Springer Science and Business Media LLC

An anatomically accurate model of the conducting airways is essential for adequately simulating gas mixing, particle deposition, heat and water transfer, and fluid distribution. We have extended a two-dimensional tree-growing algorithm to three dimensions for generation of a host-shape dependent three-dimensional conducting airway model. Terminal branches in the model are both length limited and volume-supplied limited. A limit is imposed on the maximum possible branch angle between a daughter and parent branch. Comparison of the resulting model with morphometric data shows that the algorithm produces branching and length ratios, path lengths, numbers of branches, and branching angles very close to those from the experimental data. The correlation between statistics from the generated model and those from morphometric studies suggests that the conducting airway structure can be described adequately using a “supply and demand” algorithm. The resulting model is a computational mesh that can be used for simulating transport phenomena. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8710+e

In this article, a “bedside to bench and back” approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the U.S. Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or new drug application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented.

This article is based on a lecture I presented as the recipient of the 2009 Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society annual meeting in October 2009. Here, I review more than thirty years of research from my laboratory, beginning with studies designed to test the theory that cells use tensegrity (tensional integrity) architecture to stabilize their shape and sense mechanical signals, which I believed to be critical for control of cell function and tissue development. Although I was trained as a cell biologist, I found that the tools I had at my disposal were insufficient to experimentally test these theories, and thus I ventured into engineering to find critical solutions. This path has been extremely fruitful as it has led to confirmation of the critical role that physical forces play in developmental control, as well as how cells sense and respond to mechanical signals at the molecular level through a process known as cellular mechanotransduction. Many of the predictions of the cellular tensegrity model relating to cell mechanical behaviors have been shown to be valid, and this vision of cell structure led to discovery of the central role that transmembrane adhesion receptors, such as integrins, and the cytoskeleton play in mechanosensing and mechanochemical conversion. In addition, these fundamental studies have led to significant unexpected technology fallout, including development of micromagnetic actuators for non-invasive control of cellular signaling, microfluidic systems as therapeutic extracorporeal devices for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit construction of artificial tensegrities that mimic properties of living materials for applications in tissue engineering and regenerative medicine.

Studying the mechanics of the knee joint has direct implications in understanding the state of human health and disease and can aid in treatment of injuries. In this work, we developed an axisymmetric model of the human knee joint using finite element method, which consisted of separate parts representing tibia, meniscus and femoral, and tibial articular cartilages. The articular cartilages were modeled as three separate layers with different material characteristics: top superficial layer, middle layer, and calcified layer. The biphasic characteristic of both meniscus and cartilage layers were included in the computational model. The developed model was employed to investigate several aspects of mechanical response of the knee joint under external loading associated with the standing posture. Specifically, we studied the role of the material characteristic of the articular cartilage and meniscus on the distribution of the shear stresses in the healthy knee joint and the knee joint after meniscectomy. We further employed the proposed computational model to study the mechanics of the knee joint with an artificial meniscus. Our calculations suggested an optimal elastic modulus of about 110 MPa for the artificial meniscus which was modeled as a linear isotropic material. The suggested optimum stiffness of the artificial meniscus corresponds to the stiffness of the physiological meniscus in the circumferential direction.