Source:Acta Histochemica, Volume 120, Issue 3
https://ift.tt/2GuSdaA
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Publication date: Available online 27 March 2018
Source:Acta Biomaterialia
Author(s): Jean-Philippe Buffet, Erwan Corre, Evelyne Duvernois-Berthet, Jérôme Fournier, Pascal Jean Lopez
Tube-building sabellariid polychaetes are hermatypic organisms capable of forming vast reefs in highly turbulent marine habitats. Sabellariid worms assemble their tube by gluing together siliceous and calcareous clastic particles using a polyelectrolytic biocement. Here, we performed transcriptomic analyses to investigate the genes that are differentially expressed in the parathorax region, which contains the adhesive gland and tissues, from the rest of the body. We found a large number of candidate genes to be involved in the composition and formation of biocement in two species: Sabellaria alveolata and Phragmatopoma caudata. Our results indicate that the glue is likely to be composed by a large diversity of cement-related proteins, including Poly(S), GY-rich, H-repeat and miscellaneous categories. However, sequences divergence and differences in expression profiles between S. alveolata and P. caudata, of cement-related proteins may reflect adaptation to the type of substratum used to build their tube, and/or to their habitat (temperate vs tropical, amplitude of pH, salinity ...). Related to the L-DOPA metabolic pathways and linked with the genes that were differentially expressed in the parathorax region, we found that tyrosinase and peroxidase gene families may have undergone independent expansion in the two Sabellariidae species investigated. Our data also reinforce the importance of protein modifications in cement formation. Altogether these new genomic resources help to identify novel transcripts encoding for cement-related proteins, but also important enzymes putatively involved in the chemistry of the adhesion process, such as kinases, and may correspond to new targets to develop biomimetic approaches.Statements of SignificanceThe diversity of bioadhesives elaborated by marine invertebrates is a tremendous source of inspiration to develop biomimetic approaches for biomedical and technical applications. Recent studies on the adhesion system of mussel, barnacle and sea star had highlighted the usefulness of high-throughput RNA sequencing in accelerating the development of biomimetic adhesives. Adhesion in sandcastle worms, which involves catechol and phosphate chemistries, polyelectrolyte complexes, supramolecular architectures, and a coacervation process, is a useful model to develop multipurpose wet adhesives. Using transcriptomic tools, we have explored the diversity of genes encoding for structural and catalytic proteins involved in cement formation of two sandcastle worm species, Sabellaria alveolata and Phragmatopoma caudata. The important genomic resource generated should help to design novel "blue" adhesives.
Publication date: Available online 27 March 2018
Source:Acta Biomaterialia
Author(s): Fenglin Hu, Kaimin Chen, Hong Xu, G. Hongchen
An ideal nanomaterial for use in the bio-medical field should have a distinctive surface capable of effectively preventing nonspecific protein adsorption and identifying target bio-molecules. Recently, the short-chain zwitterion strategy has been suggested as a simple and novel approach to create outstanding anti-fouling surfaces. In this paper, the carboxyl end group of short-chain zwitterion-coated silica nanoparticles (SiO2-ZWS) was found to be difficult to functionalize via a conventional EDC/NHS strategy due to its rapid hydrolysis side-reactions. Hence, a series of bi-functionalized silica nanoparticles (SiO2-ZWS/COOH) were designed and prepared by controlling the molar ratio of 3-aminopropyltriethoxysilane (APTES) to short-chain zwitterionic organosiloxane (ZWS) in order to achieve above goal. The synthesized SiO2-ZWS/COOH had similar excellent anti-fouling properties compared with SiO2-ZWS, even in 50% fetal bovine serum characterized by DLS and turbidimetric titration. Subsequently, SiO2-ZWS/COOH5/1 was chosen as a representative and then demonstrated higher detection signal intensity and more superior signal-to-noise ratios compare with the pure SiO2-COOH when they were used as a bio-carrier for chemiluminescence enzyme immunoassay (CLEIA). These unique bi-functionalized silica nanoparticles have many potential applications in the diagnostic and therapeutic fields.Statement of significanceReducing nonspecific protein adsorption and enhancing the immobilized efficiency of specific bio-probes are two of the most important issues for bio-carriers, particularly for a nanoparticle based bio-carrier. Herein, we designed and prepared a bi-functional nanoparticle with anti-fouling property and bio conjugation capacity for further bioassay by improving the short-chain zwitterionic modification strategy we have proposed previously. The heterogeneous surface of this nanoparticle showed effective anti-fouling properties both in model protein solutions and fetal bovine serum (FBS). The modified nanoparticles can also be successfully functionalized with a specific antibody for CLEIA assay with a prominent bio-detection performance even in 50% FBS. In this paper, we also investigated an unexpectedly fast hydrolysis behavior of NHS-activated carboxylic groups within the pure short-chain zwitterionic molecule that led to no protein binding in the short-chain zwitterion modified nanoparticle. Our findings pave a new way for the design of high performance bio-carriers, demonstrating their strong potential as a robust platform for diagnosis and therapy.
Publication date: Available online 26 March 2018
Source:Acta Biomaterialia
Author(s): Hua Shi, Runqi Yan, Luyan Wu, Yidan Sun, Song Liu, Zhengyang Zhou, Jian He, Deju Ye
Precise diagnosis of lymph node metastasis to guide lymphadenectomy is highly important for gastric cancer therapy in clinics. Though surgical dissection of regional metastatic lymph nodes remains the only way for gastric cancer therapy, the extended dissection may cause unavoidable postoperative risk of complications. These is still lack of effective method enabling the accurate removal of metastatic gastric cancer cells in lymph nodes with minimum injuries to normal tissue. Herein, we report a new fluorescent copper sulfide (CuS) nanoparticle (RGD-CuS-Cy5.5) enabling both non-invasive multimodality imaging and targeting photothermal therapy (PTT) of metastatic gastric cancer cells in lymph nodes. We demonstrate that RGD-CuS-Cy5.5 can easily drain into sentinel lymph nodes (SLN) after injection into primary tumors, and selectively enter into metastatic gastric MNK45 tumor cells via αvβ3 integrin-mediated endocytosis. The resulting strong near-infrared (NIR) fluorescence and computed tomography (CT) contrast in metastatic SLN compared to normal SLN can precisely differentiate SLN metastasis of gastric cancers. Guided by the imaging, localized PTT with RGD-CuS-Cy5.5 is conducted upon irradiation with an 808 nm laser, resulting in complete removal of metastatic gastric tumor cells in SLN without obvious toxicity. Moreover, RGD-CuS-Cy5.5 can also allow for the rapid and non-invasive self-monitoring of PTT efficacy against metastatic SLNs in living mice. This study highlights the potential of using RGD-CuS-Cy5.5 for imaging-guided and targeting PTT of SLN metastasis in vivo, which may be applicable for the metastatic gastric cancer therapy in clinics.Statement of SignificanceRGD-CuS-Cy5.5 nanoparticles possess NIR fluorescence and CT signals for in vivo bimodality imaging of lymph node metastasis.Strong photothermal property under irradiation at 808 nm for efficient PTT.Easy drain into sentinel lymph nodes and selective enter metastatic gastric cancer cells via αvβ3 integrin-mediated endocytosis.Rapid and non-invasive monitoring of therapeutic efficacy against lymph node metastasis.
Publication date: Available online 26 March 2018
Source:Acta Biomaterialia
Author(s): Soyon Kim, Zhong-Kai Cui, Paul Jay Kim, Lawrence Young Jung, Min Lee
Although bone morphogenetic protein-2 (BMP-2) is known to be the most potent stimulator available for bone formation, a major barrier to widespread clinical use is its inherent instability and absence of an adequate delivery system. Heparin is being widely used in controlled release systems due to its strong binding ability and protective effect for many growth factor proteins. In this work, we developed a hydrogel surface that can mimic heparin to stabilize BMP-2 and to enhance osteogenesis by introducing heparin-mimicking sulfonated molecules such as poly-vinylsulfonic acid (PVSA) or poly-4-styrenesulfonic acid (PSS), into photo-crosslinkable hydrogel. Bioactivity of BMP-2 was well preserved in the presence of polysulfonates during exposure to various therapeutically relevant stressors. The heparin-mimicking sulfonated hydrogels were effective to bind BMP-2 compared to unmodified MeGC hydrogel and significantly enhanced osteogenic differentiation of encapsulated bone marrow stromal cells (BMSCs) without the addition of exogenous BMP-2. The sulfonated hydrogels were effective in delivering exogenous BMP-2 with reduced initial burst and increased BMSCs osteogenesis induced by BMP-2. These findings suggest a novel hydrogel platform for sequestering and stabilizing BMP-2 to enhance osteoinductive activity in bone tissue engineering.Statement of significanceAlthough bone morphogenetic protein-2 (BMP-2) is believed to be the most potent cytokine for bone regeneration, its clinical applications require supraphysiological BMP dosage due to its intrinsic instability and fast enzymatic degradation, leading to worrisome side effects. This study demonstrates a novel hydrogel platform that mimics a natural protector of BMPs, heparin, to sequester and stabilize BMP-2 for increased osteoinductive signaling. This study will achieve the stabilization of BMPs with prolonged bioactivity by a synthetic heparin mimic that has not been examined previously. Moreover, the heparin mimetic hydrogel surface can augment endogenous BMP activity by sequestering and localizing the cell-produced BMPs. The additional knowledge gained from this study may suggest basis for future development of material-based therapeutics for tissue engineering.
Publication date: Available online 26 March 2018
Source:Acta Biomaterialia
Author(s): Hua Zhang, Shan Yu, Xinlian Zhao, Zhengwei Mao, Changyou Gao
Intervertebral disc (IVD) degeneration may cause many diseases and pain. Stem cell migration toward the site of IVD degeneration is a key factor for IVD regeneration. In the current study, we prepared albumin/heparin nanoparticles (BHNPs) as injectable carriers of stromal cell-derived factor-1α (SDF-1α, also known as C-X-C motif chemokine 12), a powerful chemoattractant for the homing of bone marrow resident mesenchymal stem cells (MSCs), for protection of the molecule against degradation for a sustained release. The NPs have relatively uniform small size, with a diameter of about 110 nm. The NPs possess a high loading capacity of SDF-1α with a sustained release profile. The bioactivity of the obtained BHNPs/SDF was then studied in vitro and in vivo. The BHNPs/SDF can induce migration of MSCs in a dose-dependent manner in vitro. After injected into the damaged disc, BHNPs/SDF induce much better regeneration of annulus fibrosus and nucleus pulposus, compared to SDF-1α and BHNPs alone, evidenced with better histological grade scores and higher expression of SOX9, Aggrecan, and Collagen type II at the level of both mRNA and protein. This study provides a simple nanoplatform to load SDF-1α and protect it against degradation, with potential application in inductive tissue regeneration in vivo.Statement of significanceStem cell migration toward the site of IVD degeneration is a key factor to help IVD regeneration. In current study, we prepared albumin/heparin nanoparticles (BHNPs) as injectable carriers to protect and sustained release of SDF-1α. After injected into damaged disc, BHNPs/SDF induce much better regeneration of IVD, compared to SDF-1α and BHNPs alone. This study provides a simply nanoplatform to load and protect SDF-1α, with potential application in inductive tissue regeneration in vivo.
Publication date: Available online 27 March 2018
Source:Acta Biomaterialia
Author(s): Srinidhi Nagaraja, Stacey J.L. Sullivan, Phillip R. Stafford, Anne D. Lucas, Elon Malkin
Although nitinol is used widely in percutaneous cardiovascular interventions, a causal relationship between nickel released from implanted cardiovascular devices and adverse systemic or local biological responses has not been established. The objective of this study was to investigate the relationship between nitinol surface processing, in-vivo nickel release, and biocompatibility. Nitinol stents manufactured using select surface treatments were implanted into the iliac arteries of minipigs for 6 months. Clinical chemistry profile, complete blood count, serum and urine nickel analyses were performed periodically during the implantation period. After explant, stented arteries were either digested and analyzed for local nickel concentration or fixed and sectioned for histopathological analysis of stenosis and inflammation within the artery. The results indicated that markers for liver and kidney function were not different than baseline values throughout 180 days of implantation regardless of surface finish. In addition, white blood cell, red blood cell, and platelet counts were similar to baseline values for all surface finishes. Systemic nickel concentrations in serum and urine were not significantly different between processing groups and comparable to baseline values during 180 days of implantation. However, stents with non-optimized surface finishing had significantly greater nickel levels in the surrounding artery compared to polished stents. These stents had increased stenosis around stent struts with potential for local inflammation compared to polished stents. These findings demonstrate that proper polishing of nitinol surfaces can reduce in-vivo nickel release locally, which may aid in minimizing adverse inflammatory reactions and restenosis.Statement of SignificanceNitinol is a commonly used material in cardiovascular medical devices. However, relationships between nitinol surface finishing, in-vivo metal ion release, and adverse biological responses have yet to be established. We addressed this knowledge gap by implanting single and overlapped nitinol stents with different surface finishes to assess systemic impact on minipigs (i.e. serum and urine nickel levels, liver and kidney function, immune and blood count) over the 6 month implantation period. In addition, nickel levels and histopathology in stented arteries were analyzed on explant to determine relationships between surface processing and local adverse tissue reactions. The findings presented here highlight the importance of surface processing on in-vivo nickel release and subsequent impact on local biological response for nitinol implants.
|
|
|
|