Microfluidics for Advanced Drug Delivery Systems.

Considerable efforts have been devoted towards developing effective drug delivery methods. Microfluidic systems, with their capability for precise handling and transport of small liquid quantities, have emerged as a promising platform for designing advanced drug delivery systems. Thus, microfluidic systems have been increasingly used for fabrication of drug carriers or direct drug delivery to a targeted tissue. In this review, the recent advances in these areas are critically reviewed and the shortcomings and opportunities are discussed. In addition, we highlight the efforts towards developing smart drug delivery platforms with integrated sensing and drug delivery components

Fiber-based tissue engineering: Progress, challenges, and opportunities.

Tissue engineering aims to improve the function of diseased or damaged organs by creating biological substitutes. To fabricate a functional tissue, the engineered construct should mimic the physiological environment including its structural, topographical, and mechanical properties. Moreover, the construct should facilitate nutrients and oxygen diffusion as well as removal of metabolic waste during tissue regeneration. In the last decade, fiber-based techniques such as weaving, knitting, braiding, as well as electrospinning, and direct writing have emerged as promising platforms for making 3D tissue constructs that can address the abovementioned challenges. Here, we critically review the techniques used to form cell-free and cell-laden fibers and to assemble them into scaffolds. We compare their mechanical properties, morphological features and biological activity. We discuss current challenges and future opportunities of fiber-based tissue engineering (FBTE) for use in research and clinical practice

Biomarkers and diagnostic tools for detection of Helicobacter pylori

Helicobacter pylori is responsible for worldwide chronic bacterial infection in humans affecting approximately half of the world’s population. H. pylori is associated with significant morbidity and mortality including gastric cancer. The infection has both direct and indirect impacts on economic and overall well-being of patients; hence, there is a great need for diagnostic markers that could be used in the development of diagnostic kits. Here, we briefly review general aspects of H. pylori infection and the diagnostic biomarkers used in laboratory tests today with a focus on the potential role of microfluidic systems in future immunodiagnosis platforms

Additive manufacturing of magnesium alloys

Magnesium alloys are a promising new class of degradable biomaterials that have a similar stiffness to bone, which minimizes the harmful effects of stress shielding. Use of biodegradable magnesium implants eliminates the need for a second surgery for repair or removal. There is a growing interest to capitalize on additive manufacturing\u27s unique design capabilities to advance the frontiers of medicine. However, magnesium alloys are difficult to 3D print due to the high chemical reactivity that poses a combustion risk. Furthermore, the low vaporization temperature of magnesium and common biocompatible alloying elements further increases the difficulty to print fully dense structures that balance strength and corrosion requirements. The purpose of this study is to survey current techniques to 3D print magnesium constructs and provide guidance on best additive practices for these alloys

Morphological and Physical Analysis of Natural Phospholipids-Based Biomembranes

Background: Liposomes are currently an important part of biological, pharmaceutical, medical and nutritional research, as they are considered to be among the most effective carriers for the introduction of various types of bioactive agents into target cells. Scope of Review In this work, we study the lipid organization and mechanical properties of biomembranes made of marine and plant phospholipids. Membranes based on phospholipids extracted from rapeseed and salmon are studied in the form of liposome and as supported lipid bilayer. Dioleylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC) are used as references to determine the lipid organization of marine and plant phospholipid based membranes. Atomic force microscopy (AFM) imaging and force spectroscopy measurements are performed to investigate the membranes' topography at the micrometer scale and to determine their mechanical properties. Major Conclusions The mechanical properties of the membranes are correlated to the fatty acid composition, the morphology, the electrophoretic mobility and the membrane fluidity. Thus, soft and homogeneous mechanical properties are evidenced for salmon phospholipids membrane containing various polyunsaturated fatty acids. Besides, phase segregation in rapeseed membrane and more important mechanical properties were emphasized for this type of membranes by contrast to the marine phospholipids based membranes. General Significance This paper provides new information on the nanomechanical and morphological properties of membrane in form of liposome by AFM. The originality of this work is to characterize the physico-chemical properties of the nanoliposome from the natural sources containing various fatty acids and polar head

Human Periodontal Ligament- and Gingiva-derived Mesenchymal Stem Cells Promote Nerve Regeneration When Encapsulated in Alginate/hyaluronic Acid 3D Scaffold

Repair or regeneration of damaged nerves is still a challenging clinical task in reconstructive surgeries and regenerative medicine. Here, we demonstrate that periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) isolated from adult human periodontal and gingival tissues assume neuronal phenotype in vitro and in vivo via a subcutaneous transplantation model in nude mice. PDLSCs and GMSCs were encapsulated in a three-dimensional scaffold based on alginate and hyaluronic acid hydrogels capable of sustained release of human nerve growth factor (NGF). We demonstrate that, the elasticity of the hydrogels affected the proliferation and differentiation of encapsulated MSCs within scaffolds. Moreover, we observed that PDLSCs and GMSCs were stained positive for βIII-tubulin, while exhibiting high levels of gene expression related to neurogenic differentiation (βIII-tubulin and GFAP) via qPCR. Western blot analysis showed the importance of the elasticity of the matrix and the presence of NGF in the neurogenic differentiation of encapsulated MSCs. In vivo, immunofluorescence staining for neurogenic specific protein markers confirmed islands of dense positively stained structures inside transplanted hydrogels. To our knowledge, this study is the first demonstration of the application of PDLSCs and GMSCs as promising cell therapy candidates for nerve regeneration

A paper-based in vitro model for on-chip investigation of the human respiratory system

Culturing cells at the air–liquid interface (ALI) is essential for creating functional in vitro models of lung tissues. We present the use of direct-patterned laser-treated hydrophobic paper as an effective semi-permeable membrane, ideal for ALI cell culture. The surface properties of the paper are modified through a selective CO2 laser-assisted treatment to create a unique porous substrate with hydrophilic regions that regulate fluid diffusion and cell attachment. To select the appropriate model, four promising hydrophobic films were compared with each other in terms of gas permeability and long-term strength in an aqueous environment (wet-strength). Among the investigated substrates, parchment paper showed the fastest rate of oxygen permeability (3 times more than conventional transwell cell culture membranes), with the least variation in its dry and wet tensile strengths (124 MPa and 58 MPa, remaining unchanged after 7 days of submersion in PBS).The final paper-based platform provides an ideal, robust, and inexpensive device for generating monolayers of lung epithelial cells on-chip in a high-throughput fashion for disease modelling and in vitro drug testing

In vivo printing of growth factor-eluting adhesive scaffolds improves wound healing

Acute and chronic wounds affect millions of people around the world, imposing a growing financial burden on patients and hospitals. Despite the application of current wound management strategies, the physiological healing process is disrupted in many cases, resulting in impaired wound healing. Therefore, more efficient and easy-to-use treatment modalities are needed. In this study, we demonstrate the benefit of in vivo printed, growth factor-eluting adhesive scaffolds for the treatment of full-thickness wounds in a porcine model. A custom-made handheld printer is implemented to finely print gelatin-methacryloyl (GelMA) hydrogel containing vascular endothelial growth factor (VEGF) into the wounds. In vitro and in vivo results show that the in situ GelMA crosslinking induces a strong scaffold adhesion and enables printing on curved surfaces of wet tissues, without the need for any sutures. The scaffold is further shown to offer a sustained release of VEGF, enhancing the migration of endothelial cells in vitro. Histological analyses demonstrate that the administration of the VEGF-eluting GelMA scaffolds that remain adherent to the wound bed significantly improves the quality of healing in porcine wounds. The introduced in vivo printing strategy for wound healing applications is translational and convenient to use in any place, such as an operating room, and does not require expensive bioprinters or imaging modalities

Sustainable drug release from polycaprolactone coated chitin‑lignin gel fibrous scaffolds

Non-healing wounds have placed an enormous stress on both patients and healthcare systems worldwide. Severe complications induced by these wounds can lead to limb amputation or even death and urgently require more effective treatments. Electrospun scaffolds have great potential for improving wound healing treatments by providing controlled drug delivery. Previously, we developed fibrous scaffolds from complex carbohydrate polymers [i.e. chitin-lignin (CL) gels]. However, their application was limited by solubility and undesirable burst drug release. Here, a coaxial electrospinning is applied to encapsulate the CL gels with polycaprolactone (PCL). Presence of a PCL shell layer thus provides longer shelf-life for the CL gels in a wet environment and sustainable drug release. Antibiotics loaded into core–shell fibrous platform effectively inhibit both gram-positive and -negative bacteria without inducting observable cytotoxicity. Therefore, PCL coated CL fibrous gel platforms appear to be good candidates for controlled drug release based wound dressing applications

Rheological, In Situ Printability and Cell Viability Analysis of Hydrogels for Muscle Tissue Regeneration

Advancements in additive manufacturing have made it possible to fabricate biologically relevant architectures from a wide variety of materials. Hydrogels have garnered increased attention for the fabrication of muscle tissue engineering constructs due to their resemblance to living tissue and ability to function as cell carriers. However, there is a lack of systematic approaches to screen bioinks based on their inherent properties, such as rheology, printability and cell viability. Furthermore, this study takes the critical first-step for connecting in-process sensor data with construct quality by studying the influence of printing parameters. Alginate-chitosan hydrogels were synthesized and subjected to a systematic rheological analysis. In situ print layer photography was utilized to identify the optimum printing parameters and also characterize the fabricated three-dimensional structures. Additionally, the scaffolds were seeded with C2C12 mouse myoblasts to test the suitability of the scaffolds for muscle tissue engineering. The results from the rheological analysis and print layer photography led to the development of a set of optimum processing conditions that produced a quality deposit while the cell viability tests indicated the suitability of the hydrogel for muscle tissue engineering applications