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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.

Introduction: Sacral and presacral schwannomas are rare and account for a minority of spinal schwannomas. We aim to present our institution’s experience surgically treating sacral schwannomas over twenty-one years. Additionally, we assess the literature for surgical cases of sacral schwannomas to compare tumor characteristics and outcomes following resection.Methods: Data on demographics, presenting symptoms, lesion characteristics, surgical management, and outcomes were collected for 27 patients treated surgically for sacral or presacral schwannoma between 1997 and 2018 at all Mayo Clinic locations and compared to those of patients found in the literature. Results: We identified 31 studies in the literature containing 93 patients with sacral schwannoma treated surgically. Our patients and those in the literature experienced similar symptoms, with the most common symptom being pain and the least common being sexual dysfunction, and age at diagnosis. Most of our patients (59.3%) reported full recovery from preoperative symptoms, while a minority reported a partial recovery (33.3%) and no recovery (11.1%). A smaller percentage of patients found 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%).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 rate is high when the surgical approach towards sacral schwannomas is prepared and executed appropriately.

Supplementary Information, Figure 1 from Targeted Delivery of Gemcitabine to Pancreatic Adenocarcinoma Using Cetuximab as a Targeting Agent

One of the key challenges in anticancer therapy is the toxicity and poor bioavailability of the anticancer drugs. Nanotechnology can play a pivotal role by delivering drugs in a targeted fashion to the malignant cells that will reduce the systemic toxicity of the anticancer drug. In this report, we show a stepwise development of a nanoparticle-based targeted delivery system for in vitro and in vivo therapeutic application in pancreatic cancer. In the first part of the study, we have shown the fabrication and characterization of the delivery system containing gold nanoparticle as a delivery vehicle, cetuximab as a targeting agent, and gemcitabine as an anticancer drug for in vitro application. Nanoconjugate was first characterized physico-chemically. In vitro targeting efficacy, tested against three pancreatic cancer cell lines (PANC-1, AsPC-1, and MIA Paca2) with variable epidermal growth factor receptor (EGFR) expression, showed that gold uptake correlated with EGFR expression. In the second part, we showed the in vivo therapeutic efficacy of the targeted delivery system. Administration of this targeted delivery system resulted in significant inhibition of pancreatic tumor cell proliferation in vitro and orthotopic pancreatic tumor growth in vivo. Tumor progression was monitored noninvasively by measuring bioluminescence of the implanted tumor cells. Pharmacokinetic experiments along with the quantitation of gold both in vitro and in vivo further confirmed that the inhibition of tumor growth was due to targeted delivery. This strategy could be used as a generalized approach for the treatment of a variety of cancers characterized by overexpression of EGFR. [Cancer Res 2008;68(6):1970–8]

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.

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

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.

The spinal cord has poor ability to regenerate after injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treat 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 chemistry on the other side. When the cells are cultured on OPF with the 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 the multichannel scaffold control, likely due to the greater number of axons growing across. Inflammation, scarring, and ECM deposits were equal across conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery.

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.

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.

Background and objectives Chordomas of the mobile spine (C1-L5) are rare malignant tumors. The purpose of this study was to review the outcome of surgical treatment for patients with primary mobile spine chordomas. Methods The oncologic outcomes and survival of 26 patients undergoing surgical resection for a primary mobile spine chordoma were assessed over a 25-year period. The mean follow-up was 12 ± 6 years. Results The 2-, 5-, and 10-year disease-free survivals were 95%, 61%, and 55%. The local recurrence-free survival was improved in patients receiving en bloc resection with negative margins (83% vs. 35%, p = 0.02) and similar in patients receiving adjuvant radiation therapy (43% vs. 45%, p = 0.30) at 10 years. Debulking of the tumor (hazard ratio [HR] = 6.41, p = 0.01) and a local recurrence (HR = 9.52, p = 0.005) were associated with death due to disease. Complications occurred in 19 (73%) patients, leading to reoperation in 9 (35%) patients; this rate was similar in intralesional and en bloc procedures. Conclusion Surgical resection of mobile spine chordomas is associated with a high rate of complications; however, en bloc resection can provide a hope for cure and appears to confer better oncologic outcomes for these tumors without an increase in complications compared to lesser resections.

Characterizing the release profile for materials-directed local delivery of bioactive molecules and its effect on bone regeneration is an important step to improve our understanding of, and ability to optimize, the bone healing response. This study examined the local delivery of parathyroid hormone (PTH) using a thiol-ene hydrogel embedded in a porous poly(propylene fumarate) (PPF) scaffold for bone regeneration applications. The aim of this study was to characterize the degradation-controlled in vitro release kinetics of PTH from the thiol-ene hydrogels, in vivo hydrogel degradation in a subcutaneous implant model, and bone healing in a rat critical size bone defect. Tethering PTH to the hydrogel matrix eliminated the early timepoint burst release that was observed in previous in vitro work where PTH was free to diffuse out of the matrix. Only 8% of the tethered PTH was released from the hydrogel during the first 2 weeks, but by day 21, 80% of the PTH was released, and complete release was achieved by day 28. In vivo implantation revealed that complete degradation of the hydrogel alone occurred by day 21; however, when incorporated in a three-dimensional printed osteoconductive PPF scaffold, the hydrogel persisted for >56 days. Treatment of bone defects with the composite thiol-ene hydrogel–PPF scaffold, delivering either 3 or 10 μg of tethered PTH 1-84, was found to increase bridging of critical size bone defects, whereas treatment with 30 μg of tethered PTH resulted in less bone ingrowth into the defect area. Continued development of this biomaterial delivery system for PTH could lead to improved therapies for treatment of nonunion fractures and critical size bone defects. IMPACT STATEMENT: Characterizing the release profile for materials-directed local delivery of bioactive molecules and its effect on bone regeneration is an important step to improve our understanding of, and ability to optimize, the bone healing response. The presented work details the effect of modifying the release of parathyroid hormone from a biomaterial scaffold on bone regeneration and preliminary work on the use of noninvasive imaging to monitor in vivo biomaterial scaffold degradation. These data provide a foundation for future studies aimed to understand and optimize the use of bioactive molecule delivery for bone regeneration and tissue engineering applications.

Study Design: A retrospective observational study.Purpose: Establish a quantifiable and reproducible measure of sarcopenia in patients undergoing lumbar spine surgery based on morphometric measurements from readily available preoperative computed tomography (CT) imaging. Overview of Literature: Sarcopenia—the loss of skeletal muscle mass—has been linked with poor outcomes in several surgical disciplines; however, a reliable and quantifiable measure of sarcopenia for future assessment of outcomes in spinal surgery patients has not been established.Methods: A cohort of 90 lumbar spine fusion patients were compared with 295 young, healthy patients obtained from a trauma da¬tabase. Cross-sectional vertebral body (VB) area, as well as the areas of the psoas and paravertebral muscles at mid-point of pedicles at L3 and L4 for both cohorts, was measured using axial CT imaging. Total muscle area-to-VB area ratio was calculated along with intraclass correlation coefficients for interobserver and intraobserver reliability. Finally, T-scores were calculated to help identify those patients with considerably diminished muscle-to-VB area ratios.Results: Both muscle mass and VB areas were considerably larger in males compared with those in females, and the ratio of these two measures was not enough to account for large differences. Thus, a gender-based comparison was made between spine patients and healthy control patients to establish T-scores that would help identify those patients with sarcopenia. The ratio for paravertebral muscle area-to-VB area at the L4 level was the only measure with good interobserver reliability, whereas the other three of the four ratios were moderate. All measurements had excellent correlations for intraobserver reliability.Conclusions: We postulate that a patient with a T-score

BACKGROUND Sacral tumor resections require a multidisciplinary approach to achieve a cure and a functional outcome. Currently, there is no accepted classification system that provides a means to communicate among the multidisciplinary teams in terms of approach, osseous resection, reconstruction, and acceptable functional outcome. The purpose of this study was to report the outcome of sacral tumor resection based on our classification system. METHODS In this study, 196 patients (71 female and 125 male) undergoing an oncologic en bloc sacrectomy were reviewed. The mean age (and standard deviation) was 49 ± 16 years, and the mean body mass index was 27.2 ± 6.4 kg/m. The resections included 130 sarcomas (66%). The mean follow-up was 7 ± 5 years. RESULTS Resections included total sacrectomy (Type 1A: 20 patients [10%]) requiring reconstruction, subtotal sacrectomy (Type 1B: 5 patients [3%]) requiring reconstruction, subtotal sacrectomy (Type 1C: 104 patients [53%]) not requiring reconstruction, hemisacrectomy (Type 2: 29 patients [15%]), external hemipelvectomy and hemisacrectomy (Type 3: 32 patients [16%]), total sacrectomy and external hemipelvectomy (Type 4: 5 patients [3%]), and hemicorporectomy (Type 5: 1 patient [1%]). The disease-specific survival was 66% at 5 years and 52% at 10 years. Based on the classification, the 5-year disease-specific survival was 34% for Type 1A, 100% for Type 1B, 71% for Type 1C, 65% for Type 2, 57% for Type 3, 100% for Type 4, and 100% for Type 5 (p < 0.001). Tumor recurrence occurred in 67 patients, including isolated local recurrence (14 patients), isolated metastatic disease (31 patients), and combined local and metastatic disease (22 patients). At 5 years, the local recurrence-free survival was 77% and the metastasis-free survival was 68%. Complications occurred in 153 patients (78%), most commonly wound complications (95 patients [48%]). Following the procedure, 154 patients (79%) were ambulatory, and the mean Musculoskeletal Tumor Society (MSTS93) score was 60% ± 23%. CONCLUSIONS Although resections of sacral malignancies are associated with complications, they can be curative in a majority of patients, with a majority of patients ambulatory with an acceptable functional outcome considering the extent of the resection. At our institution, this classification allows for communication between surgical teams and implies a surgical approach, staging, reconstruction, and potential functional outcomes. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Three-dimensional (3D) printing is a promising technology for tissue engineering. However, 3D-printing methods are limited in their ability to produce desired microscale features or electrochemical properties in support of robust cell adhesion, proliferation, and differentiation. This study addresses this deficiency by proposing an integrated, one-step, method to increase the cytocompatibility of 3D-printed scaffolds through functionalization leveraging conductive carbon nanotubes (CNTs). To this end, CNTs were first sonicated with water-soluble single-stranded deoxyribonucleic acid (ssDNA) to generate a negatively charged ssDNA@CNT nano-complex. Concomitantly, 3D-printed poly(propylene fumarate) (PPF) scaffolds were ammonolyzed to introduce free amine groups, which can take on a positive surface charge in water. The ssDNA@CNT nano-complex was then applied to 3D-printed scaffolds through a simple one-step coating utilizing electric-static force. This fast and facile functionalization step resulted in a homogenous and non-toxic coating of CNTs to the surface, which significantly improved the adhesion, proliferation, and differentiation of pre-osteoblast cells. In addition, the CNT based conductive coating layer enabled modulation of cell behavior through electrical stimuli (ES) leading to cellular proliferation and osteogenic gene marker expression, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Collectively, these data provide the foundation for a one-step functionalization method for simple, fast, and effective functionalization of 3D printed scaffolds that support enhanced cell adhesion, proliferation, and differentiation, especially when employed in conjunction with ES. STATEMENT OF SIGNIFICANCE: Three-dimensional (3D) printing is a promising technology for tissue engineering. However, 3D-printing methods have limited ability to produce desired features or electrochemical properties in support of robust cell behavior. To address this deficiency, the current study proposed an integrated, one-step method to increase the cytocompatibility of 3D-printed scaffolds through functionalization leveraging conductive carbon nanotubes (CNTs). This fast and facile functionalization resulted in a homogenous and non-toxic coating of CNTs to the surface, which significantly improved the adhesion, proliferation, and differentiation of cells on the 3D-printed scaffolds.

Retrospective cohort study. To determine whether patients who underwent surgical treatment of adolescent idiopathic scoliosis (AIS) in childhood would have an increased C-section risk in adulthood. Although the impact of scoliosis on future pregnancy and child delivery is a common question for patients and parents, there is limited data regarding pregnancy outcomes following childhood treatment of AIS. Between 1975 and 1992, 60 female patients underwent treatment for AIS with bracing, surgery, or observation and had data available regarding obstetrical history in the electronic medical record or in paper charts. In childhood, 28 had nonoperative treatment and 32 had fusion surgery. During the follow-up period, 2 nonoperative patients and 1 operative patient had fusion surgery in adulthood, but after childbearing years. Mean age at latest follow-up was 43 years (CI 38, 48). Meantime to follow-up since childhood treatment was 31 years (CI 26, 35). 29% of nonoperative patients had a C-section with at least one live birth compared to 38% of operative patients (p = 0.464). For surgical patients fused to L3 or lower, 46% required at least one C-section, compared to 32% of patients fused to L2 or higher (p = 0.40). Overall, 33% of the cohort of patients—including those with all scoliosis treatment methods—required at least one C-section, compared to the state weighted C-section rate of 20.5% (p = 0.014). The percentage of patients with operative treatment—including all levels of fusion—requiring at least one C-section was statistically different than the weighted state C-section rate (p = 0.020). In this long-term cohort of 60 US scoliosis patients, childhood operative fusion treatment was associated with a statistically significant increased incidence of C-section compared to the state incidence at both the patient level and the delivery level. III, comparative cohort study

The past few decades have seen a significant interest in the fumarate-based polymers for biomedical applications. Poly(caprolactone fumarate) (PCLF) and oligo[poly(ethylene glycol) fumarate] (OPF) ...

OBJECTIVEThe authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA).METHODSA retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment.RESULTSFifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1–4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2–46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from −2.4 ± 1.5 to −1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from −2.5 ± 1.1 to −2.3 ± 1.0 (p value = 0.31).CONCLUSIONSTeriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons’ subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors’ knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

Tissue engineering scaffolds have been used for curing bone defects. Poly(propylene fumarate) (PPF) is promising in bone tissue engineering. The ideal scaffolds should have high porosity and sufficient mechanical properties. In this comparative study, two models with cylindrical and spherical pore structures have been designed in the Abaqus software based on the pore opening size (L) to strut length (D) ratio (L/D). Structural analyses including compression, shear, and torsion simulation were performed using finite element analysis (FEA). Compression experiments on the PPF scaffolds fabricated using projection micro-stereolithography (PμSL) were conducted with digital image correlation (DIC). Fluid simulation was further performed to investigate the fluid permeability of the scaffolds. The porosity and surface area (Sp) to volume (Vt) ratio (Sp/Vt) are found to be generally larger in the spherical pore unit cells than in the cylindrical ones. At the same L/D or porosity, the cylindrical pore unit cells have higher compression/shear modulus with better stress distribution, higher torsional rigidity, and higher hydraulic permeability than the spherical ones. This research provides guidance to the design of bone tissue engineering scaffolds as the bulk properties and fluid permeability of the scaffolds could be adjusted by using different pore structures with varied microstructure parameters.

AimsOrthopaedic 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.MethodsWe 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).ResultsThere 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).ConclusionSupplementation 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.

A critical component of many tissue-engineered medical products (TEMPs) is the scaffold or biomaterial. The industry's understanding of scaffold properties and their influence on cell behavior has advanced, but our technical capability to reliably characterize scaffolds requires improvement, especially to enable large-scale manufacturing. In response to the key findings from the 2013 ASTM International Workshop of Standards and Measurements for Tissue Engineering Scaffolds, the National Institute of Standards and Technology (NIST), ASTM International, BiofabUSA, and the Standards Coordinating Body (SCB) organized a workshop in 2018 titled, "Characterization of Fiber-Based Scaffolds". The goal was to convene a group of 40 key industry stakeholders to identify major roadblocks in measurements of fiber-based scaffold properties. This report provides an overview of the findings from this collaborative workshop. The four major consensus findings were that (a) there is need for a documentary standard guide that would aid developers in the selection of test methods for characterizing fiber-based scaffolds; (b) there is a need for a strategy to assess the quality of porosity and pore size measurements, which could potentially be ameliorated by the development of a reference material; (b) there are challenges with the lexicon used to describe and assess scaffolds; and (d) the vast array of product applications makes it challenging to identify consensus test methods. As a result of these findings, a working group was formed to develop an ASTM Standard Guide for Characterizing Fiber-Based Constructs that will provide developers guidance on selecting measurements for characterizing fiber-based scaffolds.

BACKGROUND Local recurrence (LR) of sacral chordoma is a difficult problem and the mortality risk associated with LR remains poorly described. The purpose of this study was to evaluate the risk of mortality in patients with LR and determine if patient age is associated with mortality. METHODS A total of 218 patients (144 male, 69 female; mean age 59 ± 15 years) with sacrococcygeal chordomas were reviewed. Cumulative incidence functions and competing risks for death due to disease and nondisease mortality were employed to analyze mortality trends following LR. RESULTS The 10-year overall survival (OS) was 55%. Patients with LR had 44% 10-year OS, similar to patients without (59%; P = .38). The 10-year OS between those less than 55 compared with ≥55 years were similar (69% vs 48%; P = .52). The 10-year death due to disease was worse in patients with LR compared with those without (44% vs 84%; P

STUDY DESIGN A retrospective study. OBJECTIVES (1) To assess the reliability of using the posterior endplate valley (PEV) to predict the cranial-caudal location of the cervical pedicle intraoperatively; (2) to assess the impact of age on the cervical PEV-pedicle relationship, interpedicular distance, and foraminal height. SUMMARY OF BACKGROUND DATA The cervical pedicle, which is the anatomic landmark defining the boundaries of the foramen, is hidden from view intraoperatively in the anterior cervical approach, potentially leading to incomplete foraminal decompression. An intraoperative landmark which heralds the location of the pedicle and therefore can be relied upon as a guide for decompression has not been previously described. METHODS We retrospectively reviewed cervical computed tomography images of younger ( 50 y) patients. Using the coronal reconstructed image taken at the posterior margin of the vertebral body, we constructed a line between the superior aspect of the pedicles and measured the distance from this line to the PEV. Interpedicular distance and foraminal height were also measured. RESULTS One hundred patients were included in the final analysis. The mean distance (mm) from the pedicular line to the PEV from C3 to C7 respectively was 1.0±0.99, 0.01±0.76, 0.09±0.70, 0.20±0.71, and 0.27±0.79. No significant difference between young and elderly patients was noted (P

Cell encapsulation for treatment of diseases like type 1 diabetes (T1D) has great potential when used in combination with development of insulin responsive beta cells. However, for translation of this therapy into clinical practice, there is a need for suitable encapsulation devices. Here, we report development of polyurethane-zwitterionic acrylate double network-based membranes for macro device-based cell encapsulation. Polyurethane hydrogels with 60 to 90% water content (WC) were evaluated for permeability and hydrogels with 80 and 90% WC were found to have highest permeability. Structural characterization of these hydrogels’ samples prepared cryogenically by scanning electron microscopy (cryo-SEM) revealed that 90% WC hydrogels were nanoporous with large interconnected pores. Tuning of porosity and structure was achieved by blending of hydrogels with varying WC resulting in pores of ~ 200 nm size. These membranes supported viability of encapsulated cells after removal of cytotoxic leachables by ethanol treatment. Double network formation was performed by UV polymerization and incorporation of zwitterionic groups was confirmed by ATR and WC of hydrogels. Varying of zwitterion type is allowed for tuning of WC of hydrogels. Gene expression of RAW 264.7 macrophages on exposure to the hydrogels found the zwitterionic double network hydrogels to be less stimulating than the bare hydrogel. To determine translational potential of the hydrogel, sterilization of the hydrogels using supercritical carbon dioxide was evaluated. Survivor enumeration testing revealed that the kill rate for the process ~ 1 log10 per 8 min and 2-h treatment is sufficient for sterility assurance level (SAL) of 10−6. Thus, we have developed hydrogel polyurethane membranes suitable for cell encapsulation in macro devices. We want to develop a device for cell encapsulation which is needed for treating diseases like T1D. In these devices, cells will be loaded and implanted in the body. These encapsulated cell secretions would provide the function of various endocrine organs. We have developed a hydrogel-based nanoporous membrane which would hold the cells and allow for exchange of nutrients and cell secretions. After the development of membrane, future studies will focus on evaluating the immune response to the hydrogel as well as long term delivery of immune modulatory drugs to prevent fibrosis. Various drug encapsulation and delivery designs will be evaluated for controlled localized delivery of the drugs. The optimum combination would then be combined with the hydrogels device and test their efficacy in regulating cell viability and immune response in animal models.

BACKGROUND CONTEXT Surgical site infections (SSI) following spine surgery are debilitating complications to patients and costly to the healthcare system. PURPOSE Review the impact and cost effectiveness of 5 SSI prevention interventions on SSI rates in an orthopedic spine surgery practice at a major quaternary healthcare system over a 10-year period. STUDY DESIGN Retrospective observational study. PATIENT SAMPLE All of the surgical patients of the 5 spine surgeons in our department over a 10-year period were included in this study. OUTCOME MEASURES SSI rates per year, standardized infection ratios (SIR) for laminectomies and fusions during the most recent 3-year period, year of implementation, and frequency of use of the different interventions, cost of the techniques. METHODS The SSI prevention techniques described in this paper include application of intrawound vancomycin powder, wound irrigation with dilute betadine solution, preoperative chlorhexidine gluconate scrubs, preoperative screening with nasal swabbing, and decolonization of S. aureus, and perioperative antibiotic administration. Our institution's infection prevention and control data were analyzed for the yearly SSI rates for the orthopedic spine surgery department from 2006 to 2016. In addition, our orthopedic spine surgeons were polled to determine with what frequency and duration they have been using the different SSI prevention interventions. RESULTS SSI rates decreased from almost 6% per year the first year of observation to less than 2% per year in the final 6 years of this study. A SIR of less than 1.0 for each year was observed for laminectomies and fusions for the period from 2013 to 2016. All surgeons polled at our institution uniformly used perioperative antibiotics, Hibiclens scrub, and the nasal swab protocol since the implementation of these techniques. Some variability existed in the frequency and duration of betadine irrigation and application of vancomycin powder. A cost analysis demonstrated these methods to be nominal compared with the cost of treating a single SSI. CONCLUSIONS It is possible to reduce SSI rates in spine surgery with easy, safe, and cost-effective protocols, when implemented in a standardized manner.

Despite the wealth of innovation in the orthopaedic sciences, few technologies translate to clinical use. By way of a 2-day symposium titled "AAOS/ORS Translating Orthopaedic Technologies into Clinical Practice: Pathways from Novel Idea to Improvements in Standard of Care Research Symposium," key components of successful commercialization strategies were identified as a passionate entrepreneur working on a concept aimed at improving patient outcomes and decreasing the cost and burden of disease; a de-risking strategy that has due recognition of the regulatory approval process and associated costs while maximizing the use of institutional, state, and federal resources; and a well thought-out and prepared legal plan and high quality, protected intellectual property. Challenges were identified as a lack of education on the scale-up and commercialization processes; few opportunities to network, get feedback, and obtain funding for early stage ideas; disconnect between the intellectual property and the business model; and poor adoption of new technologies caused in part by un-optimized clinical trials. By leveraging the network of professional orthopaedic societies, there exists an opportunity to create an enlightened community of musculoskeletal entrepreneurs who are positioned to develop and commercialize technologies and transform patient care.

The spinal column is the most common site for bone metastasis. Vertebral metastases with instability have historically been treated with corpectomy of the affected vertebral body and adjacent intervertebral discs, and have more recently been treated with separation surgery. With demographics shifting towards an elderly population, a less-invasive surgical approach is necessary for the repair of vertebral defects. We modified a previously reported expandable hollow cage composed of an oligo[poly(ethylene glycol) fumarate] (OPF) containment system that could be delivered via a posterior-only approach. Then, the polymer of interest, poly (methyl methacrylate) (PMMA) bone cement, was injected into the lumen of the cage after expansion to form an OPF/PMMA cage. We compared six different cage formulations to account for vertebral body and defect size, and performed a cage characterization via expansion kinetics and mechanical testing evaluations. Additionally, we investigated the feasibility of the OPF/PMMA cage in providing spine stability via kinematic analyses. The in-vitro placement of the implant using our OPF/PMMA cage system showed improvement and mechanical stability in a flexion motion. The results demonstrated that the formulation and technique presented in the current study have the potential to improve surgical outcomes in minimally invasive procedures on the spine.

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.

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.

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.

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.

We report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES.