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Article ; Online: A biomechanical approach to advances in sacropelvic reconstruction

Peter S Rose / Michael J Yaszemski / Franklin H Sim

Hamdan Medical Journal, Vol 11, Iss 4, Pp 193-

2018 Volume 197

Abstract: The sacrum is the only mechanical connection between the spine and pelvis/lower extremities. In the setting of a primary, or in select patients a locally advanced recurrent malignancy, curative treatment requires en-bloc sacrectomy. In addition to the ... ...

Abstract	The sacrum is the only mechanical connection between the spine and pelvis/lower extremities. In the setting of a primary, or in select patients a locally advanced recurrent malignancy, curative treatment requires en-bloc sacrectomy. In addition to the surgery in this area being challenging due to the complexity of the pelvic anatomy, adjacent visceral and vascular structures; spinal-pelvic continuity is often lost. Historically following sacral resection patients were left “un-reconstructed” and the spinal column floated between the remaining pelvis, forming a soft-tissue sling which can become painful and lead to a poor patient outcome. Our institution has pioneered a means to reconstruct these defects following high sacral resection in order to restore continuity between the spine, pelvis and femur which has been shown to improve patient outcomes. The purpose of this article is to describe a biomechanical approach to sacral reconstruction.
Keywords	biomechanics ; orthopaedic and plastic ; reconstruction ; sacral resection ; Medicine ; R
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Open-Spaced Ridged Hydrogel Scaffolds Containing TiO 2 -Self-Assembled Monolayer of Phosphonates Promote Regeneration and Recovery Following Spinal Cord Injury

Ahad M. Siddiqui / Frederic Thiele / Rachel N. Stewart / Simone Rangnick / Georgina J. Weiss / Bingkun K. Chen / Jodi L. Silvernail / Tammy Strickland / Jarred J. Nesbitt / Kelly Lim / Jean E. Schwarzbauer / Jeffrey Schwartz / Michael J. Yaszemski / Anthony J. Windebank / Nicolas N. Madigan

International Journal of Molecular Sciences, Vol 24, Iss 10250, p

2023 Volume 10250

Abstract: 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 ...

Abstract	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/mm 2 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.
Keywords	axon regeneration ; biomaterials ; immune cells ; machine learning ; mesenchymal stromal cells (MSCs) ; oligo(poly(ethylene glycol)) fumarate ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: OPF/PMMA Cage System as an Alternative Approach for the Treatment of Vertebral Corpectomy

Asghar Rezaei / Hugo Giambini / Alan L. Miller / Xifeng Liu / Benjamin D. Elder / Michael J. Yaszemski / Lichun Lu

Applied Sciences, Vol 10, Iss 6912, p

2020 Volume 6912

Abstract: 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 ...

Abstract	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.
Keywords	spine ; expandable cage ; kinematic testing ; minimally invasive surgery ; OPF formulation ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	621
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessment of Renal Osteodystrophy via Computational Analysis of Label-free Raman Detection of Multiple Biomarkers

Marian Manciu / Mario Cardenas / Kevin E. Bennet / Avudaiappan Maran / Michael J. Yaszemski / Theresa A. Maldonado / Diana Magiricu / Felicia S. Manciu

Diagnostics, Vol 10, Iss 2, p

2020 Volume 79

Abstract: Accurate clinical evaluation of renal osteodystrophy (ROD) is currently accomplished using invasive in vivo transiliac bone biopsy, followed by in vitro histomorphometry. In this study, we demonstrate that an alternative method for ROD assessment is ... ...

Abstract	Accurate clinical evaluation of renal osteodystrophy (ROD) is currently accomplished using invasive in vivo transiliac bone biopsy, followed by in vitro histomorphometry. In this study, we demonstrate that an alternative method for ROD assessment is through a fast, label-free Raman recording of multiple biomarkers combined with computational analysis for predicting the minimally required number of spectra for sample classification at defined accuracies. Four clinically relevant biomarkers: the mineral-to-matrix ratio, the carbonate-to-matrix ratio, phenylalanine, and calcium contents were experimentally determined and simultaneously considered as input to a linear discriminant analysis (LDA). Additionally, sample evaluation was performed with a linear support vector machine (LSVM) algorithm, with a 300 variable input. The computed probabilities based on a single spectrum were only marginally different (~80% from LDA and ~87% from LSVM), both providing an unacceptable classification power for a correct sample assignment. However, the Type I and Type II assignment errors confirm that a relatively small number of independent spectra (7 spectra for Type I and 5 spectra for Type II) is necessary for a p < 0.05 error probability. This low number of spectra supports the practicality of future in vivo Raman translation for a fast and accurate ROD detection in clinical settings.
Keywords	renal osteodystrophy ; statistical analysis ; raman spectroscopy ; label-free detection ; multiple biomarkers ; diagnostic devices ; artificial intelligence ; Medicine (General) ; R5-920
Subject code	310
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins

Ahad M. Siddiqui / Rosa Brunner / Gregory M. Harris / Alan Lee Miller / Brian E. Waletzki / Ann M. Schmeichel / Jean E. Schwarzbauer / Jeffrey Schwartz / Michael J. Yaszemski / Anthony J. Windebank / Nicolas N. Madigan

Biomedicines, Vol 9, Iss 479, p

2021 Volume 479

Abstract: 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 ... ...

Abstract	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.
Keywords	neuronal outgrowth ; cell attachment ; Schwann cells ; extracellular matrix ; scaffolds ; spinal cord ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker

Christine U. Lee / Matthew W. Urban / A. Lee Miller / Susheil Uthamaraj / James W. Jakub / Gina K. Hesley / Benjamin G. Wood / Nathan J. Brinkman / James L. Herrick / Nicholas B. Larson / Michael J. Yaszemski / James F. Greenleaf

European Radiology Experimental, Vol 6, Iss 1, Pp 1-

a comparative investigation

2022 Volume 6

Abstract: Abstract 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 ... ...

Abstract	Abstract 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.
Keywords	Artifact ; Porosity ; Polymethyl methacrylate ; Surface properties ; Ultrasonography ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	621
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RNA-dependent protein kinase is essential for 2-methoxyestradiol-induced autophagy in osteosarcoma cells.

Caihong Yang / Kristen L Shogren / Ribu Goyal / Dalibel Bravo / Michael J Yaszemski / Avudaiappan Maran

PLoS ONE, Vol 8, Iss 3, p e

2013 Volume 59406

Abstract: Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Surgical resection and adjunctive chemotherapy are the only widely available options of treatment for this disease. Anti-tumor compound 2-Methoxyestradiol (2-ME) ... ...

Abstract	Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Surgical resection and adjunctive chemotherapy are the only widely available options of treatment for this disease. Anti-tumor compound 2-Methoxyestradiol (2-ME) triggers cell death through the induction of apoptosis in osteosarcoma cells, but not in normal osteoblasts. In this report, we have investigated whether autophagy plays a role in 2-ME actions on osteosarcoma cells. Transmission electron microscopy imaging shows that 2-ME treatment leads to the accumulation of autophagosomes in human osteosarcoma cells. 2-ME induces the conversion of the microtubule-associated protein LC3-I to LC3-II, a biochemical marker of autophagy that is correlated with the formation of autophagosomes. Conversion to LC3-II is accompanied by protein degradation in 2-ME-treated cells. 2-ME does not induce autophagosome formation in normal primary human osteoblasts. In addition, 2-ME-dependent autophagosome formation in osteosarcoma cells requires ATG7 expression. Furthermore, 2-ME does not induce accumulation of autophagosomes in osteosarcoma cells that express dominant negative mutant RNA-dependent protein kinase (PKR) and are resistant to anti-proliferative and anti-tumor effects of 2-ME. Taken together, our study shows that 2-ME treatment induces PKR-dependent autophagy in osteosarcoma cells, and that autophagy could play an important role in 2-ME-mediated anti-tumor actions and in the control of osteosarcoma.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Newly regenerated axons via scaffolds promote sub-lesional reorganization and motor recovery with epidural electrical stimulation

npj Regenerative Medicine, Vol 6, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract 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 ... ...

Abstract	Abstract 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.
Keywords	Medicine ; R
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Controlled Delivery of Vancomycin via Charged Hydrogels.

Carl T Gustafson / Felix Boakye-Agyeman / Cassandra L Brinkman / Joel M Reid / Robin Patel / Zeljko Bajzer / Mahrokh Dadsetan / Michael J Yaszemski

PLoS ONE, Vol 11, Iss 1, p e

2016 Volume 0146401

Abstract: Surgical site infection (SSI) remains a significant risk for any clean orthopedic surgical procedure. Complications resulting from an SSI often require a second surgery and lengthen patient recovery time. The efficacy of antimicrobial agents delivered to ...

Abstract	Surgical site infection (SSI) remains a significant risk for any clean orthopedic surgical procedure. Complications resulting from an SSI often require a second surgery and lengthen patient recovery time. The efficacy of antimicrobial agents delivered to combat SSI is diminished by systemic toxicity, bacterial resistance, and patient compliance to dosing schedules. We submit that development of localized, controlled release formulations for antimicrobial compounds would improve the effectiveness of prophylactic surgical wound antibiotic treatment while decreasing systemic side effects. Our research group developed and characterized oligo(poly(ethylene glycol)fumarate)/sodium methacrylate (OPF/SMA) charged copolymers as biocompatible hydrogel matrices. Here, we report the engineering of this copolymer for use as an antibiotic delivery vehicle in surgical applications. We demonstrate that these hydrogels can be efficiently loaded with vancomycin (over 500 μg drug per mg hydrogel) and this loading mechanism is both time- and charge-dependent. Vancomycin release kinetics are shown to be dependent on copolymer negative charge. In the first 6 hours, we achieved as low as 33.7% release. In the first 24 hours, under 80% of total loaded drug was released. Further, vancomycin release from this system can be extended past four days. Finally, we show that the antimicrobial activity of released vancomycin is equivalent to stock vancomycin in inhibiting the growth of colonies of a clinically derived strain of methicillin-resistant Staphylococcus aureus. In summary, our work demonstrates that OPF/SMA hydrogels are appropriate candidates to deliver local antibiotic therapy for prophylaxis of surgical site infection.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells

Mamo, Tewodros / Andre J. van Wijnen / Ann C. Mladek / Avudaiappan Maran / Carl Gustafson / Jann N. Sarkaria / Kris L. Shogren / Mario Galindo / Michael J. Yaszemski / Scott M. Riester / Shiv K. Gupta

Biochemical and biophysical research communications. 2017 Apr. 29, v. 486

2017

Abstract: Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, ... ...

Abstract	Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PKCS), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PKCS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PKCS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells inÂ vitro. DNA-PKCS was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the G2/M transition point increased by 55% and 45%, while the percentage of cells with >20 Î³H2AX foci were enhanced by 59% and 107% for 143B and U2OS cells, respectively. These results indicate that the DNA-PKCS inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma.
Keywords	cell cycle ; DNA damage ; DNA repair ; humans ; osteosarcoma ; protein subunits ; survival rate
Language	English
Dates of publication	2017-0429
Size	p. 307-313.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2017.03.033
Database	NAL-Catalogue (AGRICOLA)

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