 12 weeks demonstrated statistically significant increases in the mean bending strength (p < 0.005) and bending stiffness (p < 0.05) of the animals treated with the bmp-2 gene. direct, local adenoviral delivery of an osteogenic gene thus led to the healing of an osseous lesion that otherwise would not do so. these promising data encourage the further development of genetic approaches to enhancing bone healing.

A Systematic Review of Complications and Failures Associated With Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation

Background: Patellofemoral instability affects activities of daily living and hinders athletic participation. Over the past 2 decades, more attention has been paid to medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocations/subluxations. Numerous techniques have been reported; however, there is no consensus regarding optimal reconstruction. Purpose: This study sought to report on the various techniques for MPFL reconstruction described in the literature and to assess the rate of complications associated with the procedure. Study Design: Meta-analysis. Methods: A systematic review of the literature was performed in early October 2010 using keywords “medial patellofemoral ligament,” “MPFL,” “reconstruction,” “complication(s),” and “failure(s).” Articles meeting the inclusion criteria were reviewed. Graft choice, surgical technique, outcome measures, and complications were recorded and organized in a database. Descriptive statistical analysis was performed on the data collected. Results: Twenty-five articles were identified and reviewed. A total of 164 complications occurred in 629 knees (26.1%). These adverse events ranged from minor to major including patellar fracture, failures, clinical instability on postoperative examination, loss of knee flexion, wound complications, and pain. Twenty-six patients returned to the operating room for additional procedures. Conclusion: Medial patellofemoral ligament reconstruction has a high rate of success for patients with patellofemoral instability; however, the complication rate of 26.1% associated with this procedure is not trivial. This study quantified complications and documented the variety of complications reported in outcomes-based literature.

Failures, re-operations, and complications after autologous chondrocyte implantation – a systematic review

OBJECTIVE To determine and compare failure, re-operation, and complication rates of all generations and techniques of autologous chondrocyte implantation (ACI). METHODS A systematic review of multiple medical databases was performed according to PRISMA guidelines. Levels I-IV evidence were included. Generations of ACI and complications after ACI were explicitly defined. All subject and defect demographic data were analyzed. Modified Coleman Methodology Scores (MCMSs) were calculated for all studies. RESULTS 82 studies were identified for inclusion (5276 subjects were analyzed; 6080 defects). Ninety percent of the studies in this review were rated poor according to the MCMS. There were 305 failures overall (5.8% subjects; mean time to failure 22 months). Failure rate was highest with periosteal ACI (PACI). Failure rates after PACI, collagen-membrane cover ACI (CACI), second generation, and all-arthroscopic, second-generation ACI were 7.7%, 1.5%, 3.3%, and 0.83%, respectively. The failure rate of arthrotomy-based ACI was 6.1% vs 0.83% for all-arthroscopic ACI. Overall rate of re-operation was 33%. Re-operation rate after PACI, CACI, and second-generation ACI was 36%, 40%, and 18%, respectively. However, upon exclusion of planned second-look arthroscopy, re-operation rate was highest after PACI. Unplanned re-operation rates after PACI, CACI, second-generation, and all-arthroscopic second-generation ACI were 27%, 5%, 5%, and 1.4%, respectively. Low numbers of patients undergoing third-generation ACI precluded comparative analysis of this group. CONCLUSIONS Failure rate after all ACI generations is low (1.5-7.7%). Failure rate is highest with PACI, and lower with CACI and second-generation techniques. One out of three ACI patients underwent a re-operation. Unplanned re-operations are seen most often following PACI. Hypertrophy and delamination is most commonly seen after PACI. Arthrofibrosis is most commonly seen after arthrotomy-based ACI. Use of a collagen-membrane cover, second-generation techniques, and all-arthroscopic, second-generation approaches have reduced the failure, complication, and re-operation rate after ACI.

Proximal and distal kinematics in female runners with patellofemoral pain

BACKGROUND Female runners have a high incidence of developing patellofemoral pain. Abnormal mechanics are thought to be an important contributing factor to patellofemoral pain. However, the contribution of abnormal trunk, hip, and foot mechanics to the development of patellofemoral pain within this cohort remains elusive. Therefore the aim of this study was to determine if significant differences during running exist in hip, trunk and foot kinematics between females with and without patellofemoral pain. METHODS 32 female runners (16 patellofemoral pain, 16 healthy control) participated in this study. All individuals underwent an instrumented gait analysis. Between-group comparisons were made for hip adduction, hip internal rotation, contra-lateral pelvic drop, contra-lateral trunk lean, rearfoot eversion, tibial internal rotation, as well as forefoot dorsiflexion and abduction FINDINGS The patellofemoral pain group had significantly greater peak hip adduction and hip internal rotation. No differences in contra-lateral pelvic drop were found. A trend towards reduced contra-lateral trunk lean was found in the patellofemoral pain group. No significant differences were found in any of the rearfoot or forefoot variables but significantly greater shank internal rotation was found in the patellofemoral pain group. INTERPRETATION We found greater hip adduction, hip internal rotation and shank internal rotation in female runners with patellofemoral pain. We also found less contra-lateral trunk lean in the patellofemoral pain group. This may be a potential compensatory mechanism for the poor hip control seen. Rehabilitation programs that correct abnormal hip and shank kinematics are warranted in this population.

Hip Strengthening Prior to Functional Exercises Reduces Pain Sooner Than Quadriceps Strengthening in Females With Patellofemoral Pain Syndrome: A Randomized Clinical Trial

STUDY DESIGN Randomized clinical trial. OBJECTIVES To determine if females with patellofemoral pain syndrome (PFPS) who perform hip strengthening prior to functional exercises demonstrate greater improvements than females who perform quadriceps strengthening prior to the same functional exercises. BACKGROUND Although PFPS has previously been attributed to quadriceps dysfunction, more recent research has linked this condition to impairment of the hip musculature. Lower extremity strengthening has been deemed an effective intervention. However, research has often examined weight-bearing exercises, making it unclear if increased strength in the hip, quadriceps, or both is beneficial. METHODS Thirty-three females with PFPS performed either initial hip strengthening (hip group) or initial quadriceps strengthening (quad group) for 4 weeks, prior to 4 weeks of a similar program of functional weight-bearing exercises. Self-reported pain, function, and functional strength were measured. Isometric strength was assessed for hip abductors, external rotators, and knee extensors. A mixed-model analysis of variance was used to determine group differences over time. RESULTS After 4 weeks, there was less mean ± SD pain in the hip group (2.4 ± 2.0) than in the quad group (4.1 ± 2.5) (P = .035). From baseline to 8 weeks, the hip group demonstrated a 21% increase (P<.001) in hip abductor strength, while that remained unchanged in the quad group. All participants demonstrated improved subjective function (P<.006), objective function (P<.001), and hip external rotator strength (P = .004) from baseline to testing at 8 weeks. CONCLUSION Both rehabilitation approaches improved function and reduced pain. For patients with PFPS, initial hip strengthening may allow an earlier dissipation of pain than exercises focused on the quadriceps.

The role of lateral retinacular release in the treatment of patellar instability.

In the last 2 decades many authors have described the use of an isolated lateral retinacular release for the treatment of patellar instability. This review analyzes the published long-term results of this procedure for the treatment of patellar instability. The isolated use of a lateral retinacular release of the patella has not proven to be of long-term benefit for the treatment of patellar instability. It may be used as an adjunct procedure to a proximal or distal realignment of the extensor mechanism. Various pitfalls of a lateral release for patellar instability are discussed.

A gene therapy approach to accelerating bone healing Evaluation of gene expression in a New Zealand white rabbit model

It has been demonstrated that BMPs, IGFs, and TGFβs improve the process of bone healing in vivo. We have suggested the use of gene therapy as a possible way to deliver growth factors to fracture sites in order to improve repair. The aim of this study was to develop a minimally invasive gene therapy approach to treat bone injuries locally without damaging the local blood circulation. A segmental defect of 1.3 cm was created in the diaphysis of the femur in mature NZW rabbits. Internal fixation with 7-hole DCP plates and 2.7 mm screws was used to stabilize the bone. After building a chamber by tightly closing the muscles around the segmental defect, 0.5 ml of either saline solution or a collagen gel containing 1 × 1010 particles of adenovirus carrying cDNA encoding either the bacterial β-galactosidase gene (LacZ), or the firefly luciferase gene were injected into the gap. The control side received 0.5 ml of saline solution without virus particles. Bone marrow, cortical and trabecular bone and surrounding muscle were harvested from the injected femur and were analyzed for local gene expression through X-gal staining or measurement of local luciferase activity. To determine whether distant sites were transduced, tissue from the spleen, liver, and lung were harvested as well as bone, bone marrow and muscle from the contralateral diaphysis of the femur. The delivery of the adenoviral vector suspended in saline solution led to local transduction of the bone, bone marrow and the muscle surrounding the gap. No luciferase activity was found in the contralateral femur, lung, or spleen, and only transient luciferase activity was seen in the liver. While marker gene expression persisted within the surrounding soft tissues for at least 2 weeks, the expression in bone lasted up to 6 weeks. This study has shown that it is possible to use adenoviral vectors to transfer and express genes locally within a segmental defect. Gene expression persisted for several weeks, which may be already sufficient to accelerate repair.

Potential role for gene therapy in the enhancement of fracture healing

Various proteins have the potential to initiate and accelerate fracture healing. Although osteogenic growth factors are the most prominent of these, there also may be important roles for other agents including growth factor receptors, angiogenic factors, and cytokine antagonists. Gene based delivery systems offer the potential to achieve therapeutic levels of these proteins locally within the fracture site for sustained times. Moreover, these delivery systems may deliver their products in a more biologically active form than that achieved by the exogenous application of recombinant proteins. Genes may be transferred to fractures by direct in vivo delivery or by indirect ex vivo delivery, using viral or nonviral vectors. Two examples are described in this article. With an ex vivo procedure, it was possible to transfer lac Z and neo(r) marker genes to the bones of mice, using retroviral transduction of bone marrow stromal cells. Gene expression in vivo persisted for several weeks. This procedure has the advantage of providing not only gene products but also osteoprogenitor cells to sites of bone healing. In vivo, local transfer of the lucerifase and lac Z marker genes was accomplished in a segmental defect model in the rabbit using adenoviral vectors. Under these conditions, gene expression in most tissues in and around the defect lasted between 2 and 6 weeks. These data encourage additional development of gene therapy for fracture healing. Such developments should go hand in hand with studies in the basic biology of fracture healing.