M. Karperien (Enschede, NL)
University of Twente Developmenal BioEngineeringPresenter Of 1 Presentation
24.3.1 - Knee Joint-On-A-Chip
Abstract
Introduction
None of the currently available animal models is capable of capturing the full complexity of osteoarthritis in man. Organ-on-chip technology is an emerging field aiming at developing miniaturized humanized models for understanding organ function in health and disease. These humanized models are expected better predictive for human disease than animals and ultimately my reduce the need of animal testing. Various attempts are currently explored to engineer a human knee joint-on-chip. It is expected that these joint-on-chip models proof valuable in deciphering complex interactions between joint tissues in the initiation and progression of disease which cannot easily be studied in human. Furthermore they may proof highly valuable in drug development programs.
Content
But how to engineer a joint-on-chip? This effort requires a multidisciplinary approach. It requires input from typical engineering disciplines from diverse fields like microfluidics, polymer chemistry and processing and physics of fluids with life sciences. In my presentation I will highlight basic principles from organ-on-chip technologies and present our strategy to engineer a human knee joint on chip. In our strategy we first focus on the development of individual modules each representing one of the joint tissues (i.e. synovial membrane, ligament, meniscus, cartilage, bone). After extensive testing and validation, these individual modules will be combined in a new chip: the Joint-on-Chip using plug and play strategies. We have started with the engineering of a cartilage and a synovium on chip and have set out strategies for device characterization and validation. I will present new chip designs that allow actuation of cartilage on chip that faithfully mimics compression and shear stress in the knee joint. For the cartilage on chip we have developed a monolithic organ-on-a-chip platform, in which engineered cartilage tissue composed of cells within a 3D hydrogel can be exposed to multi-modal mechanical stimulation, such as uniform compression and bulk shear strain. This mechanical stimulation is achieved through deflection of a thin elastic vertical membrane, which is actuated using three independently addressed yet connected pressurized chambers. By tuning the pressure applied in the different chambers (positive vs. negative, and amplitude), a variety of programmable deflection patterns can be created and, in turn, various cell stimulation modalities. The device design and actuation parameters were optimized to produce physiologically relevant compression and shear strain on a 3D cartilage model (ca. 5-12% and ca. 10 millirad, respectively). Encapsulated chondrocytes within the platform could be intermittently stimulated to simulate human locomotion patterns for at least 3 days. Advantageously, the fabrication of this monolithic platform is straightforward, with a single-step process. I will show our efforts to characterize these designs in more detail. Furthermore, I will present data on the engineering of a synovial membrane-on-chip containing a functional innate immune system. To develop a physiological relevant membrane we started to explore the use of various polymers like PDMS, PTMC and silk fibroin which was processed using elektrospinning. We subjected each of these membranes to extensive testing and developed strategies for the incorporation of these membranes in the chip designs. Also in the synovial on chip we incorporated actuation units that could impose stress and strain on the membrane mimicking the mechanical forces exerted on the membrane during joint movement. I will show the first data with cellular responses in both chip designs.