Joseph R. O'Brien

3D nano/microfabrication techniques and nanobiomaterials for neural tissue regeneration

Injuries of the nervous system occur commonly among people of many different ages and backgrounds. Currently, there are no effective strategies to improve neural regeneration; however, tissue engineering provides a promising avenue for regeneration of many tissue types, including the neural context. Functional nerve conduits derived from tissue engineering techniques present bioengineered 3D artificial substitutes for implantation and rehabilitation of injured nerves. In particular, nanotechnology as a versatile vehicle to create biomimetic nanostructured tissue-engineered neural scaffolds provides great potential for the development of innovative and successful nerve grafts. Nanostructured conduits derived from traditional and novel tissue engineering techniques have been shown to be superior for successful neural function construction due to a high degree of biomimetic character. In this paper, we will focus on current progress in developing 3D nano/microstructured neural scaffolds via electrospinning, emerging 3D printing and self-assembly techniques, nanobiomaterials and bioactive cues for enhanced neural tissue regeneration.

Highly aligned nanocomposite scaffolds by electrospinning and electrospraying for neural tissue regeneration

Neural tissue engineering offers a promising avenue for repairing neural injuries. Advancement in nanotechnology and neural scaffold manufacturing strategies has shed light on this field into a new era. In this study, a novel tissue engineered scaffold, which possesses highly aligned poly-ε-caprolactone microfibrous framework and adjustable bioactive factor embedded poly (d, l-lactide-co-glycolide) core-shell nanospheres, was fabricated by combining electrospinning and electrospraying techniques. The fabricated nanocomposite scaffold has cell favorable nanostructured feature and improved hydrophilic surface property. More importantly, by incorporating core-shell nanospheres into microfibrous scaffold, a sustained bioactive factor release was achieved. Results show rat pheochromocytoma (PC-12) cell proliferation was significantly promoted on the nanocomposite scaffold. In addition, confocal microscope images illustrated that the highly aligned scaffold increased length of neurites and directed neurites extension along the fibers in both PC-12 and astrocyte cell lines, which indicates that the scaffold is promising for guiding neural tissue growth and regeneration. From the clinical editor: In an attempt to direct neural cell growth, biomimetic neural scaffold was produced by electrospinning integrated with co-axial electrospraying techniques. In-vitro data provided a framework for future designs for neuronal regeneration.

Feasibility of minimally invasive sacropelvic fixation: percutaneous S2 alar iliac fixation.

Study Design. A cadaveric study with postoperative computed tomography scan to evaluate instrumentation placement. Objective. To successfully place percutaneous sacropelvic instrumentation. Summary of Background Data. S2 iliac fixation has been in use clinically at some centers. Recently, anatomic data have been presented on the technique. The purpose of this study is to determine the feasibility of percutaneous placement of S2 iliac sacropelvic fixation (1) without damage to vital structures and (2) with in-line placement with S1 pedicle screws. Methods. Eight cadaveric spines were used in this study. Percutaneous pedicle screws were placed from L3–S1 in 4 and from L2–S1 in the remainder. Percutaneous S2 iliac screws were placed using a modification of the open technique. Rods were placed using minimally invasive techniques. All specimens were CT scanned. Trajectory of the screws was measured from CT scans. Maximal length was judged by a k-wire left in the S2 iliac screw. CT scans were critically evaluated for risks to visceral and neurovascular structures as well as cortical breaches. Results. Average length of the screws was 92.5 mm (range, 69–120 mm). No screw was intrapelvic or risked any visceral or neurovascular structure. No screws violated the cortex of the ilium. All S2 iliac screws were in-line with the S1 pedicle screws. The average cephalocaudad trajectory was 29° caudal from direct lateral. The average anterior-posterior angulation was 42° from a horizontal line connecting the PSIS. Conclusion. Use of the S2 iliac technique may be a viable option in minimally invasive thoracolumbar deformity surgery. The screws were all in-line and connected easily to the cephalad instrumentation. On average, a length of approximately 90 mm was attained. No visceral or neurovascular structure was injured. Visualization of the first dorsal foramen and a standard anteroposterior and inlet radiograph were used for placement.

Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds

The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.

An S-2 alar iliac pelvic fixation. Technical note.

Multiple techniques of pelvic fixation exist. Distal fixation to the pelvis is crucial for spinal deformity surgery. Fixation techniques such as transiliac bars, iliac bolts, and iliosacral screws are commonly used, but these techniques may require separate incisions for placement, leading to potential wound complications and increased dissection. Additionally, the use of transverse connector bars is almost always necessary with these techniques, as their placement is not in line with the S-1 pedicle screw and cephalad instrumentation. The S-2 alar iliac pelvic fixation is a newer technique that has been developed to address some of these issues. It is an in-line technique that can be placed during an open procedure or percutaneously.

The anatomic suitability of the C2 vertebra for intralaminar and pedicular fixation: a computed tomography study

BACKGROUND CONTEXT Several methods have been used to stabilize the atlantoaxial joint, including the use of C2 pedicle and laminar screws. No report has used computed tomography (CT) angiograms to compare the risk to the vertebral artery or assess the suitability for each fixation technique. PURPOSE To compare the suitability of C2 pedicle versus laminar screws using CT angiograms. STUDY DESIGN We retrospectively evaluated the anatomic dimensions of the C2 lamina and pedicle in 50 patients using CT angiograms. METHODS We retrospectively reviewed the last 50 patients admitted who underwent CT angiograms of the head and neck. Data recorded included the pedicle length and width and the laminar length and width. Vertebral artery anatomy was also assessed to determine if an aberrant location would preclude pedicle fixation. RESULTS Mean pedicle length and width were 15.5±3.5 and 4.7±1.7 mm, respectively, with 24% of patients having anatomy that would preclude 3.5-mm pedicle screw fixation. The mean lamina length and width were 25.2±3.6 and 5.5±1.4 mm, and more than 90% of patients could tolerate a 3.5-mm C2 laminar screw. CONCLUSION Preoperative CT angiography or noncontrast CT is an excellent method to delineate the anatomy at C2 to determine the suitability for pedicle or intralaminar fixation. In cases where vertebral artery anatomy precludes C2 pedicle fixation, more than 90% of patients may be a candidate for C2 intralaminar fixation.

OPEN REDUCTION OF C1-C2 SUBLUXATION WITH THE USE OF C1 LATERAL MASS AND C2 TRANSLAMINAR SCREWS

OBJECTIVE Spinal cord compression secondary to a subluxation of one vertebral body over another can be achieved with reduction of the translational deformity. Intraoperative reduction of C1–C2 subluxations can be technically challenging when one uses traditional techniques (e.g., wiring and transarticular screw fixation). The popularization of C1 lateral mass and C2 pedicle screws has allowed surgeons to achieve a more complex realignment at this region of the spine. Control of both C1 and C2 with independent fixation can be used to obtain reduction. In certain instances, placement of C2 pedicle screws is not possible. The use of C2 translaminar screws (if the C2 lamina is present and suitable) is an alternative method of fixation in C2 and can be used for intraoperative reduction. CLINICAL PRESENTATION A 15-year-old boy with juvenile rheumatoid arthritis presented with spinal cord compression secondary to a C1–C2 subluxation. The C2 pedicle anatomy precluded safe placement of C2 pedicle screws. An alternative method of fixation with the use of C2 translaminar screws and reduction was performed to obtain proper alignment and decompress the spinal cord. TECHNIQUE C1 lateral mass screws and C2 translaminar screws are inserted in the usual fashion. Two contoured rods, two rod holders, and two distractors, combined with C1 lateral mass screws and C2 translaminar screws, were used to achieve reduction. Concomitant distraction between the C2 translaminar screw head and the rod holder resulted in ventral translation of C2 on C1, decompressing the spinal cord. The reduction was maintained by tightening the C2 locking nut onto the rod. CONCLUSION The use of C2 translaminar screws (if the C2 lamina is present and suitable) is an alternative method of fixation in C2. C1 lateral mass and C2 translaminar screw fixation provide a powerful means of reducing C1–C2 subluxations and maintaining alignment, achieving indirect decompression of the spinal cord.

Comparison of computed tomography and plain radiography in assessing traumatic spinal deformity.

Study Design An imaging study assessing agreement between computed tomographic (CT) scans and plain radiographs when measuring acute thoracolumbar spinal deformity. Objective To compare the ability of the screening CT scans to measure spinal deformity in the thoracolumbar spine with that of portable plain radiographs. Summary of Background Data At the time of arrival at many trauma centers, patients undergo screening whole body CT as the initial imaging evaluation for trauma. The thoracolumbar spine is well visualized on both coronal and sagittal reconstructions. Methods Images of patients who underwent screening CT and portable supine plain radiography of thoracolumbar fractures were reviewed. Four observers, at 2 separate times, measured pathologic kyphosis and scoliosis on each image by using the Cobb method. Data were analyzed for statistical differences. Results In the sagittal plane, screening CT scans and plain radiographs showed an average mean difference of −1.13 degrees±SD of 3.76 degrees. In the coronal plane, CT scans and radiographs showed an average mean difference of 0.10 degrees±SD of 2.52 degrees. The interobserver correlation coefficients among the 4 observers were 0.913 in the sagittal plane and 0.953 in the lateral plane, indicating excellent interobserver correlation. Conclusions Screening CT demonstrates excellent correlation with plain radiography for measuring thoracolumbar spinal deformity in the coronal and sagittal planes for patients with trauma.

Complications, Readmissions, and Reoperations in Posterior Cervical Fusion.

Study Design. Retrospective cohort study of the American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2012. Objective. Minimizing the morbidity of posterior cervical fusion can be improved with identification of patient risk factors. Summary of Background Data. Posterior cervical fusion is an effective technique for treating a variety of pathology. Stability and neurological improvement have been well documented. The increasing frequency of these procedures necessitates further investigation into the factors that may negatively impact perioperative care. Methods. The American College of Surgeons National Surgical Quality Improvement Program was queried for all patients undergoing posterior cervical fusion in 2011 and 2012. Preoperative and intraoperative variables were investigated for correlation to complications, readmissions, prolonged intubation, reintubation, and reoperation. A frailty-based score was used to assess preoperative risk. Regression models for prediction were performed. Results. The study identified 5627 patients of posterior cervical fusion in 2011 and 2012. Of these, 2029 patients (36.1%) had any of our identified complications. Transfusion was the most common in 1482 (26.3%) patients. Excluding transfusion, the complication rate was 9.8%. Prolonged intubation greater than 48 hours occurred in 83 (1.5%) patients. Reintubation occurred in 72 (1.3%) patients. Readmission occurred in 398 (7.8%) patients. Reoperation was necessary in 273 (4.9%) patients with postoperative infection being the most common reason. The frailty-based score was shown to be predictive of any of the above events (P < 0.0001). The majority of patients (54.9%) in the group that had complications was found to have a frailty score of 1 or higher. Conclusion. The predictors for any event included female sex, increased surgical time, combined anterior-posterior procedures, preoperative inpatient status, diabetes, smoking, American Society of Anesthesiologists class 3 or higher, and increasing age. The frailty-based score is a viable option to predict morbidity in posterior cervical fusion. Level of Evidence: 3

Treatment of craniocervical instability using a posterior-only approach: report of 3 cases.

The object of this study was to demonstrate that a posterior-only approach for craniocervical junction pathology is feasible with intraoperative reduction. The authors reviewed 3 cases of craniocervical instability. All patients had craniocervical instability according to radiological imaging and various methods of measurement, with results outside the normal range. Posterior instrumentation aided the intraoperative reduction techniques while maintaining structural integrity and the desired fusion construct. No anterior approach was necessary in any of the patients. Neurological symptoms resolved in two patients and significantly improved in another. Follow-up imaging demonstrated stable constructs. There are many approaches to anterior cervical pathology at the craniocervical junction. Posterior instrumented reduction and stabilization of the occipitocervical spine can be safely achieved, obviating the need for a transoral approach in the setting of craniocervical junction settling.