Effect of Mixing Bioactive Nanoceramics with a Thermosensitive Hydrogel as Bone Substitute

2012 ◽  
Vol 622-623 ◽  
pp. 1794-1798 ◽  
Author(s):  
Po Liang Lai ◽  
Ding Wei Hong ◽  
Carl Tsai Yu Lin ◽  
Lih Huei Chen ◽  
Wen Jer Chen ◽  
...  
Keyword(s):  
Animal Studies ◽  
Ph Value ◽  
Sol Gel ◽  
Degradation Process ◽  
Thermosensitive Hydrogel ◽  
Composite Gels ◽  
Bone Graft Substitutes ◽  
Sol Gel Transition

The composite of methoxy polyethylene glycol (mPEG) and poly(lactic-co- glycolic acid) (PLGA) thermosensitive hydrogel mixed with different mass raio of hydroxyapatite and β-tricalcium phosphate (β-TCP) were used as bone graft substitutes. The physical properties of a series of composite gels, including the critical micelle concentration (CMC), particle sizes, zeta potential, rheological behavior, morphology of composite gels, and sol–gel transition, were characterized in vitro. These composite gels could form a gel at body temperature and could be controlled easily at room temperature. During the in vitro degradation process, composite gels demonstrated a slight decrease in pH value, a slower degradation rate, less toxicity, and a higher cell survival rate. The biocompatibility of the composite gels was validated by hemolysis test. In vivo animal studies demonstrated both radiographic and gross bone union when the ratio of HAP/ β-TCP was 7:3.

Thermosensitive Hydrogel Incorporating Microspheres for Injectable Implant Delivery of Naltrexone

2013 ◽  
Vol 647 ◽  
pp. 71-79 ◽  
Author(s):  
Guo Qiang Jiang ◽  
Yu Jie Wang ◽  
Fu Xin Ding
Keyword(s):  
Sol Gel ◽  
High Water ◽  
The Body ◽  
High Water Content ◽  
Burst Release ◽  
Thermosensitive Hydrogel ◽  
Sol Gel Transition ◽  
Gel Transition

Long-term drug delivery based on the injectable thermosensitive hydrogel is of great advantage to the administration of naltrexone, but the constant release is hard to reach due to the sol-gel transition and the high water content of the hydrogel. The aim of the present study is to develop an injectable implant delivery system by the incorporation of microspheres into thermosensitive hydrogel for the long-term constant release of naltrexone. Naltrexone was loaded in PLGA microsphere dispersed in the methylcellulose based thermosensitive sol, which formed the hydrogel containing the naltrexone-loaded microspheres at the body temperature. The presence of microsphere in the hydrogel delayed the sol-gel transition slightly but enhanced the mechanical strength of the hydrogel significantly. The microspheres degradation in water diffusion dominated phase was decelerated when they were embed in the hydrogel. The in vitro naltrexone release from the microsphere/hydrogel system showed an over 60 days constant release with no significant burst release, and the drug release rate was in proportion to the microsphere concentration in the hydrogel.

scholarly journals Preparation and Characterization of Salt-Mediated Injectable Thermosensitive Chitosan/Pectin Hydrogels for Cell Embedding and Culturing

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2674
Author(s):  
Giulia Morello ◽  
Alessandro Polini ◽  
Francesca Scalera ◽  
Riccardo Rizzo ◽  
Giuseppe Gigli ◽  
...  
Keyword(s):  
Sol Gel ◽  
Polymer Network ◽  
Cell Encapsulation ◽  
High Water ◽  
Biological Tissues ◽  
Culture Conditions ◽  
Interpenetrating Polymer Network ◽  
Sol Gel Transition

In recent years, growing attention has been directed to the development of 3D in vitro tissue models for the study of the physiopathological mechanisms behind organ functioning and diseases. Hydrogels, acting as 3D supporting architectures, allow cells to organize spatially more closely to what they physiologically experience in vivo. In this scenario, natural polymer hybrid hydrogels display marked biocompatibility and versatility, representing valid biomaterials for 3D in vitro studies. Here, thermosensitive injectable hydrogels constituted by chitosan and pectin were designed. We exploited the feature of chitosan to thermally undergo sol–gel transition upon the addition of salts, forming a compound that incorporates pectin into a semi-interpenetrating polymer network (semi-IPN). Three salt solutions were tested, namely, beta-glycerophosphate (βGP), phosphate buffer (PB) and sodium hydrogen carbonate (SHC). The hydrogel formulations (i) were injectable at room temperature, (ii) gelled at 37 °C and (iii) presented a physiological pH, suitable for cell encapsulation. Hydrogels were stable in culture conditions, were able to retain a high water amount and displayed an open and highly interconnected porosity and suitable mechanical properties, with Young’s modulus values in the range of soft biological tissues. The developed chitosan/pectin system can be successfully used as a 3D in vitro platform for studying tissue physiopathology.

scholarly journals Electrochemical Oxidation as a Tool for Generating Vitamin D Metabolites

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2369 ◽  
Author(s):  
Navarro Suarez ◽  
Thein ◽  
Kallinich ◽  
Rohn
Keyword(s):  
Vitamin D ◽  
Phase Ii ◽  
Animal Studies ◽  
Ph Value ◽  
Oxidation Products ◽  
In Vitro Test ◽  
Vitamin D Metabolites ◽  
Constant Potential

The electrochemical behavior of the vitamers cholecalciferol and ergocalciferol was investigated in order to determine whether it is possible to evaluate phase-I and phase-II metabolism of these steroids and yield metabolites that can serve as reference material. The vitamers were electrochemically-oxidized using an electrochemical system (ROXY™ EC system). The influence of pH value, solvent, and potential was evaluated. When using methanol or ethanol, the formation of artificial methoxy or ethoxy groups, respectively, was observed, while the use of acetonitrile did not show any formation of further functional groups. A neutral pH value and use of a constant potential led to the highest number of oxidation products with intensive signals. Additionally, a binding study between vitamin D and glucuronic acid as an example for phase-II conjugation was carried out. It was possible to detect adduct formation. Coupling mass spectrometry directly to electrochemistry (EC-MS) is a promising approach for generating vitamin D metabolites and/or yielding a number of metabolites without in vivo or in vitro test systems. It can support or even replace animal studies in the long-term and might be promising for yielding reference compounds.

scholarly journals Thermo-Responsive Hydrogels Based on Methylcellulose/Persian Gum Loaded With Taxifolin Enhance Bone Regeneration: An in Vitro / in Vivo Study

2021 ◽  
Author(s):  
Zahra Sadat Sajadi-Javan ◽  
Jaleh Varshosaz ◽  
Mina Mirian ◽  
Maziar Manshaei ◽  
Atousa Aminzadeh
Keyword(s):  
Animal Studies ◽  
Bone Defects ◽  
Halloysite Nanotubes ◽  
Thermosensitive Hydrogel ◽  
Alizarin Red ◽  
The Impact ◽  
Responsive Hydrogels

Abstract In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25-1.5 w/v% PG and 1-7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells.

Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization

2016 ◽  
Vol 31 (6) ◽  
pp. 923-932 ◽  
Author(s):  
Xiaoyan Wang ◽  
Yu Zhang ◽  
Wei Xue ◽  
Hong Wang ◽  
Xiaozhong Qiu ◽  
...  
Keyword(s):  
Delivery System ◽  
Sol Gel ◽  
Vaccine Delivery ◽  
In Vitro Release ◽  
Vaccine Delivery System ◽  
Th1 And Th2 Cytokines ◽  
Specific Igg ◽  
Sol Gel Transition

In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50–200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50–200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50–200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.

scholarly journals Desiccation-induced fibrous condensation of CAHS protein from an anhydrobiotic tardigrade

2021 ◽  
Author(s):  
Maho Yagi-Utsumi ◽  
Kazuhiro Aoki ◽  
Hiroki Watanabe ◽  
Chihong Song ◽  
Seiji Nishimura ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Sol Gel ◽  
Protein A ◽  
Protective Mechanisms ◽  
Self Assembling ◽  
Protein Functions ◽  
Sol Gel Transition ◽  
Helical Region

Anhydrobiosis is one of the most extensively studied forms of cryptobiosis that is induced in certain organisms as a response to desiccation. Anhydrobiotic species has been hypothesized to produce substances that can protect their biological components and/or cell membranes without water. In extremotolerant tardigrades, highly hydrophilic and heat-soluble protein families, cytosolic abundant heat-soluble (CAHS) proteins, have been identified, which are postulated to be integral parts of the tardigrades' response to desiccation. However, the molecular mechanisms underlying these protein functions remain to be fully elucidated. In this study, in vitro and in vivo characterizations of the self-assembling property of CAHS1 protein, a major isoform of CAHS proteins from Ramazzottius varieornatus, using a series of spectroscopic and microscopic techniques. Our in vitro observations showed that CAHS1 proteins homo-oligomerized via the C-terminal α-helical region and formed a hydrogel as their concentration increased, and that these molecular assembling processes were reversible. Furthermore, our in vivo observations demonstrated that the overexpressed CAHS1 proteins formed condensates under desiccation-mimicking conditions. These data strongly suggested that, upon drying, the CAHS1 proteins form oligomers and eventually underwent sol-gel transition in tardigrade cytosols. Thus, it is proposed that the CAHS1 proteins form the cytosolic fibrous condensates, which presumably have variable mechanisms for the desiccation tolerance of tardigrades. These findings provide insights into the protective mechanisms involved in the anhydrobiosis of tardigrades.

scholarly journals Desiccation-induced fibrous condensation of CAHS protein from an anhydrobiotic tardigrade

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maho Yagi-Utsumi ◽  
Kazuhiro Aoki ◽  
Hiroki Watanabe ◽  
Chihong Song ◽  
Seiji Nishimura ◽  
...  
Keyword(s):  
Sol Gel ◽  
Protein A ◽  
Extreme Environments ◽  
Self Assembling ◽  
Protein Functions ◽  
Sol Gel Transition ◽  
Microscopic Techniques ◽  
Helical Region

AbstractAnhydrobiosis, one of the most extensively studied forms of cryptobiosis, is induced in certain organisms as a response to desiccation. Anhydrobiotic species has been hypothesized to produce substances that can protect their biological components and/or cell membranes without water. In extremotolerant tardigrades, highly hydrophilic and heat-soluble protein families, cytosolic abundant heat-soluble (CAHS) proteins, have been identified, which are postulated to be integral parts of the tardigrades’ response to desiccation. In this study, to elucidate these protein functions, we performed in vitro and in vivo characterizations of the reversible self-assembling property of CAHS1 protein, a major isoform of CAHS proteins from Ramazzottius varieornatus, using a series of spectroscopic and microscopic techniques. We found that CAHS1 proteins homo-oligomerized via the C-terminal α-helical region and formed a hydrogel as their concentration increased. We also demonstrated that the overexpressed CAHS1 proteins formed condensates under desiccation-mimicking conditions. These data strongly suggested that, upon drying, the CAHS1 proteins form oligomers and eventually underwent sol–gel transition in tardigrade cytosols. Thus, it is proposed that the CAHS1 proteins form the cytosolic fibrous condensates, which presumably have variable mechanisms for the desiccation tolerance of tardigrades. These findings provide insights into molecular strategies of organisms to adapt to extreme environments.

scholarly journals Thermosensitive Poly(DHSe/PEG/PPG Urethane)-Based Hydrogel Extended Remdesivir Application in Ophthalmic Medication

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 50
Author(s):  
Sennan Xu ◽  
Lingjie Ke ◽  
Sichen Zhao ◽  
Zhiguo Li ◽  
Yang Xiao ◽  
...  
Keyword(s):  
Sol Gel ◽  
In Vitro Release ◽  
Water Soluble ◽  
Prolonged Release ◽  
In Situ Gel ◽  
Sol Gel Transition ◽  
Novel Coronavirus

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Tantalum Oxide Nanoparticles as Versatile Contrast Agents for X-ray Computed Tomography

2020 ◽  
Author(s):  
Shatadru Chakravarty ◽  
Jeremy Hix ◽  
Kaitlyn Wieweora ◽  
Maximilian Volk ◽  
Elizabeth Kenyon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Sol Gel ◽  
Tantalum Oxide ◽  
High Signal ◽  
Drug Delivery Vehicles ◽  
X Ray Computed

Here we describe the synthesis, characterization and in vitro and in vivo performance of a series of tantalum oxide (TaOx) based nanoparticles (NPs) for computed tomography (CT). Five distinct versions of 9-12 nm diameter silane coated TaOx nanocrystals (NCs) were fabricated by a sol-gel method with varying degrees of hydrophilicity and with or without fluorescence, with the highest reported Ta content to date (78%). Highly hydrophilic NCs were left bare and were evaluated in vivo in mice for micro-CT of full body vasculature, where following intravenous injection, TaOx NCs demonstrate high CT contrast, circulation in blood for ~ 3 h, and eventual accumulation in RES organs; and following injection locally in the mammary gland, where the full ductal tree structure can be clearly delineated. Partially hydrophilic NCs were encapsulated within mesoporous silica nanoparticles (MSNPs; TaOx@MSNPs) and hydrophobic NCs were encapsulated within poly(lactic-co-glycolic acid) (PLGA; TaOx@PLGA) NPs, serving as potential CT-imagable drug delivery vehicles. Bolus intramuscular injections of TaOx@PLGA NPs and TaOx@MSNPs to mimic the accumulation of NPs at a tumor site produce high signal enhancement in mice. In vitro studies on bare NCs and formuated NPs demonstrate high cytocompatibility and low dissolution of TaOx. This work solidifies that TaOx-based NPs are versatile contrast agents for CT.

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