Research with Impact
The IGERT program at WPI provides PhD candidates with the technical skills, innovative mindset, and global vision to become leaders in translational research. Our multi-investigator research projects in biofabrication have the potential to transform medicine and health care.
Research areas include soft-tissue engineering, biological responses to natural and synthetic materials, instrumentation to monitor physiological responses, and real-time assessments to guide medical interventions. IGERT fellows contribute to and benefit from this cutting-edge research and development.
Learn more about the different areas of research IGERT fellows are participating in at WPI.
One of the first considerations for cell therapy must be the cell source. There are many different types of cells available for regenerative medicine, including mesenchymal stem cells (MSCs), inducible pluripotent stem cells (iPS cells), embryonic stem cells (ESC), and tissue specific progenitor cells. However, common to all of these sources is the need for cell to be safe to the patient. For example, iPS cells are commonly derived by genetic manipulation that involves the insertion of 4 genes, some of which are common in cancer.
To eliminate the need for the introduction of oncogenes, we have developed a non-gene approach (using proteins and incubation conditions) to induce stem cell gene expression in fibroblast. Exploring the profound effects that the extracellular environment can have on cell phenotype, we have developed cell culture conditions that reproducibly support induction and maintenance of a unique, multipotent, non-tumorigenic, regeneration-competent cell phenotype. By using the most ubiquitous cell type, namely adult fibroblasts, we have demonstrated that inherent cellular multipotency can be induced and maintained, allowing for derivation of a clinically significant number of autologous, patient-matched cells for a number of engineering applications. Using fibrin microthreads as a delivery scaffold these cells stimulate endogenous skeletal muscle regeneration in vivo.
Our approach for derivation of large numbers of regeneration competent cells combined with our microthread scaffold technology will be the basis for a design of a novel bioreactor - satisfying the need for large scale 3-D implantable constructs.
Bioengineered scaffolds are important to enhance the regeneration of damaged tissues and organs. We have used bioprinting and biomimetic design strategies and novel fabrication processes to develop three-dimensional constructs that emulate native tissue architecture and cellular microenvironments. We utilized these scaffolds to characterize the roles of extracellular matrix (ECM) cues and topographic features in modulating cellular functions, including adhesion, migration, proliferation, differentiation and tissue remodeling. We anticipate that the results of these studies will provide a greater understanding of cell-matrix interactions that regulate wound healing and tissue remodeling and will enable the design of precisely tailored biomaterials that direct cell-matrix interactions and enhance the rate of tissue regeneration.
To further advance cell therapy, cells can be manipulated to form three-dimensional tissue constructs. A primary challenge for creating cell-derived tissues, such as tissue engineered blood vessels, is the need for simple, reproducible methods to achieve cellular self-assembly and organization into specific shapes, and to minimize culture time and optimize culture conditions to achieve sufficient cell-derived extracellular matrix synthesis. We have recently developed a novel bioreactor method to produce strong tissue engineered blood vessels from aggregates of smooth muscle cells. Briefly, suspensions of cells seeded into non-adhesive ring-shaped agarose wells aggregate and coalesce to form a robust, compact ring of tissue. The resulting tissue rings are strong enough to harvest from the wells after one day of seeding, and several individual rings can be fused together to create tubular tissue constructs after an additional seven days in culture. In addition, we have developed a continuous flow, magnetically stabilized bioreactor to grow scaffoldless and pseudo scaffoldless tubes of tissue from rat aorta smooth muscle cells. Thus, we have developed and validated a new method for creating vascular tissue constructs using only cells and cell-derived extracellular matrix, within a much shorter time frame than previously reported.
In Vitro Assessment
Our in vitro assessment methods range from macro-scale to nano-scale. In order to assess the mechanical strength of scaffolds, we have performed a multitude of mechanical testing. We have employed uni-axial tensile testing on collagen and fibrin microthreads; bi-axial loading has been employed to evaluate cells on scaffolds with altered stiffness; and we have also subjected tissue rings to mechanical testing.
An example of nano-scale assessment is our ability to evaluate scaffolds for nanotopography, which can be important in cell adhesion. An important component of Biofabrication is that the material to be implanted must resist microbial infection while simultaneously supporting the proper function of the cells or biomolecules that are being implanted. The nanotopography of a surface can be manipulated to control cellular function and behavior. We are modifying surfaces with self-assembled monolayers and other functional groups in order to prevent pathogen colonization of surfaces. Our work in this area has shown that the nanoscale roughness of the surface is even more critical than the type of chemical functionality, in terms of controlling bacterial adhesion.
Regardless of the target tissue, currently used methods for cell delivery, including intravenous, intramuscular and intra-arterial injections, result in low cell engraftment and have poor targeting capabilities. With our advances in fibrin and collagen microthreads for cell seeding we developed scaffolds for implantation. These microthreads can be attached to a surgical needle, thereby providing a delivery method that can be deployed similar to placing a suture. This microthread-based delivery system allows scaffold-mediated targeted delivery, resulting in precise placement of stem cells in the region of interest. We have recently applied this delivery technology to the heart for treatment of myocardial infarction.
Functional In Vivo Monitoring
With the delivery of any new technology, such as cell therapy, monitoring of function is essential. We have developed multiple methods to assure proper medical monitoring with real time physiological assessment. Investigators at WPI are working on monitoring vital organ function. For example, students working in the labs of IGERT investigators have developed a wearable and wireless device to monitor seven different vital signs. In the current environment where health care costs are ever increasing, a single sensor that has multiple functions is very attractive from a financial perspective. In addition, IGERT investigators and their students have recently developed processing methods to detect atrial arrhythmias. Cardiac arrhythmias are a major concern in cardiac regeneration. Through the interdisciplinary nature of IGERT, students will understand cell therapy from cell sourcing through delivery. This will provide them with the background to understand the needs of monitoring the outcomes of cell therapy.