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Jordan S. Miller

jordan miller-weblgAssistant Professor of Bioengineering

Postdoctoral Fellow, Department of Bioengineering, University of Pennsylvania (2008-2013)
Ph.D., Bioengineering, Rice University (2008)
B.S., Biology, minor in Biomedical Engineering, Massachusetts Institute of Technology (2003)

Bio Sketch

Assistant Professor Jordan Miller's primary research interests in regenerative medicine combine synthetic chemistry, three-dimensional (3D) printing, microfabrication, and molecular imaging to direct cultured human cells to form more complex organizations of living vessels and tissues. Precisely engineered in vitro systems at the molecular, micro- and meso-scales are well suited to decouple the relationship between tissue architecture and cell function. These systems are now permitting comprehensive closed-loop design and optimization of large-scale engineered tissues through refinement with computer models of mass transport and assessment of their therapeutic potential in vivo.

Miller's research projects explore the role of mass transport on cell survival and matrix remodeling in a 3D context, and utilize novel biomaterials and bioinspired vascular architectures to meet the metabolic requirements of densely populated engineered tissues. These studies will enable the creation of engineered tissues containing billions of cells and provide for the assessment of their therapeutic potential in vivo.

Miller is a principal investigator (PI) on a collaborative research grant by the John S. Dunn Foundation. His work with Mary Dickinson, an associate professor of developmental biology at Baylor College of Medicine involves the development of quantitative imaging methods that map time scales and probe multiscale drivers of vascular biology and tissue physiology.

A second project, funded by a multi-investigator research award by the Cancer Prevention & Research Institute of Texas (CPRIT), looks at cell-extracellular matrix interactions as drivers of tumor invasion and metastasis. Working as a Co-PI in collaboration with Rice Professor Jane Grande-Allen and Dr. Jonathan M. Kurie of MD Anderson’s Department of Thoracic/ Head and Neck Medical Oncology, Miller is developing synthetic materials that mimic the matrix architectures, investigating their intricate protein assemblies that promote or regulate angiogenesis, and providing a comprehensive understanding of downstream tumor growth processes.

More recently, Miller was awarded a Hamill Foundation research grant for the design, synthesis and characterization of strain-stiffening hydrogels. The collaborative project with Jeffrey Hartgerink, professor of chemistry and of bioengineering at Rice, involves building a hydrogel mesh that stiffens when stressed, similar to collagen tissue in biological structures.

Miller’s contributions in advanced fabrication have resulted in two patent applications. The success of his customized 3D printer led to his being named a Core Developer of the RepRap 3D Printer project by its maker community. He is the author of two book chapters, his work has been published in 22 leading peer-reviewed journals, and he is a reviewer for several scientific journals. He has been cited over 1,000 times and he has an h-index of 12.

Research accomplishments in the Miller lab have stemmed from his commitment to technology education, especially in the do-it-yourself, technology-based maker movement. Upon his arrival at Rice, he founded the Advanced Manufacturing Research Institute (AMRI). The program, which involves a summer research fellowship, supports rising stars in the hardware and software engineering field in their development of new tools and pursuits of quantitative investigations in advanced manufacturing - tissue engineering, 3D printing, and rapid prototyping. The 2013 The AMRI program was sponsored by Rice University and companies: Maryland Institute College of Art (MICA), Ultimachine, Ultimaker, MakerGear, and SeeMeCNC.

Prior to joining Rice in 2013, Miller's postdoctoral work in the lab of Professor Christopher S. Chen at Penn focused on the multiscale vascularization of engineered tissues. To understand the means by which the cellular microenvironment impinges on angiogenesis, Miller developed a new family of synthetic and degradable hydrogels to tease apart interactions between endothelial cells and the extracellular matrix (ECM). Endothelial cell sprouting requires specific adhesive and degradable characteristics of the ECM over a narrow stiffness regime. At the meso-scale, Miller developed 3D printing methodologies to enable the rapid fabrication of engineered tissues containing perfusable vascular architectures. This work was supported by fellowships through the Hartwell Foundation (2008) and the National Institutes of Health National Research Service Award (NHLBI F32 NRSA).

Miller holds a Ph.D. in bioengineering from Rice University. Working in the laboratory of Professor Jennifer L. West, he developed new laser-based microfabrication strategies for constructing synthetic microenvironments for studies of mammalian cell adhesion and migration. In surface patterning investigations, his synthesis and precise arrangement of self-assembled monolayers with laser-based micro-ablation directed cellular alignment and cytoskeletal organization of human fibroblasts. In 3D microfabrication studies, his synthetic biodegradable hydrogel scaffolds were patterned with micro-scale adhesion and stiffness domains using diffraction-limited multiphoton photopolymerization to direct 3D cell migration.   

Research Statement

The lack of sufficient numbers of donor organs for human transplantation therapies results in the loss of tens of thousands of lives and costs hundreds of billions of dollars each year in the U.S. alone. However, the ability to create, de novo, functional organ replacements for treating human pathologies is fundamentally limited by the lack of a comprehensive vascularization strategy for engineered 3D tissues. We developed new biomaterials, 3D printing methodologies, and sacrificial casting strategies to enable the rapid fabrication of engineered tissues containing perfusable vascular architectures. Patterned vasculature facilitated capillary sprouting and supported the function of primary hepatocytes in centimeter-sized constructs. Together these technologies provide a flexible platform for a wide array of specific applications, and may enable the scaling of densely populated tissue constructs to arbitrary size.

Recent select publications from the Miller lab:

Magaraci MS, Veerakumar A, Qiao P, Amurthur A, Lee JY, Miller JS*, Goulian M, and Sarkar CA*. “Engineering Escherichia coli for light-activated cytolysis of mammalian cells.” In Press, ACS Synthetic Biology. *Corresponding Authors.

Trachtenberg JE, Mountziaris PM, Miller JS, Wettergreen M, Kasper FK, Mikos AG. “Open-source three dimensional printing of biodegradable polymer scaffolds for tissue engineering.” In Press, J Biomed Mater Res Part A.

Baranski JD, Chaturvedi RR, Stevens KR, Carvahlo B, Solorzano RD, Yang MT, Miller JS, Bhatia SN, Chen CS. “Geometric control of vascular networks to enhance engineered tissue integration and function.” PNAS. 2013 May 7; 110(19):7586-91.

Legant WR, Choi CK, Miller JS, Shao L, Gao L, Betzig E, Chen CS. “Multidimensional traction force microscopy reveals rotational moments about focal adhesions.” PNAS. 2013 Jan 15; 110(3):881-6. Cited By: 24

Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM, Toro E, Chen AA, Galie PA, Yu X, Chaturvedi R, Bhatia SN, Chen CS. “Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues.” Nature Materials. 2012 Aug; 11(9):768-74. Cited By: 107

Neetu Singh, Amrita Karambelkar, Luo Gu, Kevin Lin, Miller JS, Chen CS, Sailor MJ, Bhatia SN. “Bioresponsive mesoporous silica nanoparticles for triggered drug release.” J Am Chem Soc. 2011 Dec 14; 133(49):19582-5. Cited By: 43

Legant WR, Miller JS, Blakely BL, Cohen DM, Genin GM, Chen CS. “Measurement of mechanical tractions exerted by cells in three-dimensional matrices.” Nat Methods. 2010 Dec.; 7(12):969–971. Cited By: 104