Ali Khademhosseini

Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks

Engineered tissues need a vascular network to supply cells with nutrients and oxygen after implantation. A network that can connect to the vasculature of the patient after implantation can be included during in vitro culture. For optimal integration, this network needs to be highly organized, including venules, capillaries, and arterioles, to supply all of the cells with sufficient nutrients. Owing to the importance of vascularization for the clinical applicability of tissue engineering, many approaches have been investigated to include an organized vascular network in tissue constructs. This review will give an overview of recent efforts, and will propose future perspectives to engineer the optimal, functional vascular network.

Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds

Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration.

The Synergy of Scaffold-Based and Scaffold-Free Tissue Engineering Strategies

Tissue engineering (TE) is a highly interdisciplinary research field driven by the goal to restore, replace, or regenerate defective tissues. Throughout more than two decades of intense research, different technological approaches, which can be principally categorized into scaffold-based and scaffold-free strategies, have been developed. In this opinion article, we discuss the emergence of a third strategy in TE. This synergetic strategy integrates the advantages of both of these traditional approaches, while being clearly distinct from them. Its characteristic attributes, numerous practical benefits, and recent literature reports supporting our opinion, are discussed in detail.

Wearables in Medicine

Abstract Wearables as medical technologies are becoming an integral part of personal analytics, measuring physical status, recording physiological parameters, or informing schedule for medication. These continuously evolving technology platforms do not only promise to help people pursue a healthier life style, but also provide continuous medical data for actively tracking metabolic status, diagnosis, and treatment. Advances in the miniaturization of flexible electronics, electrochemical biosensors, microfluidics, and artificial intelligence algorithms have led to wearable devices that can generate real‐time medical data within the Internet of things. These flexible devices can be configured to make conformal contact with epidermal, ocular, intracochlear, and dental interfaces to collect biochemical or electrophysiological signals. This article discusses consumer trends in wearable electronics, commercial and emerging devices, and fabrication methods. It also reviews real‐time monitoring of vital signs using biosensors, stimuli‐responsive materials for drug delivery, and closed‐loop theranostic systems. It covers future challenges in augmented, virtual, and mixed reality, communication modes, energy management, displays, conformity, and data safety. The development of patient‐oriented wearable technologies and their incorporation in randomized clinical trials will facilitate the design of safe and effective approaches.

Overview of Silk Fibroin Use in Wound Dressings

Recently, biomimetic wound dressings were introduced as potential replacements for treating skin injuries. Although there are some clinically available skin replacements, the range of wound types and locations necessitates a broader range of options for the clinic. Natural polymeric-based dressings are of central interest in this area due to their outstanding biocompatibility, biodegradability, low toxicity, and non-allergenic nature. Among them, silk fibroin (SF) has exceptional characteristics as a wound dressing. SF-based dressings can also be used as carriers for delivering drugs, growth factors, and bioactive agents to the wound area, while providing appropriate support for complete healing. In this review, we describe recent advances in the development of SF-based wound dressings for skin regeneration.

Characterization, mechanistic analysis and improving the properties of denture adhesives

OBJECTIVEnDenture adhesives are widely used to avoid the detachment and sliding of dentures. However, the adhesion properties can be affected by variation in mouth conditions such as the level of salivation. The objective of this study was to understand the effect of environmental conditions on the adhesion properties of a commercially available denture adhesive named as Poligrip® Free manufactured by GlaxoSmithKline Ltd., UK and to identify the reasons for the observed variation in its adhesion strength.nnnMETHODSnThe failure mechanisms of denture adhesive have been assessed through using different physical, mechanical and thermal characterization experiments. All methods were used in different pH, temperatures, and salivation conditions and at the end, a strategy was proposed to overcome the failure of the paste in hyposalivation as well.nnnRESULTSnIn vitro models mimicking the denture gingival interface were designed to evaluate the adhesion properties of the investigated adhesive. Changes in the adhesion strength in response to three major factors related to the oral conditions including level of salivation, pH, and temperature were measured. The results of lap shear, tensile test, and internal interactions suggested a cohesion failure, where the lowest adhesion strength was due to hyposalivation. Fourier transform infrared spectroscopy (FTIR) and rheological analysis confirmed the importance of hydrogen bonds and hydration in the adhesion strength of the paste.nnnSIGNIFICANCEnThe investigated scenarios are widely observed in patient using denture adhesives and the clinical reports have indicated the inconsistency in adhesion strength of the commercial products. After identifying the potential reasons for such behavior, methods such as the addition of tripropylene glycol methyl ether (TPME) to enhance internal hydrogen bonds between the polymers are proposed to improve adhesion in the hyposalivation scenario.

Adenosine-associated delivery systems.

Abstract Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (<10u2009s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this article, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted.

Chapter 1:Microtechnologies in the Fabrication of Fibers for Tissue Engineering

Engineering tissues and organs for implantation in the human body or research require the fabrication of constructs that reproduce a physiological environment. Moreover, the construction of complex and sizable three-dimensional tissues requires a precise control over cell distribution and an effective vasculature network to supply oxygen and nutrients, and remove waste. Fiber-based tissue engineering that forms 3D structures using fibers can address many of these challenges, but depends on the quality of the fibers. Recent progresses in microtechnologies have enabled researchers to fabricate biocompatible fibers with advanced biochemical and physical properties, including cell-laden fibers that are pre-seeded with cells. In this chapter, we discuss fiber fabrication techniques including co-axial flow spinning, wetspinning, meltspinning, and electrospinning, which have leveraged microtechnologies to improve their performance. We compare the properties of the fibers fabricated with these methods and discuss their strengths and weaknesses in the context of tissue engineering.

Anti-fouling strategies for central venous catheters

Central venous catheters (CVCs) are ubiquitous in the healthcare industry and carry two common complications, catheter related infections and occlusion, particularly by thrombus. Catheter-related bloodstream infections (CRBSI) are an important cause of nosocomial infections that increase patient morbidity, mortality, and hospital cost. Innovative design strategies for intravenous catheters can help reduce these preventable infections. Antimicrobial coatings can play a major role in preventing disease. These coatings can be divided into two major categories: drug eluting and non-drug eluting. Much of these catheter designs are targeted at preventing the formation of microbial biofilms that make treatment of CRBSI nearly impossible without removal of the intravenous device. Exciting developments in catheter impregnation with antibiotics as well as nanoscale surface design promise innovative changes in the way that physicians manage intravenous catheters. Occlusion of a catheter renders the catheter unusable and is often treated by tissue plasminogen activator administration or replacement of the line. Prevention of this complication requires a thorough understanding of the mechanisms of platelet aggregation, signaling and cross-linking. This article will look at the advances in biomaterial design specifically drug eluting, non-drug eluting, lubricious coatings and micropatterning as well as some of the characteristics of each as they relate to CVCs.

Microfabrication techniques in materiomics

Scope: This chapter deals with an overview of basic microfabrication techniques. The goal is to explain to the reader how such techniques can be utilized in the field of materiomics. The basic processes used in microfabrication including photolithography, etching, electron beam lithography and micromoulding are explained. Some classic examples of these techniques as applied to materiomics are also shown. Furthermore, possible uses of such techniques, and the development and application of hybrid techniques to be able to answer fundamental questions about biological behaviour of materials, are also suggested. Basic principles of microfabrication: Introduction: Techniques used to fabricate structures or devices smaller than 100 µm are commonly referred to as microfabrication techniques. Initially meant for the electronics industry, they have found a wide range of applications in diverse fields such as chemical engineering and the life sciences. Since the early 1990s, the application of microfabrication technologies in the area of chemical and biological analysis has been termed ‘micro total analysis systems’ (µTAS) (1). Microfabricated devices meant for µTAS initially offered the advantage of sample analysis on the microscale, but over the years, the evolution of these technologies has led to the facilitation of sample preparation, fluid handling, separation systems, cell handling and cell culturing in an integrated manner (1). The application of microtechnologies for the fabrication of devices or systems to study material properties benefits from cost efficiency, high performance, precision-based design flexibility, miniaturization and automated analysis. Miniaturization involves the convergence of multiple disciplines, such as fluid dynamics, material sciences, engineering and the life sciences, that need to join expertise in order to design functional systems. Moreover, these devices can be used to evaluate biological behaviour in vitro and can help us to test thousands of different biomaterials and surface properties without the complexity related to in vivo assays.