Celecoxib-Loaded Electrospun Fibrous Antiadhesion Membranes Reduce COX-2/PGE2 Induced Inflammation and Epidural Fibrosis in a Rat Failed Back Surgery Syndrome Model.

To date, failed back surgery syndrome (FBSS) remains a therapy-refractory clinical condition after spinal surgery. The antiadhesion membrane is applied to prevent FBSS by isolating fibrosis; however, the inflammation stimulated by the foreign body and surgical trauma needs to be further resolved simultaneously. Therefore, we developed new electrospun polycaprolactone (PCL) fibrous membranes loaded with celecoxib (CEL) to prevent fibrosis and inflammation associated with FBSS. The CEL-loaded PCL fibers were randomly distributed, and the drug was released over two weeks. Fluorescence micrographs revealed that the fibroblasts proliferated less on the PCL-CEL fibrous membranes than in the PCL group and the blank control. In the rat laminectomy model after 4 weeks, magnetic resonance imaging of epidural fibrosis was least in the PCL-CEL group. Expression of COX-2 and PGE2 was lower in the PCL-CEL group. It concluded that the CEL-loaded PCL membrane could reduce fibrosis and inflammation in a rat model of FBSS via COX-2/PGE2 signaling pathways.

Metformin-grafted polycaprolactone nanoscaffold targeting sensory nerve controlled fibroblasts reprograming to alleviate epidural fibrosis.

Epidural fibrosis (EF), associated with various biological factors, is still a major troublesome clinical problem after laminectomy. In the present study, we initially demonstrate that sensory nerves can attenuate fibrogenic progression in EF animal models via the secretion of calcitonin gene-related peptide (CGRP), suggesting a new potential therapeutic target. Further studies showed that CGRP could inhibit the reprograming activation of fibroblasts through PI3K/AKT signal pathway. We subsequently identified metformin (MET), the most widely prescribed medication for obesity-associated type 2 diabetes, as a potent stimulator of sensory neurons to release more CGRP via activating CREB signal way. We copolymerized MET with innovative polycaprolactone (PCL) nanofibers to develop a metformin-grafted PCL nanoscaffold (METG-PCLN), which could ensure stable long-term drug release and serve as favorable physical barriers. In vivo results demonstrated that local implantation of METG-PCLN could penetrate into dorsal root ganglion cells (DRGs) to promote the CGRP synthesis, thus continuously inhibit the fibroblast activation and EF progress for 8 weeks after laminectomy, significantly better than conventional drug loading method. In conclusion, this study reveals the unprecedented potential of sensory neurons to counteract EF through CGRP signaling and introduces a novel strategy employing METG-PCLN to obstruct EF by fine-tuning sensory nerve-regulated fibrogenesis.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFß) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFß/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

A predictive bone drilling force model for haptic rendering with experimental validation using fresh cadaveric bone.

PURPOSE: Bone drilling simulators with virtual and haptic feedback provide a safe, cost-effective and repeatable alternative to traditional surgical training methods. To develop such a simulator, accurate haptic rendering based on a force model is required to feedback bone drilling forces based on user input. Current predictive bone drilling force models based on bovine bones with various drilling conditions and parameters are not representative of the bone drilling process in bone surgery. The objective of this study was to provide a bone drilling force model for haptic rendering based on calibration and validation experiments in fresh cadaveric bones with different bone densities. METHODS: Using a commonly used drill bit geometry (2 mm diameter), feed rates (20-60 mm/min) and spindle speeds (4000-6000 rpm) in orthognathic surgeries, the bone drilling forces of specimens from two groups were measured and the calibration coefficients of the specific normal and frictional pressures were determined. RESULTS: The comparison of the predicted forces and the measured forces from validation experiments with a large range of feed rates and spindle speeds demonstrates that the proposed bone drilling forces can predict the trends and average forces well. CONCLUSION: The presented bone drilling force model can be used for haptic rendering in surgical simulators.

Tantalum-coated pedicle screws enhance implant integration.

Because titanium alloy (Ti) has the natural advantage of a low elastic modulus, it has become the most commonly used material for the manufacturing of pedicle screws. However, its poor shear strength and osteogenic ability are undesirable properties. The superior osteoinductivity demonstrated by tantalum (Ta) in oral and maxillofacial surgery and joint surgery leads us to assume that the tantalum-coated pedicle screws may have better osteogenic properties and bone anchoring strength. To verify this hypothesis, MC3T3-E1 cells and human mesenchymal stem cells (hBMSCs) were seeded on the surface of Ta and Ti disks to compare the effects of two different metals on cell adhesion, proliferation, and differentiation. At the same time, we observed the inhibitory effect of Ta on osteoclasts. As an in vivo study, conventional Ti pedicle screws and Ta-coated screws were implanted in bilateral pedicles of Bama pigs. The results showed that compared to titanium, tantalum promoted greater cell adhesion and proliferation and improved the level of hBMSC mineralization, and Ta-coated screws exerted an inhibitory effect on osteoclasts. More importantly, we found that the effect of tantalum on osteogenic differentiation was mediated through the Wnt/ß-catenin and TGF-ß/smad signaling pathways. Ta-coated screws significantly promoted trabecular bone growth compared with Ti as evidenced by micro-CT, histology and biomechanical examination. Our study clearly indicated that tantalum was a superior promoter of osteogenesis and proved that tantalum coating is an effective improvement for titanium alloy implants.

A comparison of the Gallie technique and casting versus the harms technique for the treatment of odontoid fractures.

OBJECTIVE: The objective of this study was to compare perioperative, clinical parameters, complications, and reoperation rate of the Gallie technique and head-neck-chest plaster with the Harms technique in the treatment of odontoid fractures. DESIGN: A retrospective study. SETTING: Level I spine center. PATIENTS: Fifty-seven patients with odontoid fractures treated either with the Gallie technique and casting or the Harms technique between July 2002 and June 2008. INTERVENTION: Surgery. MAIN OUTCOME MEASUREMENTS: At a minimum of 2-year follow-up, comparison of the two groups was conducted in terms of hospital stay, blood loss, operation time, cost of the first admission, total cost, time to fusion, time to return to previous occupation, Japanese Orthopedic Association scores, visual analog scale scores of neck pain, complications (nonunion, delayed union, hardware breakage, wound infection), and reoperation rate. RESULTS: There were no significant differences in terms of hospital stay, time to fusion, Japanese Orthopedic Association scores, neck pain visual analog scale scores, complications, or reoperation rate between the two groups. Blood loss, operation time, cost of the first admission, and total cost were significantly lower in the Gallie group than that in the Harms group. However, the Gallie group took longer to return to previous occupation than the Harms group (P < 0.001). CONCLUSIONS: Management of odontoid fractures by either the Gallie technique and casting or the Harms technique was found to be similar in clinical outcomes. Although the Harms technique was associated with more blood loss, operation time, and cost, the Harms technique was found to be superior to the Gallie technique with casting in terms of time to return to previous occupation.

Desmoplastic fibroma of the cervical spine: case report and review of the literature.

STUDY DESIGN: A case report and literature review are presented. OBJECTIVE: To present a rare case of desmoplastic fibroma (DF) in the cervical spine and discuss the diagnosis and treatment of this disorder. SUMMARY OF BACKGROUND DATA: DF is an extremely rare primary tumor of bone, especially in cervical spine. It is a benign but locally aggressive tumor of the connective tissue. It has a predilection for the mandible and the metadiaphyses of long bones. It has a propensity for local recurrence, especially after intralesional resection. METHODS: We report on a 70-year-old woman with a DF of the fourth and fifth cervical vertebrae. The patient complained of progressive neck pain and limitation of activity. After radiologic evaluation, a mass lesion was found on the fourth and fifth cervical vertebral bodies. A 2-level corpectomy with wide marginal resection of the tumor was performed through the anterior approach, and the histopathologic examination yielded the diagnosis of DF. Reconstruction was achieved with a long titanium mesh and locking plate with autologous iliac crest bone graft. RESULTS: After surgery, pain was completely relieved, and neurologic function was normal. The postoperative course was uneventful, and the patient has been well without recurrence for 35 months of follow-up evaluation. CONCLUSION: Patients with DF of the cervical spine may present with the arm and neck pain mimicking cervical disc disease. High index of suspicion by the clinicians must be practiced to make the appropriate diagnosis, and histologic confirmation of the diagnosis is essential. Surgical resection with wide margins is the preferred treatment.