Clinical treatment of Glioblastoma Multiforme (GBM) is generally ineffective in increasing patient survival. Convection-enhanced delivery (CED) is an alternative, investigative therapy in which a small caliber catheter is placed directly into the brain parenchyma. However, standard CED drug delivery techniques are unable to reach the entirety of the brain tumor, attributing to the failure of Phase III clinical trials. Fiber optic microneedle devices (FMDs), capable of simultaneous fluid and laser energy delivery, have shown potential to increase the drug dispersal volume when compared to fluid only devices. Previously described FMDs have had low laser transmission efficiency. In this work, we present two FMD manufacturing methods, a solid fiber inside capillary (SFIC) FMD and a modified fusion spliced (FS) FMD. Transmission efficiency of the two proposed FMDs were measured using a 1064 nm laser and an integrating sphere detector with air, deionized water, and black ink inside of the bore of the FMDs. The transmission efficiency of the FS FMD was between 45 and 127% larger than that of previously reported FS FMDs. Additionally, the transmission efficiency of the SFIC was significantly higher than the FS FMD (p ≤ 0.04 for all groups). However, the SFIC FMDs suffered catastrophic fracture failure at bend radii smaller than the manufacture specification, likely due to scribing of the capillary during the FMD fabrication process. Modifying FS FMDs appears to be the preferred fabrication method providing improved light transmission efficiency and mechanical strength on par with the capillary manufacturer’s specifications.

Many gastric motility disorders, including gastroparesis, are caused by dysrhythmias occurring in the stomach musculature. Microwave ablation (MWA) offers potential as a minimally invasive endoscopic approach for targeted thermal destruction of the gastric musculature to disrupt irregular electrical rhythm within the stomach wall. An experimental study was conducted in a gel phantom to analyze the transient heating profile of a water-cooled 2.45 GHz MWA antenna enclosed within a PET balloon. Fiber-optic temperature sensors were used to collect temperature data at distances 1.5–7.5 mm from the balloon surface. Ablation profiles were also characterized in ex vivo porcine skeletal muscle. With 20 W applied power and cooling water temperature of 5 °C, temperature measured at 3.5 mm from the balloon surface exceeded the temperature at 1.5 mm from the balloon surface by 3 °C. In ex vivo tissue, for 40 W applied power, tissue within 2 mm of the balloon surface remained unablated. With adequate cooling and power, it may be feasible to thermally spare tissue within 2 mm of the MWA balloon applicator.

“No-option” patients have vasculature too tortuous for existing catheters to navigate. To treat these patients, new catheter technologies are needed that are easy to actuate and can be customized for each patient. We propose using fiber-reinforced elastomeric enclosures (FREEs), which have been shown to be capable of performing screwing, spiraling, twisting, extending, and other motions when the fiber wrap angles are adjusted. Here, we present and validate an automated system capable of manufacturing FREEs with wrap angles from 0–90 degrees. The prescribed fiber angles were within 5 percent error when manufactured.

Additive Manufacturing or 3D Printing as it is commonly known is increasingly being used in the manufacturing of tissue engineering scaffold. The process allows for just in time production and customization. Hence, optimizing and varying the morphology of the tissue engineering scaffold in accordance to the application is one of the advantages of 3D printing. This paper aims to optimize the surface scaffold morphology by varying the dimensional parameters such as pore size, fibre diameter, orientation of fibres on scaffold and number of layers on the scaffold. The paper makes use of Taguchi’s Design of Experiments to understand and analyse the relationship between the different parameters that influence the morphological and mechanical characteristics of the scaffold.

While great strides continue to be made in the treatment of congestive heart failure using mechanical ventricular assist devices (VADs), several longstanding difficulties associated with pumping blood continue to limit their long-term use. Among the most troublesome has been the persistent risk of clot formation at the blood-device interface, which generally requires VAD recipients to undergo costly — and potentially dangerous — anticoagulation therapy for the duration of the implant. Another serious and persistent problem with long-term use of these pumps is the increased risk of infection associated with the use of percutaneous drivelines. To address these issues we are currently exploring a new approach to blood pump design that aims to solve both these problems by avoiding them altogether. Toward that end, we propose to harness the body’s own endogenous energy stores in order to eliminate the need to transmit energy across the skin. Further, we intend to transfer the energy from this internal power source to the circulation without contacting the blood to obviate the thrombogenic risks imposed by devices placed directly into the bloodstream. To power the implant we will employ a device developed previously by our group called a muscle energy converter (MEC), shown in Figure 1 . The MEC is, in essence, an implantable hydraulic actuator powered by the latissimus dorsi (LD) muscle with the capacity to transmit up to 1.37 joules of contractile work per stroke [ 1 ]. By training the muscle to express fatigue-resistant oxidative fibers and stimulating the LD to contract in coordination with the cardiac cycle, the MEC captures and transmits this contractile energy as a high-pressure low-volume (5 cc) hydraulic pulse that can be used, in principle, to actuate an implanted pulsatile blood pump. The goal of this research is to use the low-volume output of the MEC to drive a polymer-based aortic compression device for long-term circulatory support. In this context it is important to note that the idea of applying a counterpulsation device around the ascending aorta is not new. Indeed, this approach has been validated by clinical trials recently completed by Sunshine Heart Inc. showing that displacing 20 cc of blood at the aortic root has significant therapeutic benefits [ 2 ]. Unfortunately, while the pneumatic ‘C-Pulse’ device solves the blood-contacting problem, it suffers from the same limitations as traditional VADs — i.e., driveline infections. The device described here achieves the same volumetric displacement as the SSH device via geometric amplification of MEC outputs. Thus, through this mechanism we believe the low-volume power output of the MEC can be used to support heart failure patients while addressing the major limitations associated with long-term VAD use.

There is a trend towards miniaturization in surgical robotics with the objective of making surgeries less invasive [1]. There has also been increasing recent interest in hand-held robots because of their ability to maintain the current surgical workflow [2, 3]. We have previously presented a system that integrates small-diameter concentric tube robots [4, 5] into a hand-held robotic device [3], as shown in Figure 1. This robot was designed for transurethral laser surgery in the prostate. It provides the surgeon with two dexterous manipulators through a 5mm port in a traditional transurethral endoscope. This system enables the surgeon to retract tissue and aim a fiber optic laser simultaneously to resect prostate tissue. This robot provides the surgeon with a total of ten degrees of freedom (DOF) that must be simultaneously coordinated, including endoscope orientation (3 DOF), endoscope insertion (1 DOF), as well as the tip position of each concentric tube manipulator (3 DOF per manipulator). In [3], a simple user interface was employed that involved thumb joysticks (which also had pushbutton capability) and a unidirectional index finger trigger, as shown in Figure 2 (Left). The thumb joysticks were mapped to manipulator tip motion in the plane of the endoscope image, and the trigger was used for motion perpendicular to the plane. Whether the finger trigger extended or retracted the tip of the concentric tube manipulator was toggled via the pushbutton capability of the thumb joystick. While surgeons could learn this mapping with some effort, and were able to use it to accomplish a cadaver study, the experiments made clear that further work was needed in creating an intuitive user interface — particularly with respect to how motion perpendicular to the image plane is controlled. This paper describes a first step toward improving the user interface; we integrate a bidirectional dial input in place of the unidirectional index finger trigger, so that extension and retraction perpendicular to the image plane can be controlled without the need for a pushbutton toggle. In this paper we describe the design of this dial input and present the results of a user study comparing it to the interface in [3].

Limb sensorimotor function plays an important role in activities of daily living (ADLs) and quality of life. Spinal cord dysfunctions, such as cervical spondylotic myelopathy (CSM), often affect limb function and limit independence. In this paper, we apply technologies from the emerging field of soft robotics to develop Soft Robotic 3rd Arms (SR3As) that branch out of the body — thus providing an artificial limb that enables effective execution of ADLs for CSM patients and the like. Soft robotics is a fairly recent addition to the field of robotics. Differing from traditional, “hard”, robotics, soft robotics are made of flexible materials such as silicone rather than stiff materials such as metals. One such soft robotic actuator is the fiber-reinforced actuator (FRA). Fabricated utilizing a combination of silicone bladder(s) and inextensible materials, these actuators are able to perform one of various motions through changes of pressure [1]. Supernumerary limbs (3 rd arms), in contrast, are extra robotic limbs that can function cooperatively or independently of the user’s own limbs. These differ from exoskeletal robotics, as they are not fixated to the user’s limb to augment strength, but rather are placed elsewhere on the body to assist in tasks that would otherwise require multiple people. Examples of such devices include MIT/Boeing’s supernumerary arms to assist in the assembly of aircraft fuselage [2] or the supernumerary hand Softhand [3]. Combining these two concepts, an articulate SR3A was created (Fig. 1). By replacing traditional actuators with soft actuators, the limb is not only lighter, but it also better replicates the equivalent human limb. In addition to these benefits, the SR3A would also need to be less expensive to fabricate and actuate than an arm using rigid body components. This paper presents the design of a proof-of-concept prototype of a SR3A utilizing soft robotic actuators that could be used to assist individuals with hand impairments perform ADLs.

Many surgeons have come to view mitral valve (MV) repair as the treatment of choice in patients with mitral regurgitation (MR) [1]. According to recent long-term studies, the recurrence of significant MR after repair may be much higher than previously believed, particularly in patients with (ischemic mitral regurgitation) IMR [2]. We hypothesize that the restoration of homeostatic normal MV leaflet tissue stress in IMR repair techniques ultimately leads to improved repair durability. Therefore, the objective of this study is to develop a novel micro-anatomically accurate 3D finite element (FE) model that incorporates detailed collagen fiber architecture, accurate constitutive models, and micro-anatomically realistic valvular geometry to investigate the functional mitral valve and to aid in the assessment of the mitral valve repairs, especially the linking between the interstitial cellular deformations at the cellular level, the mechanobiological behaviors at the tissue level and the organ level mechanical responses as normal and repaired mitral valves maintaining their homeostatic state.

PLLA is a commonly used biodegradable polymer in stent designs because it is non-toxic and easily eliminated from the body. However, very little is known about the effect of loading conditions on the degradation rate. Rajagopal and Wineman developed a model of polymer degradation which is driven by load applied to the fiber [1]. Soares et. al. further developed this model for use with PLLA stent fibers under tensile loading conditions [2]. In this model the degradation rate is linearly related to deformation through the radius in the (I B , II B ) plane. Both models predict that greater deformation will induce a higher degree of degradation.

Constitutive modeling is critical for numerical simulation and analysis of soft biological tissues. The highly nonlinear and anisotropic mechanical behaviors of soft tissues are typically due to the interaction of tissue microstructure. By incorporating information of fiber orientation and distribution at tissue microscopic scale, the structural model avoids ambiguities in material characterization. Moreover, structural models produce much more information than just simple stress-strain results, but can provide much insight into how soft tissues internally reorganize to external loads by adjusting their internal microstructure. It is only through simulation of an entire organ system can such information be derived and provide insight into physiological function. However, accurate implementation and rigorous validation of these models remains very limited. In the present study we implemented a structural constitutive model into a commercial finite element package for planar soft tissues. The structural model was applied to simulate strip biaxial test for native bovine pericardium, and a single pulmonary valve leaflet deformation. In addition to prediction of the mechanical response, we demonstrate how a structural model can provide deeper insights into fiber deformation fiber reorientation and fiber recruitment.

The development of biomimetic materials for osteochondral tissue substitution and repair can be the start for a revolution in the classical procedures of orthopaedic surgery. The persisting problems, linked to the absence of a complete functional recovery of the articulation and to the stabilization and protraction of the half-life of an articular prosthesis can be overcome by the new class of osteochondral substitutes. The characteristics of the artificial bone tissue are drastically different from those of the natural one and this is mainly due to the absence of the peculiar self-organizing interaction between apatite crystals and proteic matrix. At this purpose a biomimetic approach was used in which apatitic phases are directly nucleated on different macromolecular matrices, which act as template and induce peculiar physico-chemical features in the mineral phase to create a substitute for osteochondral lesions. In particular a biologically inspired approach was applied to nucleate bone-like hydroxyapatite (HA) nanocrystals on self-assembling collagen fibers. Biohybrid composite materials were obtained mimicking composition, structure and morphology of human osteochondral interfaces. [1–4]

Colon cancer is estimated to be the third leading cause of cancer-related death in the US [1], with the cost of colorectal cancer treatment reaching $8.4 billion annually [2]. Though colonoscopy is the current standard for colon cancer screening and diagnosis, the procedure has disadvantages due from the near-blind navigation process used. During the procedure, endoscopists frequently lose sight of landmarks in the colon, losing track of their locations within the colon and becoming disoriented.

Microelectromechanical systems (MEMS) have great potential for use in gastrointestinal (GI) imaging. Ultrasound and magnetic resonant imaging can provide useful information about the GI tract, but only optical coherence tomography (OCT) delivered endoscopically can be used to perform an optical biopsy of the GI tissue. In monitoring a condition such as Barrett’s esophagus, which typically requires regular random biopsies, the ability to achieve an optical biopsy is indispensible. While the existing method for obtaining an optical biopsy of the GI tract tissue produces functional images, there are drawbacks that could be improved upon. The gear-and-shaft assembly used to couple force from the motor at the proximal end to the distal imaging end requires a complex design [1]. By introducing a rotational MEMS device into the distal imaging end, a rotating optical coupling joint is no longer required at the proximal end, there is no need to precisely align the fixed fiber with the rotational drive shaft, and the metallic reinforcement sleeve can be eliminated leaving a simpler, more flexible delivery method [2]. In order to produce 3D OCT images, displacement in the z-direction needs to be coupled with rotation. A MEMS device that can achieve both vertical displacement and rotation further increases the simplicity of the device and decreases potential alignment and coupling errors. Our MEMS devices needs to be able to bend an OCT beam of light 90°, rotate that beam of light 360°, and simultaneously scan in the z-direction in order to produce 3D OCT images. Also, the device must fit inside the 1 mm diameter available in the endoscope. To accomplish this, we have designed, and are continuing to develop, a paraffin actuated micro mirror. The thermal expansion properties of paraffin wax have often been utilized in MEMS devices [3, 4]. We have made use of these properties in designing a piston like actuator. Heat is applied to a reservoir of paraffin enclosed by a parylene membrane. The paraffin expands and pushes the post above it upward with the developed force from its expansion. The amount of paraffin in each reservoir is controlled by the reservoir’s geometry and so by controlling the amount of heat applied, we can control how far the post above it moves in the vertical direction. Each device has three heaters, three reservoirs, and three posts. All three posts are attached to a single mirror. By appropriately cycling the applied heat to each reservoir, we expect to be able to move the mirror in a spiral like fashion. This will bend an applied beam of light 90° and rotate it 360° while achieving displacement in the z-direction.

A steady-state model coupling mass transfer across cell and fiber membranes is theoretically developed to investigate the removal process of cryoprotective agents (CPAs) from cryopreserved blood with hollow fiber modules, and then CPA concentration variation and cell volume response are studied.

Cell encapsulation in hydrogels or microcapsules is one of the approaches for providing a biomimetic microenvironment to support cell survival, proliferation and functions. Microcapsules in particular have been used to improve the mass transport properties and ease of delivery through injection. More importantly, the microenvironment in hydrogels or hydrogel microcapsules can be tailored by incorporation of relevant adhesion molecules and growth factors through chemical conjugation and physical encapsulation. These functionalized hydrogels have been shown to effectively influence cell adhesion, proliferation and differentiation. In this study, we describe the preparation and characterization of a novel hydrogel fiber by polyelectrolyte complexation. This unique fiber geometry can be useful for regeneration of cylindrical tissues and for coculture of two different cell types inside and outside the fiber membrane.

Active steering at the distal tip can reduce stress on the flexible ureteroscope (FU) shaft by eliminating the internal angulation wires while also minimizing tissue trauma. A multi-segmented SMA wire actuator has been designed to produce smooth graded motion of the ultrathin scanning fiber endoscope (SFE). A steerable SFE distal tip (1-axis) is demonstrated using a three-step graded bending motion with a multi-tapped shape memory alloy (SMA) wire, power transistor switches, and binary parallel communication. The experimental bending radius and angle of the fabricated active tip (2-mm OD) is measured as 45-mm and 50°, respectively. Using nominal 4% strain of a 125-μm SMA wire, the experimental values are compared to the model predictions using a multi-link planar manipulator. A guidewire with eyes and active tip bending mechanism constitutes the new SFE, which is expected to reduce the procedural time and complications, eliminate X-ray guidance, and provide more space for adjunctive instrumentation, along with having better performance and possibly lower cost than FU.

Aethlon Medical is developing an extracorporeal blood filter as a therapeutic device designed to remove viruses and toxins from the blood of patients. The Hemopurifier is a modified hollow-fiber plasmapheresis cartridge containing an affinity matrix in the extra capillary space. The matrix contains a high mannose specific lectin as the active capture agent. The flow configuration of the device is that of Starling flow. The filter is designed to clear viruses and toxins from blood, delaying illness so the patient’s immune system can fight off the virus. Results to date indicate the efficient removal of a variety of enveloped viruses including HIV, HCV and poxviruses with in vitro evidence indicating the ability to capture Dengue fever virus, measles, mumps, influenza, Ebola and Marburg. Possible additional targets include bioweapons such as smallpox and bacterial toxins. A schematic of the use of the filter in a therapeutic application is shown in figure 1. In order to optimize the design of such a filter, the fluid mechanics of the device is modeled analytically and investigated experimentally. Additional information can be found in Tullis et al. [1], Tullis et al. [2], and Duffin and Tullis [2].