Kwang E. Kim

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.

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.

Tensile properties of the medial patellofemoral ligament: The effect of specimen orientation

For recurrent patellar dislocation, reconstruction of the medial patellofemoral ligament (MPFL) with replacement autografts has often been performed but with only little data on the tensile properties of the MPFL to guide graft selection. With its complex anatomy and geometry, these properties are difficult to obtain. In this study, we showed how the orientation of the femur-MPFL-patella complex (FMPC) during uniaxial tensile testing can have a significant effect on its structural properties. Twenty two FMPCs were isolated from porcine stifle joints and randomly assigned to two groups of 11 each. For the first group, the specimens were loaded to failure with the patella oriented 30 degrees away from the direction of the applied load to mimic its orientation in situ, called natural orientation. In the second group, the patella was aligned in the direction of the tensile load, called non-natural orientation. The stiffness for the natural orientation group was 65±13 N/mm, 32% higher than that for the non-natural orientation group (50±17 N/mm; p<0.05). The ultimate loads were 438±128 N and 386±136 N, respectively (p>0.05). Ten out of 11 specimens in the natural orientation group failed at the femoral attachment (the narrowest portion of the MPFL) compared to 6 out of 11 in the non-natural orientation group. Our findings suggest that the specimen orientation that mimics the in-situ loading conditions of the MPFL should be used to obtain more representative data for the structural properties of the FMPC.

Fiber orientation of the transverse carpal ligament

The transverse carpal ligament is the volar roof of the carpal tunnel. Gross observation shows that the ligament appears to have fibers that roughly orient in the transverse direction. A closer anatomical examination shows that the ligament also has oblique fibers. Knowledge of the fiber orientation of the transverse carpal ligament is valuable for further understanding the ligaments role in regulating the structural function of the carpal tunnel. The purpose of this study is to quantify collagen fiber orientation within the transverse carpal ligament using the small angle light scattering technique. Eight transverse carpal ligament samples from cadaver hands were used in this study. Individual 20‐μm sections were cut evenly along the thickness of the transverse carpal ligament. Sections of three thickness levels (25%, 50%, and 75% from the volar surface) were collected for each transverse carpal ligament. Fibers were grouped in the following orientation ranges: transverse, longitudinal, oblique in the pisiform‐trapezium (PT), and oblique in the scaphoid‐hamate (SH) directions. In analyzing the fiber percentages, the orientation types for the different thickness levels of the ligament showed that the transverse fibers were the most prominent (>60.7%) followed by the PT oblique (18.6%), SH oblique (13.0%), and longitudinal (8.6%) fibers. Clin. Anat. 25:478–482, 2012.

Positive effects of an extracellular matrix hydrogel on rat anterior cruciate ligament fibroblast proliferation and collagen mRNA expression

Summary Background/Objective We have previously shown that an extracellular matrix (ECM) bioscaffold derived from porcine small intestine submucosa (SIS) enhanced the healing of a gap injury of the medial collateral ligament as well as the central third defect of the patellar tendon. With the addition of a hydrogel form of SIS, we found that a transected goat anterior cruciate ligament (ACL) could also be healed. The result begs the research question of whether SIS hydrogel has positive effects on ACL fibroblasts (ACLFs) and thus facilitates ACL healing. Methods In the study, ECM-SIS hydrogel was fabricated from the digestion of decellularised and sterilised sheets of SIS derived from αGal-deficient (GalSafe) pigs. As a comparison, a pure collagen hydrogel was also fabricated from commercial collagen type I solution. The morphometrics of hydrogels was assessed with scanning electron microscopy. The ECM-SIS and collagen hydrogels had similar fibre diameters (0.105 ± 0.010 μm vs. 0.114 ± 0.004 μm), fibre orientation (0.51 ± 0.02 vs. 0.52 ± 0.02), and pore size (0.092 ± 0.012 μm vs. 0.087 ± 0.008 μm). The preservation of bioactive properties of SIS hydrogel was assessed by detecting bioactive molecules sensitive to processing and enzyme digestion, such as growth factors fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta 1 (TGF-β1), with enzyme-linked immunosorbent assay. ACLFs were isolated and expanded in culture from explants of rat ACLs (n = 3). The cells were then seeded on the hydrogels and cultured with 0%, 1%, and 10% foetal bovine serum (FBS) for 3 days and 7 days. Cell attachment was observed using a light microscope and scanning electron microscopy, whereas cell proliferation and matrix production (collagen types I and III) were examined with bromodeoxyuridine assays and reverse transcription-polymerase chain reaction, respectively. Results The results showed that FGF-2 and TGF-β1 in the SIS hydrogel were preserved by 50% (65.9 ± 26.1 ng/g dry SIS) and 90% (4.4 ± 0.6 ng/g dry SIS) relative to their contents in ECM-SIS sheets, respectively. At Day 3 of culture, ACLFs on the SIS hydrogel were found to proliferate 39%, 31%, and 22% more than those on the pure collagen hydrogel at 0%, 1%, and 10% FBS, respectively (p < 0.05). Collagen type I mRNA expression was increased by 150%, 207%, and 100%, respectively, compared to collagen hydrogel (p < 0.05), whereas collagen type III mRNA expression was increased by 123% and 132% at 0% and 1% FBS, respectively (all p < 0.05) but not at 10% FBS. By Day 7, collagen type I mRNA expression was still elevated by 137% and 100% compared to collagen hydrogel at 1% and 10% FBS, respectively (p < 0.05). Yet, collagen type III mRNA levels were not significantly different between the two groups at any FBS concentrations. Conclusion Our data showed that the ECM-SIS hydrogel not only supported the growth of ACLFs, but also promoted their proliferation and matrix production relative to a pure collagen hydrogel. As such, ECM-SIS hydrogel has potential therapeutic value to facilitate ACL healing at the early stage after injury.

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.

Orthopaedic Research in the Year 2020

By the year 2020, it is anticipated that telemedicine will become widely available so that special medical and surgical expertise can be made available worldwide. Also, novel imaging technologies will further increase our diagnostic capabilities dramatically. These and other new technologies will no doubt enhance the diagnostic aspect of medicine. However, effective treatment of diseases will continue to be lacking as it is much slower and more challenging to develop. In other words, there will be huge opportunities for scientific and clinical investigators to reduce the gap between diagnosis and treatment. In this chapter, we will review the history of the practice of orthopaedic surgery and how fundamental research had helped surgeons and rehabilitation technologists, especially those involved in the practice of sports medicine. We will then give examples of current advances made on healing of tendons and ligaments especially those by functional tissue engineering and how it has played a major role in translating the laboratory findings to the clinics. Finally, as scientific research is becoming more sophisticated as well as multidisciplinary, we identify key areas of research that would deserve our focus and suggest how the specialty laboratories should be organized to conduct collaborative work effectively.

The Effect of Patellar Orientation on the Stiffness of the Porcine Femur-Medial Patellofemoral Ligament-Patella Complex

Patellar dislocation has an incidence of 5.8 per 100,000 per year in the US, and this number increases by five-fold for adolescents 1. Conservative management has been the preferred treatment, but recent follow-up studies have revealed a high redislocation rate. Similar outcomes were also found following primary repair of the medial patellofemoral ligament (MPFL) 2. As a result, replacement with soft tissue autografts has gained attention for recurrent patellar dislocations in recent years 2, 3. As such, the selection of an appropriate graft tissue will need the knowledge of the biomechanical properties of the FMPC, particularly its stiffness for the performance of the graft.Copyright

Extracellular Matrix Bioscaffolds to Enhance ACL Healing: Impact on the Contribution of the MCL to Joint Stability

A torn anterior cruciate ligament (ACL) of the knee has poor healing potential, and thus, surgical reconstruction using soft tissue autografts is needed to restore knee stability. Unfortunately, these procedures have a high incidence of donor site morbidity and the progression to osteoarthritis in the long-term 1. In recent years, biological stimulation by means of growth factors and bioscaffolds has demonstrated successful early clinical results 2. Our research center has used extracellular matrix (ECM) bioscaffolds as a biological agent to improve ACL healing in a goat model 7, 8. Indeed, there was sufficient formation of neo-ACL tissue that led to up to a 30% reduction in the instability of the stifle joint by 12 weeks. Its biomechanical properties also increased by two-fold in comparison to those with suture repair alone 7, 8.© 2011 ASME