Background

Articular cartilage is a highly functional tissue which covers the ends of long bones and serves to ensure proper joint movement. A tissue engineering approach that recapitulates the developmental characteristics of articular cartilage can be used to examine the maturation and degeneration of cartilage and produce fully functional neotissue replacements for diseased tissue.

Methodology/principal findings

This study examined the development of articular cartilage neotissue within a self-assembling process in two phases. In the first phase, articular cartilage constructs were examined at 1, 4, 7, 10, 14, 28, 42, and 56 days immunohistochemically, histologically, and through biochemical analysis for total collagen and glycosaminoglycan (GAG) content. Based on statistical changes in GAG and collagen levels, four time points from the first phase (7, 14, 28, and 56 days) were chosen to carry into the second phase, where the constructs were studied in terms of their mechanical characteristics, relative amounts of collagen types II and VI, and specific GAG types (chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and hyaluronan). Collagen type VI was present in initial abundance and then localized to a pericellular distribution at 4 wks. N-cadherin activity also spiked at early stages of neotissue development, suggesting that self-assembly is mediated through a minimization of free energy. The percentage of collagen type II to total collagen significantly increased over time, while the proportion of collagen type VI to total collagen decreased between 1 and 2 wks. The chondroitin 6- to 4- sulfate ratio decreased steadily during construct maturation. In addition, the compressive properties reached a plateau and tensile characteristics peaked at 4 wks.

Conclusions/significance

The indices of cartilage formation examined in this study suggest that tissue maturation in self-assembled articular cartilage mirrors known developmental processes for native tissue. In terms of tissue engineering, it is suggested that exogenous stimulation may be necessary after 4 wks to further augment the functionality of developing constructs.

In this final portion of an extensive review of heart valve engineering, we focus on the computational methods and experimental studies related to heart valves. The discussion begins with a thorough review of computational modeling and the governing equations of fluid and structural interaction. We then move onto multiscale and disease specific modeling. Finally, advanced methods related to in vitro testing of the heart valves are reviewed. This section of the review series is intended to illustrate application of computational methods and experimental studies and their interrelation for studying heart valves.

In this portion of an extensive review of heart valve engineering, we focus on the current and emerging technologies and techniques to repair or replace the mitral valve. We begin with a discussion of the currently available mechanical and bioprosthetic mitral valves followed by the rationale and limitations of current surgical mitral annuloplasty methods; a discussion of the technique of neo-chordae fabrication and implantation; a review the procedures and clinical results for catheter-based mitral leaflet repair; a highlight of the motivation for and limitations of catheter-based annular reduction therapies; and introduce the early generation devices for catheter-based mitral valve replacement.

The engineering of technologies for heart valve replacement (i.e., heart valve engineering) is an exciting and evolving field. Since the first valve replacement, technology has progressed by leaps and bounds. Innovations emerge frequently and supply patients and physicians with new, increasingly efficacious and less invasive treatment options. As much as any other field in medicine the treatment of heart valve disease has experienced a renaissance in the last 10 years. Here we review the currently available technologies and future options in the surgical and transcatheter treatment of aortic valve disease. Different valves from major manufacturers are described in details with their applications.

As the first section of a multi-part review series, this section provides an overview of the ongoing research and development aimed at fabricating novel heart valve replacements beyond what is currently available for patients. Here we discuss heart valve replacement options that involve a biological component or process for creation, either in vitro or in vivo (tissue-engineered heart valves), and heart valves that are fabricated from polymeric material that are considered permanent inert materials that may suffice for adults where growth is not required. Polymeric materials provide opportunities for cost-effective heart valves that can be more easily manufactured and can be easily integrated with artificial heart and ventricular assist device technologies. Tissue engineered heart valves show promise as a regenerative patient specific model that could be the future of all valve replacement. Because tissue-engineered heart valves depend on cells for their creation, understanding how cells sense and respond to chemical and physical stimuli in their microenvironment is critical and therefore, is also reviewed.

In this final portion of an extensive review of heart valve engineering, we focus on the computational methods and experimental studies related to heart valves. The discussion begins with a thorough review of computational modeling and the governing equations of fluid and structural interaction. We then move onto multiscale and disease specific modeling. Finally, advanced methods related to in vitro testing of the heart valves are reviewed. This section of the review series is intended to illustrate application of computational methods and experimental studies and their interrelation for studying heart valves.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.