3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures

Zhang, Weilin; Zhao, Wei; Qin, Li; Zhao, Duoyi; Qu, Junxing; Yuan, Ziyang; Chen, Zhihong; Zhu, Xuemei; Zhuang, Xiuli; Zhang, Zhiyu

doi:10.1186/s12951-021-01012-1

Cited by 19 publications

(19 citation statements)

References 55 publications

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“…Compared with amputation surgery, limb salvage has become a preferred option for osteosarcoma with the advancement of surgical technology and the neoadjuvant chemotherapy regimen and is reported to have a better 5-year OS rate (4, 5). Limb salvage rates for osteosarcoma continue to increase owing to constantly improved curation including neoadjuvant chemotherapy, ablation techniques, bone transport techniques, radiotherapy regimens (6), and computer navigation techniques (7)(8)(9)(10). There are many factors that may influence the choice of surgical methods between limb salvage and amputation (11): apart from the tumor mass volume (TMV) and tumor stage, the multidisciplinary approach involving imaging, meticulous surgical procedures may have a great influence on the surgery choice for pediatric osteosarcoma (12,13).…”

Section: Introductionmentioning

confidence: 99%

Mediating effect assessment of ifosfamide on limb salvage rate in osteosarcoma: A study from a single center in China

Zhang

et al. 2022

Front. Oncol.

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Osteosarcoma is one of the most prevalent primary bone malignancies in children and adolescents. Surgery and chemotherapy are the standard treatment methods of osteosarcoma. Methotrexate, adriamycin, and cisplatin, and methotrexate, adriamycin, cisplatin, and ifosfamide regimens are both first-line neoadjuvant chemotherapy regimens for osteosarcoma. Moreover, the use of ifosfamide is highly controversial. Most studies of ifosfamide focused on the overall survival rate and event-free survival rate; few studies concentrated on surgical options. We conducted this retrospective study to compare the baseline characteristic of amputation and limb salvage osteosarcoma patients. Furthermore, we analyzed the direct and indirect roles in surgical decision-making and found that ifosfamide may play a partial mediating role in the surgery option choice by mediating tumor mass volume change, tumor response, and the shortest distance from the center of main blood vessels to the margin of the tumor lesion.

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Section: Introductionmentioning

confidence: 99%

Mediating effect assessment of ifosfamide on limb salvage rate in osteosarcoma: A study from a single center in China

Zhang

et al. 2022

Front. Oncol.

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“…To further elucidate whether the mechanism of the neuroprotective effect of NOB is through inhibition of the Rho/ROCK signaling pathway, we established an OGD model of PC12 cells in vitro , examining the apoptosis, migration, cell viability and expression levels of related proteins after treatment of OGD PC12 cells with NOB, PA (an Rho/ROCK pathway agonist) ( 24 , 25 ) or NOB + PA. As shown in Figure 4 , the results revealed that the rate of apoptosis of PC12 cells in the NOB-treated group was less than that in the OGD model group. When treated with PA, apoptosis of OGD PC12 cells was accelerated, whereas treatment with NOB reduced PA-induced apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective effects of nobiletin on cerebral ischemia/reperfusion injury rats by inhibiting Rho/ROCK signaling pathway

Huang¹,

Qin²,

Lü³

et al. 2022

Ann Transl Med

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Background: Nobiletin (NOB), an active natural flavonoid component of citrus, is used in Traditional Chinese Medicine for its anti-inflammatory activity, but its efficacy in cerebral ischemia/reperfusion (I/R) injury remains unclear. Methods: In a middle cerebral artery occlusion (MCAO) rat model, MCAO rats were administered (Sham group and MCAO model group treated with an equal volume of solvent, NOB group treated with 10 or 20 mg/kg NOB) once a day for 7 days before cerebral ischemia and again after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining was applied to assess the infarct area. Neurological function was evaluated by the modified neurological severity score and Morris water maze. The levels of inflammatory factors, interleukin 6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), were examined by enzyme-linked immunosorbent assay (ELISA). Histopathological staining evaluated neuron apoptosis in brain tissue. In an oxygen-glucose deprivation PC12 cell (OGD PC12) model, the proliferation, migration and apoptosis of OGD PC12 cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and cell migration assays and flow cytometry. The gene and protein expression levels of Ras homolog gene family, member A (Rho A), ras-related C3 botulinum toxin substrate 1 (Rac 1), Rho-associated kinase 1 (ROCK 1), ROCK 2 in the Rho/ROCK pathway were measured by Realtime PCR (RT-PCR), immunohistochemistry and western blot.Results: In rats with cerebral I/R injury, NOB significantly decreased the infarcted area, neuron apoptosis in brain tissue and expressions of IL-6, IL-1β, and TNF-α. It also improved neurological deficits in brain tissue and enhanced learning and memory ability. Further, NOB had a protective effect on OGD PC12 cells, increasing proliferation and migration and decreasing apoptosis. The expressions of Rho A, Rac 1, ROCK 1 and ROCK 2 were high in cerebral I/R injury rats, but were downregulated by NOB in I/R injury rats' brain tissue and OGD PC12 cells.Conclusions: Nobiletin had a neuroprotective effect in rats with cerebral I/R injury, and its potential mechanism is decreasing neuron apoptosis by inhibiting the Rho/ROCK signaling pathway. These results suggest NOB is a promising neuroprotective agent for patients with cerebral ischemia.

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“…It is necessary to be more cautious in the choice of implant loading drugs, and further experiments are needed. In addition, scholars have paid more and more attention to melatonin in the treatment of bone tumors in recent years, but the use of melatonin in the local drug delivery of titanium implants is rare [ 115 ].…”

Section: Discussionmentioning

confidence: 99%

Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics

Gao

Zhao

et al. 2021

Nanomaterials

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Titanium implants have always been regarded as one of the gold standard treatments for orthopedic applications, but they still face challenges such as pain, bacterial infections, insufficient osseointegration, immune rejection, and difficulty in personalizing treatment in the clinic. These challenges may lead to the patients having to undergo a painful second operation, along with increased economic burden, but the use of drugs is actively solving these problems. The use of systemic drug delivery systems through oral, intravenous, and intramuscular injection of various drugs with different pharmacological properties has effectively reduced the levels of inflammation, lowered the risk of endophytic bacterial infection, and regulated the progress of bone tumor cells, processing and regulating the balance of bone metabolism around the titanium implants. However, due to the limitations of systemic drug delivery systems—such as pharmacokinetics, and the characteristics of bone tissue in the event of different forms of trauma or disease—sometimes the expected effect cannot be achieved. Meanwhile, titanium implants loaded with drugs for local administration have gradually attracted the attention of many researchers. This article reviews the latest developments in local drug delivery systems in recent years, detailing how various types of drugs cooperate with titanium implants to enhance antibacterial, antitumor, and osseointegration effects. Additionally, we summarize the improved technology of titanium implants for drug loading and the control of drug release, along with molecular mechanisms of bone regeneration and vascularization. Finally, we lay out some future prospects in this field.

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3D-printing magnesium–polycaprolactone loaded with melatonin inhibits the development of osteosarcoma by regulating cell-in-cell structures

Cited by 19 publications

References 55 publications

Mediating effect assessment of ifosfamide on limb salvage rate in osteosarcoma: A study from a single center in China

Mediating effect assessment of ifosfamide on limb salvage rate in osteosarcoma: A study from a single center in China

Neuroprotective effects of nobiletin on cerebral ischemia/reperfusion injury rats by inhibiting Rho/ROCK signaling pathway

Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics

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