RESUMEN
BACKGROUND: Failure of surgical fixation in orthopaedic fractures occurs at a significantly higher rate in osteoporotic patients due to weakened osteoporotic bone. A therapy to acutely improve the mechanical properties of bone during fracture repair would have profound clinical impact. A previous study has demonstrated an increase in mechanical properties of acellular cortical canine bone after immersion in raloxifene. The goal of this study was to determine if similar treatment yields the same results in cancellous fetal bovine bone and whether this translates into a difference in screw pull-out strength in human cadaveric tissue. METHODS: Cancellous bone from fetal bovine distal femora underwent quasi-static four-point bending tests after being immersed in either raloxifene (20 µM) or phosphate-buffered saline as a control for 7 days (n = 10). Separately, 5 matched pairs of human osteoporotic cadaveric humeral heads underwent the same procedure. Five 3.5 mm unicortical cancellous screws were then inserted at standard surgical fixation locations to a depth of 30 mm and quasi-static screw pull-out tests were performed. RESULTS: In the four-point bending tests, there were no significant differences between the raloxifene and control groups for any of the mechanical properties - including stiffness (p = 0.333) and toughness (p = 0.546). In the screw pull-out tests, the raloxifene soaked samples and control samples had pullout strengths of 122 ± 74.3 N and 89.5 ± 63.8 N, respectively. CONCLUSIONS: Results from this study indicate that cancellous fetal bovine samples did not demonstrate an increase in toughness with raloxifene treatment, which is in contrast to previously published data that studied canine cortical bone. In vivo experiments are likely required to determine whether raloxifene will improve implant fixation.
Asunto(s)
Inmersión , Clorhidrato de Raloxifeno , Animales , Fenómenos Biomecánicos , Tornillos Óseos , Cadáver , Bovinos , Perros , Humanos , Ensayo de Materiales , Clorhidrato de Raloxifeno/farmacologíaRESUMEN
Focal cartilage injuries have poor intrinsic healing potential and often progress to osteoarthritis, a costly disease affecting almost a third of adults in the United States. To treat these patients, cartilage repair therapies often use cell-seeded scaffolds, which are limited by donor site morbidity, high costs, and poor efficacy. To address these limitations, we developed an electrospun cell-free fibrous hyaluronic acid (HA) scaffold that delivers factors specifically designed to enhance cartilage repair: Stromal Cell-Derived Factor-1α (SDF-1α; SDF) to increase the recruitment and infiltration of mesenchymal stem cells (MSCs) and Transforming Growth Factor-ß3 (TGF-ß3; TGF) to enhance cartilage tissue formation. Scaffolds were characterized in vitro and then deployed in a large animal model of full-thickness cartilage defect repair. The bioactivity of both factors was verified in vitro, with both SDF and TGF increasing cell migration, and TGF increasing matrix formation by MSCs. In vivo, however, scaffolds releasing SDF resulted in an inferior cartilage healing response (lower mechanics, lower ICRS II histology score) compared to scaffolds releasing TGF alone. These results highlight the importance of translation into large animal models to appropriately screen scaffolds and therapies, and will guide investigators towards alternative growth factor combinations. STATEMENT OF SIGNIFICANCE: This study addresses an area of orthopaedic medicine in which treatment options are limited and new biomaterials stand to improve patient outcomes. Those suffering from articular cartilage injuries are often destined to have early onset osteoarthritis. We have created a cell-free nanofibrous hyaluronic acid (HA) scaffold that delivers factors specifically designed to enhance cartilage repair: Stromal Cell-Derived Factor-1α (SDF-1α; SDF) to increase the recruitment and infiltration of mesenchymal stem cells (MSCs) and Transforming Growth Factor-ß3 (TGF-ß3; TGF) to enhance cartilage tissue formation. To our knowledge, this study is the first to evaluate such a bioactive scaffold in a large animal model and demonstrates the capacity for dual growth factor release.
Asunto(s)
Cartílago Articular , Nanofibras , Adulto , Animales , Quimiocina CXCL12 , Condrogénesis , Humanos , Ácido Hialurónico/farmacología , Modelos Animales , Andamios del Tejido , Factor de Crecimiento Transformador beta3RESUMEN
OBJECTIVE: Cartilage repair strategies have seen improvement in recent years, especially with the use of scaffolds that serve as a template for cartilage formation. However, current fixation strategies are inconsistent with regards to retention, may be technically challenging, or may damage adjacent tissues or the implant itself. Therefore, the goal of this study was to evaluate the retention and repair potential of cartilage scaffolds fixed with an easy-to-implement bioresorbable pin. DESIGN: Electrospun hyaluronic acid scaffolds were implanted into trochlear groove defects in 3 juvenile and 3 adult pigs to evaluate short-term retention (2 weeks; pin fixation vs. press-fit and fibrin fixation) and long-term repair (8 months; scaffold vs. microfracture), respectively. RESULTS: For the retention study, press-fit and fibrin fixation resulted in short-term scaffold dislodgment (n = 2 each), whereas pin fixation retained all scaffolds that were implanted (n = 6). Pin fixation did not cause any damage to the opposing patellar surface, and only minor changes in the subchondral bone were observed. For long-term repair, no differences were observed between microfracture and scaffold groups, in terms of second-look arthroscopy and indentation testing. On closer visualization with micro computed tomography and histology, a high degree of variability was observed between animals with regard to subchondral bone changes and cartilage repair quality, yet each Scaffold repair displayed similar properties to its matched microfracture control. CONCLUSIONS: In this study, pin fixation did not cause adverse events in either the short- or the long-term relative to controls, indicating that pin fixation successfully retained scaffolds within defects without inhibiting repair.
Asunto(s)
Enfermedades de los Cartílagos , Cartílago Articular , Animales , Enfermedades de los Cartílagos/patología , Cartílago Articular/patología , Cartílago Articular/cirugía , Condrogénesis , Porcinos , Andamios del Tejido , Microtomografía por Rayos XRESUMEN
The meniscus plays a central load-bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis (OA). In small animal models, progressive degenerative changes occur with the unloading of the meniscus via destabilization of the medial meniscus (DMM). However, few large animal models of DMM exist and the joint-wide initiation of the disease has not yet been defined in these models. Thus, the goal of this study is to develop and validate a large animal model of surgically induced DMM and to use multimodal (mechanical, histological, and magnetic resonance imaging) and multiscale (joint to tissue level) quantitative measures to evaluate degeneration in both the meniscus and cartilage. DMM was achieved using an arthroscopic approach in 13 Yucatan minipigs. One month after DMM, joint contact area decreased and peak pressure increased, indicating altered load transmission as a result of meniscus destabilization. By 3 months, the joint had adapted to the injury and load transmission patterns were restored to baseline, likely due to the formation and maturation of a fibrovascular scar at the anterior aspect of the meniscus. Despite this, we found a decrease in the indentation modulus of the tibial cartilage and an increase in cartilage histopathology scores at 1 month compared to sham-operated animals; these deleterious changes persisted through 3 months. Over this same time course, meniscus remodeling was evident through decreased proteoglycan staining in DMM compared to sham menisci at both 1 and 3 months. These findings support that arthroscopic DMM results in joint degeneration in the Yucatan minipig and provide a new large animal testbed in which to evaluate therapeutics and interventions to treat post-traumatic OA that originates from a meniscal injury.