Laser-Assisted Nanotexturing and Silver Immobilization on Titanium Implant Surfaces to Enhance Bone Cell Mineralization and Antimicrobial Properties.

Despite the great advancement and wide use of titanium (Ti) and Ti-based alloys in different orthopedic implants, device-related infections remain the major complication in modern orthopedic and trauma surgery. Most of these infections are often caused by both poor antibacterial and osteoinductive properties of the implant surface. Here, we have demonstrated a facile two-step laser nanotexturing and immobilization of silver onto the titanium implants to improve both cellular integration and antibacterial properties of Ti surfaces. The required threshold laser processing power for effective nanotexturing and osseointegration was systematically determined by the level of osteoblast cells mineralized on the laser nanotextured Ti (LN-Ti) surfaces using a neodymium-doped yttrium aluminum garnet laser (Nd:YAG, wavelength of 1.06 µm). Laser processing powers above 24 W resulted in the formation of hierarchical nanoporous structures (average pore 190 nm) on the Ti surface with a 2.5-fold increase in osseointegration as compared to the pristine Ti surface. Immobilization of silver nanoparticles onto the LN-Ti surface was conducted by dip coating in an aqueous silver ionic solution and subsequently converted to silver nanoparticles (AgNPs) by using a low power laser-assisted photocatalytic reduction process. Structural and surface morphology analysis via XRD and SEM revealed a uniform distribution of Ag and the formation of an AgTi-alloy interface on the Ti surface. The antibacterial efficacy of the LN-Ti with laser immobilized silver (LN-Ti/LI-Ag) was tested against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The LN-Ti/LI-Ag surface was observed to have efficient and stable antimicrobial properties for over 6 days. In addition, it was found that the LN-Ti/LI-Ag maintained a cytocompatibility and bone cell mineralization property similar to the LN-Ti surface. The differential toxicity of the LN-Ti/LI-Ag between bacterial and cellular species qualifies this approach as a promising candidate for novel rapid surface modification of biomedical metal implants.

Small intestinal sampling capsule for inflammatory bowel disease type detection and management.

Although serum and fecal biomarkers (e.g., lactoferrin, and calprotectin) have been used in management and distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), none are proven to be a differential diagnostic tool between Crohn's disease (CD) and ulcerative colitis (UC). The main challenge with laboratory-based biomarkers in the stool test is the inability to indicate the location of the disease/inflammation in the gastrointestinal (GI) tract due to the homogenous nature of the collected fecal sample. For the first time, we have designed and developed a battery-free smart capsule that will allow targeted sampling of inflammatory biomarkers inside the gut lumen of the small intestine. The capsule is designed to provide a simple and non-invasive complementary tool to fecal biomarker analysis to differentiate the type of IBD by pinpointing the site of inflammatory biomarkers secretion (e.g., small or large bowel) throughout the GI tract. The capsule takes advantage of the rapid change from an acidic environment in the stomach to higher pH levels in the small intestine to dissolve a pH-sensitive polymeric coating as a means to activate the sampling process of the capsule within the small intestine. A swelling polyacrylamide hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid while also providing the required mechanical actuation to close the capsule once the sampling is completed. The hydrogel component along with the collected GI fluid can be easily obtained from the capsule through the screw-cap design for further extraction and analysis. As a proof of concept, the capsule's performance in sampling and extraction of bovine serum albumin (BSA) and calprotectin - a key biomarker of inflammation - was assessed within the physiologically relevant ranges. The ratio of extracted biomarkers relative to that in the initial sampling environment remained constant (∼3%) and independent of the sampling matrix in both in vitro and ex vivo studies. It is believed that the demonstrated technology will provide immediate impact in more effective IBD type differential diagnostic and treatment strategies by providing a non-invasive assessment of inflammation biomarkers profile throughout the digestive tract.

A Wireless Implantable Passive Intra-Abdominal Pressure Sensing Scheme via Ultrasonic Imaging of a Microfluidic Device.

In this article, we demonstrate a wireless and passive physiological pressure sensing scheme that utilizes ultrasound imaging of an implantable microfluidic based pressure sensitive transducer. The transducer consists of a sub-mm scale pressure sensitive membrane that covers a reservoir filled with water and is connected to a hydrophobic micro-channel. Applied pressure onto the transducer deflects the membrane and pushes the water from the reservoir into the channel; the water's travelling distance in the channel is a function of the applied pressure, which is quantitatively measured by using a 40 MHz ultrasound imaging system. The sensor presents a linear sensitivity of 42 kPa/mm and a spatial resolution of 1.2 kPa/30 µm in the physiological range of abdominal compartment syndrome. Reliability assessments of the transducer confirm its ability to remain functional after more than 600 cycles of pressure up to 55 kPa over the course of 2 days. Ex vivo experimental results verify the practical capability of the technology to effectively measure pressures under a 15 mm thick porcine skin. It is anticipated that this technology can be applied to a broad range of implantable pressure measurement, by simply tuning the thickness of the thin polydimethylsiloxane membrane and the geometry of the reservoir.

Flexible Microneedle Array Patch for Chronic Wound Oxygenation and Biofilm Eradication.

Chronic nonhealing wounds are a growing socioeconomic problem that affects more than 6 million people annually solely in the United States. These wounds are colonized by bacteria that often develop into biofilms that act as a physical and chemical barrier to therapeutics and tissue oxygenation leading to chronic inflammation and tissue hypoxia. Although wound debridement and vigorous mechanical abrasion techniques are often used by clinical professionals to manage and remove biofilms from wound surfaces, such methods are highly nonselective and painful. In this study, we have developed a flexible polymer composite microneedle array that can overcome the physicochemical barriers (i.e., bacterial biofilm) present in chronic nonhealing wounds and codeliver oxygen and bactericidal agents. The polymeric microneedles are made by using a facile UV polymerization process of polyvinylpyrrolidone and calcium peroxide onto a flexible polyethylene terephthalate substrate for conformable attachment onto different locations of the human body surface. The microneedles effectively elevate the oxygen levels from 8 to 12 ppm once dissolved over the course of 2 h while also providing strong bactericidal effects on both liquid and biofilm bacteria cultures of both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacterial strains commonly found in dermal wounds. Furthermore, the results from the ex vivo assay on a porcine wound model indicated successful insertion of the microneedles into the tissue while also providing effective bactericidal properties against both Gram-positive and Gram-negative within the complex tissue matrix. Additionally, the microneedles demonstrate high levels of cytocompatibility with less than 10% of apoptosis throughout 6 days of continuous exposure to human dermal fibroblast cells. The demonstrated flexible microneedle array can provide a better approach for increasing the effectiveness of topical tissue oxygenation as well as the treatment of infected wounds with intrinsically antibiotic resistant biofilms.