Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid

The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.     

Biodegradable Implantable Sensors: Materials Design,Fabrication, and Applications

The ability to monitor diseases, therapies, and their effects on the body is a critical component of modern care and personalized medicine. Real time monitoring can be achieved by analyzing body fluids or by applying sensors on, or alternatively, inside the body. Implantable sensors, however, must be removed. Second removal procedures lead to further tissue damage, which can be a problem in tissues such as those of the central nervous system. The use of biodegradable sensors alleviates these problems since they do not require removal procedures. Recent advances in material science made it possible for all sensor components to be biodegradable. Small size and power of implants, and the limited selection of materials are the main constraints determining the capabilities of the biodegradable device. Thus, the design will be always a challenge exploring a trade-off among these parameters. Despite of the encouraging results illustrating that biodegradable sensors can be as accurate and reliable as commercially available nondegradable ones, biodegradable implantable sensors are still in their infancy. Significant advances made in this area are critically reviewed in this paper, and future prospects are highlighted.     

A Patch of Detachable Hybrid Microneedle Depot for Localized Delivery of Mesenchymal Stem Cells in Regeneration Therapy

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, a detachable hybrid microneedle depot (d‐HMND) for cell delivery is presented. The system consists of an array of microneedles with an outer poly(lactic‐co‐glycolic) acid shell and an internal gelatin methacryloyl (GelMA)‐MSC mixture (GMM). The GMM is characterized and optimized for cell viability and mechanical strength of the d‐HMND required to penetrate mouse skin tissue is also determined. MSC viability and function within the d‐HMND is characterized in vitro and the regenerative efficacy of the d‐HMND is demonstrated in vivo using a mouse skin wound model.     

Cancer Modeling‐on‐a‐Chip with Future Artificial Intelligence Integration

Cancer is one of the leading causes of death worldwide, despite the large efforts to improve the understanding of cancer biology and development of treatments. The attempts to improve cancer treatment are limited by the complexity of the local milieu in which cancer cells exist. The tumor microenvironment (TME) consists of a diverse population of tumor cells and stromal cells with immune constituents, microvasculature, extracellular matrix components, and gradients of oxygen, nutrients, and growth factors. The TME is not recapitulated in traditional models used in cancer investigation, limiting the translation of preliminary findings to clinical practice. Advances in 3D cell culture, tissue engineering, and microfluidics have led to the development of “cancer‐on‐a‐chip” platforms that expand the ability to model the TME in vitro and allow for high‐throughput analysis. The advances in the development of cancer‐on‐a‐chip platforms, implications for drug development, challenges to leveraging this technology for improved cancer treatment, and future integration with artificial intelligence for improved predictive drug screening models are discussed.     

Solution dynamics of the dextran/crosslinking agent systems

The interaction of some selective Cl‐ and N‐containing functional crosslinking agents such as epichlorohydrin (ECH), N,N′‐methylenebisacrylamide (MBAM), and bifunctional agents such as glutaraldehyde (GA) and glycidylmethacrylate (GM) with dextran (Dx) in aqueous solutions were studied by viscometric and spectroscopic methods. The dynamic viscosities of Dx‐crosslinker aqueous solutions have been measured at physiological temperature, 37°C and in the concentration range of 0.22–0.4 g/dL. Concentration of crosslinkers were kept constant at 0.001–0.35 mol/L. Viscosity behavior of the solutions was interpreted using the Huggins and Kraemer equations. Moreover, the interaction between hydroxyl groups of the Dx with crosslinkers in aqueous solutions, structure properties was also confirmed thereby use of Raman and FTIR spectroscopy. For the Dx/crosslinker systems, the decreasing order of interaction was determined as ECH > GA > MBAM > GM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Development of diclofenac sodium releasing bio-erodible polymeric nanomats

Application of nanofiber-based nanomats in medicine is attractive and thanks to the 3D nanostructure and the high surface to volume ratio they are excellent for local controlled drug delivery. The use of bioactive bioerodible polymers for developing drug delivery nanomats may allow for drug release and targeting control. Objective of the current study was to evaluate the suitability of bioerodible polymeric material based on n-butyl hemiester of [poly(maleic anhydride-alt-2-methoxyethyl vinyl ether)] (PAM14) for the preparation of nanomats for controlled administration of anti-inflammatory, diclofenac sodium (DS) drug. Samples were prepared using different polymer concentrations (5-10%) in either ethanol or acetic acid as solvent. Morphology was investigated by using scanning electron microscopy (SEM). Thermal analysis such as differential scanning calorimetry (DSC) was performed to detect effect on polymer arrangement. DS localization in electrospun nanomats was evaluated by using electron back scattering microanalysis, based on the detection of chlorine, and drug release kinetics was assessed using UV-Vis. Average fiber diameter resulted in the range of 100 nm to 1.0 microm and a homogeneous distribution of the loaded drug into the fibers was observed. The DS release was immediate and despite the preliminary nature of the performed electrospinning experiments, the achieved results appear promising for the future development of a novel system for the controlled and targeted administration of drug and active agent.     

Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering

With increasing interest in nanotechnology, development of nanofibers (n-fibers) by using the technique of electrospinning is gaining new momentum. Among important potential applications of n-fiber-based structures, scaffolds for tissue-engineering represent an advancing front. Nanoscaffolds (n-scaffolds) are closer to natural extracellular matrix (ECM) and its nanoscale fibrous structure. Although the technique of electrospinning is relatively old, various improvements have been made in the last decades to explore the spinning of submicron fibers from biodegradable polymers and to develop also multifunctional drug-releasing and bioactive scaffolds. Various factors can affect the properties of resulting nanostructures that can be classified into three main categories, namely: (1) Substrate related, (2) Apparatus related, and (3) Environment related factors. Developed n-scaffolds were tested for their cytocompatibility using different cell models and were seeded with cells for to develop tissue engineering constructs. Most importantly, studies have looked at the potential of using n-scaffolds for the development of blood vessels. There is a large area ahead for further applications and development of the field. For instance, multifunctional scaffolds that can be used as controlled delivery system do have a potential and have yet to be investigated for engineering of various tissues. So far, in vivo data on n-scaffolds are scarce, but in future reports are expected to emerge. With the convergence of the fields of nanotechnology, drug release and tissue engineering, new solutions could be found for the current limitations of tissue engineering scaffolds, which may enhance their functionality upon in vivo implantation. In this paper electrospinning process, factors affecting it, used polymers, developed n-scaffolds and their characterization are reviewed with focus on application in tissue engineering.