The advent of biocompatible and biodegradable scaffolds has opened up a plethora of possibilities in neural tissue engineering. An emerging approach to overcome some existing drawbacks of neural scaffold design and functioning is a natural conductive polymeric scaffold. It is analogous to the extracellular matrix and provides an environment conducive to neural growth. This study focuses on the fabrication of soft polymeric neural scaffold, reinforced with multi-walled carbon nanotubes (MWCNTs) in a chitosan matrix, for directional neuronal growth. The scaffolds were fabricated by varying the nanofiller content as 0.5, 1.0 and 2.0. wt%, which were aligned in the chitosan matrix by an alternating bias electric field and compared with their random counterpart. The uniform distribution of the nanofillers in the matrix, good combinatorial bonding, and the directional alignment of the MWCNTs resulted in enhancement of mechanical properties and electrical conductivity in comparison to scaffolds with randomly arranged reinforcements. Additionally, the degradation kinetics of the fabricated scaffolds was tuned to the regeneration regime of peripheral nerves. After physical characterization, the biocompatibility of the designed scaffolds was evaluated by culturing HT-22 neuronal cells on the scaffolds. Along with biocompatibility, the suitability of anisotropic conductivity of the scaffolds was evaluated by the directional growth of cells cultured on aligned MWCNT–chitosan scaffold. The preferential direction of neurite growth achieved on chitosan-aligned MWCNT films and the improved mechanical and electrical properties in the MWCNT alignment direction are very encouraging for their potential use in neural tissue engineering.
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the West and has a 5-year survival rate of only 2%–9%. Pancreatic cystic lesions are precursors of pancreatic cancers and a prime target for early diagnosis. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) enables collection of cystic fluid aiming for the diagnosis of malign and premalign cysts. However, this fluid is acellular or paucicellular in 20% of cases, hampering a proper diagnosis. Here, we introduce a minimally invasive Nitinol brush that can be operated through the 413 µm lumen of a 22G FNA needle. During operation, the brush is rotated against the inner wall of the cyst, removing cells and dispersing them in the cystic fluid, where they can be aspirated through the needle. We demonstrate the brush function using three models. An in vitro cyst model was used to visualize the brushing procedure and the mechanical interaction between the brush and the wall of a spherical cavity. Ex vivo porcine intestine and bovine ovary cyst models were used to demonstrate how brushing increases the number of harvested cells with more than one order of magnitude. These results indicate the potential of cystic brushing for the minimally invasive early diagnosis of pancreatic adenocarcinoma.
A broader revelation of the mechanisms which contribute to the formation, growth, healing and remodelling of bone tissue is essential for advancing the design and development of biomaterials and devices which directly enhance bone health. Hydroxyapatite and associated calcium phosphate-based minerals play an essential role in bone tissue formation. Further insights into how biomineral crystals form, grow and integrate within bone tissue will provide key information to direct efforts in more comprehensive bone tissue engineering products and therapies. While previous studies proposed the aggregation of amorphous calcium phosphate clusters as a precursor to biological hydroxyapatite, the exact formation mechanism of the plate-like biological hydroxyapatite is still unclear. Here we report the analysis of high-resolution electron microscopy images of bone biomineral precipitated in a biological environment. We propose that 3 nm primary biologically synthesized (biosynthesized) hydroxyapatite (BHAp) single crystal units assemble and coalesce via an oriented aggregation mechanism to form larger (approximately 46 nm × 25 nm) plate-like biological hydroxyapatite mesocrystals. A better understanding of the biomineralization process can provide insights to improve the in vitro precipitation of bone biominerals with tailored properties and unique functionality. This will help to usher in the next generation of biobased biomaterials and devices to enhance the healing and remodelling of bone at the tissue, cell and subcellular level.
It should be noted that there is an absence of satisfactory medical devices for children with many types of medical conditions due to the relatively small size of the paediatric medical service market as compared with the adult medical service market, which does not incentivize many companies to focus on the particular characteristics and needs of children (Field et al., (2006). Five to six per cent of healthcare spending is for children despite the fact the children constitute 25 per cent of the overall population (Barbella, 2014). In addition, “the reality of (the medical device companies’) business structures don't allow them to (work on paediatric products) because it's not going to be something that will help their bottom line, and they have to answer to their shareholders” according to Don Lombardi (former Chief Intellectual Property Officer, Boston Children's Hospital, and founder of the Institute for Pediatric Innovation) (Barbella, 2014). The return on investment for a paediatric medical device falls below the profit goals of many medical device manufacturers (Crosse2011). In addition, medical devices are now being used with younger patients than in earlier years. Kurt Vedder (CEO, Fixes 4 Kids Inc.) noted that ‘surgeons are operating earlier in a child's life and because of that there's a need for technology, tools and devices (Barbella, 2014)'. Another limitation to the development of paediatric medical devices is that each child exhibits a different activity level, chemical composition, height, heart rate and blood pressure from his or her peers; in addition, these values will vary in a given child over time (Barbella, 2014). This limitation hinders the development of ‘generic’ medical devices for use over a wide paediatric population. Furthermore, medical device companies may not be able to readily obtain parental consent for a study; such ethical issues are considered a significant challenge to paediatric medical device development. Finally, there is also a perception of higher liability levels associated with paediatric medical devices (Barbella, 2014). Paediatricians and patient advocates have noted the possibility of adverse outcomes associated with the unavailability of paediatric medical devices (Food & Drug Administration, 2004). Many efforts at this time involve ‘working around’ the absence of an appropriate medical device for children with a repurposed adult medical device. For example, stents for use in the bile duct are repurposed for use in paediatric heart catheterization since no paediatric heart stents are available. Although FDA regulations permit ‘off-label’ or unlabelled uses of medical devices, many such devices do not precisely fit patient needs; for example, bile duct stents are associated with risk of either perforating or blocking the blood vessel undergoing treatment (Shaffer et al., 1998). A new paediatric-specific medical device may be necessary if the workaround is insufficient (e.g. a medical device scaled for paediatric use is unavailable). Additive manufacturing is a technology that was developed approximately thirty years ago for fabrication of machine tool prototypes (Boland et al., 2007). The term additive manufacturing is used to describe fabrication of three-dimensional structures via selective joining of materials in an additive layer-by-layer manner. Additive manufacturing techniques have recently been used to create patient-specific medical devices with small-scale features. For example, data obtained from magnetic resonance imaging, computed tomography or other imaging techniques may be utilized to create patient-specific implants, prostheses and medical devices. These customized medical devices may possess suitable features, including geometry, size and weight, for diagnosis and/or treatment of a given medical condition. Unlike conventional machining-based processes, medical devices with complex internal geometries (e.g. catheters with interlocking tips) may be generated via additive manufacturing processes (Azari & Nikzad, 2002; Pham & Gault, 1998; Sun et al., 2004; Webb, 2000). It is important to note that additive manufacturing processes can create structures with fewer steps and more quickly than conventional machining-based processes; the product development cycle may be lowered to 10-20% that of traditional methods per Hou and coworkers (Hou et al., 2010; Peltola et al., 2008). Additive manufacturing can overcome the limitations associated the conventional paediatric medical device manufacturing approaches since it allows for rapid processing of medical devices with patient-specific features and complex geometries at low cost and in low volumes (Field et al., 2006). The prices for many types of additive manufacturing machines have decreased in recent months, and the trend is expected to continue as additive manufacturing patents expire (Arrowsmith, 2013). A company has demonstrated processing of a prosthetic hand for a child with symbrachydactyly for between $3.80 and $5.00 (Arrowsmith, 2013). Additive manufacturing has been recently used to create an implantable customized tracheal splints out of a degradable polycaprolactone powder (Barbella, 2014). Prof. Glenn Green and Prof. Scott Hollister at the University of Michigan obtained computed tomography scans of the respiratory tracts of two paediatric patients and used this information to create splints that matched the patients’ anatomical features (Barbella, 2014). Additive manufacturing is also being widely used to manufacture prosthetic limbs due to the advantages of customization, low cost and distributed manufacturing (Zuniga et al., 2015). It is anticipated that additive manufacturing will play a growing role in manufacturing of medical devices over the coming years.
AbstractExhaled breath test is a typical disease monitoring method for replacing blood and urine samples that may create discomfort for patients. To monitor exhaled breath markers, gas biomedical sensors have undergone rapid progress for non‐invasive and point‐of‐care diagnostic devices. Among gas sensors, metal oxide‐based biomedical gas sensors have received remarkable attention owing to their unique properties, such as high sensitivity, simple fabrication, miniaturization, portability and real‐time monitoring. Herein, we reviewed the recent advances in chemoresistive metal oxide‐based gas sensors with ZnO, SnO2 and In2O3 as sensing materials for monitoring a range of exhaled breath markers (i.e., NO, H2, H2S, acetone, isoprene and formaldehyde). We focused on the strategies that improve the sensitivity and selectivity of metal oxide‐based gas sensors. The challenges to fabricate a functional gas sensor with high sensing performance along with suggestions are outlined.
