A Collagen Fiber Membrane Aided Chondroprotective-Based Strategy for Enhancing Integration of Regenerative Neo-Cartilage

2020 ◽  
Vol 16 (5) ◽  
pp. 672-688
Author(s):  
Wenyu Yang ◽  
Ziqiang Wang ◽  
Fuchong Du ◽  
Yiting Cao ◽  
Bo Du ◽  
...  

The lack of neo-cartilage integration with host tissues is a great challenge for the clinical translation of new technologies for the repair of articular cartilage (AC) defect. Recently, we developed a promising double-layered collagen-based system for targeted delivery of fibroblast growth factor 2 (FGF2) to the subchondral bone for AC repair. The system effectively promoted the regeneration of both cartilage and subchondral bone. However, neo-cartilage integration was unsatisfactory, which might be due to the presence of a zone of cell death (ZCD) in the cartilage induced by injury. Here, we hypothesized that maintaining cell viability in the region surrounding the defect and decreasing the size of ZCD by using chondroprotective agents such as insulin-like growth factor-1 (IGF-1), might be an effective strategy to improve neo-cartilage integration. A targeted delivery system for IGF-1 to cartilage based on the FGF2 delivery system was formulated to weaken the impact on the effects of FGF2. The two growth factors were incorporated into the different layers of the membrane without interdiffusion. Due to the different densities of collagen fibers in the different layers, the in vitro and in vivo assays demonstrated that both proteins were released via unidirectional diffusion without mixing or lateral diffusion. Particularly, the released IGF-1 increased the viability of chondrocytes, decreased the ZCD size, and enhanced the integration of regenerative neo-cartilage with host tissues, without any undesirable effects on the FGF2mediated regeneration of cartilage and subchondral bone. Taken together, our findings demonstrate that the collagen fiber membrane-aided chondroprotective-based strategy is an effective way to improve neo-cartilage integration.

RSC Advances ◽  
2016 ◽  
Vol 6 (50) ◽  
pp. 44543-44551 ◽  
Author(s):  
Xin Chen ◽  
Dandan Li ◽  
Hong Wang ◽  
Yuan-yuan Jiao ◽  
Hao Wang ◽  
...  

We developed a nanodiamond-based anti-cancer drug targeted delivery system, epidermal growth factor–nanodiamonds–cisplatin (ENC) bioconjugate, which could selectively kill tumor cells and be located through 3D confocal Raman imaging.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomomitsu Kanaya ◽  
Shigeru Miyagawa ◽  
Takuji Kawamura ◽  
Yoshiki Sakai ◽  
Kenta Masada ◽  
...  

AbstractClinical outcomes of pulmonary arterial hypertension (PAH) may be improved using targeted delivery system. We investigated the efficacy of ONO1301 (prostacyclin agonist) nanospheres (ONONS) in Sugen5416/hypoxia rat models of PAH. The rats were injected with saline (control) or ONONS (n = 10, each) on days 21 and 28, respectively. Hepatocyte growth factor (HGF)-expressing fibroblasts and inflammatory cytokines were measured. Cardiac performance was assessed and targeted delivery was monitored in vivo, using Texas red-labeled nanoparticles. Compared with control, HGF-expressing fibroblasts and HGF expression levels were significantly higher in the ONONS group, while the levels of interleukin-6, interleukin-1β, transforming growth factor-β, and platelet-derived growth factor were lower. Histological assessment revealed significant amelioration of the percent medial wall thickness in pulmonary vasculature of rats in the ONONS group. Rats in the ONONS group showed decreased proliferating cell nuclear antigen-positive smooth muscle cells and improved right ventricle pressure/left ventricle pressure. No difference was seen in the accumulation of Texas red-labeled nanoparticles in the brain, heart, liver, and spleen between PAH and normal rats. However, a significant area of nanoparticles was detected in the lungs of PAH rats. ONONS effectively ameliorated PAH, with selective delivery to the damaged lung.


2017 ◽  
pp. 111-140 ◽  
Author(s):  
R. Kapeliushnikov

The paper provides a critical analysis of the idea of technological unemployment. The overview of the existing literature on the employment effects of technological change shows that on the micro-level there exists strong and positive relationship between innovations and employment growth in firms; on the sectoral level this correlation becomes ambiguous; on the macro-level the impact of new technologies seems to be positive or neutral. This implies that fears of explosive growth of technological unemployment in the foreseeable future are exaggerated. Our analysis further suggests that new technologies affect mostly the structure of employment rather than its level. Additionally we argue that automation and digitalisation would change mostly task sets within particular occupations rather than distribution of workers by occupations.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide


2018 ◽  
Vol 24 (16) ◽  
pp. 1788-1800 ◽  
Author(s):  
Kye-Soo Cho ◽  
Seo-Jin Hong ◽  
Min-Hye Ahn ◽  
Sukdeb Pal ◽  
Pill-Hoon Choung ◽  
...  

Background: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent “magic bullet” cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention. One of these promising and novel agents is the siRNA delivery system; however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA stability in the body’s circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA. Conclusion: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and 2) a description of the five major cancer-targeting ligands.


Emerging technologies have always played an important role in armed conflict. From the crossbow to cyber capabilities, technology that could be weaponized to create an advantage over an adversary has inevitably found its way into military arsenals for use in armed conflict. The weaponization of emerging technologies, however, raises challenging legal issues with respect to the law of armed conflict. As States continue to develop and exploit new technologies, how will the law of armed conflict address the use of these technologies on the battlefield? Is existing law sufficient to regulate new technologies, such as cyber capabilities, autonomous weapons systems, and artificial intelligence? Have emerging technologies fundamentally altered the way we should understand concepts such as law-of-war precautions and the principle of distinction? How can we ensure compliance and accountability in light of technological advancement? This book explores these critical questions while highlighting the legal challenges—and opportunities—presented by the use of emerging technologies on the battlefield.


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