ORCID Profile
0000-0002-4131-8299
Current Organisation
SA Pathology
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Publisher: American Vacuum Society
Date: 05-2022
DOI: 10.1116/6.0001746
Abstract: Cardiovascular disease is a leading cause of death worldwide however, despite substantial advances in medical device surface modifications, no synthetic coatings have so far matched the native endothelium as the optimal hemocompatible surface for blood-contacting implants. A promising strategy for rapid restoration of the endothelium on blood-contacting biomedical devices entails attracting circulating endothelial cells or their progenitors, via immobilized cell-capture molecules for ex le, anti-CD34 antibody to attract CD34+ endothelial colony-forming cells (ECFCs). Inherent is the assumption that the cells attracted to the biomaterial surface are bound exclusively via a specific CD34 binding. However, serum proteins might adsorb in-between or on the top of antibody molecules and attract ECFCs via other binding mechanisms. Here, we studied whether a surface with immobilized anti-CD34 antibodies attracts ECFCs via a specific CD34 binding or a nonspecific (non-CD34) binding. To minimize serum protein adsorption, a fouling-resistant layer of hyperbranched polyglycerol (HPG) was used as a “blank slate,” onto which anti-CD34 antibodies were immobilized via aldehyde-amine coupling reaction after oxidation of terminal diols to aldehydes. An isotype antibody, mIgG1, was surface-immobilized analogously and was used as the control for antigen-binding specificity. Cell binding was also measured on the HPG hydrogel layer before and after oxidation. The surface analysis methods, x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry, were used to verify the intended surface chemistries and revealed that the surface coverage of antibodies was sparse, yet the anti-CD34 antibody grafted surface-bound ECFCs very effectively. Moreover, it still captured the ECFCs after BSA passivation. However, cells also attached to oxidized HPG and immobilized mIgG1, though in much lower amounts. While our results confirm the effectiveness of attracting ECFCs via surface-bound anti-CD34 antibodies, our observation of a nonspecific binding component highlights the importance of considering its consequences in future studies.
Publisher: Elsevier BV
Date: 05-2011
Publisher: American Chemical Society (ACS)
Date: 25-08-2014
DOI: 10.1021/AM503570V
Abstract: Anionic ring-opening polymerization of glycidol was initiated from activated glass, silicon, and porous silicon substrates to yield thin, ultralow-fouling hyperbranched polyglycerol (HPG) graft polymer coatings. Substrates were activated by deprotonation of surface-bound silanol functionalities. HPG polymerization was initiated upon the addition of freshly distilled glycidol to yield films in the nanometer thickness range. X-ray photoelectron spectroscopy, contact angle measurements, and ellipsometry were used to characterize the resulting coatings. The antifouling properties of HPG-coated surfaces were evaluated in terms of protein adsorption and the attachment of mammalian cells. The adsorption of bovine serum albumin and collagen type I was found to be reduced by as much as 97 and 91%, respectively, in comparison to untreated surfaces. Human glioblastoma and mouse fibroblast attachment was reduced by 99 and 98%, respectively. HPG-grafted substrates outperformed polyethylene glycol (PEG) grafted substrates of comparable thickness under the same incubation conditions. Our results demonstrate the effectiveness of antifouling HPG graft polymer coatings on a selected range of substrate materials and open the door for their use in biomedical applications.
Publisher: Wiley
Date: 07-03-2016
Publisher: Informa UK Limited
Date: 09-03-2022
Publisher: Elsevier BV
Date: 08-2013
Publisher: American Chemical Society (ACS)
Date: 14-12-2015
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2RA00791F
Publisher: Wiley
Date: 30-11-2012
Abstract: We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti-cancer drug c tothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP.
Publisher: American Chemical Society (ACS)
Date: 07-2014
DOI: 10.1021/BM500601Z
Abstract: We demonstrate the patterned biofunctionalization of antifouling hyperbranched polyglycerol (HPG) coatings on silicon and glass substrates. The ultralow fouling HPG coatings afforded straightforward chemical handles for rapid bioconjugation of amine containing biomolecular species. This was achieved by sodium periodate oxidation of terminal HPG diols to yield reactive aldehyde groups. Patterned microprinting of sodium periodate and cell adhesion mediating cyclic peptides containing the RGD sequence resulted in an array of covalently immobilized bioactive signals. When incubated with mouse fibroblasts, the HPG background resisted cell attachment whereas high density cell attachment was observed on the peptide spots, resulting in high-contrast cell microarrays. We also demonstrated single-step, in situ functionalization of the HPG coatings by printing periodate and peptide concurrently. Our results demonstrate the effectiveness of antifouling and functionalized HPG graft polymer coatings and establish their use in microarray applications for the first time.
Publisher: Future Medicine Ltd
Date: 06-2014
DOI: 10.2217/NNM.13.93
Abstract: Aim: This study aimed to demonstrate radiofrequency (RF)-triggered release of drugs and drug carriers from drug-eluting implants using gold nanoparticles as energy transducers. Materials & methods: Titanium wire with a titania nanotube layer was used as an implant loaded with indomethacin and micelles (tocopheryl PEG succinate) as a drug and drug carrier model. RF signals were generated from a customized RF generator to trigger in vitro release. Results & discussion: Within 2.5 h, 18 mg (92%) of loaded drug and 14 mg (68%) of loaded drug carriers were released using short RF exposure (5 min), compared with 5 mg (31%) of drug and 2 mg (11%) of drug carriers without a RF trigger. Gold nanoparticles can effectively function as RF energy transducers inside titania nanotubes for rapid release of therapeutics at arbitrary times. Conclusion: The results of this study show that RF is a promising strategy for triggered release from implantable drug delivery systems where on-demand delivery of therapeutics is required. Original submitted 19 November 2012 Revised submitted 1 April 2013
Publisher: American Chemical Society (ACS)
Date: 12-05-2020
Abstract: Hyperbranched polyglycerol (HPG) was previously investigated as a nonfouling hydrophilic grafted layer on biomaterial surfaces, analogous to the well-known poly(ethylene oxide) (PEO), but the range of adsorbing cells and proteins tested was limited and at times the assays used were not the most sensitive. Thus, the questions arise whether HPG-grafted layers can indeed efficiently resist adsorption of a wider range of adsorbing biological entities, and how would different biological entities interact with such a coating. An HPG coating of 25 nm thickness was grafted onto a spin-coated and plasma-treated polystyrene (PS) layer on a silicon wafer substrate this provided a well-suited system for surface analyses by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and atomic force microscopy (AFM), which verified the presence of a uniform, smooth grafted HPG layer. Adsorption of bovine serum albumin, lysozyme, fibrinogen, and endothelial cell growth medium 2 (EGM2) was reduced by >90%, with the adsorbed amounts close to the detection limit of XPS but still detectable by ToF-SIMS using principal component analysis. With human serum, however, the reduction in adsorption was slightly less pronounced. Smooth muscle cells (SMCs) and fibroblasts were virtually unable to attach onto the grafted HPG layer, with >99% reductions at 6 h compared with plasma-treated PS the few attached cells remaining rounded and unable to spread. Their attachment might have resulted from coating defects. Testing with full blood showed that unlike for the control surface (plasma-treated PS), platelets did not adhere to the HPG surface, but there was attachment of some cells that stained CD11b positive and likely are neutrophils. Cells of the fungal organism
Publisher: Research Square Platform LLC
Date: 20-04-2022
DOI: 10.21203/RS.3.RS-1544665/V1
Abstract: Synthetic materials with an innate ability to avoid the foreign-body-response remain an unrealized goal that would transform the medical device industry. The balance of bulk material properties, that enable a device to perform as intended, with surface properties, that provide bio- and hemocompatibility, has always required the former to be prioritized. While all materials used in modern devices have an acceptable level of biocompatibility, imperfection remains, ultimately leading to device failure, or requiring pharmacological intervention for it to be tolerated. Where such devices cause damage or place strain on the normal architecture of the surrounding tissue, these impacts may initiate inflammatory responses that can also led to failure. This is most evident in the treatment of vessels in the lower extremity in patients with peripheral arterial disease (PAD), where in-stent restenosis (ISR) remains a significant challenge for vascular surgeons. Blood-contacting devices, such as stents and artificial grafts, are considered particularly difficult to shield from the foreign-body-response due to the immediate and direct exposure to blood and therefore, the full gamut of the body’s immune responses. Pharmacological treatment is currently paramount to successful percutaneous vascular intervention (PVI) with antiplatelet therapies being prescribed to manage the risk of thrombosis and cytotoxic drug-eluting coatings to reduce restenosis. Here, we present data that indicate a nano-thin coating of hyperbranched polyglycerol (HPG) can greatly improve the safety and durability of endovascular metal stents. The HPG coating successfully prevents the binding and activation of platelets and greatly reduces the thrombogenicity of nitinol stents when studied ex vivo, using fresh human blood. In vivo, HPG-coated stainless-steel stents remained patent after 28 days in apolipoprotein E (ApoE) knockout mice while control stents all became completely occluded, highlighting the HPG coating’s ability to reduce restenosis. Together, these properties could help alleviate the industry’s dependence on blood-thinning and antiproliferative drugs to resolve device compatibility issues thereby greatly improve patients’ quality of life through faster recovery, fewer complications and fewer repeat interventions. Furthermore, this coating technology is compatible with a range of materials commonly used in the production of implantable medical devices, such as stainless steel, nitinol, silicone, and polytetrafluoroethylene, while being highly scalable, cost effective and stable. Taken together, HPG presents itself as an alternative coating suitable for a broad range of vascular devices including stents and grafts.
No related grants have been discovered for Eli Moore.