Height restoration and sustainability using bilateral vertebral augmentation systems for vertebral compression fractures: a cadaveric study.

BACKGROUND CONTEXT: The treatment of vertebral compression fractures using percutaneous augmentation is an effective method to reduce pain and decrease mortality rates. Surgical methods include vertebroplasty, kyphoplasty, and vertebral augmentation with implants. A previous study suggested that a titanium implantable vertebral augmentation device (TIVAD) produced superior height restoration compared to balloon kyphoplasty (BKP) but was based on a less clinically relevant biomechanical model. Moreover, the introduction of high pressure balloons and directional instruments may further aid in restoring height. PURPOSE: The objective was to evaluate three procedures (BKP, BKP w/ Kyphon Assist (KA; directional instruments), and TIVAD) used for percutaneous augmentation of vertebral fractures with respect to height restoration and sustainability post-operatively. STUDY DESIGN/SETTING: This is an in vitro cadaver study performed in a laboratory setting. METHODS: Five osteoporotic female human cadaver thoracolumbar spines (age: 63-77 years, T-score: -2.5 to -3.5, levels: T7-S1) were scanned using computed tomography and dissected into 30 two-functional spine units (2FSUs). Vertebral wedge compression fractures were created by reducing the anterior height of the vertebrae by 25% and holding the maximum displacement for 15 minutes. Post-fracture, surgery was performed on each 2FSU with a constant 100 N load. Surgeries included BKP, BKP w/ KA, or TIVAD (n=10 per treatment group). Post-surgery, cyclic loading was performed on each 2FSU for 10,000 cycles at 600 N (walking), followed by 5,000 cycles at 850 N (standing up/sitting down), and 5,000 cycles at 1250 N (lifting a 5-10kg weight from the floor). Fluoroscopic images were taken and analyzed at the initial, post-fracture, post-surgery, and post-loading timepoints. Anterior, central, and posterior heights, Beck Index, and angle between endplates were assessed. RESULTS: No difference in height restoration was observed among treatment groups (p=.72). Compared to the initial height, post-surgery anterior height was 96.3±8.7% for BKP, 94.0±10.0% for BKP w/ KA, and 95.3±5.8% for TIVAD. No difference in height sustainability in response to 600 N (p=.76) and 850 N (p=.20) load levels was observed among treatment groups. However, after 1250 N loading, anterior height decreased to 93.8±6.8% of the post-surgery height for BKP, 95.9±6.4% for BKP w/ KA, and 86.0±6.6% for TIVAD (p=.02). Specifically, the mean anterior height reduction between post-surgery and post-1250 N loading timepoints was lower for BKP w/ KA compared to TIVAD (p=.02), but not when comparing BKP to TIVAD (p=.07). No difference in Beck Index or angle between endplates was observed at any timepoint among the treatment groups. CONCLUSIONS: The present study, utilizing a clinically relevant biomechanical model, demonstrated equivalent height restoration post-surgery and at relatively lower-level cyclic loading using BKP, BKP w/ KA, and TIVAD, contrary to results from a previous study. Less anterior height reduction in response to high-level cyclic loading was observed in the BKP w/ KA group compared to TIVAD. CLINICAL SIGNIFICANCE: All three treatments can restore height similarly after a vertebral compression fracture, which may lead to pain reduction and decreased mortality. BKP w/ KA may exhibit less height loss in higher-demand patients who engage in physical activities that involve increased weight resistance.

Osseointegrative properties of electrospun hydroxyapatite-containing nanofibrous chitosan scaffolds.

Our long-term goal is to develop smart biomaterials that can facilitate regeneration of critical-size craniofacial lesions. In this study, we tested the hypothesis that biomimetic scaffolds electrospun from chitosan (CTS) will promote tissue repair and regeneration in a critical size calvarial defect. To test this hypothesis, we first compared in vitro ability of electrospun CTS scaffolds crosslinked with genipin (CTS-GP) to those of mineralized CTS-GP scaffolds containing hydroxyapatite (CTS-HA-GP), by assessing proliferation/metabolic activity and alkaline phosphatase (ALP) levels of murine mesenchymal stem cells (mMSCs). The cells' metabolic activity exhibited a biphasic behavior, indicative of initial proliferation followed by subsequent differentiation for all scaffolds. ALP activity of mMSCs, a surrogate measure of osteogenic differentiation, increased over time in culture. After 3 weeks in maintenance medium, ALP activity of mMSCs seeded onto CTS-HA-GP scaffolds was approximately two times higher than that of cells cultured on CTS-GP scaffolds. The mineralized CTS-HA-GP scaffolds were also osseointegrative in vivo, as inferred from the enhanced bone regeneration in a murine model of critical size calvarial defects. Tissue regeneration was evaluated over a 3 month period by microCT and histology (Hematoxylin and Eosin and Masson's Trichrome). Treatment of the lesions with CTS-HA-GP scaffolds induced a 38% increase in the area of de novo generated mineralized tissue area after 3 months, whereas CTS-GP scaffolds only led to a 10% increase. Preseeding with mMSCs significantly enhanced the regenerative capacity of CTS-GP scaffolds (by ∼3-fold), to 35% increase in mineralized tissue area after 3 months. CTS-HA-GP scaffolds preseeded with mMSCs yielded 45% new mineralized tissue formation in the defects. We conclude that the presence of HA in the CTS-GP scaffolds significantly enhances their osseointegrative capacity and that mineralized chitosan-based scaffolds crosslinked with genipin may represent a unique biomaterial with possible clinical relevance for the repair of critical calvarial bone defects.

Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering.

Reconstruction of large bone defects remains problematic in orthopedic and craniofacial clinical practice. Autografts are limited in supply and are associated with donor site morbidity while other materials show poor integration with the host's own bone. This lack of integration is often due to the absence of periosteum, the outer layer of bone that contains osteoprogenitor cells and is critical for the growth and remodeling of bone tissue. In this study we developed a one-step platform to electrospin nanofibrous scaffolds from chitosan, which also contain hydroxyapatite nanoparticles and are crosslinked with genipin. We hypothesized that the resulting composite scaffolds represent a microenvironment that emulates the physical, mineralized structure and mechanical properties of non-weight bearing bone extracellular matrix while promoting osteoblast differentiation and maturation similar to the periosteum. The ultrastructure and physicochemical properties of the scaffolds were studied using scanning electron microscopy and spectroscopic techniques. The average fiber diameters of the electrospun scaffolds were 227 ± 154 nm as spun, and increased to 335 ± 119 nm after crosslinking with genipin. Analysis by X-ray diffraction, Fourier transformed infrared spectroscopy and energy dispersive spectroscopy confirmed the presence of characteristic features of hydroxyapatite in the composite chitosan fibers. The Young's modulus of the composite fibrous scaffolds was 142 ± 13 MPa, which is similar to that of the natural periosteum. Both pure chitosan scaffolds and composite hydroxyapatite-containing chitosan scaffolds supported adhesion, proliferation and osteogenic differentiation of mouse 7F2 osteoblast-like cells. Expression and enzymatic activity of alkaline phosphatase, an early osteogenic marker, were higher in cells cultured on the composite scaffolds as compared to pure chitosan scaffolds, reaching a significant, 2.4 fold, difference by day 14 (p < 0.05). Similarly, cells cultured on hydroxyapatite-containing scaffolds had the highest rate of osteonectin mRNA expression over 2 weeks, indicating enhanced osteoinductivity of the composite scaffolds. Our results suggest that crosslinking electrospun hydroxyapatite-containing chitosan with genipin yields bio-composite scaffolds, which combine non-weight-bearing bone mechanical properties with a periosteum-like environment. Such scaffolds will facilitate the proliferation, differentiation and maturation of osteoblast-like cells. We propose that these scaffolds might be useful for the repair and regeneration of maxillofacial defects and injuries.