About

Shyni Varghese is a Professor of Biomedical Engineering, Mechanical Engineering & Materials Science, and Orthopaedic Surgery at Duke University. She is the Principal Investigator of the Varghese Lab, where her research focuses on the development of smart bioimaterials, miniature organs, and rejuvenation techniques, aiming to translate bench research to bedside applications. Her work involves interdisciplinary approaches to advance regenerative medicine and biomaterials, contributing to innovative solutions in tissue engineering and regenerative therapies.

Research topics

• Biology
• Chemistry
• Immunology
• Materials science
• Medicine
• Nanotechnology
• Biomedical engineering
• Computer Science
• Internal medicine
• Cell biology
• Composite material
• Cancer research
• Surgery
• Pharmacology
• Optics
• Genetics
• Biophysics
• Anatomy
• Telecommunications

Selected publications

• Advances and Challenges in Human 3D Solid Tumor Models

  Advanced Functional Materials · 2025-01-24 · 7 citations

  articleOpen accessSenior authorCorresponding

  Abstract The field of cancer biology and therapeutics has soared in the past several decades with new therapeutic modalities and options for patients, such as chemoradiotherapy, immunotherapy, and combination therapy. This dramatic success in expanding patient options is primarily attributed to the development of various model systems to elucidate drivers of oncogenesis, tumor maturation and evolution, and response to therapeutics. While mouse models have been a workhorse of cancer research, technological progress in ex vivo patient‐derived tumor models has afforded more tunable and scrutable systems for patient‐predictive platforms and mechanistic study. This review explores the technological innovations in 3D solid tumor models and their applicability to various aspects of cancer biology and the identification of therapeutics. Features of the tumor and tumor microenvironment like spatial heterogeneity, multicellular populations, and genomic variations are addressed and elaborated through the establishment of new in vitro models. The integration of perfusable vasculature with 3D tumor models and the potentially wide‐ranging applications of these more complex platforms in precision medicine and cancer immunotherapy are further addressed. Finally, an outlook on the future of experimental cancer models for both biological investigation and bench‐to‐bedside pipeline development is provided.

  PublisherOA PDFDOI

• Exosome injection as a prevention strategy for early postoperative mesh complications in a porcine model of sacrocolpopexy

  npj Regenerative Medicine · 2025-09-29

  articleOpen accessSenior author

  Exosomes, an acellular regenerative biologic, have demonstrated success in resolving vaginal mesh exposures after pelvic reconstructive surgery; little data exists for their use for prevention of mesh-based complications. This study evaluated the early efficacy of purified exosome product (PEP) for preventing mesh exposures. Ten Yorkshire-crossed pigs underwent mesh sacrocolpopexy with two high-risk-for-exposure configurations: mesh fold ventrally, vaginotomy dorsally. PEP in hyaluronic acid (HA) or HA-only (control) was injected at baseline. Twelve weeks later, animals were euthanized and evaluated for mesh exposure and histologic changes. None of the PEP-treated tissues demonstrated mesh exposure (0/6); all control group animals experienced a mesh exposure (4/4 mesh fold configuration, 2/4 vaginotomy configuration). Control tissues exhibited higher fibrosis (vaginotomy fibrosis score: median(IQR); 3(3,3) control, 2(1,2) PEP; p = 0.03) and greater epithelial apoptosis (mesh fold TUNEL+area fraction: median 18.9 control vs 0.43 PEP; p = 0.02). Our study demonstrated that PEP treatment mitigated the risk of early mesh exposure.

  PublisherDOI

• Synovial Tissue Models and Their Applications in Osteoarthritis Research

  SSRN Electronic Journal · 2025-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Targeting allograft inflammatory factor 1 reprograms kidney macrophages to enhance repair

  Journal of Clinical Investigation · 2025-01-21 · 7 citations

  articleOpen access

  The role of macrophages (MΦs) remains incompletely understood in kidney injury and repair. The plasticity of MΦs offers an opportunity to polarize them toward mediating injury resolution in both native and transplanted kidneys undergoing ischemia and/or rejection. Here, we show that infiltrating kidney MΦs augmented their own allograft inflammatory factor 1 (AIF-1) expression after injury. Aif1 genetic deletion led to MΦ polarization toward a reparative phenotype while halting the development of kidney fibrosis. The enhanced repair was mediated by higher levels of antiinflammatory and proregenerative markers, leading to a reduction in cell death and an increase in proliferation of kidney tubular epithelial cells after ischemia followed by reperfusion injury (I/RI). Adoptive transfer of Aif1-/- MΦs into Aif1+/+ mice conferred protection against I/RI. Conversely, depletion of MΦs reversed the tissue-reparative effects in Aif1-/- mice. We further demonstrated increased expression of AIF-1 in human kidney biopsies from native kidneys with acute kidney injury or chronic kidney disease, as well as in biopsies from kidney allografts undergoing acute or chronic rejection. We conclude that AIF-1 is a MΦ marker of renal inflammation, and its targeting uncouples MΦ reparative functions from profibrotic functions. Thus, therapies inhibiting AIF-1 when ischemic injury is inevitable have the potential to reduce the global burden of kidney disease.

  PublisherOA PDFDOI

• Hybrid Extracellular Vesicle for Targeted Delivery of Therapeutic Cargoes to Combat Osteoporotic Bone Loss

  SSRN Electronic Journal · 2025-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Enabling adenosine signaling to promote aged fracture healing

  npj Regenerative Medicine · 2025-04-09 · 2 citations

  articleOpen accessSenior author

  Bone fractures and related complications are a significant concern for older adults, particularly with the growing aging population. Therapeutic interventions that promote bone tissue regeneration are attractive for geriatric fracture repair. Extracellular adenosine plays a key role in bone homeostasis and regeneration. Herein, we examined the changes in extracellular adenosine with aging and the potential of local delivery of adenosine to promote fracture healing using aged mice. Extracellular adenosine level was found to be significantly lower in aged bone tissue compared to young mice. Concomitantly, the ecto-5'-nucleotidase CD73 expression was also lower in aged bone. Local delivery of adenosine using injectable, in situ curing microgel delivery units yielded a pro-regenerative environment and promoted fracture healing in aged mice. This study offers new insights into age-related physiological changes in adenosine levels and demonstrates the therapeutic potential of adenosine supplementation to circumvent the compromised healing of geriatric fractures.

  PublisherOA PDFDOI

• Modeling functional responses to pollutant exposure using modular hydrogel supported vascularized alveolosphere-on-a-chip

  Biomaterials Science · 2025-01-01

  articleOpen accessSenior author

  Alveolar type 2 (AT2) cells play a pivotal role in maintaining lung homeostasis, and the generation of three-dimensional cultures, such as alveolospheres, provides a valuable model for studying lung development, pathologies, and drug responses. Here, we investigate the critical extracellular matrix (ECM) characteristics that influence AT2 alveolosphere formation and growth. By encapsulating AT2 cells in different extracellular matrix-based hydrogels, we identified laminin as a key ECM protein supporting robust alveolosphere formation akin to Matrigel. Our results show that laminin-rich hydrogels support alveolosphere formation across murine and human primary AT2 cells as well as induced human pluripotent stem cell derived AT2 cells (iAT2 cells). Notably, matrix stiffness strongly influenced alveolosphere formation. Hydrogels with a low Young's modulus and high compliance supported a greater number of alveolospheres, exhibiting a broader size distribution and a higher proportion of larger alveolospheres. Moreover, inhibition of matrix degradation and cellular contractility disrupted alveolosphere formation. Leveraging these insights, we developed a multicellular vascularized alveolosphere-on-a-chip model by integrating alveolospheres with endothelial cells and lung fibroblasts within a microfluidic device. Application of this model to assess the inflammatory effects of menthol, a common e-cigarette flavor, demonstrates its utility in evaluating the pulmonary effects of chemical exposures on alveolar cells. Our findings highlight the critical role of matrix physicochemical properties on alveolosphere formation and establish a versatile platform for advancing the study of lung biology, disease mechanisms, and drug discovery.

  PublisherOA PDFDOI

• Depletion of senescent cells improves surgery-induced neuroinflammation in aged mice

  PNAS Nexus · 2025-03-27 · 2 citations

  articleOpen accessSenior author

  Aging has been identified as a leading risk factor for many diseases, including neurodegenerative disorders. While cellular senescence has been linked to age-related neurodegenerative conditions, its involvement in peripheral stress-associated brain disorders is just beginning to be explored. In this study, we investigated the impact of senescent cells on peripheral stress-induced neuroinflammation using orthopedic surgery as a model. Our results demonstrate an increased accumulation of senescent cells and neuroinflammation in the aged mouse hippocampus following surgery. Intermittent treatment of the mice with the senolytic drugs dasatinib and quercetin (D/Q) showed a significant reduction in surgery-induced senescent cell burden. This reduction in senescent cell accumulation was correlated with reduced surgery-induced neuroinflammation, as evidenced by decreased glial cell activity. Consistent with these observations, we also observed reduced levels of proinflammatory senescence-associated secretory phenotype factors in circulation, following fracture surgery, in mice treated with D/Q. Overall, our findings underscore the pivotal role of cellular senescence in surgery-induced neuroinflammation and highlight the therapeutic potential of eliminating senescent cells as a potential strategy to manage peripheral stress-induced neuroinflammatory conditions.

  PublisherOA PDFDOI

• A subset of transposable elements as mechano-response enhancer elements in controlling human embryonic stem cell fate

  Nature Cell Biology · 2025-09-17 · 5 citations

  article
  PublisherDOI

• Extensive Periosteal Injury During Fracture Induces Long‐Term Pain in Mice

  Journal of Orthopaedic Research® · 2025-03-10

  articleOpen accessSenior authorCorresponding

  Bone fractures pose a significant public health challenge, often necessitating surgical interventions to facilitate bone healing and functional recovery. Sensory nerve fibers innervate various compartments of the bone tissue, with the periosteum exhibiting the most extensive innervation that is susceptible to injury during trauma. Despite its importance, the effect of injured periosteum on fracture pain remains unknown. This study examines the impact of extensive periosteal injury on fracture pain by using a mouse model. Periosteal injury is induced by mechanical resection during unilateral transverse fracture and compared to transverse fractures with no periosteal injury. Our results demonstrate that extensive periosteal injury induces severe and long-term pain, as assessed by von Frey and dynamic weight bearing measurements, for up to 12 weeks postfracture. Immunofluorescence staining revealed an increase in local neurofilament heavy polypeptide (NF200 +) nerve innervation and an elevated number of calcitonin gene-related peptide (CGRP +) expressing neurons in the dorsal root ganglion (DRG). Additionally, flow cytometric analyses revealed increased presence of myeloid immune cells in the DRG. Furthermore, bone healing in fractures with extensive periosteal injury exhibited reduced callus size at all time points as assessed by Faxitron X-ray imaging. This study describes a previously unknown effect of extensive periosteal injury in exacerbating fracture pain and establishes a potential model to study long-term orthopedic fracture pain.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AR06318402

  NIH · $329k · 2018

• NIH Grant R01AR06318401A1

  NIH · $329k · 2018

• I-Corps: 3D Organ on a Chip

  NSF · $50k · 2015–2016

• NIH Grant R01AR063184

  NIH · $1.1M · 2019

• Modulation of local adenosine signaling to attenuate fracture pain

  NIH · $2.8M · 2021–2027

Frequent coauthors

• Yu‐Ru V. Shih

  Duke University

  72 shared

• Aereas Aung

  University of Toronto

  59 shared

• Nathaniel S. Hwang

  Seoul National University

  48 shared

• Vardhman Kumar

  Duke University

  43 shared

• Yongsung Hwang

  Soonchunhyang University

  43 shared

• Jennifer H. Elisseeff

  Johns Hopkins Medicine

  41 shared

• Jomkuan Theprungsirikul

  Duke University

  37 shared

• Shruti K. Davey

  34 shared

Labs

• Varghese LabPI

  Current lab members