Citations 7

Bioorthogonal “Click Chemistry” Bone Cement Enables Pro-Translational Spinal Fusion in a Large Animal Sheep Model

ACS Biomaterials Science & Engineering | May 4, 2026 | Volume: 12 | Issue: 6 | Pages: 3054-3068

10.1021/acsbiomaterials.6c00348 | PMID 42080332

Evaluating longitudinal changes of gait parameters following shunt placement in patients with idiopathic normal pressure hydrocephalus

Journal of Neurosurgery | June 27, 2025 | Volume: 143 | Issue: 5 | Pages: 1254-1261

10.3171/2025.3.jns241416 | PMID 40513237

OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is characterized by gait deterioration, cognitive disturbances, and urinary incontinence. Gait deficits pose safety hazards due to frequent falls, yet objective investigations of gait improvement following ventriculoperitoneal shunt (VPS) placement are limited. Therefore, the aim of this study was to assess objective improvement in gait parameters for patients with iNPH after VPS placement. METHODS All patients treated with a VPS for iNPH by the senior author at a single tertiary care center from December 2017 to January 2023 were retrospectively reviewed. Patients who underwent detailed motion analysis testing before surgery with > 1 follow-up assessment were included. Analyzed parameters included gait velocity, gait cadence, stride length, stride width, gait stability ratio, total support, and single support. Time-dependent linear mixed-effects models and generalized additive mixed-effects models (GAMMs) were used to model short-term and longitudinal gait parameter changes, respectively. RESULTS A total of 212 patients (137 male, median age was 75.2 years) who underwent VPS placement for iNPH were included, with a total of 747 gait analyses performed at a median last-gait analysis follow-up duration of 12.0 months. Statistically significant changes in all gait parameter values were seen between the preoperative time point and first postoperative follow-up (within 3 months) time point (paired Wilcoxon p < 0.001), with a statistically significant majority of patients experiencing improvement (binominal p < 0.0001). Longitudinal analyses using a GAMM showed increased gait velocity, single support, and stride length, with decreased stability ratio, step width, and total support at early time points, while a plateau was achieved around 6 months. CONCLUSIONS A detailed gait analysis demonstrated significant improvements in objective ambulation metrics, particularly in the gait velocity, stride length, and gait stability ratio, following VPS placement in patients with iNPH. Most patients maintained marked improvement from baseline to the last follow-up assessment, although a plateau of the benefit was experienced over longer follow-up.
Impact of contrast administration and CT reconstruction plane on Hounsfield units for assessing underlying bone quality in the lumbar spine

Journal of Neurosurgery: Spine | December 14, 2024 | Volume: No volume available | Issue: No issue available | Pages: 1-9

10.3171/2024.8.spine24732 | PMID 39671592

OBJECTIVE Hounsfield units (HUs) may better predict biomechanical complications of instrumented fusion than conventional bone quality measures. Typically, noncontrast axial slices are used. This study aims to address the influence of reconstruction plane and contrast administration on measured HUs in patients undergoing lumbar spine imaging. METHODS Patients without prior spine surgery, infection, or tumor were identified for 3 groups: 1) 150 patients with high-resolution noncontrast lumbar CT, 2) 109 patients with noncontrast and contrast-enhanced lumbar CT, and 3) 100 patients with noncontrast lumbar CT and lumbar CT myelograms. Noncontrast HU measures in group 1 were compared between axial, sagittal, and coronal reconstructions. HU measures for groups 2 and 3 were compared on axial slice averages. HU measures between groups were compared using the Wilcoxon signed-rank test to investigate the presence of a statistically significant difference between groups (α = 0.05). Linear regression was also used to determine the degree of correlation between HU measures on noncontrast axial CT slices and HU measures on other sequences. RESULTS The mean patient age was 58.8 ± 15.9 years for group 1 (54.0% male), 65.5 ± 15.9 years for group 2 (61.5% male), and 65.2 ± 14.2 years (53.5% male) for group 3. Comparison of HU measures in group 1 showed significant differences across measurement modalities with the exception of axial average versus coronal average measures (p = 0.257) and sagittal average versus midsagittal measures (p = 0.726). There were significant differences in average axial HUs for each vertebral body between contrast and noncontrast lumbar CT and between CT myelography and noncontrast CT. Linear regression analysis demonstrated an extremely high correlation between measures for all methodologies (r2 = 0.950–0.986, all p < 0.001), and between contrast-enhanced and noncontrast studies (r2 = 0.870, p < 0.001). Measurements on CT myelography were significantly correlated with those in noncontrast studies, although to a lesser degree (r2 = 0.745, p < 0.001). CONCLUSIONS HU measures on noncontrast CT appear similar across multiple different planes, suggesting that a simpler methodology such as single-slice measurement on midsagittal reconstruction may allow for more rapid assessment of underlying bone quality. Consistent with prior work, contrast-enhanced CT sequences appear to reliably mirror underlying bone quality, although CT myelogram measures may vary in a more unpredictable way that precludes their use to interpret underlying bone quality. HU measures on contrast-enhanced studies are on average greater, suggesting the need for higher cutoff values.
Injectable bioactive poly(propylene fumarate) and polycaprolactone based click chemistry bone cement for spinal fusion in rabbits

Journal of Biomedical Materials Research Part A | April 22, 2024 | Volume: 112 | Issue: 10 | Pages: 1803-1816

10.1002/jbm.a.37725 | PMID 38644548

AbstractDegenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano‐hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano‐hydroxyapatite (nHA) and the released rhBMP‐2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.
Biodegradable poly(caprolactone fumarate) 3D printed scaffolds for segmental bone defects within the Masquelet technique

Journal of Orthopaedic Research | March 24, 2024 | Volume: 42 | Issue: 9 | Pages: 1974-1983

10.1002/jor.25839 | PMID 38522018

Abstract Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one‐stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4‐week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone‐specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen‐rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one‐stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical‐sized segmental bone defects, supporting their use in one‐stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP‐2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.
Bioactive Moldable Click Chemistry Polymer Cement with Nano-Hydroxyapatite and Growth Factor-Enhanced Posterolateral Spinal Fusion in a Rabbit Model

ACS Applied Bio Materials | March 19, 2024 | Volume: 7 | Issue: 4 | Pages: 2450-2459

10.1021/acsabm.4c00073 | PMID 38500414

Significant Reduction in Bone Density as Measured by Hounsfield Units in Patients with Ankylosing Spondylitis or Diffuse Idiopathic Skeletal Hyperostosis

Journal of Clinical Medicine | March 1, 2024 | Volume: 13 | Issue: 5 | Pages: 1430

10.3390/jcm13051430 | PMID 38592686

Background: Multisegmental pathologic autofusion occurs in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). It may lead to reduced vertebral bone density due to stress shielding. Methods: This study aimed to determine the effects of autofusion on bone density by measuring Hounsfield units (HU) in the mobile and immobile spinal segments of patients with AS and DISH treated at a tertiary care center. The mean HU was calculated for five distinct regions—cranial adjacent mobile segment, cranial fused segment, mid-construct fused segment, caudal fused segment, and caudal adjacent mobile segment. Means for each region were compared using paired-sample t-tests. Multivariable regression was used to determine independent predictors of mid-fused segment HUs. Results: One hundred patients were included (mean age 76 ± 11 years, 74% male). The mean HU for the mid-construct fused segment (100, 95% CI [86, 113]) was significantly lower than both cranial and caudal fused segments (174 and 108, respectively; both p < 0.001), and cranial and caudal adjacent mobile segments (195 and 115, respectively; both p < 0.001). Multivariable regression showed the mid-construct HUs were predicted by history of smoking (−30 HU, p = 0.009). Conclusions: HUs were significantly reduced in the middle of long-segment autofusion, which was consistent with stress shielding. Such shielding may contribute to the diminution of vertebral bone integrity in AS/DISH patients and potentially increased fracture risk.