About

The Caliari Lab is based in the Departments of Chemical Engineering and Biomedical Engineering at the University of Virginia. We engineer biomaterials to better understand the dynamic reciprocity between cells and their microenvironment. We apply these platforms to address fundamental human health challenges including: Treatment of fibrotic diseases, Repair and replacement of musculoskeletal tissues. Life is constantly evolving and happening in three dimensions, and yet most of what we know about how cells interact with their environment comes from work on flat and hard surfaces that do a poor job of recapitulating the architecture, mechanics, and biologics of tissues and organs. We believe that the development of dynamic biomaterial tools that re-create the heterogeneous microenvironments of physiological and pathological conditions is essential to addressing challenges facing modern medicine.

Research topics

• Chemistry
• Materials science
• Composite material
• Biology
• Biophysics
• Cell biology
• Anatomy
• Biomedical engineering
• Engineering
• Medicine
• Polymer chemistry
• Nanotechnology
• Pathology
• Biochemistry

Selected publications

• Heparin‐Modified Aligned Collagen Scaffolds Enhance <i>In Vitro</i> Myogenesis

  Journal of Biomedical Materials Research Part A · 2026-02-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Biomaterial-based skeletal muscle tissue engineering approaches have largely focused on mimicking the 3D aligned architecture of native muscle, which is critical for guiding myotube formation and force transmission. In contrast, fewer studies incorporate glycosaminoglycan (GAG)-mediated biochemical cues despite their known role in regulating myogenesis and growth factor sequestration. In this study, we develop aligned collagen-GAG (CG) scaffolds using directional freeze-drying and systematically vary GAG type by incorporating GAGs of increasing sulfation levels (hyaluronic acid, chondroitin sulfate, and heparin). While all scaffold variants support myoblast adhesion, metabolic activity, and myotube alignment, heparin-modified CG scaffolds significantly enhance myoblast metabolic activity and myogenic differentiation as measured by myosin heavy chain (MHC) expression and myotube size. We additionally show that heparin-modified scaffolds sequester and retain significantly higher levels of insulin-like growth factor-1 (IGF-1), a potent promoter of myogenesis, compared to other scaffold groups. Together, these results highlight the importance of tailoring GAG type in CG scaffolds for targeted applications and underscore the promise of heparin-modified CG scaffolds as a material platform for skeletal muscle tissue engineering.

  PublisherOA PDFDOI

• Lung tissue viscoelasticity is preserved with bleomycin-induced fibrosis in mice

  Acta Biomaterialia · 2026-02-21 · 1 citations

  articleSenior authorCorresponding
  PublisherDOI

• Engineering thermoresponsive biointerfaces using graft-to strategies: connecting polymer architecture to temperature-dependent surface wettability

  ChemRxiv · 2026-02-20

  articleOpen access

  Temperature-responsive substrates provide a promising strategy for addressing issues in biomaterials design, but their utility hinges on achieving predictable, tunable surface response through deliberate thermoresponsive polymer design. Here, we investigate how varying polymer architecture, namely, surface attachment point density and chain length, influence wettability above and below the lower critical solution temperature (LCST) and magnitude of temperature-driven contact angle change of polymer-grafted glass surfaces. Using random copolymers of thermoresponsive di(ethylene glycol) methyl ether methacrylate (DEGMA) units and surface attachment point aminoethyl methacrylate (AEMA) units, we show that increasing polymer attachment point density from 2 to 30 mol% while holding degree of polymerization constant decreases the magnitude of the temperature-driven contact angle change from 15.2 ± 0.5 to 5.7 ± 0.03º. This suggests higher attachment point densities produce compact polymer loop structures on the surface that constrain thermoresponsive units and hinder hydration below the LCST. In contrast, increasing the degree of polymerization from 49 to 350 at a constant attachment point density increases the magnitude of contact angle shift from 7.4 ± 4.4 to 22 ± 2.2º, likely attributed to enhanced chain mobility with increasing chain length. Notably, all surfaces converge to approximately the same contact angle above the LCST, regardless of polymer architecture, likely owing to the formation of similarly collapsed, dehydrated polymer layers that present comparable surface compositions to the interface. This work demonstrates polymer architectures that allow greater chain mobility, achieved through lower attachment point density or longer chain length, produce larger thermal surface responses below the LCST, driven by enhanced hydration. By linking polymer loop structure and chain mobility to surface behavior, these insights provide a framework for designing biointerfaces with predictable and tunable properties.

  PublisherDOI

• An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-06

  articleOpen accessSenior authorCorresponding

  Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease of aging, driven by dysregulated fibroblast activation and accompanied by collagen accumulation in the lung interstitium, resulting in tissue stiffening. While the accumulation of senescent cells has been increasingly implicated in IPF pathogenesis, understanding the reciprocal dynamics of senescent fibroblast levels and evolving tissue mechanics is difficult to achieve with experimental approaches alone. To address this limitation, we developed an agent-based model (ABM) of fibroblast activation in the lung that couples cell behavior to the dynamic mechanical changes accompanying fibrosis. This model was parameterized entirely from experimental data in young mice to enable robust validation and then adapted to fit aged mouse biology for additional validation. Both young and aged models accurately reflected changes in collagen accumulation and stiffness burden of experimental systems. We then incorporated senescent cell behavior into the aged model to investigate how senescent cell burden influences fibrosis progression and how cell-cell interactions drive senescent cell accumulation. These simulations identified a unique role for juxtacrine-mediated contact between non-senescent and senescent fibroblasts in expanding the total senescent cell burden. Our ABM also revealed that the timing of immune-mediated senescent cell clearance critically regulates fibrotic outcomes. Together, this ABM provides useful insights into how the interrelated dynamics of tissue mechanics and senescent fibroblasts drive fibrosis progression.

  PublisherOA PDFDOI

• Emergent directional persistence in fibrous granular scaffolds guides myotube organization

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-06

  articleOpen accessSenior authorCorresponding

  Granular scaffolds have emerged as promising platforms for tissue regeneration, offering injectability and cell-scale porosity that support robust cell infiltration and tissue formation. However, the isotropic pore structure of spherical building blocks does not provide the directional cues needed to guide organized tissue formation. Addressing this requires asking not just whether granular scaffolds can be made anisotropic, but whether directional cues persist across the pore network at scales relevant to cell behavior. Using high aspect ratio GelMA hydrogel fibers as building blocks, we demonstrate that spherical granular materials lose orientational coherence at the cellular scale, confirming that isotropic building blocks are fundamentally incapable of providing structural guidance beyond individual pore neighborhoods. In contrast, fibrous building blocks extend persistence into the multicellular range, occupying an intermediate architectural regime exhibiting locally coherent but globally variable organization, rather than simple isotropic or uniaxial alignment, that has previously been inaccessible to granular scaffold design. We show this regime is functionally meaningful: myotubes undergo contact guidance through locally persistent but globally variable pore structure, and greater persistence is associated with increased myotube elongation and multinucleation in primary human muscle progenitor cells. Together these results expand the design space for granular scaffolds beyond pore size and porosity, and establish persistence as a variable linking granular scaffold architecture to organized tissue formation.

  PublisherDOI

• Enhancing stability of 3-(aminopropyl)triethoxysilane (APTES) and glutaraldehyde (GA)-anchored glass coatings through Schiff base reduction

  ChemRxiv · 2026-01-28

  articleOpen access

  Glass functionalization with 3-aminopropyltriethoxysilane (APTES) is widely used to introduce surface amines; however, these films hydrolyze within minutes under physiologic conditions, limiting their utility in subsequent conjugation steps. Glutaraldehyde (GA) treatment stabilizes these coatings while introducing pendant aldehyde groups for conjugation with amine-bearing molecules, yet the resulting Schiff base linkages are also hydrolytically labile. Here, we show the importance of a reductive amination step in enhancing the stability of APTES-GA-based coatings. After conjugating a model thermoresponsive copolymer to APTES-GA coatings, we evaluate temperaturedependent surface wettability of reduced and unreduced polymer coatings following incubation in phosphate buffered saline (PBS) for 24 h. While prior to PBS incubation, both coatings demonstrated an ~11º difference in contact angle between temperatures above and below the lower critical solution temperature (LCST), only reduced polymer coatings maintained this behavior after incubation. By demonstrating Schiff base reduction as a critical step in surface functionalization workflows, this work highlights a strategy for stabilizing grafted coatings in aqueous/physiologic environments.

  PublisherOA PDFDOI

• Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation

  Biomaterials Science · 2026-01-01 · 1 citations

  articleOpen accessSenior author

  Persistent fibroblast activation drives tissue fibrosis, yet how mechanical and inflammatory cues are integrated to promote this aberrant behavior remains unclear. Using a hyaluronic acid (HA)-based hydrogel platform to model normal and fibrotic lung mechanics, we examine the roles of Piezo1 and cadherin-11 (CDH11), both implicated in M2 macrophage-fibroblast crosstalk during pulmonary fibrosis progression, in interleukin (IL)-6-mediated fibroblast activation. While both Piezo1 and CDH11 expression increase in activated fibroblasts, blocking IL-6 signaling decreases CDH11, but not Piezo1, expression. Instead, Piezo1 activity promotes nuclear accumulation of the calcium-dependent transcription factor NFAT1. While Piezo1 inhibition moderately reduces CDH11 expression, it does not prevent fibroblast activation as measured by spreading and type I collagen expression, whereas CDH11 knockout suppresses fibroblast activation metrics, reduces Piezo1 expression, and decreases IL-6 secretion in both fibroblast only and fibroblast-M2 macrophage co-cultures. Furthermore, CDH11 levels increase in parallel with progressive fibroblast activation, highlighting its role in promoting this pro-fibrotic phenotype. Together, these findings underscore a previously unrecognized signaling axis in which CDH11 serves as a key mediator of sustained fibroblast activation, coordinating mechanical and inflammatory cues, and highlight CDH11 as a potential therapeutic target in pulmonary fibrosis.

  PublisherOA PDFDOI

• Lung tissue viscoelasticity is preserved with bleomycin-induced fibrosis in mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-11 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT In pulmonary fibrosis, excessive scar tissue accumulates in the alveolar interstitial space, impairing gas exchange and compromising lung function. This fibrotic remodeling results in tissue stiffening, but more complex lung mechanical properties critical to tissue function, such as viscoelasticity and stress relaxation, remain poorly defined. To address this gap, we use the bleomycin aged mouse model to characterize both bulk and spatially-resolved viscoelastic mechanical properties of normal and fibrotic lungs. Our analysis reveals that while bleomycin-induced fibrosis leads to heterogeneously increased lung stiffness, viscoelasticity as measured by tan delta (ratio of loss to storage modulus) and stress relaxation timescales remains remarkably consistent as a function of both age and bleomycin treatment. This unexpected preservation of viscoelasticity despite fibrotic stiffening highlights a previously underappreciated mechanical phenotype of fibrotic lungs. To model these distinct mechanical features in vitro , we utilize a hyaluronic acid-based hydrogel system that largely recapitulates the viscoelastic mechanical properties observed in both normal and fibrotic lungs. These findings provide new insight into the mechanical consequences of fibrosis and establish a tunable in vitro hydrogel platform mimicking key tissue viscoelastic properties.

  PublisherOA PDFDOI

• Substrate stiffness and viscoelasticity influence fibroblast senescence

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-27

  preprintOpen accessSenior authorCorresponding

  Senescent cell accumulation has been implicated in aging and fibrotic disease, which are both characterized by increased tissue stiffness. However, the direct connection between tissue mechanics and senescence induction remains disputed in the literature. Thus, this work investigates the influence of hydrogel stiffness and viscoelasticity in promoting fibroblast senescence both in combination with genotoxic stress and independently. We show that while lung fibroblast YAP signaling declines with senescence induction, senescent fibroblasts maintain their mechanosensing capabilities with increased YAP nuclear localization on higher stiffness hydrogels. Most notably, we find a unique role for hydrogel viscoelasticity in senescence induction with soft (2 kPa) viscoelastic substrates promoting both the onset and amplification of senescence, even in the absence of genotoxic stress. These changes are not associated with a decline in YAP activity, but instead with a decline in nuclear DAPI intensity, suggesting a role of nuclear organization in driving this phenotype. Overall, this work highlights the influence of mechanics on the induction of senescence and supports the key role of viscoelasticity.

  PublisherOA PDFDOI

• M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote IL-6-dependent fibroblast activation

  Cell Biomaterials · 2025-04-08 · 15 citations

  articleOpen accessSenior author

  Fibroblast activation drives fibrotic disease; however, the complex interplay of how tissue mechanics and macrophage signaling combine to influence fibroblast activation remains unclear. Using hyaluronic acid hydrogels to mimic lung stiffness and viscoelasticity, we investigated macrophage influence on fibroblast activation. Fibroblasts cultured on stiff (50 kPa) hydrogels mimicking fibrotic tissue exhibit increased activation, as measured by cell spreading and type I collagen and cadherin-11 expression, compared to fibroblasts cultured on soft (1 kPa) viscoelastic hydrogels mimicking normal lung. Macrophage-conditioned media did not alter these trends, however co-culture with M2 macrophages increased fibroblast activation independent of direct macrophage contact, even on soft viscoelastic hydrogels. Blocking interleukin 6 (IL6) signaling mitigated this pro-fibrotic effect but did not affect fibroblast-only cultures. These findings demonstrate that M2 macrophages override hydrogel viscoelasticity to promote fibroblast activation independent of direct contact in an IL6-dependent manner and highlight the utility of hydrogels in deconstructing complex tissue microenvironments.

  PublisherDOI

Recent grants

• Aligned and Conductive 3D Collagen Scaffolds for Skeletal Muscle Tissue Engineering

  NIH · $356k · 2019–2022

• Designing cell-instructive hydrogels to understand and exploit mechanobiology

  NIH · $1.8M · 2020–2025

• NIH Grant F32DK103463

  NIH · $114k · 2017

• CAREER: Mechanically dynamic and viscoelastic hydrogels as tools for studying fibroblast epigenetic memory

  NSF · $579k · 2021–2025

Frequent coauthors

• Brendan A.C. Harley

  University of Illinois Urbana-Champaign

  23 shared

• Daniel W. Weisgerber

  University of California, San Francisco

  12 shared

• Jason A. Burdick

  University of Colorado Boulder

  11 shared

• Maryna Perepelyuk

  7 shared

• Rebecca G. Wells

  University of Pennsylvania

  7 shared

• Jenna L. Sumey

  University of Virginia

  7 shared

• B J Miller

  University of Virginia

  6 shared

• George J. Christ

  University of Virginia

  6 shared

Education

• PhD, Chemical Engineering

  University of Illinois at Urbana-Champaign

  2013

• MS, Chemical Engineering

  University of Illinois at Urbana-Champaign

  2010

• BS, Chemical Engineering

  University of Florida

  2007

Awards & honors

• SEAS Copenhaver Fellow 2023
• UVA Research Excellence Award 2021
• Young Innovator in Cellular and Molecular Bioengineering 202…
• NSF CAREER Award 2021
• NIH (NIGMS) Maximizing Investigators’ Research Award (MIRA)…