About

Sarah Calve is an Associate Professor and Associate Chair of Personnel in the Department of Mechanical Engineering at the University of Colorado Boulder, where she began her position in January 2020. Her research primarily focuses on the mechanics of soft biological materials, musculoskeletal development and regeneration, and the extracellular matrix (ECM). Her work aims to develop techniques to visualize ECM architecture and quantify how changes in local stiffness and cyclic loading affect the material properties of soft tissues during musculoskeletal development. She and her research group utilize bio-orthogonal labeling strategies to identify newly synthesized ECM proteins in the developing musculoskeletal system, employing confocal microscopy and novel decellularization and clearing protocols to visualize the 3D architecture of ECM in developing mouse models. Additionally, she has established a new atomic force microscopy-based method to measure how changes in tissue composition influence the mechanical properties of cells and ECM in developing limbs. Her long-term goal is to fully characterize the composition, organization, and mechanics of soft tissues such as muscle, tendon, ligament, and cartilage to guide the design of therapies that restore functionality to damaged tissues.

Research topics

• Cell biology
• Biology
• Chemistry
• Materials science
• Biophysics
• Genetics
• Nanotechnology
• Anatomy
• Computational biology
• Cancer research
• Biochemistry
• Immunology
• Medicine
• Biomedical engineering

Selected publications

• Application of Tendon‐Derived Matrix and Carbodiimide Crosslinking Matures the Engineered Tendon‐Like Proteome on Meltblown Scaffolds

  Journal of Tissue Engineering and Regenerative Medicine · 2025-01-01 · 1 citations

  articleOpen access

  Background: Tendon injuries are increasingly common and heal by fibrosis rather than scar‐less regeneration. Tissue engineering seeks to improve repair using synthetic polymer scaffolds with biomimetic factors to enhance the regenerative potential. Methods: In this study, we compared three groups, namely, poly(lactic acid) (PLA) meltblown scaffolds, PLA meltblown scaffolds coated with tendon‐derived matrix (TDM), and PLA meltblown scaffolds with carbodiimide crosslinked TDM (2.5:1:1 EDC:NHS:COOH ratio) (EDC‐TDM) and determined their potential for engineered tendon development. We cultured human adipose stem cells (hASCs) for 28 days on meltblown scaffolds ( n = 4–6/group) and measured tensile mechanical function, matrix synthesis, and matrix composition using biochemical assays and proteomics. Results: Coating PLA meltblown scaffolds with TDM improved yield stretch and stress at 28 days compared with PLA. Matrix synthesis rates for TDM or EDC‐TDM were similar to PLA. Proteomic analysis revealed that hASCs produced a collagen‐rich extracellular matrix, with many tendon‐related matrix proteins. Coating scaffolds with TDM led to an increase in collagen type I whereas EDC‐TDM scaffolds had an increase in glycoproteins and ECM regulators compared with other groups, consistent with increased maturity of the newly deposited matrix. Conclusions: TDM coating and crosslinking of meltblown scaffolds demonstrated matricellular benefits for the proteome of engineered tendon development but provided fewer clear benefits toward mechanical, biochemical, and rate of matrix accumulation than expected, and that previous work with electrospun scaffolds would suggest. However, electrospun scaffolds have different fiber structure and microarchitecture than meltblown, suggesting that further consideration of these differences and refinement of TDM application methods to meltblown scaffolds is required.

  PublisherDOI

• Effect of pregnancy, vaginal delivery, postpartum remodeling, and age on the tensile behavior and biochemical composition of the murine ulterosacral ligament (USL)

  Acta Biomaterialia · 2025-07-05 · 3 citations

  article
  PublisherDOI

• Fiber Type and Stimulus Determine Progression of Skeletal Muscle Atrophy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-14

  preprintOpen access

  Background: Skeletal muscle atrophy is prevalent worldwide and is a major detractor from length and quality of life. It is often diagnosed and treated as a single disorder, but the causal stimuli and progression of atrophy vary widely. Malnutrition and disuse are two common causes of muscle atrophy, and despite their prevalence and extensive characterization, there have been no direct comparisons of how these two types of atrophy progress and whether they differentially affect skeletal muscle fiber types. The purpose of this study is to directly compare atrophy from fasting and disuse and provide a transcriptomic resource for future research on both conditions. Methods: We fasted or hindlimb suspended (HS) two cohorts of 12-week-old female C57/bl6 mice. Mice were fasted for up to 72 hours to induce malnutrition atrophy or were hindlimb suspended for 0, 3, 7, 14, or 28 days to induce disuse atrophy. At each timepoint, mice were euthanized and three muscles (tibialis anterior (TA), extensor digitorum longus (EDL), and soleus) were weighed and collected for RNA sequencing. Atrophy progression and gene expression changes were compared across muscle fiber types and atrophy stimuli. Results: We found differences in atrophy progression between muscle fiber types based on fiber twitch speed and atrophy stimulus. Fasted mice lost 25% of their body weight and 23% of fast-twitch TA mass with little change in soleus. In contrast, HS mice lost 40% of the slower-twitch soleus but the effect on the TA was negligible. Gene expression varied in response to both atrophy stimuli, but a greater number of genes changed with fasting compared to HS in the EDL and soleus. By muscle type, a greater transcriptional shift occurred in the EDL with fasting while the soleus showed more gene changes during HS. Enrichment analysis of transcriptional changes showed similarities (downregulation in muscle growth pathways) and differences (increased fatty acid metabolism in fasting and increased neuronal activity in HS) between atrophy stimuli. Conclusions: Atrophy progression varies based on stimuli and muscle fiber type. This study provides a large, matched data set where the effects of different atrophic stimuli can be easily and directly compared in multiple fiber types. To our knowledge, this is the first study to closely compare these two atrophy stimuli in a muscle type-specific context. This work demonstrates that atrophy is not a single disorder and that the development of therapies may need to be tailored to the atrophic stimulus.

  PublisherOA PDFDOI

• The 2025 Young Innovators of Cellular and Molecular Bioengineering

  Cellular and Molecular Bioengineering · 2025-10-01

  editorialOpen access
  PublisherOA PDFDOI

• Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis

  Communications Biology · 2025-08-12 · 2 citations

  articleOpen accessSenior author

  The development of a functional musculoskeletal system requires the combination of contractile muscle and extracellular matrix (ECM)-rich tendons that transmit muscle-generated force to bone. Despite the different embryologic origins, muscle and tendon integrate at the myotendinous junction (MTJ) to connect across this interface. While the cell-cell signaling factors have received considerable attention, how the ECM links these tissues remains unclear. Here, we show the 3D distribution of ECM during forelimb development in wildtype (WT) and muscle-less Pax3Cre/Cre mice. At E12, prior to MTJ integration, an aligned ECM is present at the presumptive insertion of the long triceps into the ulna. Tendon-like and muscle compartmentalization structures still form when muscle is knocked out; however, MTJ-specific ECM is not observed when muscle is absent. Our results show that the architecture of the muscle-tendon unit is established independent of muscle, but muscle is needed for the proper assembly of ECM at the MTJ. The authors show that the muscle-tendon unit is established independently of muscle in the developing mouse forelimb; however, muscle is needed for the proper assembly of the extracellular matrix at the myotendinous junction.

  PublisherOA PDFDOI

• Advancing mechanical testing of biological tissues and hydrogels: A buoy-based approach

  Journal of Biomechanics · 2024-11-27 · 1 citations

  articleSenior authorCorresponding
  PublisherDOI

• Extracellular matrix protein composition dynamically changes during murine forelimb development

  iScience · 2024-01-08 · 10 citations

  articleOpen accessSenior authorCorresponding

  The extracellular matrix (ECM) is an integral part of multicellular organisms, connecting different cell layers and tissue types. During morphogenesis and growth, tissues undergo substantial reorganization. While it is intuitive that the ECM remodels in concert, little is known regarding how matrix composition and organization change during development. Here, we quantified ECM protein dynamics in the murine forelimb during appendicular musculoskeletal morphogenesis (embryonic days 11.5–14.5) using tissue fractionation, bioorthogonal non-canonical amino acid tagging, and mass spectrometry. Our analyses indicated that ECM protein (matrisome) composition in the embryonic forelimb changed as a function of development and growth, was distinct from other developing organs (brain), and was altered in a model of disease (osteogenesis imperfecta murine). Additionally, the tissue distribution for select matrisome was assessed via immunohistochemistry in the wild-type embryonic and postnatal musculoskeletal system. This resource will guide future research investigating the role of the matrisome during complex tissue development.

  PublisherOA PDFDOI

• Advancing Mechanical Testing of Biological Tissues and Hydrogels: A Buoy-Based Approach

  SSRN Electronic Journal · 2024-01-01

  preprintOpen access1st authorCorresponding
  PublisherDOI

• EdU detection on tissue sections v1

  2024-12-06

  preprintOpen accessSenior author

  This protocol describes the procedure for EdU detection used by the Seifert Lab. It assumes a starting sample of a paraffin-embedded tissue section and refers to the Seifert Lab protocol for fluorescent immunohistochemistry [add link when published]. It is adapted from the procedure described in A.Salic,T.J.Mitchison,A chemical method for fast and sensitive detection of DNA synthesisin vivo,Proc. Natl. Acad. Sci. U.S.A. 105 (7) 2415-2420, https://doi.org/10.1073/pnas.0712168105(2008).

  PublisherOA PDFDOI

• Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues

  Annual Review of Biomedical Engineering · 2024-01-02 · 10 citations

  articleOpen accessSenior author

  Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease.

  PublisherDOI

Recent grants

• Defining the mechanical link that unites the musculoskeletal system during limb development

  NIH · $2.2M · 2017–2022

• Imaging the role of hyaluronic acid in skeletal muscle assembly during murine for

  NIH · $214k · 2014–2017

• Bioorthogonal labeling of extracellular matrix assembly

  NIH · $355k · 2016–2019

• Biomechanical influence of ECM remodeling on the developing enthesis

  NIH · $1.7M · 2020–2023

Frequent coauthors

• Sarah N. Lipp

  Indiana University – Purdue University Indianapolis

  64 shared

• Kathryn R. Jacobson

  Purdue University West Lafayette

  48 shared

• Tamara L. Kinzer‐Ursem

  Purdue University West Lafayette

  38 shared

• Aya M. Saleh

  Technion – Israel Institute of Technology

  36 shared

• David S. Hains

  Indiana University – Purdue University Indianapolis

  24 shared

• Corey P. Neu

  Purdue University West Lafayette

  21 shared

• Ellen M. Arruda

  University of Michigan–Ann Arbor

  21 shared

• Tyler VanDyk

  University of Vermont

  19 shared

Awards & honors

• NIH Director’s New Innovator Award (2017)
• Rising Star Junior Faculty Award, Biomedical Engineering Soc…
• National Academy of Engineering, Japan – America Frontiers o…
• Spotlight on the Future” Invited Paper, Journal of Biomechan…
• Young Faculty Travel Award, American Association of Anatomis…