Non-Cytotoxic Agarose/Hydroxyapatite Composite Scaffolds for Drug Release

Healing of large bone defects requires implants or scaffolds that provide structural guidance for cell growth, differentiation, and vascularization. In the present work, an agarose-hydroxyapatite composite scaffold was developed that acts not only as a 3D matrix, but also as a release system. Hydroxyapatite (HA) was incorporated into the agarose gels in situ in various ratios by a simple procedure consisting of precipitation, cooling, washing, and drying. The resulting gels were characterized regarding composition, porosity, mechanical properties, and biocompatibility. A pure phase of carbonated HA was identified in the scaffolds, which had pore sizes of up to several hundred micrometers. Mechanical testing revealed elastic moduli of up to 2.8 MPa for lyophilized composites. MTT testing on Lw35human mesenchymal stem cells (hMSCs) and osteosarcoma MG-63 cells proved the biocompatibility of the scaffolds. Furthermore, scaffolds were loaded with model drug compounds for guided hMSC differentiation. Different release kinetic models were evaluated for adenosine 5′-triphosphate (ATP) and suramin, and data showed a sustained release behavior over four days.

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Comparision of electro spun tassar silk fibroin-hydroxyapatite composite scaffold prepared by soaking and in-situ methods

Materials Today Proceedings ◽

10.1016/j.matpr.2016.05.001 ◽

2016 ◽

Vol 3 (6) ◽

pp. 1330-1337 ◽

Cited By ~ 2

Author(s):

K.S Sekar ◽

Karthic Kumar Balan ◽

Subramanian Sundaramoorthy

Keyword(s):

Silk Fibroin ◽

Composite Scaffold ◽

Hydroxyapatite Composite ◽

In Situ Methods

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In situ mineralized PLGA/zwitterionic hydrogel composite scaffolds enable high-efficiency rhBMP‑2 release for critical-sized bone healing

Biomaterials Science ◽

10.1039/d1bm01521d ◽

2022 ◽

Author(s):

Peiming Liu ◽

Tianyi Bao ◽

Lian Sun ◽

Zeyi Wang ◽

Jin Sun ◽

...

Keyword(s):

Glycolic Acid ◽

High Efficiency ◽

Ammonium Hydroxide ◽

Bone Defects ◽

Functional Restoration ◽

Composite Scaffolds ◽

Hydrogel Composite ◽

Large Bone ◽

Large Bone Defects

Seeking an osteoconductive and osteoinductive scaffold is highly desirable for functional restoration of large bone defects. Here, we report an in situ mineralized poly(lactic-co-glycolic acid)/poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)ammonium hydroxide hydrogel (PLGA/PSBMA) scaffolds...

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Use of Adipose Derived Stem Cells to Treat Large Bone Defects. Addendum

10.21236/ada586568 ◽

2009 ◽

Author(s):

Barbara D. Boyan ◽

Robert E. Gulderg

Keyword(s):

Stem Cells ◽

Bone Defects ◽

Adipose Derived Stem Cells ◽

Large Bone ◽

Large Bone Defects

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Factors related to large bone defects of bipolar lesions and a high number of instability episodes with anterior glenohumeral instability

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02395-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Noboru Matsumura ◽

Kazuya Kaneda ◽

Satoshi Oki ◽

Hiroo Kimura ◽

Taku Suzuki ◽

...

Keyword(s):

Humeral Head ◽

Glenohumeral Joint ◽

Three Dimensional ◽

Clinical Results ◽

Bone Defects ◽

Symptom Duration ◽

Glenohumeral Instability ◽

Explanatory Variables ◽

Large Bone ◽

Large Bone Defects

Abstract Background Significant bone defects are associated with poor clinical results after surgical stabilization in cases of glenohumeral instability. Although multiple factors are thought to adversely affect enlargement of bipolar bone loss and increased shoulder instability, these factors have not been sufficiently evaluated. The purpose of this study was to identify the factors related to greater bone defects and a higher number of instability episodes in patients with glenohumeral instability. Methods A total of 120 consecutive patients with symptomatic unilateral instability of the glenohumeral joint were retrospectively reviewed. Three-dimensional surface-rendered/registered models of bilateral glenoids and proximal humeri from computed tomography data were matched by software, and the volumes of bone defects identified in the glenoid and humeral head were assessed. After relationships between objective variables and explanatory variables were evaluated using bivariate analyses, factors related to large bone defects in the glenoid and humeral head and a high number of total instability episodes and self-irreducible dislocations greater than the respective 75th percentiles were evaluated using logistic regression analyses with significant variables on bivariate analyses. Results Larger humeral head defects (P < .001) and a higher number of total instability episodes (P = .032) were found to be factors related to large glenoid defects. On the other hand, male sex (P = .014), larger glenoid defects (P = .015), and larger number of self-irreducible dislocations (P = .027) were related to large humeral head bone defects. An increased number of total instability episodes was related to longer symptom duration (P = .001) and larger glenoid defects (P = .002), and an increased number of self-irreducible dislocations was related to larger humeral head defects (P = .007). Conclusions Whereas this study showed that bipolar lesions affect the amount of bone defects reciprocally, factors related to greater bone defects differed between the glenoid and the humeral head. Glenoid defects were related to the number of total instability episodes, whereas humeral head defects were related to the number of self-irreducible dislocations.

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The Influence of Temperature and Viscosity of Polyethylene Glycol on the Rate of Microwave-Induced In Situ Amorphization of Celecoxib

Molecules ◽

10.3390/molecules26010110 ◽

2020 ◽

Vol 26 (1) ◽

pp. 110

Author(s):

Nele-Johanna Hempel ◽

Tra Dao ◽

Matthias M. Knopp ◽

Ragna Berthelsen ◽

Korbinian Löbmann

Keyword(s):

Polyethylene Glycol ◽

Microwave Radiation ◽

Magnesium Stearate ◽

Einstein Equations ◽

Dissolution Process ◽

Target Temperature ◽

Peg 4000 ◽

Lower Viscosity ◽

Model Drug

Microwaved-induced in situ amorphization of a drug in a polymer has been suggested to follow a dissolution process, with the drug dissolving into the mobile polymer at temperatures above the glass transition temperature (Tg) of the polymer. Thus, based on the Noyes–Whitney and the Stoke–Einstein equations, the temperature and the viscosity are expected to directly impact the rate and degree of drug amorphization. By investigating two different viscosity grades of polyethylene glycol (PEG), i.e., PEG 3000 and PEG 4000, and controlling the temperature of the microwave oven, it was possible to study the influence of both, temperature and viscosity, on the in situ amorphization of the model drug celecoxib (CCX) during exposure to microwave radiation. In this study, compacts containing 30 wt% CCX, 69 wt% PEG 3000 or PEG 4000 and 1 wt% lubricant (magnesium stearate) were exposed to microwave radiation at (i) a target temperature, or (ii) a target viscosity. It was found that at the target temperature, compacts containing PEG 3000 displayed a faster rate of amorphization as compared to compacts containing PEG 4000, due to the lower viscosity of PEG 3000 compared to PEG 4000. Furthermore, at the target viscosity, which was achieved by setting different temperatures for compacts containing PEG 3000 and PEG 4000, respectively, the compacts containing PEG 3000 displayed a slower rate of amorphization, due to a lower target temperature, than compacts containing PEG 4000. In conclusion, with lower viscosity of the polymer, at temperatures above its Tg, and with higher temperatures, both increasing the diffusion coefficient of the drug into the polymer, the rate of amorphization was increased allowing a faster in situ amorphization during exposure to microwave radiation. Hereby, the theory that the microwave-induced in situ amorphization process can be described as a dissolution process of the drug into the polymer, at temperatures above the Tg, is further strengthened.

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In Situ Vitrification of Lung Cancer Organoids on a Microwell Array

Micromachines ◽

10.3390/mi12060624 ◽

2021 ◽

Vol 12 (6) ◽

pp. 624

Author(s):

Qiang Liu ◽

Tian Zhao ◽

Xianning Wang ◽

Zhongyao Chen ◽

Yawei Hu ◽

...

Keyword(s):

Lung Cancer ◽

Drug Sensitivity ◽

Simple Procedure ◽

Three Dimensional ◽

Cancer Drug ◽

Microwell Array ◽

Sensitivity Tests ◽

Anti Cancer

Three-dimensional cultured patient-derived cancer organoids (PDOs) represent a powerful tool for anti-cancer drug development due to their similarity to the in vivo tumor tissues. However, the culture and manipulation of PDOs is more difficult than 2D cultured cell lines due to the presence of the culture matrix and the 3D feature of the organoids. In our other study, we established a method for lung cancer organoid (LCO)-based drug sensitivity tests on the superhydrophobic microwell array chip (SMAR-chip). Here, we describe a novel in situ cryopreservation technology on the SMAR-chip to preserve the viability of the organoids for future drug sensitivity tests. We compared two cryopreservation approaches (slow freezing and vitrification) and demonstrated that vitrification performed better at preserving the viability of LCOs. Next, we developed a simple procedure for in situ cryopreservation and thawing of the LCOs on the SMAR-chip. We proved that the on-chip cryopreserved organoids can be recovered successfully and, more importantly, showing similar responses to anti-cancer drugs as the unfrozen controls. This in situ vitrification technology eliminated the harvesting and centrifugation steps in conventional cryopreservation, making the whole freeze–thaw process easier to perform and the preserved LCOs ready to be used for the subsequent drug sensitivity test.

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Vascularization of Nanohydroxyapatite/Collagen/Poly(L-lactic acid) Composites by Implanting Intramuscularly In Vivo

International Journal of Polymer Science ◽

10.1155/2014/153453 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Hai Wang ◽

Xiao Chang ◽

Guixing Qiu ◽

Fuzhai Cui ◽

Xisheng Weng ◽

...

Keyword(s):

Lactic Acid ◽

Orthopaedic Surgery ◽

Bone Substitutes ◽

Bone Defects ◽

Large Defect ◽

Natural Bone ◽

Composition And Structure ◽

Large Bone ◽

Large Bone Defects

It still remains a major challenge to repair large bone defects in the orthopaedic surgery. In previous studies, a nanohydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composite, similar to natural bone in both composition and structure, has been prepared. It could repair small sized bone defects, but they were restricted to repair a large defect due to the lack of oxygen and nutrition supply for cell survival without vascularization. The aim of the present study was to investigate whether nHAC/PLA composites could be vascularized in vivo. Composites were implanted intramuscularly in the groins of rabbits for 2, 6, or 10 weeks (n=5×3). After removing, the macroscopic results showed that there were lots of rich blood supply tissues embracing the composites, and the volumes of tissue were increasing as time goes on. In microscopic views, blood vessels and vascular sprouts could be observed, and microvessel density (MVD) of the composites trended to increase over time. It suggested that nHAC/PLA composites could be well vascularized by implanting in vivo. In the future, it would be possible to generate vascular pedicle bone substitutes with nHAC/PLA composites for grafting.

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