Kathryn F. Farraro

Revolutionizing orthopaedic biomaterials: The potential of biodegradable and bioresorbable magnesium-based materials for functional tissue engineering

In recent years, there has been a surge of interest in magnesium (Mg) and its alloys as biomaterials for orthopaedic applications, as they possess desirable mechanical properties, good biocompatibility, and biodegradability. Also shown to be osteoinductive, Mg-based materials could be particularly advantageous in functional tissue engineering to improve healing and serve as scaffolds for delivery of drugs, cells, and cytokines. In this paper, we will present two examples of Mg-based orthopaedic devices: an interference screw to accelerate ACL graft healing and a ring to aid in the healing of an injured ACL. In vitro tests using a robotic/UFS testing system showed that both devices could restore function of the goat stifle joint. Under a 67-N anterior tibial load, both the ACL graft fixed with the Mg-based interference screw and the Mg-based ring-repaired ACL could restore anterior tibial translation (ATT) to within 2mm and 5mm, respectively, of the intact joint at 30°, 60°, and 90° of flexion. In-situ forces in the replacement graft and Mg-based ring-repaired ACL were also similar to those of the intact ACL. Further, early in vivo data using the Mg-based interference screw showed that after 12 weeks, it was non-toxic and the joint stability and graft function reached similar levels as published data. Following these positive results, we will move forward in incorporating bioactive molecules and ECM bioscaffolds to these Mg-based biomaterials to test their potential for functional tissue engineering of musculoskeletal and other tissues.

Thirdhand cigarette smoke in an experimental chamber: evidence of surface deposition of nicotine, nitrosamines and polycyclic aromatic hydrocarbons and de novo formation of NNK

Background A growing body of evidence shows that secondhand cigarette smoke undergoes numerous chemical changes after it is released into the air: it can adsorb to indoor surfaces, desorb back into the air and undergo chemical changes as it ages. Objectives To test the effects of aging on the concentration of polycyclic aromatic hydrocarbons (PAHs), nicotine and tobacco-specific nitrosamines in cigarette smoke. Methods We generated sidestream and mainstream cigarette smoke with a smoking machine, diluted it with conditioned filtered air, and passed it through a 6 m3 flow reactor with air exchange rates that matched normal residential air exchange rates. We tested the effects of 60 min aging on the concentration of 16 PAHs, nicotine, cotinine and tobacco-specific nitrosamines. We also measured sorption and deposition of nicotine, cotinine and tobacco-specific nitrosamines on materials placed within the flow reactor. Results We observed mass losses of 62% for PAHs, 72%, for nicotine, 79% for N-nitrosonornicotine and 80% for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Extraction of cotton cloth exposed to smoke yielded nicotine and NNK. The ratio of NNK:nicotine on the exposed cloth was 10-fold higher than that in aerosol samples. Conclusions Our data suggest that the majority of the PAHs, nicotine, cotinine and tobacco-specific nitrosamines that are released during smoking in homes and public places deposit on room surfaces. These data give an estimate of the potential for accumulation of carcinogens in thirdhand cigarette smoke. Exposure to PAHs and tobacco-specific nitrosamines, through dermal absorption and inhalation of contaminated dust, may contribute to smoking-attributable morbidity and mortality.

Biomechanical Evaluation of the Quadriceps Tendon Autograft for Anterior Cruciate Ligament Reconstruction A Cadaveric Study

Background: Recently, many surgeons have chosen the quadriceps tendon (QT) as an autograft for anterior cruciate ligament (ACL) reconstruction. However, there have not been biomechanical studies that quantitatively evaluated knee function after reconstruction using a QT autograft. Purpose: To measure the 6 degrees of freedom knee kinematics and in situ graft forces after reconstruction with a QT autograft compared with a quadrupled semitendinosus and gracilis (QSTG) tendon autograft. Study Design: Controlled laboratory study. Methods: Ten human cadaveric knees (age, 54-64 years) were tested in 3 conditions: (1) intact, (2) ACL deficient, and (3) after ACL reconstruction using a QT or QSTG autograft. With use of a robotic/universal force-moment sensor testing system, knee kinematics and in situ forces in the ACL and autografts were obtained at 5 knee flexion angles under externally applied loads: (1) 134-N anterior tibial load, (2) 134-N anterior tibial load with 200-N axial compression, and (3) 10-N·m valgus and 5-N·m internal tibial torque. Results: Under the anterior tibial load, both autografts restored anterior tibial translation to within 2.5 mm of the intact knee and in situ forces to within 20 N of the intact ACL at 15°, 30°, and 60°. Adding compression did not change these findings. With the combined rotatory load, the anterior tibial translation and graft in situ forces were again not significantly different from the intact ACL. There were no significant differences between the grafts under any experimental condition. Conclusion: Reconstruction of the ACL with a QT autograft restored knee function to similar levels as that reconstructed with a QSTG autograft under loads simulating clinical examinations. Clinical Relevance: The positive biomechanical results of this cadaveric study lend support to the use of a QT autograft for ACL reconstruction, as it could restore knee function immediately after surgery under applied loads that mimic clinical examinations.

An Apparatus for Generating Aged Cigarette Smoke for Controlled Human Exposure Studies

Research has shown that cigarette smoke changes chemically and physically after it is released into indoor air, that these changes can increase secondhand smoke (SHS) toxicity, and that acute exposures to even low levels of SHS increase the risk of cardiopulmonary disease. We designed a system to reproduce realistic SHS exposures in the laboratory for use in controlled human exposure studies. We generated cigarette smoke with a smoking machine, diluted it and conducted it through a 6 m3 stainless steel flow reactor at rates equivalent to the upper ranges of normal residential air exchange rates, to create aged cigarette smoke as a model for secondhand cigarette smoke. We observed that approximately 50% of the particle mass deposited within the system and that particle deposition percentage was higher when absorbent materials were placed within the system. The particle size ranges and deposition percentages, coefficients and velocities observed for this smoke aerosol are in good agreement with published values for SHS observed in residences and vehicles. This apparatus also permits the study of the physical and chemical interactions between SHS and indoor surfaces. The apparatus delivers stable aerosol concentrations to a human subject, which will permit accurate analysis of dose-response relationships in studies of the cardiovascular and respiratory effects of SHS exposure. Copyright 2012 American Association for Aerosol Research

Magnesium ring device to restore function of a transected anterior cruciate ligament in the goat stifle joint

A bioresorbable, mono‐crystalline magnesium (Mg) ring device and suture implantation technique were designed to connect the ends of a transected anterior cruciate ligament (ACL) to restabilize the knee and load the ACL to prevent disuse atrophy of its insertion sites and facilitate its healing. To test its application, cadaveric goat stifle joints were evaluated using a robotic/universal force‐moment sensor testing system in three states: Intact, ACL‐deficient, and after Mg ring repair, at 30°, 60°, and 90° of joint flexion. Under a 67‐N anterior tibial load simulating that used in clinical examinations, the corresponding anterior tibial translation (ATT) and in‐situ forces in the ACL and medial meniscus for 0 and 100 N of axial compression were obtained and compared with a control group treated with suture repair. In all cases, Mg ring repair reduced the ATT by over 50% compared to the ACL‐deficient joint, and in‐situ forces in the ACL and medial meniscus were restored to near normal levels, showing significant improvement over suture repair. These findings suggest that Mg ring repair could successfully stabilize the joint and load the ACL immediately after surgery, laying the framework for future in vivo studies to assess its utility for ACL healing.

Ligament and Tendon Enthesis: Anatomy and Mechanics

The insertions of ligaments and tendons to bone are morphologically and biomechanically complex. Within a short distance, the insertion (“enthesis”) is transformed from soft connective tissue to hard bone. In this chapter, we discuss the anatomy of the enthesis, including a review of the gross morphology as well as histology and appearance of two distinct types of insertions: the direct and indirect insertions to bone. The biomechanical function of insertion sites is then presented, including some challenges with methods involved in determining their properties. We then review the changes that occur across the insertion site during growth and skeletal maturity, using the femur-MCL-tibia complex as an example. The negative effects of immobilization on the insertion and its slow recovery following remobilization, together with positive effects of exercise, will then be presented.