Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects

A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of compositein vitroandin vivoand had potential application in bone regeneration.

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Bioglass-Incorporated Methacrylated Gelatin Cryogel for Regeneration of Bone Defects

Polymers ◽

10.3390/polym10080914 ◽

2018 ◽

Vol 10 (8) ◽

pp. 914 ◽

Cited By ~ 18

Author(s):

Song Kwon ◽

Seunghun Lee ◽

A. Sivashanmugam ◽

Janet Kwon ◽

Seung Kim ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Defects ◽

Micro Ct ◽

Defect Model ◽

Cranial Defect ◽

In Vivo Testing ◽

Regeneration Of Bone ◽

Adhesion Site

Cryogels have recently gained interest in the field of tissue engineering as they inherently possess an interconnected macroporous structure. Considered to be suitable for scaffold cryogel fabrication, methacrylated gelatin (GelMA) is a modified form of gelatin valued for its ability to retain cell adhesion site. Bioglass nanoparticles have also attracted attention in the field due to their osteoinductive and osteoconductive behavior. Here, we prepare methacrylated gelatin cryogel with varying concentration of bioglass nanoparticles to study its potential for bone regeneration. We demonstrate that an increase in bioglass concentration in cryogel leads to improved mechanical property and augmented osteogenic differentiation of mesenchymal cells during in vitro testing. Furthermore, in vivo testing in mice cranial defect model shows that highest concentration of bioglass nanoparticles (2.5 w/w %) incorporated in GelMA cryogel induces the most bone formation compared to the other tested groups, as studied by micro-CT and histology. The in vitro and in vivo results highlight the potential of bioglass nanoparticles incorporated in GelMA cryogel for bone regeneration.

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Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Journal of Tissue Engineering ◽

10.1177/2041731417712073 ◽

2017 ◽

Vol 8 ◽

pp. 204173141771207 ◽

Cited By ~ 28

Author(s):

Mathieu Maisani ◽

Daniele Pezzoli ◽

Olivier Chassande ◽

Diego Mantovani

Keyword(s):

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Critical Issue ◽

Bone Defects ◽

Bone Tissue Regeneration ◽

Differentiation Potential ◽

Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

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Biocompatible Mesoporous Silica–Polydopamine Nanocomplexes as MR/Fluorescence Imaging Agent for Light-Activated Photothermal–Photodynamic Cancer Therapy In Vivo

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.752982 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jiahui Lu ◽

Chen Ni ◽

Jie Huang ◽

Yawen Liu ◽

Yingkai Tao ◽

...

Keyword(s):

Magnetic Resonance ◽

Mesoporous Silica ◽

Fluorescence Imaging ◽

Colloidal Stability ◽

Silica Nanoparticle ◽

Photothermal Conversion ◽

Normal Tissues ◽

Irradiation Power

Conventional cancer phototherapy with single modality suffers from low therapeutic efficacy and undesired posttreatment damage for adjacent normal tissues. Therefore, the lower NIR laser irradiation power is vital to the reduction or preclusion of risk of scalds and burns in normal tissues. Herein, we rationally proposed a novel multifunctional nanocomplex, which enabled good magnetic resonance (MR) imaging contrast effect and promising photothermal conversion efficacy. The prepared core/shell nanocomplexes [MSN-Ce6@PDA (Mn)] were composed of chlorin e6-embedded mesoporous silica/nanoparticle composites as the cores, and then polydopamine and manganese ions were conjugated on the cores to form protective shells. The MSN-Ce6@PDA (Mn) nanocomplexes revealed superior properties in colloidal stability, photothermal conversion, reaction oxygen species generation, magnetic resonance imaging, etc. Under the guidance of MR and fluorescence imaging, these MSN-Ce6@PDA (Mn) nanocomplexes were found to be primarily accumulated in the MDA-MB-231 tumor area. Furthermore, the combined photodynamic and photothermal therapy exhibited strong inhibition to the growth of MDA-MB-231 tumor in vitro and in vivo. Besides, the MSN-Ce6@PDA (Mn) nanocomplexes also exhibited excellent biocompatibility and low damage to the healthy animals. Hence, the results demonstrated that the prepared MSN-Ce6@PDA (Mn) nanocomplex would be a promising potential for multimodal imaging-guided phototherapy.

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The Antistaphylococcal Activity of Amoxicillin/Clavulanic Acid, Gentamicin, and 1,8-Cineole Alone or in Combination and Their Efficacy through a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Osteomyelitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4271017 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Soukayna Hriouech ◽

Ahmed A. Akhmouch ◽

Aouatef Mzabi ◽

Hanane Chefchaou ◽

Mariam Tanghort ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Bone Marrow ◽

Synergistic Effect ◽

Clavulanic Acid ◽

Rabbit Model ◽

Methicillin Resistant ◽

Antistaphylococcal Activity ◽

Amoxicillin Clavulanic Acid

The aim of this research paper is to test the antistaphylococcal effect of 1,8-cineole, amoxicillin/clavulanic acid (AMC), and gentamicin, either separately or in combination against three Staphylococcus aureus strains isolated from patients suffering from osteomyelitis. This activity was tested in vitro by using the microdilution method and the checkerboard assay. The efficacy of these three antibacterial agents was then tested in vivo by using an experimental model of methicillin-resistant S. aureus osteomyelitis in rabbits. This efficacy was assessed after four days of treatment by counting the number of bacteria in the bone marrow. The obtained results in vitro showed that the combination of the AMC with gentamicin did not induce a synergistic effect, whereas the combination of the two antibiotics with 1,8-cineole did. This effect is stronger when AMC is combined with 1,8-cineole as a total synergistic effect was obtained on the three strains used (FIC ≤ 0.5). In vivo, a significant reduction was noted in the number of colonies in the bone marrow when rabbits were treated with AMC associated with either 1,8-cineole or gentamicin compared to rabbits treated with AMC, gentamicin, or 1,8-cineole alone. These results demonstrated that 1,8-cineole showed a synergistic effect in combination with both AMC and gentamicin, which offer possibilities for reducing antibiotic usage. Also, the AMC associated with 1,8-cineole could be used to treat MRSA osteomyelitis.

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Cell membrane enveloped polymeric nanosponge for detoxification of chlorpyrifos poison: In vitro and in vivo studies

Human & Experimental Toxicology ◽

10.1177/0960327121993207 ◽

2021 ◽

pp. 096032712199320

Author(s):

S Altaf ◽

F Muhammad ◽

B Aslam ◽

MN Faisal

Keyword(s):

Glycolic Acid ◽

Rabbit Model ◽

Acetylcholinesterase Activity ◽

In Vivo Studies ◽

Organophosphate Poisoning ◽

Neurotoxic Effects ◽

Life Threatening ◽

Red Blood Cell Membranes

Organophosphates are highly toxic compounds as they are involved in irreversible inhibition of acetylcholinesterase, causing various neurotoxic effects via acetylcholine accumulation throughout the nervous system. Traditional treatments for organophosphate poisoning are not effective enough to overcome all the toxic effects. There is a need for alternate treatment of life threatening poisoning of organophosphates. For this purpose a biomimetic nanosponge of poly (lactic- co-glycolic acid) is prepared, characterized and analysed as an antidote for organophosphate poisoning. In this nanosponge red blood cell membranes are used for coating poly lactic co-glycolic acid nanoparticles. In vitro studies are conducted to investigate the retention of acetylcholinesterase activity on the prepared nanosponge as well as to assess the scavenging ability of prepared nanosponge for model organophosphate, chlorpyrifos. In vivo studies are conducted to evaluate the detoxification potential of nanosponge in rabbit model, poisoned with chlorpyrifos. Hepatotoxicity and renal toxicity of nanosponge/chlorpyrifos complex is also studied in survived rabbits and the data is analysed statistically.

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Intratumoral H2O2-triggered release of CO from a metal carbonyl-based nanomedicine for efficient CO therapy

Chemical Communications ◽

10.1039/c7cc01576c ◽

2017 ◽

Vol 53 (40) ◽

pp. 5557-5560 ◽

Cited By ~ 39

Author(s):

Zhaokui Jin ◽

Yanyuan Wen ◽

Liwei Xiong ◽

Tian Yang ◽

Penghe Zhao ◽

...

Keyword(s):

Mesoporous Silica ◽

Metal Carbonyl ◽

Silica Nanoparticle ◽

Triggered Release ◽

Mesoporous Silica Nanoparticle ◽

Hollow Mesoporous Silica ◽

Manganese Carbonyl ◽

Co Gas

H2O2-triggered release of CO: an intratumoral H2O2-responsive nanomedicine is constructed by effectively encapsulating the hydrophilic manganese carbonyl prodrug into an advanced hollow mesoporous silica nanoparticle carrier to realize selective killing of tumor cells, exhibiting high in vitro and in vivo efficacies of CO gas therapy.

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3D-printed HA15-loaded β-Tricalcium Phosphate/Poly (Lactic-co-glycolic acid) Bone Tissue Scaffold Promotes Bone Regeneration in Rabbit Radial Defects

International Journal of Bioprinting ◽

10.18063/ijb.v7i1.317 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Chuanchuan Zheng ◽

Shokouh Attarilar ◽

Kai Li ◽

Chong Wang ◽

Jia Liu ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Tissue ◽

Tricalcium Phosphate ◽

Glycolic Acid ◽

Bone Conduction ◽

Biomechanical Properties ◽

Bone Defects ◽

Tissue Scaffold ◽

3D Printed

In this study, a β-tricalcium phosphate (β-TCP)/poly (lactic-co-glycolic acid) (PLGA) bone tissue scaffold was loaded with osteogenesis-promoting drug HA15 and constructed by three-dimensional (3D) printing technology. This drug delivery system with favorable biomechanical properties, bone conduction function, and local release of osteogenic drugs could provide the basis for the treatment of bone defects. The biomechanical properties of the scaffold were investigated by compressive testing, showing comparable biomechanical properties with cancellous bone tissue. Furthermore, the microstructure, pore morphology, and condition were studied. Moreover, the drug release concentration, the effect of anti-tuberculosis drugs in vitro and in rabbit radial defects, and the ability of the scaffold to repair the defects were studied. The results show that the scaffold loaded with HA15 can promote cell differentiation into osteoblasts in vitro, targeting HSPA5. The micro-computed tomography scans showed that after 12 weeks of scaffold implantation, the defect of the rabbit radius was repaired and the peripheral blood vessels were regenerated. Thus, HA15 can target HSPA5 to inhibit endoplasmic reticulum stress which finally leads to promotion of osteogenesis, bone regeneration, and angiogenesis in the rabbit bone defect model. Overall, the 3D-printed β-TCP/PLGA-loaded HA15 bone tissue scaffold can be used as a substitute material for the treatment of bone defects because of its unique biomechanical properties and bone conductivity.

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The Co-Culture of ASCs and EPCs Promotes Vascularized Bone Regeneration in Critical-Sized Bone Defects of Cranial Bone in Rats

10.21203/rs.3.rs-24037/v1 ◽

2020 ◽

Author(s):

yuanjia he ◽

Shuang Lin ◽

Qiang Ao ◽

Xiaoning He

Keyword(s):

Bone Regeneration ◽

Bone Tissue ◽

Bone Defect ◽

Culture System ◽

Donor Site ◽

Bone Defects ◽

Cranial Bone ◽

Vascularized Bone

Abstract Background: The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.Results The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could promote bone regeneration and vascularization in the meantime and, then significantly accelerate the repair of critical-sized bone defects.Conclusion It is feasible to replace traditional single seed cells with ASCs/EPCs co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

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Preconditioning with Melatonin Enhances Osteogenic Differentiation of Dental Pulp Mesenchymal Stem Cells by Regulating MAPK Pathways and Promotes the Efficiency of Bone Regeneration in Calvarial Bone Defects

10.21203/rs.3.rs-936574/v1 ◽

2021 ◽

Author(s):

Ya-Hui Chan ◽

Kuo-Ning Ho ◽

Yu-Chieh Lee ◽

Meng-Jung Chou ◽

Wei-Zhen Lew ◽

...

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Dental Pulp ◽

Bone Defects ◽

Calvarial Bone ◽

Alp Activity ◽

Cox 2

Abstract Background:Mesenchymal stem cell (MSC)-based tissue engineering plays a major role in regenerative medicine. However, the efficiency of MSC transplantation and survival of engrafted stem cells remain challenging. Melatonin can regulate MSC biology. However, its function in the osteogenic differentiation of dental pulp-derived MSCs (DPSCs) remains unclear. We investigated the effects and mechanisms of melatonin preconditioning on the osteogenic differentiation and bone regeneration capacities of DPSCs.Methods:The biological effects and signaling mechanisms of melatonin with different concentrations on DPSCs were evaluated using a proliferation assay, the quantitative alkaline phosphatase (ALP) activity, Alizarin red staining, a real-time polymerase chain reaction, and a western blot in vitro cell culture model. The in vivo bone regeneration capacities were assessed among empty control, MBCP, MBCP+DPSCs, and MBCP+DPSCs+melatonin preconditioning in four-created calvarial bone defects by using micro–computed tomographic, histological, histomorphometric, and immunofluorescence analyses after 4 and 8 weeks of healing.Results:In vitro experiments revealed that melatonin (1, 10, and 100 μM) significantly and concentration-dependently promoted proliferation, surface marker expression (CD 146), ALP activity and extracellular calcium deposition, and osteogenic gene expression of DPSCs (p < 0.05). Melatonin activated the phosphorylation of RUNX-2 and OCN and inhibited COX-2/NF-κB phosphorylation. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPK) P38/ERK signaling was significantly increased in DPSCs treated with 100 μM melatonin, and their inhibitors significantly decreased osteogenic differentiation. In vivo experiments demonstrated that bone defects implanted with MBCP bone-grafting materials and melatonin-preconditioned melatonin exhibited significantly greater bone volume fraction, trabecular bone structural modeling, new bone formation, and osteogenesis-related protein expression than the other three groups at 4 and 8 weeks postoperatively (p < 0.05).Conclusions:These results suggest that melatonin promotes the proliferation and osteogenic differentiation of DPSCs by regulating COX-2/NF-κB and p38/ERK MAPK signaling pathways. Preconditioning DPSCs with melatonin before transplantation can efficiently enhance MSC function and regenerative capacities.

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