Open-Spaced Ridged Hydrogel Scaffolds Containing TiO2-Self-Assembled Monolayer of Phosphonates Promote Regeneration and Recovery Following Spinal Cord Injury.

The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50-120 cells/mm2 in all conditions), scarring (5-10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10-20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery.

Outcomes of Recurrent Mobile Spine Chordomas.

INTRODUCTION: Chordomas of the mobile spine are rare malignant tumors. The purpose of this study was to review the outcomes of treatment for patients with recurrent mobile spine chordomas. METHODS: The oncologic outcomes and survival of 30 patients undergoing treatment of a recurrent mobile spine chordoma were assessed over a 24-year period. The mean follow-up was 3.5 years. RESULTS: In patients presenting with a recurrent mobile spine chordoma, the mean 2- and 5-year overall survival was 73% and 39%, respectively. Enneking appropriate resection trended toward improved overall survival at 5 years (100% vs. 32%, P = 0.24). Those undergoing surgical resection for recurrence had improved metastatic-free survival (hazard ratio 0.29, CI 0.08 to 0.99, P = 0.05). Positive margins were found to be a risk factor of further local recurrence (hazard ratio 7.92, CI 1.02 to 61.49, P = 0.04). Those undergoing nonsurgical management trended toward having an increase in new neurologic deficits (P = 0.09), however, there was no difference in overall complications based on treatment type (P = 0.13). CONCLUSION: Recurrent mobile spine chordoma portends a poor prognosis with an overall survival of less than 40% at 5 years. Surgical resection may help prevent new neurologic deficits and tumor metastasis while en bloc excision with negative surgical margins is associated with improved local recurrence-free survival.

Delayed open treatment of aortic penetration by a thoracic pedicle screw: illustrative case.

BACKGROUND: Iatrogenic aortic injury from pedicle screw malpositioning or anterior prominence in posterior spinal fusion represents a rare but potentially devasting complication. While intraoperative aortic injury is associated with hemodynamic instability, delayed presentations of pedicle screw aortic impingement or violation often present insidiously with pseudoaneurysm or vascular remodeling in clinically asymptomatic patients. Currently, there is a lack of guidance in the field for the recommended surveillance, urgency of operative intervention, and optimal surgical management of delayed pedicle screw aortic injuries. OBSERVATIONS: The following case study discusses the open treatment of delayed thoracic aortic penetration from an excessively long T12 pedicle screw in an asymptomatic adolescent patient with idiopathic scoliosis. The pedicle screw prominence anteriorly was corrected by burring the screw tip until it was flush with the vertebral body. The associated aortic injury was addressed with open vascular repair via primary anastomosis supplemented with a bovine pericardial patch. LESSONS: Complete aortic wall penetration from an excessively long thoracic pedicle screw with otherwise stable screw positioning may be addressed most effectively with a single anterior surgical approach for open aortic repair and screw tip burring.

Ultrasonographic Detection and Surgical Retrieval of a Nonmetallic Twinkle Marker in Breast Cancer: Pilot Study.

Purpose To evaluate the short-term safety of a nonmetallic twinkle marker and compare its conspicuity at color Doppler US with that of standard breast biopsy clips and radioactive seeds by using B-mode US in axillary lymph nodes. Materials and Methods This prospective study (November 2020-July 2021) of participants with node-positive breast cancer who completed chemotherapy involved placing a twinkle marker at the time of preoperative radioactive seed localization. A five-point scoring system (1 = easiest, 5 = most difficult) was used to rate the ease of identifying the clip, seed, and twinkle marker on postlocalization sonograms, mammograms, specimen radiographs, and gross pathologic specimens. Descriptive statistics were used. Results Eight women (mean age, 57 years ± 16 [SD]) were enrolled. The median scores for US conspicuity of each device were 3.9 (range, 3.7-5.0) for the radioactive seed, 2.4 (range, 1.0-5.0) for the clip, and 2.0 (range, 1.0-4.3) for the twinkle marker. In six of eight participants, the twinkle marker was the most identifiable at US. The seeds, clips, and twinkle markers were scored "very easy" to identify on seven of eight postlocalization mammograms. The surgeon retrieved all eight twinkle markers 1-3 days after localization. In all 16 interpretations, the seeds, clips, and twinkle markers were rated as very easy to identify on specimen radiographs. The clip was the most difficult device to identify at pathologic examination in all participants, and the twinkle marker was the easiest to identify in seven of eight participants. Conclusion This pilot study demonstrates that the safety and ease of US detection of a twinkling tissue marker may be comparable to a biopsy clip. Keywords: Ultrasonography, US-Doppler, Breast, Localization, Surgery Clinical trial registration no. NCT04674852 © RSNA, 2022.

At Mean 30-Year Follow-Up, Cervical Spine Disease Is Common and Associated with Thoracic Hypokyphosis after Pediatric Treatment of Adolescent Idiopathic Scoliosis.

Patients with adolescent idiopathic scoliosis (AIS) often have reduced sagittal thoracic kyphosis (hypokyphosis) and cervical lordosis causing an uneven distribution of physiologic load. However, the long-term consequences of hypokyphosis in AIS patients have not been previously documented. To evaluate whether uneven load distribution leads to future complications in patients with AIS, we conducted a retrospective chart review and subsequently surveyed 180 patients treated for idiopathic scoliosis between 1975 and 1992. These patients all had a minimum follow-up time of 20 years since their treatment. We observed a ten-fold increase in the incidence of anterior cervical discectomy and fusion (ACDF) compared to reported rates in the non-pathologic population. Out of the 180 patients, 33 patients met the criteria and returned for follow-up radiographs. This population demonstrated a statistically significant increased rate of cervical osteoarthritis and disc degeneration. Overall, our study suggests that hypokyphosis in patients with AIS presents with increased rates of cervical spine degeneration and dysfunction, suggesting that these patients may require additional follow-up and treatment.

Surgical management of sacral schwannomas: a 21-year mayo clinic experience and comparative literature analysis.

INTRODUCTION: Sacral and presacral schwannomas are rare, accounting for a minority of spinal schwannomas. We present our institution's experience surgically treating spinal schwannomas and compare it to the literature. METHODS: Data were collected for 27 patients treated surgically for sacral or presacral schwannoma between 1997 and 2018 at all Mayo Clinic locations and 93 patients in the literature. Kaplan-Meier disease-free survival analysis was conducted. Unpaired two-sample t tests and Fisher's exact tests assessed statistical significance between groups. RESULTS: Our patients and those in the literature experienced a similar age at diagnosis (49.9 y/o. vs 43.4 y/o., respectively). Most of our patients (59.3%) reported full recovery from symptoms, while a minority reported partial recovery (33.3%) and no recovery (11.1%). A smaller percentage in the literature experienced full recovery (31.9%) and partial recovery (29.8%) but also no recovery (1.1%). Our patients experienced fewer complications (14.8% versus 25.5%). Disease-free survival curves for all patients showed no significant variation in progression by extent of resection of schwannoma (log-rank P = 0.26). No lesion progression was associated with full or partial symptom improvement (p = 0.044), and female patients were more likely to undergo resection via a posterior approach (p = 0.042). CONCLUSION: Outcomes of patients with sacral or presacral schwannomas vary based on patient demographics, tumor characteristics, symptoms, and surgical treatment. Among the range of symptoms experienced by these patients, the most common is pain. Prognosis improves and overall survival is high when the surgical approach towards sacral schwannomas is prepared and executed appropriately.

Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker: a comparative investigation.

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored.

Newly regenerated axons via scaffolds promote sub-lesional reorganization and motor recovery with epidural electrical stimulation.

Here, we report the effect of newly regenerated axons via scaffolds on reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation (EES). Motor recovery was evaluated for 7 weeks after spinal transection and following implantation with scaffolds seeded with neurotrophin producing Schwann cell and with rapamycin microspheres. Combined treatment with scaffolds and EES-enabled stepping led to functional improvement compared to groups with scaffold or EES, although, the number of axons across scaffolds was not different between groups. Re-transection through the scaffold at week 6 reduced EES-enabled stepping, still demonstrating better performance compared to the other groups. Greater synaptic reorganization in the presence of regenerated axons was found in group with combined therapy. These findings suggest that newly regenerated axons through cell-containing scaffolds with EES-enabled motor training reorganize the sub-lesional circuitry improving motor recovery, demonstrating that neuroregenerative and neuromodulatory therapies cumulatively enhancing motor function after complete SCI.

Single-level subject-specific finite element model can predict fracture outcomes in three-level spine segments under different loading rates.

Osteoporosis-related vertebral compression fracture can occur under normal physiological activities. Bone metastasis is another source of vertebral fracture. Different loading rates, either high-energy traumas such as falls or low-energy traumas under normal physiological activities, can result in different fracture outcomes. The aim of the current study was to develop a quantitative computed tomography-based finite element analysis (QCT/FEA) technique for single vertebral bodies to predict fracture strength of three-level spine segments. Developed QCT/FEA technique was also used to characterize vertebral elastic moduli at two loading rates of 5 mm/min, representing a physiologic loading condition, and 12000 mm/min, representing a high-energy trauma. To this end, a cohort of human spine segments divided into three groups of intact, defect, and augmented were mechanically tested to fracture; then, experimental stiffness and fracture strength values were measured. Outcomes of this study showed no significant difference between the elastic modulus equations at the two testing speeds. Areal bone mineral density measured by dual x-ray absorptiometry (DXA/BMD) explained only 53% variability (R2 = 0.53) in fracture strength outcomes. However, QCT/FEA could explain 70% of the variability (R2 = 0.70) in experimentally measured fracture strength values. Adding disk degeneration grading, testing speed, and sex to QCT/FEA-estimated fracture strength values further increased the performance of our statistical model by 14% (adjusted R2 of 0.84 between the prediction and experimental fracture forces). In summary, our results indicated that a single-vertebra model, which is computationally less expensive and more time efficient, is capable of estimating fracture outcomes with acceptable performance (range: 70-84%).

RNA-dependent protein kinase is required for interferon-γ-induced autophagy in MG63 osteosarcoma cells.

Osteosarcoma is a bone tumor that mainly affects children and adolescents. Interferons (IFNs) have been shown to exert antitumor effects in osteosarcoma cells, although the molecular mechanisms have not been fully realized. We investigated IFN-γ actions on osteosarcoma cells. Our results show that IFN-γ induces the accumulation of autophagosomes in osteosarcoma cells. IFN-γ treatment leads to the conversion of autophagy marker light chain 3 (LC3)-I to LC3-II in osteosarcoma cells, and this conversion is accompanied by puncta formation. Also, IFN-γ-mediated induction of autophagosome formation and autophagic flux require RNA-dependent protein kinase (PKR) activity. In addition, our findings show that IFN-γ-mediated osteosarcoma cell death is not dependent on PKR. Our study suggests that IFN-γ has differential effects that lead to induction of cell death and autophagy in osteosarcoma cells. Further evaluation of the IFN-γ-mediated molecular mechanism could lead to improved understanding of and targeted treatment strategies for osteosarcoma.

Comparison of free vascularized fibular flaps and allograft fibular strut grafts to supplement spinopelvic reconstruction for sacral malignancies.

AIMS: Orthopaedic and reconstructive surgeons are faced with large defects after the resection of malignant tumours of the sacrum. Spinopelvic reconstruction is advocated for resections above the level of the S1 neural foramina or involving the sacroiliac joint. Fixation may be augmented with either free vascularized fibular flaps (FVFs) or allograft fibular struts (AFSs) in a cathedral style. However, there are no studies comparing these reconstructive techniques. METHODS: We reviewed 44 patients (23 female, 21 male) with a mean age of 40 years (SD 17), who underwent en bloc sacrectomy for a malignant tumour of the sacrum with a reconstruction using a total (n = 20), subtotal (n = 2), or hemicathedral (n = 25) technique. The reconstructions were supplemented with a FVF in 25 patients (57%) and an AFS in 19 patients (43%). The mean length of the strut graft was 13 cm (SD 4). The mean follow-up was seven years (SD 5). RESULTS: There was no difference in the mean age, sex, length of graft, size of the tumour, or the proportion of patients with a history of treatment with radiotherapy in the two groups. Reconstruction using an AFS was associated with nonunion (odds ratio 7.464 (95% confidence interval (CI) 1.77 to 31.36); p = 0.007) and a significantly longer mean time to union (12 months (SD 3) vs eight (SD 3); p = 0.001) compared with a reconstruction using a FVF. Revision for a pseudoarthrosis was more likely to occur in the AFS group compared with the FVF group (hazard ratio 3.84 (95% CI 0.74 to 19.80); p = 0.109); however, this was not significant. Following the procedure, 32 patients (78%) were mobile with a mean Musculoskeletal Tumor Society Score 93 of 52% (SD 24%). There was a significantly higher mean score in patients reconstructed with a FVF compared with an AFS (62% vs 42%; p = 0.003). CONCLUSION: Supplementation of spinopelvic reconstruction with a FVF was associated with a shorter time to union and a trend towards a reduced risk of hardware failure secondary to nonunion compared with reconstruction using an AFS. Spinopelvic fixation supplemented with a FVF is our preferred technique for reconstruction following resection of a sacral tumour. Cite this article: Bone Joint J 2021;103-B(8):1414-1420.

Injectable catalyst-free "click" organic-inorganic nanohybrid (click-ON) cement for minimally invasive in vivo bone repair.

Injectable polymers have attracted intensive attention in tissue engineering and drug delivery applications. Current injectable polymer systems often require free-radical or heavy-metal initiators and catalysts for the crosslinking process, which may be extremely toxic to the human body. Here, we report a novel polyhedral oligomeric silsesquioxane (POSS) based strain-promoted alkyne-azide cycloaddition (SPAAC) "click" organic-inorganic nanohybrids (click-ON) system that can be click-crosslinked without any toxic initiators or catalysts. The click-ON scaffolds supported excellent adhesion, proliferation, and osteogenesis of stem cells. In vivo evaluation using a rat cranial defect model showed outstanding bone formation with minimum cytotoxicity. Essential osteogenic alkaline phosphatase (ALP) and vascular CD31 marker expression were detected on the defect site, indicating excellent support of in vivo osteogenesis and vascularization. Using salt leaching techniques, an injectable porous click-ON cement was developed to create porous structures and support better in vivo bone regeneration. Beyond defect filling, the click-ON cement also showed promising application for spinal fusion using rabbits as a model. Compared to the current clinically used poly (methyl methacrylate) (PMMA) cement, this click-ON cement showed great advantages of low heat generation, better biocompatibility and biodegradability, and thus has great potential for bone and related tissue engineering applications.

3D Printing in alloy design to improve biocompatibility in metallic implants.

3D Printing (3DP) or additive manufacturing (AM) enables parts with complex shapes, design flexibility, and customization opportunities for defect specific patient-matched implants. 3DP or AM also offers a design platform that can be used to innovate novel alloys for application-specific compositional modifications. In medical applications, the biological response from a host tissue depends on a biomaterial's structural and compositional properties in the physiological environment. Application of 3DP can pave the way towards manufacturing innovative metallic implants, combining structural variations at different length scales and tailored compositions designed for specific biological responses. This study shows how 3DP can be used to design metallic alloys for orthopedic and dental applications with improved biocompatibility using in vitro and in vivo studies. Titanium (Ti) and its alloys are used extensively in biomedical devices due to excellent fatigue and corrosion resistance and good strength to weight ratio. However, Ti alloys' in vivo biological response is poor due to its bioinert surface. Different coatings and surface modification techniques are currently being used to improve the biocompatibility of Ti implants. We focused our efforts on improving Ti's biocompatibility via a combination of tantalum (Ta) chemistry in Ti, the addition of designed micro-porosity, and nanoscale surface modification to enhance both in vitro cytocompatibility and early stage in vivo osseointegration, which was studied in rat and rabbit distal femur models.

Teriparatide Treatment Increases Hounsfield Units in the Thoracic Spine, Lumbar Spine, Sacrum, and Ilium Out of Proportion to the Cervical Spine.

STUDY DESIGN: This was a retrospective chart review. OBJECTIVE: The objective of this study was to compare the effect of teriparatide on Hounsfield Units (HU) in the cervical spine, thoracic spine, lumbar spine, sacrum, and pelvis. Second, to correlate HU changes at each spinal level with bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA). SUMMARY OF BACKGROUND DATA: HU represent a method to estimate BMD and can be used either separately or in conjunction with BMD from DXA. MATERIALS AND METHODS: A retrospective chart review included patients who had been treated with at least 6 months of teriparatide. HU were measured in the vertebral bodies of the cervical, thoracic, and lumbosacral spine and iliac crests. Lumbar and femoral neck BMD as measured on DXA was collected when available. RESULTS: One hundred twenty-five patients were identified for analysis with an average age of 67 years who underwent a mean (±SD) of 22±8 months of teriparatide therapy. HU improvement in the cervical spine was 11% (P=0.19), 25% in the thoracic spine (P=0.002), 23% in the lumbar spine (P=0.027), 17% in the sacrum (P=0.11), and 29% in the iliac crests (P=0.09). Lumbar HU correlated better than cervical HU with BMD as measured on DXA. CONCLUSIONS: Teriparatide increased average HU in the thoracolumbar spine to a proportionally greater extent than the cervical spine. The cervical spine had a higher baseline starting HU than the thoracolumbar spine. Lumbar HU correlated better than cervical and thoracic HU with BMD as measured on DXA.

The inhibitory effects of vancomycin on rat bone marrow-derived mesenchymal stem cell differentiation.

OBJECTIVE: The use of intrawound vancomycin powder in spine surgery has been shown to decrease the rate of surgical site infections; however, the optimal dose is unknown. High-dose vancomycin inhibits osteoblast proliferation in vitro and may decrease the rate of solid arthrodesis. Bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent cells that are a source of osteogenesis in spine fusions. The purpose of this study was to determine the effects of vancomycin on rat BMSC viability and differentiation in vitro. METHODS: BMSCs were isolated from the femurs of immature female rats, cultured, and then split into two equal groups; half were treated to stimulate osteoblastic differentiation and half were not. Osteogenesis was stimulated by the addition of 50 µg/mL l-ascorbic acid, 10 mM ß-glycerol phosphate, and 0.1 µM dexamethasone. Vancomycin was added to cell culture medium at concentrations of 0, 0.04, 0.4, or 4 mg/mL. Early differentiation was determined by alkaline phosphatase activity (4 days posttreatment) and late differentiation by alizarin red staining for mineralization (9 days posttreatment). Cell viability was determined at both the early and late time points by measurement of formazan colorimetric product. RESULTS: Viability within the first 4 days decreased with high-dose vancomycin treatment, with cells receiving 4 mg/mL vancomycin having 40%-60% viability compared to the control. A gradual decrease in alizarin red staining and nodule formation was observed with increasing vancomycin doses. In the presence of the osteogenic factors, vancomycin did not have deleterious effects on alkaline phosphatase activity, whereas a trend toward reduced activity was seen in the absence of osteogenic factors when compared to osteogenically treated cells. CONCLUSIONS: Vancomycin reduced BMSC viability and impaired late osteogenic differentiation with high-dose treatment. Therefore, the inhibitory effects of high-dose vancomycin on spinal fusion may result from both reduced BMSC viability and some impairment of osteogenic differentiation.

CT-based structural analyses of vertebral fractures with polymeric augmentation: A study of cadaveric three-level spine segments.

Pathologic vertebral fractures due to metastasis can occur under normal physiologic activities, leading to pain and neurologic deficit. Prophylactic vertebroplasty is a technique used to augment vertebral strength and reduce the risk of fracture. Currently, no technique is available to objectively assess vertebral fracture risk in metastatically-involved vertebral bodies. The aim of the current study was to develop an image-based computational technique to estimate fracture force outcomes during bending. To this end, mechanical testing was performed on intact, simulated defect, PMMA-augmented, and PPF-augmented 3-level spine segments from both sexes under a compression/flexion-type loading condition. The augmentation performance of poly(methyl methacrylate) (PMMA) and poly(propylene fumarate) (PPF) were also evaluated and compared. Cylindrical defects were created in 3-level spine segments with attached posterior elements and ligaments. Using CT images of each segment, a rigidity analysis technique was developed and used for predicting fracture forces during bending. On average, PPF strengthened the segments by about 630 N, resulting in fracture forces similar to those observed in the intact and PMMA-augmented groups. Female spines fractured at about 1150 N smaller force than did male spines. Rigidity analysis, along with age, explained 66% variability in experimental outcomes. This number increased to 74% when vertebral size and age were added to the rigidity analysis as explanatory variables. Both PPF and PMMA similarly increased fracture strength to the level of intact specimens. The results suggest that PPF can be a suitable candidate for augmentation purposes and rigidity analysis can be a promising predicting tool for vertebral fracture forces.

Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins.

Spinal cord injury (SCI) results in cell death, demyelination, and axonal loss. The spinal cord has a limited ability to regenerate, and current clinical therapies for SCI are not effective in helping promote neurologic recovery. We have developed a novel scaffold biomaterial that is fabricated from the biodegradable hydrogel oligo(poly(ethylene glycol)fumarate) (OPF). We have previously shown that positively charged OPF scaffolds (OPF+) in an open spaced, multichannel design can be loaded with Schwann cells to support axonal generation and functional recovery following SCI. We have now developed a hybrid OPF+ biomaterial that increases the surface area available for cell attachment and that contains an aligned microarchitecture and extracellular matrix (ECM) proteins to better support axonal regeneration. OPF+ was fabricated as 0.08 mm thick sheets containing 100 µm high polymer ridges that self-assemble into a spiral shape when hydrated. Laminin, fibronectin, or collagen I coating promoted neuron attachment and axonal outgrowth on the scaffold surface. In addition, the ridges aligned axons in a longitudinal bipolar orientation. Decreasing the space between the ridges increased the number of cells and neurites aligned in the direction of the ridge. Schwann cells seeded on laminin coated OPF+ sheets aligned along the ridges over a 6-day period and could myelinate dorsal root ganglion neurons over 4 weeks. This novel scaffold design, with closer spaced ridges and Schwann cells, is a novel biomaterial construct to promote regeneration after SCI.

Three-dimensional surface strain analyses of simulated defect and augmented spine segments: A biomechanical cadaveric study.

While several studies have investigated fracture outcomes of intact vertebrae, fracture properties in metastatically-involved and augmented vertebrae are still far from understood. Consequently, this study was aimed to use 3D digital image correlation (3D-DIC) method to investigate the failure properties of spine segments with simulated metastatic lesions, segments augmented with poly(propylene fumarate) (PPF), and compare the outcomes with intact spines. To this end, biomechanical experiments accompanied by 3D-DIC were performed on spine segments consisting of three vertebrae and two intervertebral discs (IVDs) at loading rates of 0.083 mm/s, mimicking a physiological loading condition, and 200 mm/s, mimicking an impact-type loading condition such as a fall or an accident. Full-field surface strain analysis indicated PPF augmentation reduces the superior/inferior strain when compared with the defect specimens; Presence of a defect in the middle vertebra resulted in shear band fracture pattern. Failure of the superior endplates was confirmed in several defect specimens as the superior IVDs were protruding out of defects. The augmenting PPF showed lower superior/inferior surface strain values at the fast speed as compared to the slow speed. The results of our study showed a significant increase in the fracture force from slow to fast speeds (p = 0.0246). The significance of the study was to determine the fracture properties of normal, pathological, and augmented spinal segments under physiologically-relevant loading conditions. Understanding failure properties associated with either defect (i.e., metastasis lesion) or augmented (i.e., post-treatment) spine segments could potentially provide new insights on the outcome prediction and treatment planning. Additionally, this study provides new knowledge on the effect of PPF augmentation in improving fracture properties, potentially decreasing the risk of fracture in osteoporotic and metastatic spines.

Defining Spatial Relationships Between Spinal Cord Axons and Blood Vessels in Hydrogel Scaffolds.

Positively charged oligo(poly(ethylene glycol) fumarate) (OPF+) hydrogel scaffolds, implanted into a complete transection spinal cord injury (SCI), facilitate a permissive regenerative environment and provide a platform for controlled observation of repair mechanisms. Axonal regeneration after SCI is critically dependent upon nutrients and oxygen from a newly formed blood supply. Our objective was to investigate fundamental characteristics of revascularization in association with the ingrowth of axons into hydrogel scaffolds, thereby defining spatial relationships between axons and the neovasculature. A novel combination of stereologic estimates and precision image analysis techniques quantitate neurovascular regeneration in rats. Multichannel hydrogel scaffolds containing Matrigel-only (MG), Schwann cells (SCs), or SCs with rapamycin-eluting poly(lactic co-glycolic acid) microspheres (RAPA) were implanted for 6 weeks following complete spinal cord transection. Image analysis of 72 scaffold channels identified a total of 2494 myelinated and 4173 unmyelinated axons at 10 µm circumferential intervals centered around 708 individual blood vessel profiles. Blood vessel number, density, volume, diameter, intervessel distances, total vessel surface and cross-sectional areas, and radial diffusion distances were compared. Axon number and density, blood vessel surface area, and vessel cross-sectional areas in the SC group exceeded that in the MG and RAPA groups. Individual axons were concentrated within a concentric radius of 200-250 µm from blood vessel walls, in Gaussian distributions, which identified a peak axonal number (Mean Peak Amplitude) corresponding to defined distances (Mean Peak Distance) from each vessel, the highest concentrations of axons were relatively excluded from a 25-30 µm zone immediately adjacent to the vessel, and from vessel distances >150 µm. Higher axonal densities correlated with smaller vessel cross-sectional areas. A statistical spatial algorithm was used to generate cumulative distribution F- and G-functions of axonal distribution in the reference channel space. Axons located around blood vessels were definitively organized as clusters and were not randomly distributed. A scoring system stratifies 5 direct measurements and 12 derivative parameters influencing regeneration outcomes. By providing methods to quantify the axonal-vessel relationships, these results may refine spinal cord tissue engineering strategies to optimize the regeneration of complete neurovascular bundles in their relevant spatial relationships after SCI. Impact statement Vascular disruption and impaired neovascularization contribute critically to the poor regenerative capacity of the spinal cord after injury. In this study, hydrogel scaffolds provide a detailed model system to investigate the regeneration of spinal cord axons as they directly associate with individual blood vessels, using novel methods to define their spatial relationships and the physiologic implications of that organization. These results refine future tissue engineering strategies for spinal cord repair to optimize the re-development of complete neurovascular bundles in their relevant spatial architectures.

2D phosphorene nanosheets, quantum dots, nanoribbons: synthesis and biomedical applications.

Phosphorene, also known as black phosphorus (BP), is a two-dimensional (2D) material that has gained significant attention in several areas of current research. Its unique properties such as outstanding surface activity, an adjustable bandgap width, favorable on/off current ratios, infrared-light responsiveness, good biocompatibility, and fast biodegradation differentiate this material from other two-dimensional materials. The application of BP in the biomedical field has been rapidly emerging over the past few years. This article aimed to provide a comprehensive review of the recent progress on the unique properties and extensive medical applications for BP in bone, nerve, skin, kidney, cancer, and biosensing related treatment. The details of applications of BP in these fields were summarized and discussed.