Regenerative medicine and diagnostics

HCMP in spheroids

We have developed multiple spheroid- and microtissue-based in vitro models to study the growth, repair, and regeneration of human tissues. Particular attention has been paid to the musculoskeletal system and adult mesenchymal stem cells, but our work has also touched on other targets including neurological and tumor models. Outside of these tissue engineering efforts, we have focused on implementing the hyper-compliant microparticle (HCMP) technology developed in the lab for multiple drug delivery applications. Other health-related applications include the development of novel diagnostic tools, specifically cell-like calibration particles and mechanocytometers.

  1. Dubay R, Darling EM, Fiering J. (2023) Microparticles with tunable, cell-like properties for quantitative acoustic mechanophenotyping. Microsyst Nanoeng. PMCID: PMC10336031. DOI: 10.1038/s41378-023-00556-6 (open access)
  2. Tandar CE, Dubay R, Turo MJ, Doyle RP, Darling EM, Fiering J. (2023) Physiologically relevant microparticles with mechanically tunable properties for acoustophoretic and microfluidic device calibration. Proc Mtgs Acoust. 50, 045004 (2022). DOI: 10.1121/2.0001809
  3. 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)
  4. Dubary R, Urban JN, Darling EM. (2021) Single‐Cell Microgels for Diagnostics and Therapeutics. Adv Func Mat. PMCID pending. DOI:  10.1016/j.biomaterials.2021.120684
  5. Parsons AM, Darling EM. (2021) Temporal responsiveness of adipose-derived stem/stromal cell immune plasticity. Exp Cell Rep. 406(1): 112738. PMID: 34270981. DOI: 10.1016/j.yexcr.2021.112738
  6. Microfluidic systemDubay R, Fiering J, Darling EM. (2020) Effect of elastic modulus on inertial displacement of cell-like particles in microchannels. Biomicrofluidics. 14(4): 044110. PMCID: PMC7402708. DOI: 10.1063/5.0017770
  7. Shah MK, Leary EA, Darling EM. (2019) Integration of hyper-compliant microparticles into a 3D melanoma tumor model. J Biomech. 82(3): 46-53. PMCID: PMC6310620. DOI: 10.1016/j.jbiomech.2018.10.018
  8. Azagury A, Fonseca VC, Cho DY, Perez-Rogers J, Baker CM, Steranka E, Goldenshtein V, Calvao D, Darling EM, Mathiowitz E. (2018) Single Step Double-walled Nanoencapsulation (SSDN). J Control Release. 280: 11-19. PMCID: PMC5993621. DOI: 10.1016/j.jconrel.2018.04.048
  9. Parsons AM, Ciombor M, Liu P, Darling EM. (2018) Regenerative potential and inflammation-induced secretion profile of human adipose-derived stromal vascular cells are influenced by donor variability and prior breast cancer diagnosis. Stem Cell Rev Rep. 14(4): 546–557. PMCID: PMC6014910. DOI: 10.1007/s12015-018-9813-1
  10. Dempsey ME*, Marble HD*, Shin T, Fawzi NL, Darling EM. (2018) Synthesis and characterization of a magnetically active 19F molecular beacon. ACS Bioconjug Chem. 29(2): 335-342. PMCID: PMC5821531. DOI: 10.1021/acs.bioconjchem.7b00671 (*Co-first authors)
  11. Labriola NR, Azagury A, Gutierrez R, Mathiowitz E, Darling EM. (2018) Concise Review: Fabrication, customization, and application of cell mimicking microparticles in stem cell science. Stem Cell Trans Med. (7): 232-240. PMCID: PMC5788880. DOI: 10.1002/sctm.17-0207
  12. Beane OS, Fonseca VC, Darling LEO, Darling EM. (2016) Disparate response to methotrexate in stem versus non-stem cells. Stem Cell Rev Reports. 12 (3): 340-51. PMCID: PMC4880537. DOI: 10.1007/s12015-016-9645-9
  13. Beane OS, Fonseca VC, Cooper LL, Koren G, Darling EM. (2014). Impact of aging on the regenerative properties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells. PLoS ONE. 9(12): e115963. PMCID: PMC4277426. DOI: 10.1371/journal.pone.0115963
  14. 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
  15. 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/b15085-23
  16. 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
  17. Athanasiou KA, Darling EM, Hu JCY. (2009). Articular Cartilage Tissue Engineering. Morgan & Claypool Publishers: San Rafael, CA. DOI: 10.2200/S00212ED1V01Y200910TIS003
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. Darling EM, Athanasiou KA. (2003) Biomechanical strategies for articular cartilage regeneration. Ann Biomed Eng. 31: 1114-1124. PMID: 14582614. DOI: 10.1114/1.1603752
  24. Darling EM, Athanasiou KA. Articular cartilage bioreactors and bioprocesses. (2003) Tissue Eng. 9 (1): 9-26. PMID: 12625950. DOI: 10.1089/107632703762687492