Comparison of Soluble and Liposome Encapsulated, Sustained Release Latanoprost for Focal Adipose Reduction.

Background: To address the lack of non-cytotoxic, non-surgical options to treat undesirable focal adiposity of the face, we propose use of the anti-glaucoma medication and prostaglandin F2α analogue latanoprost, which has a well-described side effect of periorbital adipose shrinkage. Objective: To evaluate the safety and efficacy of soluble and liposomal latanoprost for focal fat reduction. Approach: To compare efficacy, single administrations of either the FDA-approved cytolytic drug deoxycholic acid (DOCA), latanoprost, or liposomal latanoprost were injected into ob/ob mouse inguinal fat pads. Study outcomes included mouse weight, inguinal fat pad volume, architecture, and cytotoxicity. Results: Both DOCA and soluble latanoprost significantly reduced inguinal fat pad volume whereas liposome encapsulation reduced inguinal fat pad volume insignificantly over the 14-day study period. Hematoxylin and eosin demonstrated effective reduction in adipocyte volume without histologic evidence of cytolysis or inflammation whereas DOCA caused dermal ulcerations, adipocyte lysis, and increased tissue inflammation. Conclusion: Latanoprost reduced fat volume without inducing cell lysis or inflammation.

In vitro and in vivo degradation of microfiber bioresorbable coronary scaffold.

The degradation of Mirage Bioresorbable Microfiber Scaffold was evaluated in vitro and in vivo. The degradation in polymer molecular weight (MW), strut morphology, and integrity was accessed using gel permeation chromatography (GPC), X-ray micro-computed tomography (micro-CT) evaluation. To simulate the physiological degradation in vitro, scaffolds were deployed in silicone mock vessels connected to a peristaltic pumping system, which pumps 37°C phosphate-buffered saline (PBS, pH 7.4) at a constant rate. At various time points (30D, 60D, 90D, 180D, 270D, and 360D), the MW of microfibers decreased to 57.3, 49.8, 36.9, 13.9, 6.4, and 5.1% against the baseline. The in vivo degradation study was performed by implanting scaffolds in internal thoracic arteries (ITAs) of mini-swine. At the scheduled sacrifice time points (30D, 90D, 180D, 270D, 360D, and 540D), the implanted ITAs were excised for GPC analysis; the MW of the implanted scaffolds dropped to 58.5, 34.7, 24.8, 16.1, 12.9, and 7.1, respectively. Mass loss of scaffolds reached 72.4% at 540D of implantation. Two stages of hydrolysis were observed in in vitro and in vivo degradation kinetics, and the statistical analysis suggested a positive correlation between in vivo and in vitro degradation. After 6 months of incubation in animals, significant strut degradation was seen in the micro-CT evaluation in all sections as strut fragments and separations. The micro-CT results further confirmed that every sample at 720D had X-ray transmission similar to surrounding tissue, thereby indicating full degradation within 2 years. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1842-1850, 2018.

Randomized Comparison of Absorb Bioresorbable Vascular Scaffold and Mirage Microfiber Sirolimus-Eluting Scaffold Using Multimodality Imaging.

OBJECTIVES: The primary objective of this study was to evaluate the safety and effectiveness of the Mirage (Manli Cardiology, Singapore) bioresorbable microfiber sirolimus-eluting scaffold compared with the Absorb (Abbott Vascular, Santa Clara, California) bioresorbable vascular scaffold in the treatment of stenotic target lesions located in native coronary arteries, ranging from ≥2.25 to ≤4.0 mm in diameter. Secondary objectives were to establish the medium-term safety, effectiveness, and performance of the Mirage device. BACKGROUND: The current generation of bioresorbable scaffolds has several limitations, such as thick square struts with large footprints that preclude their deep embedment into the vessel wall, resulting in protrusion into the lumen with microdisturbance of flow. The Mirage sirolimus-eluting bioresorbable microfiber scaffold is designed to address these concerns. METHODS: In this prospective, single-blind trial, 60 patients were randomly allocated in a 1:1 ratio to treatment with a Mirage sirolimus-eluting bioresorbable microfiber scaffold or an Absorb bioresorbable vascular scaffold. The clinical endpoints were assessed at 30 days and at 6 and 12 months. In-device angiographic late loss at 12 months was quantified. Secondary optical coherence tomographic endpoints were assessed post-scaffold implantation at 6 and 12 months. RESULTS: Median angiographic post-procedural in-scaffold minimal luminal diameters of the Mirage and Absorb devices were 2.38 mm (interquartile range [IQR]: 2.06 to 2.62 mm) and 2.55 mm (IQR: 2.26 to 2.71 mm), respectively; the effect size (d) was -0.29. At 12 months, median angiographic in-scaffold minimal luminal diameters of the Mirage and Absorb devices were not statistically different (1.90 mm [IQR: 1.57 to 2.31 mm] vs. 2.29 mm [IQR: 1.74 to 2.51 mm], d = -0.36). At 12-month follow-up, median in-scaffold late luminal loss with the Mirage and Absorb devices was 0.37 mm (IQR: 0.08 to 0.72 mm) and 0.23 mm (IQR: 0.15 to 0.37 mm), respectively (d = 0.20). On optical coherence tomography, post-procedural diameter stenosis with the Mirage was 11.2 ± 7.1%, which increased to 27.4 ± 12.4% at 6 months and remained stable (31.8 ± 12.9%) at 1 year, whereas the post-procedural optical coherence tomographic diameter stenosis with the Absorb was 8.4 ± 6.6%, which increased to 16.6 ± 8.9% and remained stable (21.2 ± 9.9%) at 1-year follow-up (Mirage vs. Absorb: dpost-procedure = 0.41, d6 months = 1.00, d12 months = 0.92). Angiographic median in-scaffold diameter stenosis was significantly different between study groups at 12 months (28.6% [IQR: 21.0% to 40.7%] for the Mirage, 18.2% [IQR: 13.1% to 31.6%] for the Absorb, d = 0.39). Device- and patient-oriented composite endpoints were comparable between the 2 study groups. CONCLUSIONS: At 12 months, angiographic in-scaffold late loss was not statistically different between the Mirage and Absorb devices, although diameter stenosis on angiography and on optical coherence tomography was significantly higher with the Mirage than with the Absorb. The technique of implantation was suboptimal for both devices, and future trials should incorporate optical coherence tomographic guidance to allow optimal implantation and appropriate assessment of the new technology, considering the novel mechanical properties of the Mirage.

Randomized comparison of absorb bioresorbable vascular scaffold and mirage microfiber sirolimus-eluting scaffold using multimodality imaging

ObjectivesThe primary objective of this study was to evaluate the safety and effectiveness of the Mirage (Manli Cardiology, Singapore) bioresorbable microfiber sirolimus-eluting scaffold compared with the Absorb (Abbott Vascular, Santa Clara, California) bioresorbable vascular scaffold in the treatment of stenotic target lesions located in native coronary arteries, ranging from ≥2.25 to ≤4.0 mm in diameter. Secondary objectives were to establish the medium-term safety, effectiveness, and performance of the Mirage device.BackgroundThe current generation of bioresorbable scaffolds has several limitations, such as thick square struts with large footprints that preclude their deep embedment into the vessel wall, resulting in protrusion into the lumen with microdisturbance of flow. The Mirage sirolimus-eluting bioresorbable microfiber scaffold is designed to address these concerns....

Modulation of chondrocyte behavior through tailoring functional synthetic saccharide-peptide hydrogels.

Tailoring three-dimensional (3D) biomaterial environments to provide specific cues in order to modulate function of encapsulated cells could potentially eliminate the need for addition of exogenous cues in cartilage tissue engineering. We recently developed saccharide-peptide copolymer hydrogels for cell culture and tissue engineering applications. In this study, we aim to tailor our saccharide-peptide hydrogel for encapsulating and culturing chondrocytes in 3D and examine the effects of changing single amino acid moieties differing in hydrophobicity/hydrophilicity (valine (V), cysteine (C), tyrosine (Y)) on modulation of chondrocyte function. Encapsulated chondrocytes remained viable over 21 days in vitro. Glycosaminoglycan and collagen content was significantly higher in Y-functionalized hydrogels compared to V-functionalized hydrogels. Extensive matrix accumulation and concomitant increase in mechanical properties was evident over time, particularly with the presence of Y amino acid. After 21 days in vitro, Y-functionalized hydrogels attained a modulus of 193 ± 46 kPa, compared to 44 ± 21 kPa for V-functionalized hydrogels. Remarkably, mechanical and biochemical properties of chondrocyte-laden hydrogels were modulated by change in a single amino acid moiety. This unique property, combined with the versatility and biocompatibility, makes our saccharide-peptide hydrogels promising candidates for further investigation of combinatorial effects of multiple functional groups on controlling chondrocyte and other cellular function and behavior.

Biodegradable and biocompatible synthetic saccharide-Peptide hydrogels for three-dimensional stem cell culture.

Saccharide-peptide hydrogels have been developed in our laboratory as new synthetic extracellular matrices for regenerative medicine applications. In this work, we have expanded on our previously reported system and applied copolymerization of cysteine (Cys) and vinyl sulfone (VS)-functionalized saccharide-peptide polymers via Michael-type addition for encapsulation and 3D culture of cells. Specifically, our aims were to (1) develop a novel hydrogel platform, which could be applied for encapsulating and culturing mesenchymal stem cells (MSCs) in a 3D environment, (2) characterize the tunable properties of the hydrogel, specifically, degradation, mechanical, and gel network properties, and (3) determine the biocompatibility of the saccharide-peptide hydrogel material with MSCs. Hydrogel mechanical properties were tunable by varying the VS:Cys ratio (= 0.5, 1, or 2) as well as the pH (6, 7, or 8) of the cross-linking components. Stiffer gels were formed at VS:Cys = 1 and pH 6 or 7. Gels formed at pH 8 or with excess Cys (VS:Cys = 0.5) or VS (VS:Cys = 2) were significantly softer. Cross-linking pH and VS:Cys ratio also had an effect on the degradation behavior of the VS:Cys gels, with higher cross-linking pH resulting in an accelerated loss of mass. On the basis of environmental scanning electron microscopy (ESEM) analysis and fluorescence microscopy, all hydrogels appeared to exhibit porous gel networks. MSCs cultured in monolayer and exposed to soluble Cys or VS copolymers (0.1-5 mg/mL) did not exhibit measurable cytotoxicity. In addition, MSCs were cultured in 3D for up to 14 days in vitro without deleterious effects on cell viability. In summary, we have established and characterized a tunable 3D saccharide-peptide hybrid copolymer hydrogel platform for culturing MSCs. Future studies will focus on utilizing the hydrogel system for controlling the differentiation of MSCs.

De novo design of saccharide-peptide hydrogels as synthetic scaffolds for tailored cell responses.

A new class of functional saccharide-peptide copolymer-based hydrogels was synthesized and investigated as synthetic extracellular matrices for regenerative medicine applications. The polymer was composed entirely of natural building blocks, namely, galactaric acid and lysine on the backbone, with tyrosine grafted onto the side chain as a handle for enzyme-catalyzed hydrogelation. The resulting hydrogels are degradable under simulated physiological conditions and exhibit minimal cytotoxicity on dermal fibroblast and PC-12 cells. As a demonstration of the versatility of the system, the mechanical properties of the gels can be independently controlled without changing the polymer chemical composition. Using an identical copolymer solution, by simply allowing different lengths of cross-linking time, a series of hydrogels was obtained with different mechanical moduli at constant chemical structure. The moduli of the resulting hydrogels varied stepwise from 1.7, 4.1, 6.9, and 12.5 kPa to allow for systematic studies on the effects of modulus on cell behavior. It was exciting to observe that a simple change in hydrogel physical properties could induce a direct phenotypic change in cell adhesion and proliferation. Depending on the substrate mechanical modulus, the cell morphology changed and proliferation rate differed by an order of magnitude for different cell lines. These data suggest our saccharide-peptide hydrogels as promising synthetic extracellular matrices for cell culture and tissue regeneration.

Phage wrapping with cationic polymers eliminates nonspecific binding between M13 phage and high pI target proteins.

M13 phage have provided scaffolds for nanostructure synthesis based upon self-assembled inorganic and hard materials interacting with phage-displayed peptides. Additionally, phage display has been used to identify binders to plastic, TiO(2), and other surfaces. However, synthesis of phage-based materials through the hybridization of soft materials with the phage surface remains unexplored. Here, we present an efficient "phage wrapping" strategy for the facile synthesis of phage coated with soluble, cationic polymers. Polymers bearing high positive charge densities demonstrated the most effective phage wrapping, as shown by assays for blocking nonspecific binding of the anionic phage coat to a high pI target protein. The results establish the functional group requirements for hybridizing phage with soft materials and solve a major problem in phage display-nonspecific binding by the phage to high pI target proteins.

Gold nanoparticle-based competitive colorimetric assay for detection of protein-protein interactions.

A gold nanoparticle-based competitive colorimetric assay uses the ensemble of Concanavalin (ConA) and mannopyranoside-encapsulated gold nanoparticles (Man-GNPs) to identify the binding partners for ConA and the binding constants are determined based on the wavelength shifts.