We have previously presented a MEMS viscometric sensor for continuous glucose monitoring using protein Concanavalin A (Con A). To address its drawbacks including immunotoxicity and instability issues, we have synthesized stable, biocompatible copolymers poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA) for viscosity based glucose sensing. We found that PAA-ran-PAAPBA showed very high binding specificity to glucose. Several key factors such as polymer compositions, polymer molecular weights and polymer concentrations have been investigated to optimize viscometric responses. This polymer is able to detect glucose under physiological conditions in a reversible manner. Therefore, it has the potential to enable the highly reliable, continuous monitoring of glucose in subcutaneous tissue using the MEMS device.

Atherosclerosis is primarily responsible for cardiovascular diseases (CVDs) in millions of patients every year. Drug-coated balloons (DCBs) are commonly used to treat various CVDs. However, in several currently used DCBs, a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. In this study, paclitaxel containing polyethylene oxide (PEO) films were developed to provide unique advantages including drug release profiles specifically tailored for balloon-based therapy, homogeneous films with molecularly dispersed drug, flexible and ductile films, and exhibits significant inhibitory effect on smooth muscle cell growth. Thus, this study demonstrated the use of PEO as an alternate drug delivery platform for DCBs to improve its efficacy.

In this study, the effect of different structures (flat, expanded, and electrospun) of polytetrafluoroethylene (PTFE) on the interactions of endothelial cells (ECs), smooth muscle cells (SMCs), and platelets was investigated. In addition, the mechanisms that govern the interactions between ECs, SMCs, and platelets with different structures of PTFE were discussed. The surface characterizations showed that the different structures of PTFE have the same surface chemistry, similar surface wettability and zeta potential, but uniquely different surface topography. The viability, proliferation, morphology, and phenotype of ECs and SMCs interacted with different structures of PTFE were investigated. Expanded PTFE (ePTFE) provided a relatively better surface for the growth of ECs. In case of SMC interactions, although all the different structures of PTFE inhibited SMC growth, a maximum inhibitory effect was observed for ePTFE. In case of platelet interactions, the electrospun PTFE provided a better surface for preventing the adhesion and activation of platelets. Thus, this study demonstrated that the responses of ECs, SMCs, and platelets strongly dependent on the surface topography of the PTFE. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2291-2304, 2016.

The surface topography of a biomaterial plays a vital role in determining macrophage interactions and influencing immune response. In this study, we investigated the effect of smooth and microrough topographies of commonly used metallic biomaterials such as 316 L stainless steel (SS) and cobalt-chromium (CoCr) alloys on macrophage interactions. The macrophage adhesion was greater on CoCr compared to SS, irrespective of their topographies. The macrophage activation and the secretion of most pro-inflammatory cytokines (TNF-α, IL-6, and IP-10) were greater on microrough surfaces than on smooth surfaces by day-1. However, by day-2, the macrophage activation on smooth surfaces was also significantly increased up to the same level as observed on the microrough surfaces, with more amount of cytokines secreted. The secretion of anti-inflammatory cytokine (IL-10) was significantly increased from day-1 to day-2 on all the alloy surfaces with the effect most prominently observed on microrough surfaces. The production of nitric oxide by the macrophages did not show any major substrate-dependent effect. The foreign body giant cells formed by macrophages were least observed on the microrough surfaces of CoCr. Thus, this study demonstrated that the nature of material (SS or CoCr) and their surface topographies (smooth or microrough) strongly influence the macrophage responses. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2658-2672, 2016.

Polytetrafluoroethylene (PTFE) is one of the commonly used materials in making various cardiovascular implants. However, the success rates of these implants in several occasions are hindered by unwanted immune responses from immune cells, such as macrophages. In this study, we investigated the response of macrophages with different structures (flat, expanded, and electrospun) of PTFE having varied surface topographies: smooth planar surface (flat PTFE), node-fibrils (ePTFE), and randomly oriented microfibers (electrospun PTFE). The electrospun PTFE showed the least adhesion of macrophages. Also, the morphology of macrophages adhered on electrospun PTFE exhibited minimal activation. The macrophage pro-inflammatory cytokine secretions showed that the lowest level of TNF-α was produced on electrospun PTFE whereas IP-10 was produced in lowest levels on expanded PTFE (ePTFE). The production of IL-6 and MCP-1 cytokines was also dependent on the structure of PTFE that the macrophages interacted with, but in a time-dependent manner. Confocal microscopy images taken at 7, 14, and 21 days showed that the electrospun PTFE resulted in the lowest percentage of macrophage fusion, thus indicating the least possible chance of foreign body giant cell (FBGC) formation. Therefore, this study showed that electrospun PTFE with randomly oriented microfibers can provide reduced adhesion, activation, and FBGC formation of macrophages compared to the smooth and planar surface of flat PTFE and node-fibril structured surface of ePTFE. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2441-2450, 2017.

The amorphous PAT in the PEO balloon provided comparable drug tissue retention levels to those of the commercially available DCB and fewer particulates. Thus prepared PEO balloon proved to be safe and effective in the preclinical experimental setting. The clinical outcomes of these findings need further investigation.

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Drug‐coated balloons (DCBs) have now emerged as a promising approach to treat peripheral artery disease. However, a significant amount of drug from the balloon surface is lost during balloon tracking and results in delivering only a subtherapeutic dose of drug at the diseased site. Hence, in this study, the use of dextran sulfate (DS) polymer was investigated as a platform to control the drug release from balloons. An antiproliferative drug, paclitaxel (PAT), was incorporated into DS films (PAT‐DS). The characterizations using SEM, FT‐IR, and DSC showed that the films prepared were smooth and homogenous with PAT molecularly dispersed in the bulk of DS matrix in amorphous form. An investigation on the interaction of smooth muscle cells (SMCs) with control‐DS and PAT‐DS films showed that both films inhibited SMC growth, with a superior inhibitory effect observed for PAT‐DS films. PAT‐DS coatings were then produced on balloon catheters. The integrity of coatings was well‐maintained when the balloons were either deflated or inflated. In this study, up to 2.2 µg/mm2 of PAT was loaded on the balloons using the DS platform. Drug elution studies showed that only 10 to 20% of the total PAT loaded was released from the PAT‐DS coated balloons during the typical time period of balloon tracking (1 min) and then ∼80% of the total PAT loaded was released during the typical time period of balloon inflation and treatment (from 1 min to 4 min). Thus, this study demonstrated the use of DS as a platform to control drug delivery from balloons. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1416–1430, 2016.