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Article: Daily low-intensity pulsed ultrasound stimulation mitigates joint degradation and pain in a post-traumatic osteoarthritis rat model.

Lee, Wonsae / Georgas, Elias / Komatsu, David E / Qin, Yi-Xian

2023 Volume 44, Page(s) 9–18

Abstract: Objectives: The aim of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) in a post-traumatic osteoarthritis (OA) rat model and : Methods: Thirty-eight male, four-month-old Sprague Dawley rats were randomly assigned ... ...

Abstract	Objectives: The aim of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) in a post-traumatic osteoarthritis (OA) rat model and Methods: Thirty-eight male, four-month-old Sprague Dawley rats were randomly assigned to Sham, Sham + US, OA, and OA + US. Sham surgery was performed to serve as a negative control, and anterior cruciate ligament transection was used to induce OA. Three days after the surgical procedures, Sham + US and OA + US animals received daily LIPUS treatment, while the rest of the groups received sham ultrasound (US) signals. Behavioral pain tests were performed at baseline and every week thereafter. After 31 days, the tissues were collected, and histological analyses were performed on knees and innervated dorsal root ganglia (DRG) neurons traced by retrograde labeling. Furthermore, to assess the activation of osteoclasts by LIPUS treatment, RAW264.7 cells were differentiated into osteoclasts and treated with LIPUS. Results: Joint degradation in cartilage and bone microarchitecture were mitigated in OA + US compared to OA. OA + US showed improvements in behavioral pain tests. A significant increase of large soma-sized DRG neurons was located in OA compared to Sham. In addition, a greater percentage of large soma-sized innervated neurons were calcitonin gene-related peptide-positive. Daily LIPUS treatment suppressed osteoclastogenesis Conclusion: Our findings demonstrate that early intervention using LIPUS treatment has protective effects from the progression of knee OA, including reduced tissue degradation, mitigated pain characteristics, improved subchondral bone microarchitecture, and less sensory innervation. Furthermore, daily LIPUS treatment has a suppressive effect on osteoclastogenesis, which may be linked to the suppression of sensory innervation in OA. The translational potential of this article: This study presents a new potential for early intervention in treating OA symptoms through the use of LIPUS, which involves the suppression of osteoclastogenesis and the alteration of DRG profiles. This intervention aims to delay joint degradation and reduce pain.
Language	English
Publishing date	2023-12-20
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2747531-1
ISSN	2214-031X
ISSN	2214-031X
DOI	10.1016/j.jot.2023.09.002
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Article ; Online: Bioactive superparamagnetic iron oxide-gold nanoparticles regulated by a dynamic magnetic field induce neuronal Ca

Georgas, Elias / Yuan, Muzhaozi / Chen, Jingfan / Wang, Ya / Qin, Yi-Xian

Bioactive materials

2023 Volume 26, Page(s) 478–489

Abstract: Treating neurodegenerative diseases, e.g., Alzheimer's Disease, remains a significant challenge due to the limited neuroregeneration rate in the brain. The objective of this study is to evaluate the hypothesis that external magnetic field (MF) ... ...

Abstract	Treating neurodegenerative diseases, e.g., Alzheimer's Disease, remains a significant challenge due to the limited neuroregeneration rate in the brain. The objective of this study is to evaluate the hypothesis that external magnetic field (MF) stimulation of nerve growth factor functionalized superparamagnetic iron oxide-gold (NGF-SPIO-Au) nanoparticles (NPs) can induce Ca
Language	English
Publishing date	2023-04-05
Publishing country	China
Document type	Journal Article
ISSN	2452-199X
ISSN (online)	2452-199X
DOI	10.1016/j.bioactmat.2023.01.007
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Article: MC3T3 infiltration and proliferation in bovine trabecular scaffold regulated by dynamic flow bioreactor and augmented by low-intensity pulsed ultrasound.

Moonga, Surinder S / Qin, Yi-Xian

Journal of orthopaedic translation

2018 Volume 14, Page(s) 16–22

Abstract: Background: Low-intensity pulsed ultrasound (LIPUS) has been used in both basic research and clinical settings for its therapeutic potential in promoting tissue healing. Clinical data has shown that LIPUS can accelerate fresh fracture healing. However, ... ...

Abstract	Background: Low-intensity pulsed ultrasound (LIPUS) has been used in both basic research and clinical settings for its therapeutic potential in promoting tissue healing. Clinical data has shown that LIPUS can accelerate fresh fracture healing. However, the treatment for aging osteoporosis and non-union is still unclear. In addition, the mechanism of ultrasound promoted bone healing has remained unknown. Objective: It is proposed that noninvasive ultrasound treatment can enhance local fluid flow within the tissue to initiate remodeling and regeneration. The goal of this study was to evaluate the effects of dynamic ultrasound in promoting cellular mechanotransduction within bioengineered organic scaffolds to trigger osteogenesis and mineralization. Methods: The experiment was designed in two-fold: to evaluate the role of LIPUS on osteoblastic-like (MC3T3) cell proliferation and mineralization in response to acoustic waves, using biomechanical rate-dependent signals in a bioreactor; and, to evaluate the new scaffold experimentation techniques, in order to generate a potential implantable biomaterial for orthopedic tissue regeneration and repair. Results: LIPUS treatment on MC3T3 cells yielded enhanced cellular mineralization (*p < 0.001) in 3-D scaffolding, but reduced the total cell numbers (p < 0.05), using Alizarin Red staining and cell counting analyses, respectively, in comparison to the control. Conclusion: This study suggests that LIPUS, if applied at proper frequency and duty cycle, can promote cell mineralization within the 3-D organic scaffold under The translational potential of this article: LIPUS stimulation was critical in contributing to the mechanical signaling transductions that activated bone enhancement parameters in MC3T3 cells regulated by bioreactor, and thus has potential to change how we pretreat scaffolds for orthopedic surgery and noninvasively accelerate healing in the future, e.g., in an extreme condition such as long-term space mission.
Language	English
Publishing date	2018-03-15
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2747531-1
ISSN	2214-031X
ISSN	2214-031X
DOI	10.1016/j.jot.2018.02.002
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Article ; Online: Calcium phosphate coatings enhance biocompatibility and degradation resistance of magnesium alloy: Correlating

Gao, Julia / Su, Yingchao / Qin, Yi-Xian

Bioactive materials

2020 Volume 6, Issue 5, Page(s) 1223–1229

Abstract: Magnesium (Mg) and its alloys are promising biodegradable materials for orthopedic applications. However, one of the major problems is their rapid degradation rate with quick evolution of hydrogen gas. To overcome this problem, calcium phosphate (CaP) ... ...

Abstract	Magnesium (Mg) and its alloys are promising biodegradable materials for orthopedic applications. However, one of the major problems is their rapid degradation rate with quick evolution of hydrogen gas. To overcome this problem, calcium phosphate (CaP) coatings have been used to improve the degradation resistance and the biocompatibility of Mg materials. This study focuses on the comparison and correlation of the
Language	English
Publishing date	2020-11-07
Publishing country	China
Document type	Journal Article
ISSN	2452-199X
ISSN (online)	2452-199X
DOI	10.1016/j.bioactmat.2020.10.024
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Article: Piezo1 channel activation in response to mechanobiological acoustic radiation force in osteoblastic cells.

Zhang, Guangdao / Li, Xiaofei / Wu, Lin / Qin, Yi-Xian

Bone research

2021 Volume 9, Issue 1, Page(s) 16

Abstract: Mechanobiological stimuli, such as low-intensity pulsed ultrasound (LIPUS), have been shown to promote bone regeneration and fresh fracture repair, but the fundamental biophysical mechanisms involved remain elusive. Here, we propose that a ... ...

Abstract	Mechanobiological stimuli, such as low-intensity pulsed ultrasound (LIPUS), have been shown to promote bone regeneration and fresh fracture repair, but the fundamental biophysical mechanisms involved remain elusive. Here, we propose that a mechanosensitive ion channel of Piezo1 plays a pivotal role in the noninvasive ultrasound-induced mechanical transduction pathway to trigger downstream cellular signal processes. This study aims to investigate the expression and role of Piezo1 in MC3T3-E1 cells after LIPUS treatment. Immunofluorescence analysis shows that Piezo1 was present on MC3T3-E1 cells and could be ablated by shRNA transfection. MC3T3-E1 cell migration and proliferation were significantly increased by LIPUS stimulation, and knockdown of Piezo1 restricted the increase in cell migration and proliferation. After labeling with Fluo-8, MC3T3-E1 cells exhibited fluorescence intensity traces with several high peaks compared with the baseline during LIPUS stimulation. No obvious change in the fluorescence intensity tendency was observed after LIPUS stimulation in shRNA-Piezo1 cells, which was similar to the results in the GsMTx4-treated group. The phosphorylation ratio of ERK1/2 in MC3T3-E1 cells was significantly increased (P < 0.01) after LIPUS stimulation. In addition, Phalloidin-iFluor-labeled F-actin filaments immediately accumulated in the perinuclear region after LIPUS stimulation, continued for 5 min, and then returned to their initial levels at 30 min. These results suggest that Piezo1 can transduce LIPUS-induced mechanical signals into intracellular calcium. The influx of Ca
Language	English
Publishing date	2021-03-10
Publishing country	China
Document type	Journal Article
ZDB-ID	2803313-9
ISSN	2095-6231 ; 2095-4700
ISSN (online)	2095-6231
ISSN	2095-4700
DOI	10.1038/s41413-020-00124-y
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Article ; Online: Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Zhou, Juncen / Georgas, Elias / Su, Yingchao / Zhou, Jiayi / Kröger, Nadja / Benn, Felix / Kopp, Alexander / Qin, Yi-Xian / Zhu, Donghui

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2023 Volume 10, Issue 26, Page(s) e2302702

Abstract: Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most ... ...

Abstract	Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.
MeSH term(s)	Humans ; Biocompatible Materials ; Alloys ; Bone and Bones ; Prostheses and Implants ; Magnesium ; Titanium ; Zinc
Chemical Substances	Biocompatible Materials ; Alloys ; Magnesium (I38ZP9992A) ; Titanium (D1JT611TNE) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2023-07-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202302702
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Article ; Online: Engineered nanomedicine for neuroregeneration: light emitting diode-mediated superparamagnetic iron oxide-gold core-shell nanoparticles functionalized by nerve growth factor.

Yuan, Muzhaozi / Wang, Ya / Qin, Yi-Xian

Nanomedicine : nanotechnology, biology, and medicine

2019 Volume 21, Page(s) 102052

Abstract: This paper reports nerve growth factor functionalized superparamagnetic iron oxide-gold core-shell nanoparticles (NGF-SPIO-Au NPs), an engineered nanomedicine for non-invasive neuron regeneration when irradiated by a low-intensity light-emitting diode ( ... ...

Abstract	This paper reports nerve growth factor functionalized superparamagnetic iron oxide-gold core-shell nanoparticles (NGF-SPIO-Au NPs), an engineered nanomedicine for non-invasive neuron regeneration when irradiated by a low-intensity light-emitting diode (LED). NGF-SPIO-Au NPs of 20 μg/ml, were tested on PC-12 neuron-like cells, irradiated by LEDs (525 nm, 1.09, 1.44, and 1.90 mW/cm
MeSH term(s)	Animals ; Cell Adhesion Molecules/genetics ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Ferric Compounds/chemistry ; Ferric Compounds/pharmacology ; Gold/chemistry ; Humans ; Light ; Magnetite Nanoparticles/administration & dosage ; Magnetite Nanoparticles/chemistry ; Metal Nanoparticles/administration & dosage ; Metal Nanoparticles/chemistry ; Nanomedicine/trends ; Nerve Growth Factor/chemistry ; Nerve Growth Factor/pharmacology ; Nerve Regeneration/drug effects ; PC12 Cells ; Rats
Chemical Substances	Cell Adhesion Molecules ; Ferric Compounds ; Magnetite Nanoparticles ; ferric oxide (1K09F3G675) ; Gold (7440-57-5) ; Nerve Growth Factor (9061-61-4)
Language	English
Publishing date	2019-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2019.102052
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Article ; Online: Evaluation of nucleus pulposus fluid velocity and pressure alteration induced by cartilage endplate sclerosis using a poro-elastic finite element analysis.

Hassan, Chaudhry Raza / Lee, Wonsae / Komatsu, David Edward / Qin, Yi-Xian

Biomechanics and modeling in mechanobiology

2020 Volume 20, Issue 1, Page(s) 281–291

Abstract: The nucleus pulposus (NP) in the intervertebral disk (IVD) depends on diffusive fluid transport for nutrients through the cartilage endplate (CEP). Disruption in fluid exchange of the NP is considered a cause of IVD degeneration. Furthermore, CEP ... ...

Abstract	The nucleus pulposus (NP) in the intervertebral disk (IVD) depends on diffusive fluid transport for nutrients through the cartilage endplate (CEP). Disruption in fluid exchange of the NP is considered a cause of IVD degeneration. Furthermore, CEP calcification and sclerosis are hypothesized to restrict fluid flow between the NP and CEP by decreasing permeability and porosity of the CEP matrix. We performed a finite element analysis of an L3-L4 lumbar functional spine unit with poro-elastic constitutive equations. The aim of the study was to predict changes in the solid and fluid parameters of the IVD and CEP under structural changes in CEP. A compressive load of 500 N was applied followed by a 10 Nm moment in extension, flexion, lateral bending, and axial rotation to the L3-L4 model with fully saturated IVD, CEP, and cancellous bone. A healthy case of L3-L4 physiology was then compared to two cases of CEP sclerosis: a calcified cartilage endplate and a fluid constricted sclerotic cartilage endplate. Predicted NP fluid velocity increased for the calcified CEP and decreased for the calcified + less permeable CEP. Decreased NP fluid velocity was prominent in the axial direction through the CEP due to a less permeable path available for fluid flux. Fluid pressure and maximum principal stress in the NP were predicted to increase in both cases of CEP sclerosis compared to the healthy case. The porous medium predictions of this analysis agree with the hypothesis that CEP sclerosis decreases fluid flow out of the NP, builds up fluid pressure in the NP, and increases the stress concentrations in the NP solid matrix.
MeSH term(s)	Cartilage/diagnostic imaging ; Cartilage/physiopathology ; Elasticity ; Finite Element Analysis ; Humans ; Imaging, Three-Dimensional ; Intervertebral Disc/physiopathology ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/physiopathology ; Male ; Middle Aged ; Nucleus Pulposus/diagnostic imaging ; Nucleus Pulposus/physiopathology ; Permeability ; Porosity ; Pressure ; Reproducibility of Results ; Rheology ; Sclerosis/diagnostic imaging ; Sclerosis/physiopathology ; Stress, Mechanical ; Tomography, X-Ray Computed
Language	English
Publishing date	2020-09-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2093052-5
ISSN	1617-7940 ; 1617-7959
ISSN (online)	1617-7940
ISSN	1617-7959
DOI	10.1007/s10237-020-01383-8
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Article: Evolution of metallic cardiovascular stent materials: A comparative study among stainless steel, magnesium and zinc

Fu, Jiayin / Su, Yingchao / Qin, Yi-Xian / Zheng, Yufeng / Wang, Yadong / Zhu, Donghui

Biomaterials. 2020 Feb., v. 230

2020

Abstract: A cardiovascular stent is a small mesh tube that expands a narrowed or blocked coronary artery. Unfortunately, current stents, regardless metallic or polymeric, still largely fall short to the ideal clinical needs due to late restenosis, thrombosis and ... ...

Abstract	A cardiovascular stent is a small mesh tube that expands a narrowed or blocked coronary artery. Unfortunately, current stents, regardless metallic or polymeric, still largely fall short to the ideal clinical needs due to late restenosis, thrombosis and other clinical complications. Nonetheless, metallic stents are preferred clinically thanks to their superior mechanical property and radiopacity to their polymeric counterparts. The emergence of bioresorbable metals opens a window for better stent materials as they may have the potential to reduce or eliminate late restenosis and thrombosis. In fact, some bioresorbable magnesium (Mg)-based stents have obtained regulatory approval or under trials with mixed clinical outcomes. Some major issues with Mg include the too rapid degradation rate and late restenosis. To mitigate these problems, bioresorbable zinc (Zn)-based stent materials are being developed lately with the more suitable degradation rate and better biocompatibility. The past decades have witnessed the unprecedented evolution of metallic stent materials from first generation represented by stainless steel (SS), to second generation represented by Mg, and to third generation represented by Zn. To further elucidate their pros and cons as metallic stent materials, we systematically evaluated their performances in vitro and in vivo through direct side-by-side comparisons. Our results demonstrated that tailored Zn-based material with proper configurations could be a promising candidate for a better stent material in the future.
Keywords	biocompatibility ; biocompatible materials ; comparative study ; coronary vessels ; magnesium ; mechanical properties ; polymers ; stainless steel ; thrombosis ; zinc
Language	English
Dates of publication	2020-02
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2019.119641
Database	NAL-Catalogue (AGRICOLA)

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Zs.B 2371: Show issues

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Article ; Online: Promoting neuroregeneration by applying dynamic magnetic fields to a novel nanomedicine: Superparamagnetic iron oxide (SPIO)-gold nanoparticles bounded with nerve growth factor (NGF).

Yuan, Muzhaozi / Wang, Ya / Qin, Yi-Xian

Nanomedicine : nanotechnology, biology, and medicine

2018 Volume 14, Issue 4, Page(s) 1337–1347

Abstract: Neuroregeneration imposes a significant challenge in neuroscience for treating neurodegenerative diseases. The objective of this study is to evaluate the hypothesis that the nerve growth factor (NGF) functionalized superparamagnetic iron oxide (SPIO)- ... ...

Abstract	Neuroregeneration imposes a significant challenge in neuroscience for treating neurodegenerative diseases. The objective of this study is to evaluate the hypothesis that the nerve growth factor (NGF) functionalized superparamagnetic iron oxide (SPIO)-gold (Au) nanomedicine can stimulate the neuron growth and differentiation under external magnetic fields (MFs), and dynamic MFs outperform their static counterparts. The SPIO-Au core-shell nanoparticles (NPs) (Diameter: 20.8 nm) possessed advantages such as uniform quasi-spherical shapes, narrow size distribution, excellent stabilities, and low toxicity (viability >96% for 5 days). NGF functionalization has enhanced the cellular uptake. The promotion of neuronal growth and orientation using NGF functionalized SPIO-Au NPs, driven by both the static and dynamic MFs, was revealed experimentally on PC-12 cells and theoretically on a cytoskeletal force model. More importantly, dynamic MFs via rotation performed better than the static ones, i.e., the cellular differentiation ratio increased 58%; the neurite length elongation increased 63%.
MeSH term(s)	Animals ; Ferric Compounds/chemistry ; Gold/chemistry ; Magnetic Fields ; Magnetite Nanoparticles/chemistry ; Microscopy, Electron, Transmission ; Nanomedicine/methods ; Nerve Growth Factor/chemistry ; PC12 Cells ; Rats
Chemical Substances	Ferric Compounds ; Magnetite Nanoparticles ; ferric oxide (1K09F3G675) ; Gold (7440-57-5) ; Nerve Growth Factor (9061-61-4)
Language	English
Publishing date	2018-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2018.03.004
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