shyni varghese
Principal Investigator
Shyni Varghese
Laszlo Ormandy Distinguished Professor of Orthopaedic Surgery
Professor of Orthopaedic Surgery
Professor in the Department of Mechanical Engineering and Materials Science
Professor in the Department of Biomedical Engineering
Affiliate of the Duke Regeneration Center
Contact Information

shyni.varghese@duke.edu

Home

Our active research can be broadly categorized into four areas:

  • Smart Biomaterials
  • Miniature Organs
  • Rejuvenation
  • Bench-to-Bedside

We are an interdisciplinary team of researchers comprised of engineers, biologists, material scientists, physicists, and clinicians striving to solve pressing biomedical problems and innovate technologies.

New discoveries, approaches & technologies include: Bone bandage • Cell pouch • DraBot • Self-healing hydrogel • Self-repairing lubricants •, and, more!

Research

Overview

In our research, we bring an interdisciplinary approach—combining principles of physical sciences, engineering, materials science, biology, and medicine, and solid collaborations with basic scientists and physicians—to tackle several rising challenges. Our laboratory works in diverse areas, from basic sciences to tools to translatable technologies. A recurring theme in our approach is developing ex vivo platforms (innovative biomaterials and miniature organs) with organ/tissue-specific properties and employing them to address biomedical questions and gain new fundamental understandings with a focus on health, disease, and aging. We test these findings in vivo using clinically relevant animal models through a series of “why,” “how,” and “so what’, we have made discoveries leading to new approaches and technologies. Some examples include the: “bone bandage,” “cell pouch,” “DraBot,” “self-healing hydrogel,” “self-repairing lubricants,” etc. Current research activities in our lab can be broadly divided into four categories: Smart Biomaterials, which includes 3D hydrogel cultures for cells-to-cell transplantation devices to stimuli-responsive delivery units and active materials; Miniature Organs, which includes organoids and organ-on-chip models; Rejuvenation which includes healthy healing to age-mediated tissue degeneration and impaired healing to pain, and Bench to Bedside, which involves novel therapies and technologies to promote tissue regeneration, treat diseases, and restore organ function.

Smart Biomaterials

Our interest in biomaterials ranges from designing and developing synthetic analogs of ECM to medical devices to stimuli-responsive systems and actuators. In the case of the former, we not only design biomaterials with tissue-specific functions and properties but also use these engineered ECM mimetics to unravel the effect of the physicochemical properties of ECM on various cellular functions in health and disease. We also use these engineered materials to deliver cells, promote their in vivo integration, and/or activate endogenous tissue repair. Below, we briefly discuss various research activities centered around biomaterials and polymers.

Engineered ECM mimetics: 

It is now well established that ECM-based cues play a critical role in modulating various cellular functions such as adhesion, differentiation, and functional tissue formation. However, the underlying mechanisms remain largely unknown. To dissect the role of the biophysical and biochemical cues of the ECM in directing stem cell commitment, we are developing artificial ECMs recapitulating various physicochemical cues of the native tissue. Some examples include development of hydrogels with varying interfacial properties to regulate adhesion and migration of stem cells, biomaterials for ex vivo expansion of human ESCs and iPSCs, biomaterials to activate endogenous cell-mediated tissue repair, and hydrogel-based actuators for stem cell culture.

H Kang, Y Zeng, and S Varghese. "Functionally graded multilayer scaffolds for in vivo osteochondral tissue engineering." Acta Biomater 78 (2018): 365-377.

H Kang, Y-RV Shih, Y Hwang, C Wen, V Rao, T Seo, and S Varghese. "Mineralized gelatin methacrylate-based matrices induce osteogenic differentiation of human induced pluripotent stem cells." Acta Biomater 10, no. 12 (2014): 4961-4970.

C-W Chang, Y Hwang, D Brafman, T Hagan, C Phung, and S Varghese. "Engineering cell-material interfaces for long-term expansion of human pluripotent stem cells." Biomaterials 34, no. 4 (2013): 912-921.

HL Lim, JC Chuang, T Tran, A Aung, G Arya, and S Varghese. "Dynamic electromechanical hydrogel matrices for stem cell culture." Advanced Functional Materials 21, no. 1 (2011): 55-63.

Biomaterials to unravel molecular mechanism: 

Besides directing cell fate, we also utilize engineered materials to understand the molecular and cellular mechanisms through which ECM maintains tissue function and homeostasis. For instance, by using dynamic mineralized materials and stem cells, we have unraveled a previously unknown molecular mechanism, the phosphate-ATP-adenosine metabolic signaling axis, by which the calcium phosphate (CaP)-rich mineral environment in bone tissues supports bone homeostasis. These studies have also shed light on the role of A2B receptor activity on bone formation vs. fat formation. Specifically, A2B activation promotes osteogenic commitment of bone marrow progenitor cells while their inhibition promotes adipogenesis. 

Y-RV Shih, M Liu, SK Kwon, M Iida, Y Gong, N Sangaj, and S Varghese. "Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss." Science Advances 5, no. 8 (2019): eaax1387.

 H Kang, Y-RV Shih, and S Varghese. "Biomineralized matrices dominate soluble cues to direct osteogenic differentiation of human mesenchymal stem cells through adenosine signaling." Biomacromolecules 16, no. 3 (2015): 1050-1061.

 V Rao, YRV Shih, H Kang, H Kabra, and S Varghese. "Adenosine signaling mediates osteogenic differentiation of human embryonic stem cells on mineralized matrices." Frontiers in Bioengineering and Biotechnology 3, no. NOV (2015).

Y-RV Shih, Y Hwang, A Phadke, H Kang, NS Hwang, EJ Caro, S Nguyen, M Siu, EA Theodorakis, NC Gianneschi et al. "Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling." Proc Natl Acad Sci U S A 111, no. 3 (2014): 990-995.

Cell Therapy:

Cell therapy, or regenerative medicine, is a transformative therapy to treat compromised tissues. The goal of cell therapy is to restore or augment the function of compromised organs. Biomaterials have played a key role in advancing cell therapy, which includes promoting organ-specific differentiation of stem cells to engraftment and integration of transplanted cells to assist allogenic and xenogeneic cell transplantation. While the differentiation and in vivo engraftment of cells relies on promoting the interaction between the cells and the biomaterial, allogenic and xenogeneic transplantation of cells demands the biomaterial to “hide” the transplanted cells from the host. We have devised biomaterials to promote stem cell differentiation and support in vivo survival and function of transplanted cells. A recurring theme in our design is interfacial engineering— i.e., tailoring the cell-matrix interface via molecular engineering of the biomaterial to alter cell attachment and function. One example is developing a microencapsulation device, a “cell pouch,” for xenogeneic transplantation of cells in an immunocompetent host.

N Seale, S Ramaswamy, Y-R Shih, I Verma, and S Varghese. "Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes." Transplantation 102, no. 9 (2018): e373-e381.

SK Madhurakka Perikamana, N Seale, J Hoque, JH Ryu, V Kumar, YV Shih, and S Varghese. "Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation." Advanced Functional Materials (2021): 2108221.

Y-R Shih, H Kang, V Rao, Y-J Chiu, SK Kwon, and S Varghese. "In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism." Proceedings of the National Academy of Sciences of the United States of America 114, no. 21 (2017): 5419-5424.

H Kabra, Y Hwang, HL Lim, M Kar, G Arya, and S Varghese. "Biomimetic material-assisted delivery of human embryonic stem cell-derived cells for enhanced in vivo survival and engraftment." ACS Biomaterials Science & Engineering 1 (2015): 7-12.

Localization of pro-regenerative molecules: 

In mammals, tissue regeneration is achieved through a cascade of pro-regenerative events. Most organs experience a progressive decline in tissue regenerative ability with aging. The contribution of cell-intrinsic and cell-extrinsic factors on tissue regeneration is established. Rejuvenating the cellular and molecular landscape of the injured tissue environment could be a potential therapeutic approach to activate endogenous tissue repair. The sequestration of endogenous molecules or delivering such molecules to the site can localize pro-regenerative molecules at the injury site. In our research, we use both the sequestration of endogenous molecules and the delivery of pro-regenerative molecules to promote healing. For example, we have devised a biomaterial technology to sequester adenosine, a multi-functional osteoanabolic molecule to promote fracture healing. Localization of osteoanabolic adenosine promoted fracture healing. We have also utilized biomaterial (nanocarrier) to deliver adenosine to the bone to treat osteoporosis.

J Hoque, Y-RV Shih, Y Zeng, H Newman, N Sangaj, N Arjunji, and S Varghese. "Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss." Biomaterials 273 (2021).

Y Zeng, Y-RV Shih, GS Baht, and S Varghese. "In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing." Adv Mater 32, no. 8 (2020).

Y Zeng, J Hoque, and S Varghese. "Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair." Acta Biomater 93 (2019): 152-168.

M Kar, Y-R Vernon Shih, DO Velez, P Cabrales, and S Varghese. "Poly(ethylene glycol) hydrogels with cell cleavable groups for autonomous cell delivery." Biomaterials 77 (2016): 186-197.

Self-healing biomaterials and soft robotics: 

Another area of our interest is designing synthetic materials or hydrogels emulating various attributes of biological systems such as sensitivity, self-organization, and self-healing. Our research has resulted in new design principles enabling self-healing in chemically crosslinked hydrogels. We have now extended these approaches to creating self-repairing lubricants and dermal fillers. Our initial studies with the self-repairing HA lubricants showed seamless injectability (due to shear thinning), enhanced lubrication, and chondroprotective function. We have recently incorporated some of these design principles and stimuli-responsive materials towards the development of environment-responsive soft robots.

V Kumar, UH Ko, Y Zhou, J Hoque, G Arya, and S Varghese. "Microengineered Materials with Self‐Healing Features for Soft Robotics." Advanced Intelligent Systems 3, no. 7 (2021): 2100005.iples and stimuli-responsive materials towards the development of environment-responsive soft robots.

A Gilpin, Y Zeng, J Hoque, JH Ryu, Y Yang, S Zauscher, W Eward, and S Varghese. "Self-Healing of Hyaluronic Acid to Improve In Vivo Retention and Function." Adv Healthc Mater (2021).

A Phadke, C Zhang, B Arman, C-C Hsu, RA Mashelkar, AK Lele, MJ Tauber, G Arya, and S Varghese. "Rapid self-healing hydrogels." Proc Natl Acad Sci U S A 109, no. 12 (2012): 4383-4388.

HL Lim, Y Hwang, M Kar, and S Varghese. "Smart hydrogels as functional biomimetic systems." Biomaterials Science 2, no. 5 (2014): 603-618.

People

Current Members:

Principal Investigator

Shyni Varghese
Professor of Biomedical Engineering, Mechanical Engineering & Materials Science, and Orthopaedic Surgery

Clinical & Research Faculty

Yuru Vernon Shih
Assistant Professor

Postdoctoral Fellows

PhD Students

 

Masters Students

Jerry Holland III
MS Biomedical Engineering

Undergraduates

Publications

Selected Publications

2023

Cigliola, Valentina, Adam Shoffner, Nutishia Lee, Jianhong Ou, Trevor J. Gonzalez, Jiaul Hoque, Clayton J. Becker, et al. “Spinal cord repair is modulated by the neurogenic factor Hb-egf under the direction of a regeneration-associated enhancer.” Nat Commun 14, no. 1 (August 11, 2023): 4857. https://doi.org/10.1038/s41467-023-40486-5.

Gonzales, G., S. Zauscher, and S. Varghese. “Progress in the design and synthesis of viscosupplements for articular joint lubrication.” Current Opinion in Colloid and Interface Science 66 (August 1, 2023). https://doi.org/10.1016/j.cocis.2023.101708.

Aung, Aereas, Shruti K. Davey, Jomkuan Theprungsirikul, Vardhman Kumar, and Shyni Varghese. “Deciphering the Mechanics of Cancer Spheroid Growth in 3D Environments through Microfluidics Driven Mechanical Actuation.” Adv Healthc Mater 12, no. 14 (June 2023): e2201842. https://doi.org/10.1002/adhm.202201842.

Newman, Hunter, and Shyni Varghese. “Extracellular adenosine signaling in bone health and disease.” Curr Opin Pharmacol 70 (June 2023): 102378. https://doi.org/10.1016/j.coph.2023.102378.

Rana, Isha, Sunny Kataria, Tuan Lin Tan, Edries Yousaf Hajam, Deepak Kumar Kashyap, Dyuti Saha, Johan Ajnabi, et al. “Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.” J Invest Dermatol 143, no. 5 (May 2023): 699-710.e10. https://doi.org/10.1016/j.jid.2022.10.011.

Kumar, Vardhman, David Kingsley, Sajeeshkumar Madhurakkat Perikamana, Pankaj Mogha, C Rory Goodwin, and Shyni Varghese. “Self-assembled innervated vasculature-on-a-chip to study nociception.” Biofabrication 15, no. 3 (April 13, 2023). https://doi.org/10.1088/1758-5090/acc904.

Yang, Ting, Ravikanth Velagapudi, Cuicui Kong, Unghyeon Ko, Vardhman Kumar, Paris Brown, Nathan O. Franklin, et al. “Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behavior in mice.” Br J Anaesth 130, no. 2 (February 2023): e370–80. https://doi.org/10.1016/j.bja.2022.05.025.

2022

Hoque, Jiaul, Yuze Zeng, Hunter Newman, Gavin Gonzales, Cheryl Lee, and Shyni Varghese. “Microgel-Assisted Delivery of Adenosine to Accelerate Fracture Healing.” Acs Biomater Sci Eng 8, no. 11 (November 14, 2022): 4863–72. https://doi.org/10.1021/acsbiomaterials.2c00977.

Chansoria, P., J. Blackwell, E. L. Etter, E. E. Bonacquisti, N. Jasiewicz, T. Neal, S. A. Kamal, et al. “Rationally Designed Anisotropic and Auxetic Hydrogel Patches for Adaptation to Dynamic Organs.” Advanced Functional Materials 32, no. 43 (October 1, 2022). https://doi.org/10.1002/adfm.202207590.

Newman, Hunter, Jiaul Hoque, Yu-Ru V. Shih, Gabrielle Marushack, Unghyeon Ko, Gavin Gonzales, and Shyni Varghese. “pH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss.” Biomater Sci 10, no. 18 (September 13, 2022): 5340–55. https://doi.org/10.1039/d2bm00843b.

Bartholf DeWitt, Suzanne, Sarah Hoskinson Plumlee, Hailey E. Brighton, Dharshan Sivaraj, E. J. Martz, Maryam Zand, Vardhman Kumar, et al. “Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin binding.” Jci Insight 7, no. 17 (September 8, 2022). https://doi.org/10.1172/jci.insight.151583.

Madhurakkat Perikamana, S. K., N. Seale, J. Hoque, J. H. Ryu, V. Kumar, Y. V. Shih, and S. Varghese. “Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation.” Advanced Functional Materials 32, no. 4 (January 1, 2022). https://doi.org/10.1002/adfm.202108221.

Kumar, Vardhman, Sajeesh Kumar Madhurakkat Perikamana, Aleksandra Tata, Jiaul Hoque, Anna Gilpin, Purushothama Rao Tata, and Shyni Varghese. “An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics.” Front Bioeng Biotechnol 10 (2022): 848699. https://doi.org/10.3389/fbioe.2022.848699.

Ko, Ung Hyun, Vardhman Kumar, Benjamin Rosen, and Shyni Varghese. “Characterization of bending balloon actuators.” Front Robot Ai 9 (2022): 991748. https://doi.org/10.3389/frobt.2022.991748.

2021

Gilpin, Anna, Yuze Zeng, Jiaul Hoque, Ji Hyun Ryu, Yong Yang, Stefan Zauscher, William Eward, and Shyni Varghese. “Self-Healing of Hyaluronic Acid to Improve In Vivo Retention and Function.” Adv Healthc Mater 10, no. 23 (December 2021): e2100777. https://doi.org/10.1002/adhm.202100777.

Andress, Benjamin, Jason H. Kim, Hattie C. Cutcliffe, Annunziato Amendola, Adam P. Goode, Shyni Varghese, Louis E. DeFrate, and Amy L. McNulty. “Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding.” J Orthop Res 39, no. 10 (October 2021): 2177–86. https://doi.org/10.1002/jor.24954.

Newman, Hunter, Yuru Vernon Shih, and Shyni Varghese. “Resolution of inflammation in bone regeneration: From understandings to therapeutic applications.” Biomaterials 277 (October 2021): 121114. https://doi.org/10.1016/j.biomaterials.2021.121114.

Kumar, Vardhman, Ung Hyun Ko, Yilong Zhou, Jiaul Hoque, Gaurav Arya, and Shyni Varghese. “Microengineered Materials with Self‐Healing Features for Soft Robotics.” Advanced Intelligent Systems 3, no. 7 (July 2021). https://doi.org/10.1002/aisy.202100005.

Hoque, Jiaul, Yu-Ru V. Shih, Yuze Zeng, Hunter Newman, Nivedita Sangaj, Neha Arjunji, and Shyni Varghese. “Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.” Biomaterials 273 (June 2021): 120819. https://doi.org/10.1016/j.biomaterials.2021.120819.

Nayak, P., A. Colas, M. Mercola, S. Varghese, and S. Subramaniam. “Temporal mechanisms of myogenic specification in human induced pluripotent stem cells.” Sci Adv 7, no. 12 (March 2021). https://doi.org/10.1126/sciadv.abf7412.

Jabba, S. V., A. N. Diaz, A. I. Caceres, H. C. Erythropel, V. Kumar, S. Varghese, J. B. Zimmerman, and S. E. Jordt. “Cellular Respiratory Toxicity of Novel Flavor-Solvent Adducts in Electronic Cigarettes.” In American Journal of Respiratory and Critical Care Medicine, Vol. 203, 2021.

2020

Moreno, Ana M., Xin Fu, Jie Zhu, Dhruva Katrekar, Yu-Ru V. Shih, John Marlett, Jessica Cabotaje, et al. “In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.” Mol Ther 28, no. 8 (August 5, 2020): 1931. https://doi.org/10.1016/j.ymthe.2020.06.027.

Zeng, Yuze, Yu-Ru V. Shih, Gurpreet S. Baht, and Shyni Varghese. “In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.” Adv Mater 32, no. 8 (February 2020): e1906022. https://doi.org/10.1002/adma.201906022.

Aung, Aereas, Vardhman Kumar, Jomkuan Theprungsirikul, Shruti K. Davey, and Shyni Varghese. “An Engineered Tumor-on-a-Chip Device with Breast Cancer-Immune Cell Interactions for Assessing T-cell Recruitment.” Cancer Res 80, no. 2 (January 15, 2020): 263–75. https://doi.org/10.1158/0008-5472.CAN-19-0342.

 

Research Opportunities

Contact our team if you are interested to join!

Admin Assistant: 
Name: Lynn  Montoya 
Email: lynda.montoya@duke.edu 
Phone: 1-919-681-1195

Physical Address: 
Medical Science Research Building (MSRB1), Room No. 381 
Duke University 
Durham, NC USA

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