Musculoskeletal systems

Forcescanning technique

Our research into musculoskeletal systems includes study of adult stem cell differentiation into cartilage, bone, and fat tissues and well as developing in vitro models for the repair and regeneration of these tissues. Much of our work in this area dovetails with other research thrusts in the lab. This includes mechanical characterization of tissue microenvironments using force sensors, enrichment of lineage-specific stem cell populations, and investigations into the heterogeneity of resident cell types. Our work has contributed to a better understanding of chondrocyte and stem cell subpopulations, with significant findings related to cartilage-specific gene expression changes during in vitro expansion and measurements of the mechanical microenvironment of cell-dense tissues.

  1. Gutierrez RA, Fonseca VC, Darling EM. (2022) Chondrogenesis of Adipose-Derived Stem Cells Using an Arrayed Spheroid Format. Cell Mol Bioeng. PMCID: PMC9751248. DOI: 10.1007/s12195-022-00746-8 (open access viewing)
  2. Gutierrez RA, Fang W, Kesari H*, Darling EM*. (2021) Force sensors for measuring microenvironmental forces during mesenchymal condensation. Biomaterials. 270: 120684. PMCID: PMC7906959. DOI: 10.1016/j.biomaterials.2021.120684 (*Co-corresponding author)
  3. Labriola NR, Sadick JS, Morgan JR, Mathiowitz E, Darling EM. (2018) Cell mimicking microparticles influence the organization, growth, and mechanophenotype of stem cell spheroids. Ann Biomed Eng. 46(8): 1146-1159. PMCID: PMC6039261. DOI: 10.1007/s10439-018-2028-4
  4. Athanasiou KA, Darling EM, Duraine GD, Hu JC, Reddi AH. (2017) Articular Cartilage, Second Edition. DOI: 10.1201/9781315194158
  5. Yang X, Darling EM, Herzog W. (2017) Functional properties of chondrocytes and articular cartilage using optical imaging to ccanning probe microscopy. J Orthop Res. PMCID: PMC5839958. DOI: 10.1002/jor.23757
  6. Chen Y, Cossman J, Jayasuriya CT, Li X, Guan Y, Fonseca VC, Yang K, Charbonneau C, Yu H, Kanbe K, Ma P, Darling EM, Chen Q. (2016) Deficient mechanical activation of anabolic transcripts and post-traumatic cartilage degeneration in matrilin-1 knockout mice. PLoS ONE. 11(6): E0156676. PMCID: PMC4896629. DOI: 10.1371/journal.pone.0156676
  7. Labriola NR, Darling EM. 2015. Temporal heterogeneity in single-cell gene expression and mechanical properties during adipogenic differentiation. J Biomech. 28(2015): 1058-66. PMCID: PMC4380682. DOI: 10.1016/j.jbiomech.2015.01.033
  8. Marble HD, Sutermaster BA, Kanthilal M, Fonseca VC, Darling EM. (2014). Gene expression-based enrichment of live cells from adipose tissue produces subpopulations with improved osteogenic potential. Stem Cell Res Ther. 5(5):145. PMCID: PMC4619280. DOI: 10.1186/scrt502
  9. Beane OS, Fonseca VC, Cooper LL, Koren G, Darling EM. (2014). Impact of aging on the regenerative preoperties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells. PLoS ONE. 9(12): e115963. PMCID: PMC4277426. DOI: 10.1371/journal.pone.0115963
  10. Kanthilal M, Darling EM. (2014). Characterization of mechanical and regenerative properties of human, adipose stromal cells. Cell Mol Bioeng. 7 (4): 585-97. PMCID: PMC4255916. DOI: 10.1007/s12195-014-0350-y
  11. Beane OS, Fonseca VC, Darling EM. (2014). Adipose-derived stem cells retain their regenerative potential after methotrexate treatment. Exp Cell Res. 327 (2014): 222-233. PMCID: PMC4164584. DOI: 10.1016/j.yexcr.2014.06.015
  12. Desai HV, Voruganti IS, Jayasuriya C, Chen Q, Darling EM. (2014). Live-cell, temporal gene expression analysis of osteogenic differentiation in adipose-derived stem cells. Tissue Eng Pt A. 20(5-6): 899-907. PMCID: PMC3938923. DOI: 10.1089/ten.TEA.2013.0761
  13. Athanasiou KA, Darling EM, Duraine GD, Hu JC, Reddi AH. (2013). “Articular Cartilage.” Taylor & Francis Group, LLC: Boca Raton, FL. IBSN: 9781439853245
  14. Darling EM, Athanasiou KA. (2013) Bioactive scaffold design for articular cartilage engineering. Biomedical Technology and Devices Handbook. 2nd edition. Ed. by J. Moore and D. Maitland. DOI: 10.1201/b15085-23Quartz crystal microplate
  15. Beane OS, Darling EM. (2012). Isolation, Characterization, and Differentiation of Stem Cells for Cartilage Regeneration. Ann Biomed Eng. 40 (10): 2079-97. PMCID: PMC3457050. DOI: 10.1007/s10439-012-0639-8
  16. González-Cruz RD, Fonseca VC, Darling EM. (2012). Cellular mechanical properties reflect differentiation potential of adipose-derived mesenchymal stem cells. Proc Natl Acad Sci USA. 109 (24): E1523-9. PMCID: PMC3386052. DOI: 10.1073/pnas.1120349109
  17. Desai HV, Darling EM. (2012). Force Scanning for Simultaneous Collection of Topographical and Mechanical Properties. Microscopy and Analysis, January 2012. Volume 26, Issue 1. DOI: 10.1002/micro.235/full
  18. Darling EM. (2011). Force scanning: A rapid, high-resolution approach for spatial mechanical property mapping. Nanotechnology. 22 (17) 175707. PMCID: PMC3150532. DOI: 10.1088/0957-4484/22/17/175707 *Recognized by Nanotechnology in their “Highlights 2011” Collection.
  19. Gilchrist CL, Darling EM, Chen J, Setton LA. (2011). Extracellular matrix ligand and stiffness modulate immature nucleus pulposus cell‐cell interactions. PLoS One. 6 (11): e27170. PMCID: PMC3210142. DOI: 10.1371/journal.pone.0027170
  20. Darling EM*, Wilusz RE*, Bolognesi MP, Zauscher S, Guilak F. (2010). Spatial mapping of the biomechanical properties of the pericellular matrix of articular cartilage measured in situ via atomic force microscopy. Biophys J. 98: 2848-2856. PMCID: PMC2884253. DOI: 10.1016/j.bpj.2010.03.037 (*co-first author)
  21. Darling EM, Pritchett PE, Evans BA, Superfine R, Zauscher S, Guilak F. (2009). Mechanical properties and gene expression of chondrocytes on micropatterned substrates following dedifferentiation in monolayer. Cell Molec Bioeng. 2 (3): 395-404. PMCID: PMC2898162. DOI: 10.1007/s12195-009-0077-3
  22. Athanasiou KA, Darling EM, Hu JCY. (2009). Articular Cartilage Tissue Engineering. Morgan & Claypool Publishers: San Rafael, CA. DOI: 10.2200/S00212ED1V01Y200910TIS003
  23. Darling EM, Guilak F. (2008) A neural network model for cell classification based on single-cell biomechanical properties. Tissue Eng Part A. 14 (9): 1507-1515. PMCID: PMC2748927. DOI: 10.1089/ten.tea.2008.0180
  24. Coles J, Blum J, Jay G, Darling EM, Guilak F, Zauscher S. (2008) In situ friction measurement on murine cartilage by atomic force microscopy. J Biomech. 41 (3): 541-548. PMCID: PMC2274896. DOI: 10.1016/j.jbiomech.2007.10.013
  25. Darling EM, Topel M, Zauscher S, Vail TP, Guilak F. (2008) Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. J Biomech. 41 (2): 454-464. PMCID: PMC2897251. DOI: 10.1016/j.jbiomech.2007.06.019
  26. Darling EM, Zauscher S, Block JA, Guilak F. (2007) A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: Do cell properties reflect metastatic potential? Biophys J. 92: 1784-1791. PMCID: PMC1796808. DOI: 10.1529/biophysj.106.083097
  27. Darling EM, Zauscher S, Guilak F. (2006) Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy. Osteoarthritis Cartilage. 14 (6): 571-579. PMID: 16478668. DOI: 10.1016/j.joca.2005.12.003
  28. Darling EM, Athanasiou KA. (2005) Growth factor impact on articular chondrocyte subpopulations. Cell Tissue Res. 322: 463-473. PMID: 16047167. DOI: 10.1007/s00441-005-0020-4
  29. Darling EM, Athanasiou KA. (2005) Retaining zonal chondrocyte phenotype by means of novel growth environments. Tissue Eng. 11 (3/4): 395-403. PMID: 15871669. DOI: 10.1089/ten.2005.11.395
  30. Darling EM, Athanasiou KA. (2005) Rapid phenotypic changes in passaged articular chondrocyte subpopulations. J Orthop Res. 23 (2): 425-432. PMID: 15734258. DOI: 10.1016/j.orthres.2004.08.008
  31. Darling EM, Hu JCY, Athanasiou KA. (2004) Zonal and topographical gene expression in articular cartilage. J Orthop Res. 22 (6): 1182-1187. PMID: 15475195. DOI: 10.1016/j.orthres.2004.03.001
  32. Darling EM, Athanasiou KA. (2004) Bioactive scaffold design for articular cartilage engineering. Biomedical Technology and Devices Handbook. Ed. by J. Moore and G. Zouridakis. Chapter 21. CRC Press: Boca Raton, FL. ISBN: 9780849311406
  33. Darling EM, Athanasiou KA. (2003) Biomechanical strategies for articular cartilage regeneration. Ann Biomed Eng. 31: 1114-1124. PMID: 14582614. DOI: 10.1114/1.1603752
  34. Darling EM, Athanasiou KA. Articular cartilage bioreactors and bioprocesses. (2003) Tissue Eng. 9 (1): 9-26. PMID: 12625950. DOI: 10.1089/107632703762687492