Chen Lab
Christopher Chen is a professor of biomedical engineering at Boston University and the College of Engineering Director of materials science engineering at the Biological Design Center. One of the world’s leading experts on regenerative medicine, Chen investigates tissue engineering and mechanobiology, which combines engineering and biology to study how physical forces and changes in cell or tissue mechanics affect development, physiology, and disease.
The Chen Lab seeks to understand how adhesive, mechanical, and biochemical interactions drive cell and tissue function, to use this knowledge to build biomimetic tissues as experimental models of disease and physiology, and to direct tissue remodeling and regeneration. 
Prof. Chen is studying how the cooperation between adhesive, mechanical and biochemical signaling drives tissues to organize during development, adapt to physical stresses, and devolve during disease. Dr. Chen’s laboratory examines these questions through the development and application of innovative technologies to control how cells interact with their surroundings, advancing numerous technologies from microfluidics, microelectromechanical systems (MEMS), nanofabrication, mechanobiology, biomaterials, and synthetic and stem cell biology. Dr. Chen’s research applies insights from these efforts to the biology and engineering of stem cells, tissue vascularization, cardiac tissue, and cancer.
Projects
Engineering Vascular Beds that Connect to Ex Vivo Tissue (2023)
PROJECT DESCRIPTION
Following a myocardial infarction, the necrotic tissue in the infarction zone is replaced by a fibrotic scar. Even though this scar tissue helps to hold the heart together and maintain its structure, it does not contribute to the heart’s function and can impair its ability to contract and relax properly. One of the main goals of the Cell-MET program is to engineer a vascularized cardiac patch that can be grafted onto scar tissue to assist the heart with its pumping action. Successful engraftment of the cardiac patch into the host tissue depends on rapid anastomosis of the engineered vasculature to the host vasculature because failure to establish adequate blood flow within the first few days can lead to necrosis of the patch and ultimately graft failure.
To better study vascular engraftment, the Chen lab is currently developing a vascular-engraftment-on-chip model that is composed of a microfluidic device with an engineered vascular bed and a living tissue explant. Together with Terry Ching, a postdoctoral researcher in the Chen lab, the REU student will help with the design and manufacturing of diverse prototypes of the microfluidic chip and conduct ex vivo engraftment experiments with engineered vasculature. Through this process REU students gain technical expertise in vascular engineering; learn wet lab skills such as vascular cell expansion and maintenance, immunofluorescence, time-lapse, and confocal microscopy, as well as the design and manufacturing of microfluidic devices. They also gain experience in experimental design and data analysis. The specific research goals were to:
1. Manufacturing microfluidic devices for studying vascular engraftment: Using sheet lamination, the REU student will manufacture two-channel devices with an engineered vascular bed and a tissue chamber so that the engineered vasculature can grow into a mouse adipose tissue explant.
2. Describing the dynamics of vascular engraftment of the engineered vascular bed into the tissue explant. The REU student will visualize and quantitatively evaluate vascular ingrowth into the tissue explant over the course of one week using time-lapse microscopy and fluorescently labeled cell.
LABORATORY MENTOR
Terry Ching
TIMELINE
Weeks 1-2: Orientation in the lab, manufacturing first iteration of devices, learning vascular cell culture.
Weeks 3-5: conduct first round of ex vivo engraftment experiments, and optimize the design of the model system if required.
Weeks 6-9: Conduct second round of ex vivo engraftment experiments with optimized model system.
Week 10: Finish data analysis and synthesize final presentation.
Exploratory Study of Contractile Force in Cardiomyocytes (2018)
ABSTRACT
Cardiac disease is a leading cause of death and even though researchers have been able to make extensive progress in different ways to study the human heart in vivo. There is still a gap between in vivo and in vitro models that has not yet been totally bridged. In vitro models are simple enough to create controlled conditions but still cannot replicate the complex conditions that an in vivo model can provide. In this work we explored two methods of modeling heart function and disease… Using traction force microscopy in an established PDMS (PolyDiMethylSiloxane) device. We studied the difference in contractile force between a wild-type and a desmosome mutant cardiomyocyte cell line. With this device, statistically significant reduction in contractile force due to mutation was noticed. Then, scale up the model creating a protocol for a catheter balloon device was attempted. The scale up method allowed to replicate the in vivo environment more accurately. It was able to successfully maintain the new tissue attached to the device for up to 8 days. This finding opens a different way to relate a more accurate in vivo-like cardiac studies.
CONCLUSION
In this work we built an in-vitro device in a controlled environment to be able to test different heart diseases in the future. It was demonstrated that wild type, when uniformly contracted, has more force than mutants.
Biomimetic in Vitro Model to Reveal Endothelial-Fibroblast Interaction (2018)
ABSTRACT
This project explores the study of angiogenesis by investigating the interactions between endothelial and fibroblast cells in a two-channel microfluidic device. A critical role of angiogenesis occurs when vessels are damaged, for fibroblasts are essential connective tissue cells used to repair damages. Therefore, it was hypothesized that fibroblast induces the growth and sprouting of endothelial cells. To explore the different effects on endothelial cells sprouting, an experiment was conducted varying the concentration of fibroblasts. It was found that a greater concentration of fibroblast resulted in a greater number of endothelial cell sprouts, its length, and node formations. This ensures that the fibroblasts have the ability to stimulate cell growth; which could potentially be used in other applications such as repairing damaged vessels.
CONCLUSION
After experimenting with different concentrations of fibroblast, the results confirmed that fibroblast induces endothelial cell proliferation. As expected, the greater concentration of fibroblast correlated with the longest endothelial sprouting growth. Within the control, it could be observed that the endothelial cells did not sprout to the extent of the other devices, for they did not have a structure nor any interconnection. In contrast, as the concentration of fibroblast increased, the endothelial cells sprouted extensively, developing vessel-like structures between the two channels… A possible explanation behind such observation is that fibroblasts contain characteristics that stimulate the bonding of VEGFA with VEGFR2 which increases the tip cells proliferation. When a tip cell is selected, the activities of VEGFR2 is inhibited, preventing neighboring cells from proliferating as well. Therefore, if fibroblast interferes the inhibition, endothelial cells will continue to grow and sprout. Hence, the more presence of fibroblast around endothelial cells, encourages more neighboring cells to sprout alongside each other.
