Frank A. Petrigliano

Anterior Cruciate Ligament Reconstruction with a Four-Strand Hamstring Tendon Autograft

BACKGROUND In this study, we analyzed the clinical outcomes at a minimum of two years following reconstruction of the anterior cruciate ligament with use of a four-strand hamstring tendon autograft in patients who had presented with a symptomatic torn anterior cruciate ligament. METHODS One hundred and twenty-two consecutive patients who had an isolated, symptomatic anterior tibial subluxation associated with rupture of the anterior cruciate ligament were treated with reconstruction of the anterior cruciate ligament with a four-strand autologous semitendinosus-gracilis tendon graft. One surgeon performed all of the operations. Prior to surgery and at the follow-up examination, physical findings and functional scores were recorded and knee radiographs were analyzed. Following surgery, a six-month rehabilitation regimen was implemented. RESULTS Eighty-five patients (70%) were available for follow-up, which included physical examination, scoring of function, KT-1000 arthrometric testing, and radiographs, at a mean of twenty-eight months. Seventy-six (89%) of the patients had negative Lachman and pivot shift tests. The mean Lysholm score improved from 55 points preoperatively to 91 points at the time of follow-up (p < 0.01). The mean Tegner score improved from 5 to 6 points (p < 0.01). Sixty-five patients had <3 mm of knee translation on arthrometric testing, but six patients with marked laxity were not tested. Three patients (4%) had a positive pivot shift test but had no history of additional trauma to the knee. Six patients (7%) had a traumatic rupture of the graft, occurring at a mean of 10.7 months postoperatively. Assessment of the follow-up radiographs demonstrated no evidence of progressive degenerative change compared with the appearance on the preoperative radiographs. However, tunnel expansion was noted in all patients. The tibial tunnel expanded a mean of 17% (range, 0% to 32%), and the femoral tunnel expanded a mean of 29% (range, 0% to 40%). CONCLUSIONS Reconstruction of the anterior cruciate ligament with use of a four-strand hamstring tendon autograft eliminated anterior tibial subluxation in 89% of patients who were examined at a minimum of two years postoperatively. The overall rate of failure was 11%. The functional knee scores were significantly increased at the time of follow-up, but these results did not correlate with the results of knee arthrometric testing.

Mesenchymal stem cell concentration and bone repair: potential pitfalls from bench to bedside.

BACKGROUND Mesenchymal stem cells are multipotent and have the ability to differentiate into bone. We conducted a preclinical trial comparing the osteogenic potential of human bone marrow aspirate with that of mesenchymal stem cell-enriched bone marrow aspirate (both mixed with demineralized bone matrix) in a critical-sized rat femoral defect model. METHODS The buffy coat was extracted from human bone marrow aspirate to obtain mesenchymal stem cell-enriched bone marrow aspirate. Fifty-nine athymic rats, each with a 6-mm femoral defect, were divided into six treatment groups: defect only (Group I), demineralized bone matrix and saline solution (Group II), demineralized bone matrix and bone marrow aspirate (Group III), demineralized bone matrix and mesenchymal stem cell-enriched bone marrow aspirate (Group IV), demineralized bone matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2) (Group V [positive control]), and absorbable collagen sponge and rhBMP-2 (Group VI [positive control]). All animals were killed at twelve weeks for radiographic, micro-computed tomography, histomorphometric, and histologic analysis. RESULTS There was wide variability in the mesenchymal stem cell concentrations obtained from the human donors. All ten defects healed in the positive control groups (Groups V and VI). Only one defect healed in each experimental group (Groups II, III, and IV) (i.e., three of forty-four defects healed). There was no significant difference among the radiographic scores of Groups II, III, and IV (p = 0.59), and the score for each of those groups was significantly higher than that for Group I (p <or= 0.005) and significantly lower than those for Groups V and VI (p <or= 0.001). The bone volume and mineral density did not differ among Groups III, IV, and V (p = 0.53). The percent total bone volume and percent normal bone volume in Group VI were significantly higher than those values in Groups I, III, and IV (p < 0.0001) and those in Group II (p = 0.048). In Groups II through V, the cortical bone was more dense than the lace-like bone in Group VI. CONCLUSIONS Neither bone marrow aspirate nor mesenchymal stem cell-enriched bone marrow aspirate mixed with demineralized bone matrix resulted in reliable healing of critical-sized bone defects. It is possible that a greater number of mesenchymal stem cells or an enhanced osteoinductive signal is required for adequate bone-healing. Mesenchymal stem cell and/or carrier variability may also contribute to differences in bone formation.

Current tissue engineering strategies in anterior cruciate ligament reconstruction

Rupture of the anterior cruciate ligament (ACL) is one of the most common ligamentous injuries of the knee. Limitations of allografts and autografts in ACL reconstruction as well as recent advancements in biology and materials science have spurred interest in developing tissue-engineered ACL replacements that have the potential to mimic the native ACL in terms of both biological and mechanical properties. This article reviews the current literature regarding contemporary tissue engineering strategies. The four basic components of tissue engineering, biomaterial scaffolds, cell sources, growth factors, and mechanical stimuli, as applied to the development of tissue-engineered ACL replacement grafts, will be systematically addressed. In addition, animal models that have been used to test these tissue-engineered ACL replacements will also be reviewed. To date, there is no tissue-engineered ACL construct that has been successfully implanted in humans. We expect that continued progress in designing a viable tissue-engineered ACL replacement will accompany rapidly advancing techniques in materials science and biology.

Vascular and Nerve Injury After Knee Dislocation: A Systematic Review

BackgroundVascular injury is a devastating complication of acute knee dislocation. However, there are wide discrepancies in the reported frequency of vascular injury after knee dislocations, as well as important differences among approaches for diagnosis of this potentially limb-threatening problem.Questions/purposesWe determined (1) the frequency of vascular and neurologic injury after knee dislocation and whether it varied by the type of knee dislocation, (2) the frequency with which surgical intervention was performed for vascular injury in this setting, and (3) the frequency with which each imaging modality was used to detect vascular injury.MethodsWe searched the MEDLINE® literature database for studies in English that examined the clinical sequelae and diagnostic evaluation after knee dislocation. Vascular and nerve injury incidence after knee dislocation, surgical repair rate within vascular injury, and amputation rate after vascular injury were used to perform a meta-analysis. Other measures such as diagnostic modality used and the vessel injured after knee dislocation were also evaluated.ResultsWe identified 862 patients with knee dislocations, of whom 171 sustained vascular injury, yielding a weighted frequency of 18%. The frequency of nerve injuries after knee dislocation was 25% (75 of 272). We found that 80% (134 of 160) of vascular injuries underwent repair, and 12% (22 of 134) of vascular injuries resulted in amputation. The Schenck and Kennedy knee dislocation classifications with the highest vascular injury prevalence were observed in knees that involved the ACL, PCL, and medial collateral liagment (KDIIIL) (32%) and posterior dislocation (25%), respectively. Selective angiography was the most frequently used diagnostic modality (61%, 14 of 23), followed by nonselective angiography and duplex ultrasonography (22%, five of 23), ankle-brachial index (17%, four of 23), and MR angiography (9%, two of 23).ConclusionsThis review enhances our understanding of the frequency of vascular injury and repair, amputation, and nerve injuries after knee dislocation. It also illustrates the lack of consensus among practitioners regarding the diagnostic and treatment algorithm for vascular injury. After pooling existing data on this topic, no outcomes-driven conclusions could be drawn regarding the ideal diagnostic modality or indications for surgical repair. In light of these findings and the morbidity associated with a missed diagnosis, clinicians should err on the side of caution in ruling out arterial injury.

Incidence of Acute Postoperative Infections Requiring Reoperation After Arthroscopic Shoulder Surgery

Background: An acute infection after arthroscopic shoulder surgery is a rare but serious complication. Previous studies estimating the incidence of infections after arthroscopic surgery have been conducted, but the majority of these had either relatively small study groups or were not specific to shoulder arthroscopic surgery. Purpose: To investigate the incidence of acute infections after arthroscopic shoulder surgery and compare infection rates by age group, sex, geographic region, and specific procedures. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of a large insurance company database was performed for all shoulder arthroscopic surgeries performed in the United States between 2004 and 2009 that required additional surgery for infections within 30 days. The data were stratified by sex, age group, and region. Data were also stratified for specific procedures (capsulorrhaphy, treatment for superior labrum anterior-posterior tears, claviculectomy, decompression, and rotator cuff repair) and used to assess the variation in the incidence of infections across different arthroscopic shoulder procedures. Linear regression was used to determine the significance of differences in the data from year to year. χ2 analysis was used to assess the statistical significance of variations among all groups. Poisson regression analysis with exposure was used to determine significant differences in a pairwise comparison between 2 groups. Results: The total number of arthroscopic shoulder surgeries performed was 165,820, and the number of infections requiring additional surgery was 450, resulting in an overall infection rate of 0.27%. The incidence of infections varied significantly across age groups (P < .001); the infection rate was highest in the ≥60-year age group (0.36%) and lowest in the 10- to 39-year age group (0.18%). The incidence of infections also varied by region (P < .001); the incidence was highest in the South (0.37%) and lowest in the Midwest (0.11%). The incidence of infection treatments was also significantly different between different arthroscopic procedures (P < .01) and was highest for rotator cuff repair (0.29%) and lowest for capsulorrhaphy (0.16%). The incidence did not significantly vary by year or sex. Conclusion: The overall infection rate for all arthroscopic shoulder procedures was 0.27%. The incidence was highest in elderly patients, in the South, and for rotator cuff repair. The incidence was lowest in young patients, in the Midwest, and for capsulorrhaphy. In general, shoulder arthroscopic surgery in this study population had a low rate of reoperation in the acute period.

Human Developmental Chondrogenesis as a Basis for Engineering Chondrocytes from Pluripotent Stem Cells

Summary Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166low/negCD146low/negCD73+CD44lowBMPR1B+) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5–6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166low/negBMPR1B+ putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.

The Effect of Proximal Tibial Slope on Dynamic Stability Testing of the Posterior Cruciate Ligament– and Posterolateral Corner–Deficient Knee

Background: Proximal tibial slope has been shown to influence anteroposterior translation and tibial resting point in the posterior cruciate ligament (PCL)–deficient knee. The effect of proximal tibial slope on rotational stability of the knee is unknown. Hypothesis: Change in proximal tibial slope produced via osteotomy can influence both static translation and dynamic rotational kinematics in the PCL/posterolateral corner (PLC)–deficient knee. Study Design: Controlled laboratory study. Methods: Posterior drawer, dial, and mechanized reverse pivot-shift (RPS) tests were performed on hip-to-toe specimens and translation of the lateral and medial compartments measured utilizing navigation (n = 10). The PCL and structures of the PLC were then sectioned. Stability testing was repeated, and compartmental translation was recorded. A proximal tibial osteotomy in the sagittal plane was then performed achieving either +5° or −5° of tibial slope variation, after which stability testing was repeated (n = 10). Analysis was performed using 1-way analysis of variance (ANOVA; α = .05). Results: Combined sectioning of the PCL and PLC structures resulted in a 10.5-mm increase in the posterior drawer, 15.5-mm increase in the dial test at 30°, 14.5-mm increase in the dial test at 90°, and 17.9-mm increase in the RPS (vs intact; P < .05). Increasing the posterior slope (high tibial osteotomy [HTO] +5°) in the PCL/PLC-deficient knee reduced medial compartment translation by 3.3 mm during posterior drawer (vs deficient; P < .05) but had no significant effect on the dial test at 30°, dial test at 90°, or RPS. Conversely, reversing the slope (HTO −5°) caused a 4.8-mm increase in medial compartment translation (vs deficient state; P < .05) during posterior drawer and an 8.6-mm increase in lateral compartment translation and 9.0-mm increase in medial compartment translation during RPS (vs deficient state; P < .05). Conclusion: Increasing posterior tibial slope diminished static posterior instability of the PCL/PLC-deficient knee as measured by the posterior drawer test but had little effect on rotational or dynamic multiplanar stability as assessed by the dial and RPS tests, respectively. Conversely, decreasing posterior slope resulted in increased posterior instability and a significant increase in the magnitude of the RPS. Clinical Relevance: These results suggest that increasing posterior tibial slope may improve sagittal stability in the PCL/PLC-deficient knee. Moreover, a knee with diminished posterior tibial slope may demonstrate greater multiplanar instability in this setting. Consequently, proximal tibial slope should be considered when treating combined PCL/PLC injuries of the knee.

Influence of simultaneous targeting of the bone morphogenetic protein pathway and RANK/RANKL axis in osteolytic prostate cancer lesion in bone.

Metastasis to bone is the leading cause of morbidity and mortality in advanced prostate cancer patients. Considering the complex reciprocal interactions between the tumor cells and the bone microenvironment, there is increasing interest in developing combination therapies targeting both the tumor growth and the bone microenvironment. In this study, we investigated the effect of simultaneous blockade of BMP pathway and RANK/RANKL axis in an osteolytic prostate cancer lesion in bone. We used a retroviral vector encoding noggin (RetroNoggin) to antagonize the effect of BMPs and RANK:Fc, which is a recombinant RANKL antagonist was used to inhibit RANK/RANKL axis. The tumor growth and bone loss were evaluated using plain radiographs, hind limb tumor measurements, micro PET/CT ((18)FDG and (18)F-fluoride tracer), and histology. Tibias implanted with PC-3 cells developed pure osteolytic lesions at 2-weeks with progressive increase in cortical bone destruction at successive time points. Tibias implanted with PC-3 cells over expressing noggin (RetroNoggin) resulted in reduced tumor size and decreased bone loss compared to the implanted tibias in untreated control animals. RANK:Fc administration inhibited the formation of osteoclasts, delayed the development of osteolytic lesions, decreased bone loss and reduced tumor size in tibias implanted with PC-3 cells. The combination therapy with RANK:Fc and noggin over expression effectively delayed the radiographic development of osteolytic lesions, and decreased the bone loss and tumor burden compared to implanted tibias treated with noggin over expression alone. Furthermore, the animals treated with the combination strategy exhibited decreased bone loss (micro CT) and lower tumor burden (FDG micro PET) compared to animals treated with RANK:Fc alone. Combined blockade of RANK/RANKL axis and BMP pathway resulted in reduced tumor burden and decreased bone loss compared to inhibition of either individual pathway alone in osteolytic prostate cancer lesion in bone. These results suggest that simultaneous targeting of tumor cells and osteoclasts may be the most effective method of inhibiting the progression of established osteolytic metastatic lesions in vivo.

Recent insights into the identity of mesenchymal stem cells

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses. Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure. In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Biologic Treatments for Sports Injuries II Think Tank—Current Concepts, Future Research, and Barriers to Advancement, Part 1 Biologics Overview, Ligament Injury, Tendinopathy

Biologic therapies, including stem cells, platelet-rich plasma, growth factors, and other biologically active adjuncts, have recently received increased attention in the basic science and clinical literature. At the 2015 AOSSM Biologics II Think Tank held in Colorado Springs, Colorado, a group of orthopaedic surgeons, basic scientists, veterinarians, and other investigators gathered to review the state of the science for biologics and barriers to implementation of biologics for the treatment of sports medicine injuries. This series of current concepts reviews reports the summary of the scientific presentations, roundtable discussions, and recommendations from this think tank.